Essential of Pharmaceuticals care 1

CHAPTER ONE

MODELS OF PHARMACY PRACTICE

Azuka C Oparah
Learning Objectives
At the end of this chapter, you should be able to:
I. List and explain the different models in the evolution of pharmacy
practice
II. Define pharmaceutical care and compare it with other practice
models

Introduction
Professions exist because of the social need for them; every profession
consciously makes efforts to meet the social needs, or else, it goes into
oblivion. Pharmacy being an international profession, is part of this social
evolutionary process. The events in one part of the world tend to
influence the practice of the profession in the other parts. The history of
the evolution of pharmacy practice in the United States of America (USA)
has greatly influenced what we see today of the profession. Pharmacy
practice in the USA as at today is representative of the most advanced in
the world and documents exist to trace its history.
The profession of pharmacy has undergone series of changes in terms
of philosophy and practice as it seeks to meet the dynamics of societal
expectations and changes in the legal/regulatory standards, as well as
technology of health care provision. In this evolutionary process of
pharmacy, there has been an uneven adoption of a new practice model
as opportunities for its exercise emerge, rather than a series of abrupt
changes in practice occurring simultaneously throughout the profession
and across the globe.1-2
Stages in the evolution of the profession from product to patient
 Models Of Pharmacy Practice 2

orientations are briefly presented:3

Apothecary model
In this first stage, the main function of pharmacy was manufacturing of
drugs and this began as a cottage industry serving the individual.
Pharmacists made patent medicines according to their own recipe,
prescribed, and sold them from their own dispensaries. The apothecary
was the equivalent of today's pharmaceutical industry, drugstore, and
primary care provider all rolled into one. Both product and process were
valued: patients came to the pharmacist for the medication itself and for
advice and guidance on its selection and use. At that time, pharmacy
had a clearly defined social value.3

Compounding model
The period around 1945, during the industrial revolution saw a
phenomenal growth in the manufacturing industry that took over the
mass production of drugs in the industry. Pharmacists then moved to
compounding the mixing of medicines already manufactured
according to prescription and guiding patients on self-care.
Distribution model
In the third stage, the main task of pharmacists diverged, depending on
the setting of practice. Increased availability of manufactured drugs and
the 1951 Durham Humphrey Amendment to the 1938 US Food, Drug,
and Cosmetic Act. This amendment introduced prescription only legal
status of medicines, thereby limiting who could prescribe and advice on
use of medications, confined community pharmacists to dispensing.
Community pharmacy became a channel of distribution for the
pharmaceutical industry. Hospital pharmacists functioned primarily in a
support role for the management of drug products. Their daily activities
were more varied than those of the community pharmacist and included
 Essential of Pharmaceuticals care 3

distribution, management, large-volume compounding, teaching

of nurses, and participation in Pharmacy and Therapeutics
Committees. As in community practice, the emphasis was on the
product and not the patient.3

Clinical Pharmacy Model

Clinical Pharmacy originated in the US in the 1960s. In this
practice model, community pharmacists resumed providing drug
information by way of advice and medication counseling, providing
consultations on generic substitution and non-prescription drug
use. While physicians maintained responsibility for medication
therapy outcomes, hospital pharmacists provided a valuable
supporting service founded in their specialized knowledge of the
action and use of medications. Adoption of the clinical pharmacy
practice model may be viewed as the beginning of social value for
hospital pharmacists. This stage was the re-emergence of patient
oriented pharmacy. Pharmacists performed clinical functions such
as:4
· Interpreting, questioning, and validating drug orders;
· Monitoring patients' drug therapy;
· Managing selected drug therapies (e.g.
aminoglycosides, heparin, aminophylline, parenteral
nutrition);
· Detecting and reporting drug allergies and adverse
drug reactions;
· Providing drug-use education;
· Answering drug information requests;
· Conducting patient reviews;
· Participating in patient care rounds;
· Performing drug use review and patient
 Models Of Pharmacy Practice 4

· Care audits; and performing drug therapy research.

Pharmaceutical Care Model

Professionals do not merely perform functions but take responsibility for

functions that they perform and those performed under their supervision.
The fifth stage in the transition of pharmacy practice is the era of taking
responsibility in the performance of clinical functions such as disease
management with the drug product as the foundation. Hepler and Strand
(1990) defined pharmaceutical care as the responsible provision of drug
therapy for the purpose of achieving definite outcomes that improve a
patient's quality of life. The outcomes are curing a disease, eliminating or
reducing symptoms, arresting or slowing a disease process, and
preventing a disease or symptoms. To achieve these ends, pharmacists
cooperate with patients and with other health care professionals in
designing, implementing, and monitoring a care plan aimed at
preventing and resolving drug-related problems (DRPs). This in turn
involves three major functions namely: identifying potential and actual
drug related problems; resolving actual drug related problems; and
preventing potential drug related problems.

The International Pharmaceutical Federation (FIP) 1998 statement

describes pharmaceutical care as the responsible provision of
pharmacotherapy for the purpose of achieving definite outcomes that
improve a patient's quality of life. It is a collaborative process that aims to
prevent or identify and solve medicinal product and health related
problems. This is a continuous quality improvement process for the use
of medicinal products. The new role requires pharmacists to apply a
higher level of drug knowledge, clinical skill and independent judgment
to their work and to accept the burden of responsibility. Pharmaceutical
care thus emphasizes the role of pharmacists in two broad areas:
 Essential of Pharmaceuticals care 5

medicines management and health promotion.

Dispensing remains pharmacy function/responsibility, irrespective of

whether the pharmacist performs the process directly or pharmacy
supportive staff do it under a pharmacist's supervision. Some
differences between the traditional dispensing and pharmaceutical care.
5-6
These differences are shown in the Table 1.1 below.

Table 1.1: Differences between traditional drug dispensing and pharmaceutical care
Traditional Drug Dispensing Pharmaceutical Care
Focus on patient’s management and
Focus on dispensing the medicine outcomes with the drug treatment

In addition with technical advice, the

Patient’s education and counselling pharmacist is training the patient to
concentrate on technical advice. practice the drug treatment in everyday
life.

The pharmacist is finding methods to

No monitoring of the outcomes of drug
monitor the outcomes of drug treatment.
treatment.

The pharmacist is actively and

Drug related problems would emerge if the
systematically identifying possible
patient tells about them.
problems in the drug treatment.

No responsibility for the drug treatment.

The pharmacist takes responsibility that
the drug treatment will be achieved.
 Models Of Pharmacy Practice 6

Total Pharmacy Care Model

Holland and Nimmo (1999)3 have proposed this model of pharmacy
practice using a reductionist and subjective interpretation of events.
Total pharmacy care (TPC) is the delivery of a comprehensive range of
services that result in the maximum possible contribution to the health
care of a nation's population within the limits of the health care delivery
structure. TPC combines five existing practice models: distribution, self
care, drug information, clinical pharmacy, and pharmaceutical care.
Their logic is that there will be an ongoing need for the existing practice
models, which the proportion of pharmacists employing each will reflect
the needs of a given health care environment at a given time, and that if
changes in health care provide more opportunities for pharmaceutical
care, pharmacists will shift increasingly toward that type of practice.

The evolution of pharmacy practice is still going on, and no single

practice model can best explain the observed practices in different parts
of the world. However, the system of drug use wherein pharmacists
share responsibility for optimizing outcomes of drug therapy with other
health care professionals represents the accepted professional ideal for
pharmacy. Furthermore, as managed care organizations coordinate
patient care models that attempt to provide a continuum of care, it is
fitting that the provision of pharmaceutical care by pharmacists be the
7
expectation of benefits to managers and physicians. Unlike other
settings, involvement with managed care presents pharmacists with new
8
opportunities to provide continuity of care and outpatient monitoring.
This is due largely to the development of community-based information
systems that can enhance the exchange of information between
pharmacists and other members of the health care team. Current
pharmaceutical care models suggest that pharmacists need to develop
patient care plans, but developing these plans and providing effective
 Essential of Pharmaceuticals care 7

drug treatment require a strong communication link between the

9
physician and the pharmacist. This team relationship is possible in a
managed care organization.
Introspection into the profession of pharmacy and into the expectations
of future services delivery by managed care organizations suggests a
potentially synergistic relationship and the logical evolution of
pharmaceutical care practice into managed care environments. Berger
and Grimley (1997) have suggested that pharmacists be directed toward
a change in attitude before they are expected to develop innovative
10
practices and offer new services.

Pharmaceutical care practice: global perspectives

Pharmaceutical care, which was an American concept, is
developing in several European countries, but perhaps most
visibly in countries such as the Netherlands, Spain, Denmark,
Germany and increasingly in the United Kingdom and Canada. In
all countries, pharmaceutical care starts and progresses largely
due to the enthusiasm and efforts of a few individuals. Some
11-12
representative accounts are given below.
United States of America
13
Hepler and Strand (1990) published the paper on pharmaceutical care
that changed the direction of pharmacy practice worldwide. Their
concept of pharmaceutical care has been widely adopted in the USA,
and has evolved into different practice settings: health systems
pharmacy, community pharmacy, physician office, GP surgeries, home
7
and hospice services, and Managed Care Organizations. Hepler is now
involved in developing the concept of pharmaceutical care by focusing
on one disease state at a time, and monitoring therapeutic outcomes for
 Models Of Pharmacy Practice 8

these specific patient groups. Ongoing studies of pharmaceutical care

include applications and assessment in medical conditions such as
asthma, diabetes, angina, hypertension, and hyperlipidemia.14 Mason
reported that Strand updated conference delegates on developments
in Minnesota where pharmaceutical care is now being provided in
nearly 50 practices.11 As at 2002, 45,000 pharmaceutical care
encounters have been documented for over 15,000 patients and over
19,000 drug therapy problems identified, prevented and resolved. The
financial impact has been considerable with the ratio of savings to costs
ranging between two and 10 to one.

Pharmaceutical care researchers in Iowa two Colleges of Pharmacy,

the University of Iowa and the Drake University in response to the call
by their local pharmacists founded the Iowa Center for Pharmaceutical
15
Care in 1994. They have adopted the theory and practice of
pharmaceutical care developed by Strand (1998) and her colleagues at
the University of Minnesota in training pharmacists to become
16
pharmaceutical care practitioners. The efforts of the Iowa group
resulted in the textbook: A practical guide to pharmaceutical care, now
15
in the second edition.

New Zealand

The pharmaceutical care concept used in New Zealand is essentially

5
that of Hepler and Strand (1990). It is a clearly defined patient care
process, separate from dispensing, provided only by specially
accredited pharmacists. Some 28 per cent of community pharmacists
and 16 per cent of all pharmacists in New Zealand are now trained to
provide pharmaceutical care and, by August 2001, 183 were practicing
11
pharmaceutical care. Doctors, nursing homes as well as pharmacists
identify prospective patients. The service is reimbursed partly by third
party payers and patients, but mainly by the government, which pays
 Essential of Pharmaceuticals care 9

NZ$160 for each pharmaceutical care plan submitted. By August 2001,

87 community pharmacists had claimed for a total of 4,123 care plans.
The government encouraged pharmaceutical care and there were
negotiations for an expanded role in health care for pharmacists in New
11
Zealand. The future for pharmacists lies in resolving drug therapy
problems, and that the traditional dispensing role could disappear, to
be replaced by mail order delivery. Many different models could
develop, and there might evolve a new profession of pharmacotherapy
11
that could eventually take over from the pharmacist.

Australia

Pharmaceutical care is also growing in Australia where pharmacists

are paid for providing it to patients in nursing homes, domiciliary
settings and at the hospital/community interface. The main driver in
Australia is a national policy on the quality use of medicines (QUM).
This policy was formulated in the early 1990s in response to the
growing data on overuse, under use, inappropriate use and adverse
health consequences of medicines, particularly in older people. Illness
caused by medication in these elderly was considered to be the most
significant health problem amenable to treatment. Interestingly,
however, there was also a strong pressure from the consumer lobby.
Services are patient focused and multidisciplinary in approach, and
according to The QUM policy is claimed to have created the
environment in which ideas consistent with pharmaceutical care can
11
flourish.

The Netherlands

The term pharmaceutical care applies to the services that pharmacists

provide. However, leading researchers in that disagree with having a
uniform approach worldwide. They believe that differences in health
 Models Of Pharmacy Practice 10

care systems, and differences in pharmacy practice, such as size of

pharmacies, dispensing workload, staff numbers and so on, do have an
impact on the provision of pharmaceutical care.17 The definition of
pharmaceutical care used in the Netherlands emphasizes the role of the
whole pharmacy team and not just the pharmacist in caring for the
individual patient in the field of pharmacotherapy, and aims to improving
the patient's quality of life. However, the pharmacy team in the
Netherlands includes pharmacy assistants who are trained for three
years beyond secondary school, and therefore well qualified to be able
to participate in the care process.

Dutch pharmacies only provide medicines and medical aids, so they do

not look like shops and thus have a strong professional image. Patients
are loyal, with 95 per cent using one pharmacy only, and pharmacists
have a well-established role in advising patients on their medicines. All
pharmacies have a private room for consultations. Working
relationships with doctors are good and pharmacists regularly meet
doctors (68 times a year) to discuss pharmacotherapeutics, thus raising
awareness of pharmacists as experts on medication, and all pharmacies
have conducted automated medication surveillance for more than 10
17
years. The provision of pharmaceutical care is therefore not such a
culture shock for Dutch pharmacists, although such services are not
universal across the Netherlands. Pharmacists are not paid for
pharmaceutical care but their income from dispensing is good and
pharmacies are large, usually employing two pharmacists. One of the
big strengths in the Netherlands is that the pharmacist can view part of
the patient's medical record remotely, because most pharmacy and GP
systems are compatible. Moreover, the pharmacy software allows the
pharmacist to document drug therapy problems and record any action
taken. A new development in the Netherlands is that doctors will have to
write down the indication for each medicine on the prescription and this
 Essential of Pharmaceuticals care 11

practice is expected to be of enormous help in pharmaceutical care.17

England

England is in the process of developing medicines management

services, which are in line with current well-known Government policy for
the NHS, particularly the target identified in the NHS plan for all general
practices to have medicine management services in place in 2004. The
development of medicines management services is also linked to other
initiatives such as local pharmaceutical services, repeat dispensing
schemes, patient partnerships in medicine taking, and new prescribing
responsibilities for professions other than medicine and new structures
and responsibilities for NHS organizations. Medicines management
services therefore fit in well with the current NHS agenda in England, and
although they seem to find little parallel with pharmaceutical care
developments in other countries, there is the same focus on medication
related problems as being an important driver for change. Of significance
is the fact that services include all aspects relating to the supply and
therapeutic use of medicines from the individual patient level to the
organizational level.11

Germany

Hepler's visit to Europe led, in 1992, to the initiation of an asthma

therapeutic outcome monitoring (TOM) project in Denmark and then, in
1994, to a pharmaceutical care of the elderly project, in which Germany,
Northern Ireland, the Netherlands, Sweden and Portugal participated.12
One of the lessons learnt from these two projects was the difficulty that
pharmacists had in delivering pharmaceutical care without a focus on a
single disease state. Although the approach of providing pharmaceutical
care to every patient is considered the ideal, it is also acknowledged that
pharmacists' knowledge of disease states needs to be built up first. In
Germany, it may be easier for pharmacists to work with protocols and
 Models Of Pharmacy Practice 12

checklists so that, until they are experienced in this type of work, they
know exactly what to do. As in every other country, persuading
pharmacists in Germany to implement pharmaceutical care is difficult.
Payment for pharmaceutical care in Germany is, like everywhere else, a
problem. The fee-for-service model is commonly applied to health care.
Nine pharmacy software companies in Germany produced some
programs for supporting pharmaceutical care based on the steps of the
pharmaceutical care process, which have developed and
12
standardized.
Africa
In South Africa, pharmaceutical care is widely accepted as the
relationship between the pharmacy profession and society in which the
profession accepts responsibility for the supply and use of drugs by
18
society as a whole and for each and every patient. This definition is
deliberately broad in that it describes the overall responsibility that the
profession has for pharmacotherapy. The Good Pharmacy Practice
Guidelines published by the Pharmacy Council are based on
pharmaceutical care. With this insight it will be possible to identify how
much change has to take place and where the change must occur. The
concept of pharmaceutical care is neither well developed nor
adequately documented in Uganda. A study that involved an 8-month
observation period in Kampala showed that 15 percent of respondents
came to fill prescriptions, 29 per cent to receive pharmacy-initiated
therapy and 57 per cent came for self-medication with all drugs including
19
antibiotics at 22 per cent. Most clients 75 per cent received treatment.
All the 26 pharmacists in Kumasi Ghana were aware of the concept of
pharmaceutical care and claimed to be implementing it. 84 per cent of
them counselled their patients. A cumulative frequency of 66
prescription interventions were indicated as changes commonly carried
 Essential of Pharmaceuticals care 13

out. However, 88 per cent of the pharmacists kept no record of the

20
services rendered. These reports indicate that there are elements of
pharmaceutical care in pharmacy practice in these African countries.

Pharmacy practice in Nigeria

The hospital and community settings are representative of what may be
considered as professional practice. Nigeria is the most populous Black
Country in the world with an estimated population of 0ver 150 million
people. About 70% live in rural areas where poverty interacts with high
disease morbidity rates.21 The scenario of hospital pharmacy practice in
Nigeria may be described as undeveloped. Until recently, few
pharmacists were attracted to the public health sector due to poor
remuneration and lack of job satisfaction. Government hospitals widely
utilize pharmacy technicians that have two years post secondary
education in a school of health technology in the dispensing of drugs.
The role of the pharmacist in the hospital is yet limited to the traditional
dispensing of drugs and inventory management. Only few hospitals
practice the unit dose dispensing system, but not in a consistent manner.
The layout and the design of the pharmacies are also unsuitable for
effective dispensing. Drugs are dispensed through pigeonholes in most
hospitals, which form a big barrier to patient counselling. Medication
profile is not kept as an essential component of pharmaceutical service,
as the records kept in the pharmacy are those of stock, which is
suggestive of product oriented pharmacy practice. A drug revolving fund
scheme was introduced in the country some years ago to reduce the
problem of out of stock. The drug revolving fund scheme is a cost
recovery system of pricing drugs sold to patients in government
hospitals. This scheme is part of the Bamako Initiative in the
implementation of Primary Health Care. Patients pay for their drugs,
foods, and supplies as the National Health Insurance Scheme is yet to
 Models Of Pharmacy Practice 14

fully take off.

Community pharmacy practice is facing numerous challenges, the most

important of which is low returns on investment due to low aggregate
consumer demand. There are numerous open drug markets, patent and
proprietary medicine shops that sell all classes of drugs against national
pharmacy laws. Traditional healers, who are known to embed orthodox
drugs in their preparations, are seen to pose a challenge to community
pharmacists. The incidence of substandard and counterfeit medicines
is reportedly high. Self-medication with both OTC and prescription
medicines is common among all socioeconomic strata of the society.
Private hospitals and clinics prescribe and dispense medicines without
the expertise of the pharmacist. Patients are only referred to the
community pharmacy to procure expensive medicines or when the
facilities do not have the necessary stock. Community pharmacists
recommend both OTC and prescription medicines when responding to
22
symptoms and most patients are comfortable with that. A number of
reasons account for this observed pattern of drug use, including the
peculiar environment of health care delivery. Many community
pharmacies employ young school leavers as supportive staff that are
widely referred to as sales boys/girls, pharmacy attendants or counter
staff. These terminologies tend to suggest the commercial inclination of
the community pharmacy as opposed to pharmaceutical care, which is a
patient centered practice. The counter staff activities have been
23
investigated. They were found to lack the relevant knowledge and
competence to perform judgmental roles that ought to be the exclusive
preserve of the pharmacist. These activities partly explain the reported
difficulty by the public in differentiating a pharmacist from a pharmacy
22
attendant in the community, and a pointer to poor personal control.
 Essential of Pharmaceuticals care 15

These findings reflect the need for the pharmacists to learn of these
findings and act upon them since the measures undertaken by support
staff in relation to their clients affect the quality of pharmacy service. A
previous Nigerian study had also indicated ethical lapses in the
24
performance of community pharmacists in a Nigerian urban city.
The country in principle took an official position towards patient oriented
pharmacy practice in 1988 when a policy statement of the Federal
Ministry of Health adopted clinical pharmacy as a strategy in rational
drug use. Despite that, pharmacy practice in the country is largely
product focused, though it contains fragments of clinical pharmacy, and
pharmaceutical care, especially at the community pharmacy setting.
There is not yet an official statement or policy on pharmaceutical care
philosophy. The concept of pharmaceutical care as being enunciated by
Hepler and Strand (1990) is being widely discussed in different
professional fora, and efforts are underway to introduce pharmaceutical
care in Nigeria. Some pharmaceutical care standards that can be
effectively applied in improving effective pharmaceutical services in
Benin City have been identified. The identified 47 standards are most
likely to stimulate the widespread implementation of pharmaceutical
care in Nigeria, if seriously addressed by the Pharmacists Council of
25
Nigeria and the Pharmaceutical Society of Nigeria.

Pharmaceutical care activities of community pharmacists

A study has employed a subjective and reductionist method to assess
the activities of community pharmacists that may be considered as
elements of pharmaceutical care. This must be seen as a preliminary
step towards pharmaceutical care development in Nigeria where
pharmaceutical care does not yet exist as a form of practice.
Respondents claimed high involvement in the education and counselling
of their hypertensive patients. These services have always existed as
 Models Of Pharmacy Practice 16

extension of traditional drug dispensing. Identification of drug therapy

problems, documentation of intervention, and patient referral were
reported lacking. These are vital elements. Pharmaceutical care cannot
be performed without documentation. Drug therapy problems are the
26
“heart and soul” of the practice of pharmaceutical care. Several
observational studies have examined the extent to which community
27-29
pharmacists identify and assist patients with drug therapy problems. It
is important to note that the respondents did not seem to see time
constraints, lack of patient medical records, lack of additional financial
benefits, and absence of legal backing as major impediments to their
rendering pharmaceutical care services to hypertensive patients. Some
30
of such barriers are known to exist elsewhere. The implication is that
there is need for breaking the inertia of implementing pharmaceutical
care in Nigeria. This will be a matter of taking responsibility rather than
31
merely providing functions. The first step would logically be retraining of
pharmacists. Less than half of the respondents (45.6 per cent) claimed to
identify drug therapy problems and when asked specific questions on
drug therapy problem identification, all the items received very poor
rating. Compliance was the only item up to 20 per cent claimed to identify.
This shows lack of relevant pharmaceutical care knowledge and skill.
 Essential of Pharmaceuticals care 17

Key Learning Points

· Five models of pharmacy practice have been highlighted

· These models are apothecary, compounding, distribution,
clinical pharmacy, pharmaceutical care and total pharmacy
care
· Apothecary model combined product and patient oriented
services
· Compounding and distribution models are product oriented
· Pharmacists are patient oriented and perform clinical
functions under the clinical pharmacy model without taking
professional responsibility
· Pharmaceutical care model is patient oriented and the
pharmacist shares responsibilities for drug therapy
outcomes
· Total pharmacy care model is an integration of the existing
models and the proportion of each model depends on the
practice setting and other factors.

References
1. Higby GJ (1997). American pharmacy in the twentieth
century. Am J Health-Syst Pharm; 54:1805-1815.
2. Hepler CD (1987) The third wave in pharmaceutical education
and clinical movement. Am J Pharm Ed; 51: 369-385.
3. Holland RW and Nimmo CM (1999). Transitions, part 1: Beyond
pharmaceutical care. Am J Health- Syst Pharm; 56: 1758 1764.
4. Al-Shaqha WM, Zairi M (2001). Pharmaceutical care
management: a modern approach to providing seamless and
integrated health care. Int J Health Care Quality Assur 14(7):
282-301.
 Models Of Pharmacy Practice 18

5. Hepler CD, Strand LM. (1990) Opportunities and responsibilities

in pharmaceutical care. Am J Hosp Pharm; 47,533-543.
6. Strand LM, Cipolle RJ, Morley PC, Perrier DG. (1991) Levels of
pharmaceutical care: a needs-based approach. Am J Hosp
Pharm; 48,547-550.
7. Desselle S, Hunter TS (1998). The Evolution of Pharmaceutical
Care into Managed Care Environments. J Managed Care Pharm;
4: 55-58.
8. Hatoum, HT (1991). Managed care: should pharmacists really
care? Drug Topics; 135: 67-75.
9. Klotz RS (1994). Pharmacist-physician link: keys to effective
outcomes management. Am Pharm; NS34: 46-59.
10. Berger BA, Grimley D (1997). Pharmacist readiness for
rendering pharmaceutical care. A Paper Presented at the Annual
Meeting of the American Pharmaceutical Association. Los
Angeles, CA.
11. Mason P (2001a). Pharmaceutical care: where we are now.
Pharm J 267(7170):569-573.
12. Mason P (2001b). Pharmaceutical care-the German experience
Pharm J 266(7132): 122.
13. Hepler CD, Strand LM. (1990) Opportunities and responsibilities
in pharmaceutical care. Am J Hosp Pharm; 47,533-543.
14. Posey LM (1997). Pharmaceutical care: will pharmacy
incorporate its philosophy of practice? J Am Pharm Assoc;
NS37:145-148.
15. Rovers JP, Currie JD, Hagel HP, McDonough RP, Sobotka JL
(2003) Ed. A practical guide to pharmaceutical care 2nd ed.
Washington DC: American Pharmaceutical Association; ISBN: 1-
58212-049-8.
 Essential of Pharmaceuticals care 19

16. Strand L (1998). Building a practice in pharmaceutical care.

Pharm J; 260:874-878.

17. Van Mil JWF, De Boer WO, and Tromp T FJ (2001). European

barriers to the implementation of pharmaceutical care. Int J

Pharm Pract; 9:163-168

18. Futter WT (1996) Towards a South African Model of
Pharmaceutical Care. Rhodes University

19. Anyama N, Adome RO (2003). Community pharmaceutical care:

an 8-month critical review of two pharmacies in Kampala. Afr

Health Sci; 3(2):87-93.

20. Duwiejua M, Dodoo A, Plange-Rhule J (2001). Quality of

counseling on salbutamol metered dose inhalers in community

pharmacies in Kumasi. Ghana Pharm J; 20 (1): 20-23.

21. UNDP (2000). United Nations Development Programme,
Population Report
22. Oparah CA, Iwuagwu MA (2001). Public perceptions of
community pharmacists in Benin City, Nigeria. Int J Pharm Pract;
9: 191-195.
23. Oparah CA, Enato EFO, Odili VU, Aghomo OE (2002). Activities
of community pharmacy counter staff in Benin City, Nigeria. J
Soc Admin Pharm; 19(4):141-144.
24. Oparah CA (2002). An evaluation of ethical performance of
community pharmacists in Benin City Nigeria. West Afr J Pharm
16 (1):51-53.
25. Erah PO, Nwazuoke JC (2002). Identification of Standards for
Pharmaceutical Care in Benin City. Trop J Pharm Res; 1 (2): 55-
66.
 Models Of Pharmacy Practice 20

26. Cipolle RJ, Strand LM and Morley PC (1998). Pharmaceutical

care practice. McGraw-Hill, NY; 76-83.
27. Rupp MT (1992): Value of community pharmacists' interventions
to correct prescribing errors. Ann Pharmacother; 26:1580-1584.

28. Poston J, Kennedy R, Waruszynski B (1995). Initial results from

the community pharmacist intervention study. Can Pharm J;
127:18-25.
29. Caleo S, Benrimoj S, Collins D, Lauchlan R, Stewart K. (1996).
Clinical evaluation of community pharmacists' interventions. Int
J Pharm Pract; 4:221-227.
30. Van Mil JWF, De Boer WO, and Tromp T FJ (2001). European
barriers to the implementation of pharmaceutical care. Int J
Pharm Pract; 9:163-168
31. Westerfund T, Almarsdottir A, Melander A (1999). Drug-related
problems and pharmacy interventions in community practice. Int
J Pharm Pract; 7:40-50.
 Essential of Pharmaceuticals care 21

CHAPTER TWO

PHARMACEUTICAL CARE CONCEPT AND PHILOSOPHY

Azuka C Oparah
Learning Objectives
At the end of this chapter, you should be able to:
i. Understand the concept of pharmaceutical care
ii. Describe the four components of pharmaceutical care
as espoused by Hepler and Strand
iii. List and explain the steps to provide pharmaceutical care
Pharmaceutical Care Concept
Pharmacy has evolved and developed as a caring profession. However,
the focus of that caring has shifted over time from the drug product to the
1
patient. During the compounding, and manufacturing era of the 1950s,
pharmacists expressed their caring by preparing drug products in
accordance with stringent quality-control procedures. The unit dose era
saw pharmacists caring by seeking to eliminate unnecessary nursing
manipulations, ensuring that the patients received their medications,
and reducing the incidence of medication errors. The clinical pharmacy
era had pharmacists providing drug information and monitoring
1
pharmacokinetics.
Today, the pharmacy profession is undergoing “reprofessionalization”,
exploring the opportunity to mature as a profession by accepting its
social responsibility to reduce preventable drug-related morbidity and
2
mortality. Mikeal et al. (1975) first defined pharmaceutical care as “the
care that a given patient requires and receives which assures safe and
3
rational drug usage. Although the term has been in use since then, it
 Pharmaceutical Care Concept and Philosophy 22

became topical when Brodie et al. (1980)4 suggested that

pharmaceutical care includes the determination of the drug needs for a
given individual and the provision not only of the required drugs but also
of the services necessary (before, during, and after treatment) to ensure
optimally safe and effective therapy. However, the changes that
occurred following this work focused primarily on controlling the
availability and distribution of the drug product and not specifically on
patient need within identifiable clinical parameters.
Hepler (1987) philosophically defined pharmaceutical care as “ a
covenantal relationship between a pharmacist and a patient in which the
pharmacist performs drug use control functions (with appropriate
knowledge and skill) governed by the awareness of and commitment of
the patient's interest.5 In 1990, Hepler and Strand published a seminal
paper, which further developed pharmaceutical care by connecting the
philosophy and practice concepts. This foundational conceptualization
visualized pharmaceutical care as that component of pharmacy practice
that entails direct interaction of the pharmacist with the patient for the
purpose of caring for the patient's drug related- needs.2

Hepler and Strand (1990) defined pharmaceutical care as the

responsible provision of drug therapy for the purpose of achieving
definite outcomes that improve a patient's quality of life.2 Strand (1998)
contended that the above definition was incomplete. The definition she
espoused is that pharmaceutical care is "a practice in which the
practitioner takes responsibility for a patient's drug related needs and
holds himself or herself accountable for meeting these needs." Strand
places great emphasis on the word "practice".6 A pharmacist working to
this new definition ascertains all the medicines that a patient is taking,
from whatever source, assesses them for reasonableness and
effectiveness in the light of the patient's condition, develops a care plan
 Essential of Pharmaceuticals care 23

and follows up progress on a regular basis.

Furthermore, in the 1990 definition by Hepler and Strand, some

outcomes of therapy are difficult to evaluate or to attribute uniquely to a
pharmaceutical contribution, since both the patient's current and future
health status may be affected by numerous health care interventions. In
the absence of distinct outcome measures, performance indicators
relating to structure and process, where clearly linked to an evidence
base, have as much if not more to offer to outcome measures and are
likely to be more practical to monitor. This was pointed out in a Scottish
report (1998). A more practical definition that allows qualitative
performance indicators with respect to patient's needs in addition to the
quantitative indicators more commonly employed to assess pharmacy
services is that “ the pharmacist takes responsibility for a patient's drug
related needs and is held accountable for meeting those needs”.6 This
view seems to be derived from the new definition of pharmaceutical care
that Strand advocates.

The origins of pharmaceutical care have been discussed with special

emphasis on the development of the practice itself. The initial objectives
of the practice were to apply the concepts of clinical pharmacy to
community or ambulatory practice settings. After many attempts and
hard lessons learned, it became clear that clinical pharmacy activities
were not recognizable or reimbursable as patient care services. At this
point the objectives of the practice had to be revised. The revised
objectives were the following: establish a new standard for medication
use by an individual patient, create a patient care practice that interfaces
with the standards of medicine and nursing, employ the vocabulary and
standards that already exist in the health care system, and achieve
recognition and reimbursement as a patient care service that actually
 Pharmaceutical Care Concept and Philosophy 24

stands for the same as 'Pharmaceutical Care' in the rest of Europe.7

Over the past decades, there have been moves to change the traditional
role of the community pharmacist in United Kingdom (UK) from
medicines' supplier to pharmaceutical care provider. There has also
been some debate around whether health promotion is an integral part of
pharmaceutical care. In the UK the term medicines management is
widely used in place of pharmaceutical care. It has recently been defined
as “the process of optimizing beneficial outcomes and minimizing harm
from medicines, including medication review (appropriateness),
monitoring and advice to patients and prescribers”.8

One speculates that it is a matter of time for the concepts of

pharmaceutical care and medicines management, which profess the
same philosophy to merge. Additionally, the term pharmaceutical care
should have a wider appeal since the fourth component in Hepler and
Strand's definition (1990) encompasses health promotion. If pharmacy
profession seeks to address societal needs with an emphasis on drug
therapy, health promotion must be an integral part of the practice.
Anderson sees health promotion as an implicit component of
pharmaceutical care.8
Some attributes of pharmaceutical care are shown below:
• Patient centered
• Outcome oriented
• A process and not an event i.e. follow-up is necessary
• Collaborative with patient and other care givers
• Shared responsibility for outcomes of pharmacotherapy.

The Pharmaceutical Care Philosophy

Pharmaceutical care is both a philosophy and model of pharmacy
practice. Consequently, pharmaceutical care affects the way
 Essential of Pharmaceuticals care 25

pharmacists think and act. The philosophy of pharmaceutical care as

espoused by Hepler and Strand (1990) has four basic components:
"social need", "patient-centered care", "caring," and "pharmacist
2
responsibilities". The “social need” indicates that pharmacists would
assure that all the patients' drug therapy is appropriately indicated,
effective, safe and convenient. The only way that pharmacists can
achieve that is to develop a practice wherein they take one patient at a
time. Drug therapy related problems are the hearts and souls of
pharmaceutical care. For practical purposes pharmacists should view
drug therapy problems as either potential (likely to occur) or actual
(occur in the course of drug use).

Pharmaceutical industry studies have indicated that in the United

States, 1.3 million hospitalizations and 63,000 deaths are caused by the
10
inappropriate use of prescription drugs each year. This would suggest
that one is ten times more likely to get injured by a prescription drug than
by an auto accident in any given year. It also indicates that the number of
people who commit suicide, are murdered, or die in auto accidents
combined is roughly equal to the number of people who die as a result of
what comes of the prescription bottle in any given year. In a similar
report, 12,000 deaths and 15,000 hospitalizations due to adverse drug
reactions (ADRs) were reported to the FDA in 1987, and many went
unreported. Another report indicated that 76 billion dollars saved in
health care expenditures and 120,000 deaths per year prevented
nationally if pharmacists were more fully utilized in community health
11
care. This means that for every health care dollar spent on purchasing
medications, an additional dollar is being spent to deal with misuse of
medications. These sobering figures are pointing to a major public
health problem.The poor and the elderly are the most likely to suffer from
prescription drug misuse. Pharmacists are the most accessible health
care professional and they are being greatly underutilized. The potential
for improvement in quality of life and in cost reductions is great.

Pharmacists and their institutions must therefore stop looking inward

and start redirecting their energies to the greater social good. Drug
related morbidity and mortality are often preventable, and
pharmaceutical services can reduce the number of ADRs, the length of
hospitalization, and cost of care (Hepler and Strand, 1990). When
pharmacists prevent drug induced diseases, they are contributing to
public health, and when they cause appropriate drug use thereby
preventing disease complications, they improve the quality of life of
patients. Pharmaceutical care offers a concrete opportunity to become a
patient advocate. Since drug therapy is associated with risks and
benefits, the pharmacist becomes a risk manager thereby optimizing the
goal of drug therapy improving on existing results or getting some,
12
where none existed.

The "patient-centred" approach means to see the patient as a whole.

Pharmacists could not choose one disease or one set of patients.
Pharmaceutical care is a generalist practice. Practitioners need to use
the same patient care process irrespective of the practice setting
hospital, community. Pharmacists need to understand this concept of
having a "practice". They have never had one, and they need to
understand that a "practice" relies on practitioners and is not dependent
on a place or a setting. Pharmaceutical care is patient-centred.
Practitioners' inclination is to care for the patient's needs using quality
assurance tools analogous to pharmacists' care of the drug product.

In the health care context, "caring,” means something very specific.

There are three components. The first one is to assess the patient's
needs. Then resources have to be brought to bear to meet those needs.
Finally, there should be follow-up to determine whether what has been
done was beneficial or otherwise. Without these three components,
there is no pharmaceutical care. Caring in the context of pharmaceutical
care is analogous to medical, dental, and nursing care and provision of
such care requires that pharmacists have a generalist, rather than
specialist orientation and be held responsible for the outcomes of drug
therapy. Taking care of patients, which is what pharmaceutical care is
about, demands a different mindset from traditional pharmacy. Providing
pharmaceutical care might, for example, involve being available for
consultation out of hours.6

Defining pharmacists' responsibilities, Strand (1998) said that they had

to be able to identify a patient's drug related needs and meet those
needs better than anybody else. If they did not do so, they would not be
paid as a patient care provider. Pharmacists had to build a practice just
as a dentist or a physician would, one patient at a time.6 To be
responsible implies that the pharmacist has both the cognitive base and
right attitude to render the service to the patient as a professional
responsibility and not an option. Professionals do not merely perform
functions they take responsibility for functions performed. Taking
responsibility for outcomes of therapy represents a turf professional
area and professional conflict may arise. In the practice of clinical
pharmacy, the profession played advisory role. In the model of
pharmaceutical care, pharmacists would have to share responsibility for
outcomes of medications they dispense, with other health care givers.
Pharmaceutical care is enabling pharmacists to rethink their approach to
practice and at the same time, it is helping pharmacy students to
understand the way in which the pharmacist's contribution to patient
care is evolving.
Philosophy of Professions

PHILOSOPHY OF PROFESSIONS

MEDICINE Professes HEALTH

LAW Professes JUSTICE

EDUCATION Professes TRUTH

MINISTRY Professes SALVATION

PHARMACY Professes PHARMACEUTICAL CARE

13
Principles of Practice for Pharmaceutical Care
The American Pharmaceutical Association adopted some principles for
the practice of pharmaceutical care. The Association sees
pharmaceutical care as a patient-centered, outcomes oriented
pharmacy practice that requires the pharmacist to work in concert with
the patient and the patient's other healthcare providers to promote
health, to prevent disease, and to assess, monitor, initiate, and modify
medication use to assure that drug therapy regimens are safe and
effective. The goal of pharmaceutical care is to optimize the patient's
health-related quality of life, and achieve positive clinical outcomes,
within realistic economic expenditures. To achieve this goal, the
following must be accomplished:

A. Establishment and maintenance of a professional relationship

Interaction between the pharmacist and the patient must occur to assure
that a relationship based upon caring, trust, open communication,
cooperation, and mutual decision making is established and maintained.
In this relationship, the pharmacist holds the patient's welfare
paramount, maintains an appropriate attitude of caring for the patient's
welfare, and uses all his/her professional knowledge and skills on the
patient's behalf. In exchange, the patient agrees to supply personal
information and preferences, and participates in the therapeutic plan.
The pharmacist develops mechanisms to assure the patient has access
to pharmaceutical care at all times.

B. Development of patient-specific database

It is necessary for pharmacists to collect and/or generate subjective and

objective information regarding the patient's general health and activity
status, past medical history, medication history, social history, diet and
exercise history, history of present illness, and economic situation
(financial and insured status). Sources of information may include, but
are not limited to, the patient, medical charts and reports, pharmacist-
conducted health/physical assessment, the patient's family or caregiver,
insurer, and other healthcare providers including physicians, nurses,
middle-level practitioners and other pharmacists. Since this information
will form the basis for decisions regarding the development and
subsequent modification of the drug therapy plan, it must be timely,
accurate, and complete, and it must be organized and recorded to
assure that it is readily retrievable and updated as necessary and
appropriate. Patient information should be maintained in a confidential
manner.
C. Evaluation of patient data and development of a care plan

Based upon a thorough understanding of the patient and his/her

condition or disease and its treatment, the pharmacist should, with the
patient and with the patient's other healthcare providers as necessary,
develop an outcomes-oriented drug therapy plan. The plan may have
various components, which address each of the patient's diseases or
conditions. In designing the plan, the pharmacist must carefully consider
the psychosocial aspects of the disease as well as the potential
relationship between the cost and/or complexity of therapy and patient
adherence. As one of the patient's advocates, the pharmacist assures
the coordination of drug therapy with the patient's other healthcare
providers and the patient. In addition, the patient must be apprised of (a)
various pros and cons (i.e., cost, side effects, different monitoring
aspects, etc.) of the options relative to drug therapy and (b) instances
where one option may be more beneficial based on the pharmacist's
professional judgment. The essential elements of the plan, including the
patient's responsibilities, must be carefully and completely explained to
the patient. Information should be provided to the patient at a level the
patient will understand. The drug therapy plan should be documented in
the patient's pharmacy record and communicated to the patient's other
healthcare providers as necessary.

D. Provision of necessary information and supplies

The pharmacist providing pharmaceutical care assumes ultimate

responsibility for assuring that his/her patient has been able to obtain,
and is appropriately using, any drugs and related products or equipment
called for in the drug therapy plan. The pharmacist should also assure
that the patient has a thorough understanding of the disease and the
therapy/medications prescribed in the plan. Furthermore, the
pharmacist is responsible for monitoring the patient's progress in
achieving the specific outcomes according to strategy developed in the
drug therapy plan. The pharmacist coordinates changes in the plan with
the patient and the patient's other healthcare providers as necessary
and appropriate in order to maintain or enhance the safety and/or
effectiveness of drug therapy and to help minimize overall healthcare
costs. Patient progress is accurately documented in the pharmacy
record and communicated to the patient and to the patient's other
healthcare providers as appropriate. The pharmacist shares information
with other healthcare providers as the setting for care changes thus
helping assure continuity of care as the patient moves between the
community setting, the institutional setting, and the long-term care
setting.
Steps in providing Pharmaceutical Care (PC) to patients
A stepwise approach would ensure consistency and make it easy to
adopt pharmaceutical care in a practice setting. Cipolle et al. (1998)
14
have defined pharmaceutical care as a nine-step process. Strand
identified the three basic components as: assessment of patient needs;
6
development of a care plan; and follow up evaluation. This book,
although portraying a similar process delineates six steps in the overall
process.

Establish a professional/therapeutic relationship

Pharmaceutical care is patient-centered and the pharmacist is expected
to interact with one patient at a time. When one greets a patient, shows
empathy and asks how the patient feels, one has initiated a therapeutic
relationship. The pharmacist then lets the patient feel that he or she is
concerned about the patient's health and then introduces
pharmaceutical care and its benefits to the patient. Establishing a
therapeutic relationship facilitates patients' granting of authority to the
pharmacist to undertake responsibility on the patients' behalf. As this
relationship develops the patient will begin to identify the pharmacist by
name or as “my pharmacist”.

Collect patient specific subjective and objective data

What the pharmacist can do for a patient depends on how much
information about the patient he has, and how it is utilized. Sources of
patient data include: patient interview, interview of other caregivers and
patients relatives/friends, review of existing medical records, laboratory
reports, and physical assessment using the skills of inspection,
palpation, percussion, and auscultation as appropriate. These
procedures would yield subjective and objective patient data that include
15
a minimum of:

Table 2.3: Some minimum contents of patient specific data

· Patient demographics name, age, gender, contact address etc

· Diagnoses and past medical history

· Present medications and medication history including herbal

medicines

· Medication allergies/intolerances

· Smoking/alcohol/caffeine/drug use history

· Abnormal laboratory and physical examination results

· Renal and liver function

Evaluate data and identify health and drug therapy problems

A systematic approach is essential to perform this process effectively.
Critical thinking and problem solving skills are also needed. The
practitioner compares problems and treatments to ensure that every
drug is managing a condition and that every condition is being managed
with or without a drug. Where a drug is used, assess the drug for
indication (correlate drug with disease or symptom), safety, efficacy,
compliance, and appropriateness of dosage regimen and form. Health
problems may include a medical or psychiatric diagnosis, patient
complaint, an abnormal laboratory test result, an abnormal observation
(sign or symptom), a social or financial situation, a psychological
concern or a physical limitation/disability.
Drug therapy problems should be identified and briefly described. The
severity of problems is assessed and they are prioritized to determine
whether an intervention is necessary immediately, later, or not really
needed. The pharmacist should provide adequate evidence (such as
primary literature) supporting the existence of a drug-related problem,
and therapeutic principles that are used as a basis for solving the
problem.

Develop and implement pharmaceutical care plans (Pharmacist's

interventions)
A pharmaceutical care plan is a means of solving the problems you have
identified. The first section of the written plan of action should define
patient specific goals (“what”) and this should not be confused with the
methods (“how”). Goals should be definite, achievable (realistic), if
possible measurable, and consistent with professional responsibilities of
the pharmacist. Examples of patient specific goals are: to maintain the
blood pressure below 140/90 mm Hg, to demonstrate the need for
compliance with his drug therapy and to refill 80% of his prescription
15
within 5 days, and to demonstrate understanding of his disease state.

Two major types of pharmacists' interventions are patient-focused and

drug-focused interventions. Patientfocused interventions include
assisting patients with compliance problems, patient education and
counseling beyond Omnibus Budget Reconciliation Act (OBRA,
16
1990) , monitoring the patient, implementing non-drug therapy, and
patient referral. Drug-focused interventions include adding a new drug,
discontinuing medication, changing drug, dose, interval, duration or
dosage form, and monitoring parameters. Monitoring parameters are
those laboratory tests, clinical measurements, generic/disease specific
quality of life instruments, patient knowledge/satisfaction
questionnaires, and observations that are to be prospectively followed
in order to provide feedback on the status of the patient's health and
drug therapy problems. Each parameter should include the time when it
will be obtained and by which health professional, if that is not explicitly
clear. In making a drugfocused intervention, the recommendation has to
be specific and the cooperation of the prescriber is sought.
Prior to implementing pharmaceutical care plans the pharmacist should
ensure that the patient has all the supplies (drugs and information)
needed for the patient to comply.

Evaluate the interventions and follow-up

Pharmaceutical care is outcome-oriented. The pharmacist should
determine whether his intervention improved patient outcomes (clinical,
humanistic, and economic). A follow-up indicates the need to modify
care plans and lessons for the future.

Document activities
Pharmaceutical care activities must be documented in the appropriate
data forms. This step runs throughout the entire pharmaceutical care
process. Documentation provides evidence for what was done, audit
trail, and continuity of care when another pharmacist is on duty.
Furthermore, it accumulates data for practice research. Product
oriented pharmacists keep records about their drugs while patient-
oriented pharmacists maintain patient records. Cipolle et. al. have noted
14
that documentation generates three types of records namely:
pharmaceutical care patient chart, created primarily for the practitioner's
use; patient's personalized pharmaceutical care plan, generated for the
patient's use; and practice management report that is used to manage
the practice. These records can be maintained manually, electronically or
a combination of both.
Pharmaceutical Care Competency
Competency refers to the knowledge, attitudes, skills, and behaviors that
a professional acquires, accumulates, and develops through education,
training, and work experience. Competency indicates the ability to
perform one's duties accurately and confidently, make correct
judgments, and interact appropriately with patients and with colleagues.
Competency is characterized by a strong knowledge base, good
problem-solving and decision-making abilities, and the ability to apply
knowledge and experience to diverse patient-care situations.

Fig. 2.1 Components of Pharmaceutical Care Competency

Knowledge - in the two broad components of pharmaceutical care
namely managing therapy and communication with patients and other
care givers.
Values/Attitudes positive values and attitudes toward pharmaceutical
care are essential for its implementation.
Skills deriving from the components of pharmaceutical care including
pharmacotherapeutic skills, physical assessment skills, drug
information skills, communication skills, critical thinking and problem
solving skills.
Behaviors some pharmaceutical care behaviors have been identified as
shown below:
17-18
Pharmaceutical Care Behaviors

Novel activities
Individualize the treatment regimen for the patient
Obtain applicable laboratory values
Establish a monitoring plan
Monitor patient's outcomes
Identify the therapeutic alternatives
Obtain patient's medical history
Obtain patient's compliance history
Obtain patient's social history
Obtain or measure patient's vital signs
Identify the patient's desired therapeutic goal/s

Traditional activities
Provide advice about a prescription (OTC) medication
Obtain information about the patient's symptoms
Make a recommendation/intervention with the patient
Obtain patient's medication history
Obtain patient's description
Given that a problem exists, identify a patient-
Specific drug related problem
Make a drug or non-drug recommendation/intervention

Documentation
Document an intervention with a patient
Document an intervention with the patient's physician
Document pharmaceutical care activities on a
Computerized or manual system
 BENEFITS OF PHARMACEUTICAL CARE

TO THE PATIENT
PC improves patient care outcomes: Clinical, Humanistic, and
Economic:
v Cure rate
v Reduction in target symptoms
v Reduction in ADRs
v Improves patient knowledge
v Optimizes patient expectations
v Enhances patient satisfaction
V Improves quality of life
v Prolongs life
v Reduces hospitalization: frequency of visits and length of stay
v Reduces cost of care to the patient
v Frees man hour for patient to be more productive and earn more
TO PHARMACY PROFESSION
v Professional survival
v Improves professional image
v Promotes professional growth & development
v Enhances job satisfaction
v Improves patient expectations & satisfaction with the profession
v Provides additional earning by getting reimbursed from cost
saving
TO THE GOVERNMENT
V Reduces escalating cost of care
v Reduces burden on the healthcare delivery system
v Enhances productivity through a healthy workforce

Key Learning Points

· Pharmaceutical care (PC) is a philosophy as well as a
model of pharmacy practice
· PC affects the way pharmacists think and act in relation
to patients
· PC is a patient-centred, outcome oriented practice
wherein a pharmacist takes responsibility for a patient's
 drug related needs and holds himself or herself
accountable for meeting these needs
· The four components of pharmaceutical care philosophy
are: social need, patient-centeredness, caring, and
pharmacist's responsibility
· The social need for PC is to reduce the burden of drug
therapy problems
· Patient-centeredness indicates a generalist approach
whereby the patient is taken as a whole
· Caring has three components namely:
ü An assessment of the patient's needs
ü A care plan to meet those needs
ü And a follow-up evaluation to determine the
progress the patient is making toward meeting the
goals of therapy
· The pharmacist takes responsibility for identifying
potential and actual drug therapy problems,
preventing potential drug therapy problems, and
resolving actual drug therapy problems better than
another professional
· A pharmacist that intends to provide PC should:
ü Establish a professional relationship
ü Collect patient-specific subjective and objective
data
ü Evaluate data to identify health and drug therapy
problems
ü Develop and implement care plans or interventions
ü Assess the outcomes of such interventions, an
ü Document activities
References
1. Kleimann K. Harvey A.K (1994) Whitney Lecture. We really do
care. Am J Hosp Pharm; 51(16): 2011-2015.
2. Hepler CD, Strand LM. (1990) Opportunities and responsibilities
in pharmaceutical care. Am J Hosp Pharm; 47,533-543.
3. Mikeal, RL; Brown, TP; Lazarus HL; Vinson, MC (1975) Quality
of pharmaceutical care in hospitals. Am J Hosp Pharm 32: 567-
574.
4. Brodie, DC; Parish, PA; Poston, JW (1980) Societal needs for
drugs and drug-related services. Am J Pharm Ed; 44: 276-278.
5. Hepler CD (1987) The third wave in pharmaceutical education
and clinical movement. Am J Pharm Ed; 51: 369-385.
6. Strand L (1998). Building a practice in pharmaceutical care.
Pharm J; 260:874-878.
7. Strand LM (2002). Plenary Lecture on 20 Years of
Pharmaceutical Care: What have we learned? Pharm World Sci;
24 (1):19.
8. Anderson C (2002). Plenary Lecture on Pharmaceutical care or
medicines management? Pharm World Sci; 24 (1):19.
9. Anderson C (1999). Health promotion: an implicit part of
pharmaceutical care. Pharm J ;263(7063):463.
10. Johnson, JA and Bootman, JL (1997) Drug related morbidity
and mortality and the economic impact of pharmaceutical care.
Am J Health- Syst Pharm; 54: 554-558.
11. Johnson J A, and Bootman J L (1995). Drug-related Morbidity
and Mortality: A Cost-of- Illness Model. Arch of Intern Med;
155:1949-1956.
12. Oparah CA, Arigbe Osula ME (2003). Pharmaceutical care: the
“reprofessionalization” movement. Nig J Pharm; 34: 20-26.
13. 13. APhA (1996) American Pharmaceutical Association
Principles for the Practice of Pharmaceutical Care. In: A practical
guide to pharmaceutical care. Rovers JP et al (Ed.) American
Pharmaceutical Association, Washington DC, pp221 226.
14. 14. Cipolle RJ, Strand LM and Morley PC (1998). Pharmaceutical
care practice. McGraw-Hill, NY; 76-83.
15. 15. Rovers JP, Currie JD, Hagel HP, McDonough RP, Sobotka JL
(2003) Ed. A practical guide to pharmaceutical care 2nd ed.
Washington DC: American Pharmaceutical Association; ISBN:
1-58212-049-8.
16. 16. OBRA (1990). Omnibus Budget Reconciliation Act: A
Practical Guide to Effecting Pharmaceutical care, American
Pharmaceutical Association, Washington DC.

17. Farris KB, Schopflocher DP (1999). Between intention and

behaviour: an application of community pharmacists'
assessment of pharmaceutical care. Soc Sci Med; 49:55-66.
18. Odedina FT, Segal R (1996). Pharmaceutical care behavior
scale. Am J Health-Syst Pharm; 53:855-865.
 CHAPTER THREE

LEVELS OF PHARMACEUTICAL CARE (PC)

AND PATIENTS' RIGHTS TO PC
Azuka C Oparah
Learning Objectives
At the end of this chapter, you should be able to:
i. Identify pharmaceutical care levels in the continuity of
care process
ii. List pharmaceutical care functions at various levels of
health care
iii. Outline management requirements for pharmaceutical
care
iv. List patients' rights and responsibilities toward
pharmaceutical care
Levels of Pharmaceutical Care
Generally, the complexity, effectiveness, efficiency and risks of drug
therapy have evolved to the point that patient care cannot succeed
without pharmaceutical care. By definition, pharmaceutical care is the
integration of both traditional dispensing functions and newer, evolving
clinical activities into a philosophy of patient care in which pharmacists
share in the responsibility with other health professionals caring for
1-2
patients for the outcomes (effects) of that care.
Patient needs determine the type of pharmaceutical care services that
pharmacists should provide. These services, which are necessary to
ensure desired outcomes, are applications of pharmaceutical care. The
pharmacist is responsible for achieving the desired outcome of drug
therapy at all levels of the pharmaceutical care system. Established
pharmaceutical care levels could provide the pharmacy profession with
a model to use in evaluating pharmaceutical services in relation to
patient care. Levels of pharmaceutical care are organized according to
level of care, namely primary, secondary and tertiary.3

Primary Pharmaceutical Care

Cipolle et al., contend that pharmaceutical care in theory and practice is
primary health care.4 The themes of the common foci in the philosophy of
both primary health care and pharmaceutical care include: patient-
centeredness, addressing both acute and chronic conditions,
emphasizing prevention, and implementing documentation systems that
continuously record patient need and care provided. Other themes are:
being accessible to front-line first contact, offering continuous
systematic care, being accountable, placing emphasis on ambulatory
patients, and including education/health promotional intervention.
Pharmaceutical care is also a generalist practice. Primary health care
includes all of a patient's health care needs; pharmaceutical care
involves only the patient's entire drug related needs.4
Primary pharmaceutical care begins when it is first determined that drug
therapy may be needed for a condition not requiring hospitalization. The
basic pharmacist functions are listed in 3.1.3 In addition, the pharmacist
must be competent in: monitoring for compliance and proper drug use;
dispensing outpatient medications with appropriate labelling including
auxiliary labels; counselling patients about proper self-administration
and storage of medications in the home; and assisting the physicians in
choosing the right drug and the right dosage. Primary pharmaceutical
care is practiced in outpatient pharmacies in hospitals and community
pharmacies.5
 3
Table 3.1: Basic Primary Pharmaceutical Care Functions

1. Develop and use a patient medication profile.

2. Interpret, question, clarify, verify and validate all drug-related
orders.
3. Provide a safe and efficient drug dispensing system.
4. Monitor drug therapy for safety, efficacy and desired clinical
outcomes.
5. Screen for drug allergies, drug-drug interactions, drug-food
interactions and concomitant drug use.
6. Detect and report drug allergies and adverse drug reactions.
7. Recommend initial or alternative drug therapies.
8. Respond to drug information requests from physicians, nurses,
and patients.
9. Teach health-care providers and patients about drug use.
10. Obtain medication histories by interviewing.
11. Assist in the selection of the drug of choice and dosage forms.
12. Conduct drug use evaluations to gauge the appropriateness of
drug use and achievement of desired therapeutic outcomes.
13. Apply pharmaceutical principles for selected drug therapy

Secondary Pharmaceutical Care

Secondary pharmaceutical care begins with the initial drug therapy for a
more complex medical condition than in primary care. In addition to the
common basic pharmacist's functions already listed, six other tasks are
performed in secondary pharmaceutical care: managing selected drug
therapies by using approved protocols; managing drug delivery;
providing formal pharmacokinetic services; participation in
cardiopulmonary resuscitation; answering nurses' drug related-
questions; and assisting the physician in choosing the right drug and
ancillary therapy. Secondary pharmaceutical care is practiced in acute-
care setup and specialized care programmes such as oncology and pain
5
control.

Tertiary Pharmaceutical Care

Tertiary pharmaceutical care takes place in institutions that render
critical-care services. Here, the most comprehensive clinical pharmacy
services are offered. Rapid pharmacological and pharmacodynamic
changes are occurring in the patient. Patients in the tertiary care setting
require the most complex judgements, skills and knowledge from the
pharmacist. Tertiary pharmaceutical care includes all the functions
already listed, plus the functions performed in secondary pharmaceutical
care. Tertiary pharmaceutical care is practised in hospitals that provide
in-patient critical-care services. These institutions frequently have
5
corresponding teaching programmes for providers.

Management requirements of pharmaceutical care systems

Management is the process that helps groups of people to achieve a
common purpose effectively and efficiently. Pharmaceutical
management helps groups of pharmacists, technicians and patients to
achieve optimum drug therapy management. Management, especially
the management necessary for the successful delivery of
pharmaceutical care, is a complex activity to master. The delivery of
pharmaceutical care is a relatively new practice and needs to be
managed as such. Hepler and Strand's now widely promulgated and
accepted definition of pharmaceutical care has become a key construct
and galvanising force for the entire pharmacy community. Its realisation,
however, requires not only a new management and leadership paradigm
but significant introspection and corresponding attitudinal and
behavioural changes on the part of the profession, departmental
practices, and, more importantly, individual practitioners. Moreover, the
introduction of any new service requires that a standard set of structural
and functional prerequisites be in place and functioning before
successful outcomes can be expected. The organization of the
department and its policies, procedure and rules provide the structure
that facilitates professional work towards pharmaceutical care
objectives, and provides consistent performance when coordination is
of importance.

Smith effectively described the major determinants of excellence in the

management of clinical pharmacy services well before Hepler and
Strand's published definition of pharmaceutical care.6 He outlined the
differences in the management of clinical and non-clinical
pharmaceutical services and identified a spectrum of ten issues. These
issues ranged from a need for a basic philosophical tenet of
management that recognises the important potential for adverse drug
events and the pharmacist's assumption of new responsibility for
outcomes to the documentation and evaluation of cost-effectiveness.
Smith's theme reflected the need to manage the people aspects of
change, to obtain appropriate resources, and to design a supportive
operational system. The basic management theory describes the
minimum structural and functional prerequisites that must be
successfully implemented for a manager to ensure delivery of service.7
These prerequisites are necessary regardless of the specific
management style practised, the relative availability of financial
resources, the number of personnel managed, or the specific service
delivered. A practice management system should include all the
support required to provide pharmaceutical care to patients in an
effective and efficient manner. To accomplish this, a practice
management system is a prerequisite to provide pharmaceutical care
 8
that includes:
a. Defining a philosophical framework and a clear mission for the
practice that integrates the dual mission of the pharmacy
department
Delivery of the drug to the right patient at the right time; and delivery of the
drug information needed to ensure that each patient receives the
appropriate drug in the correct dose for the optimal duration of time, with
the necessary precautions taken to prevent complications from these
decisions. The integrated philosophical framework needs to be
expressed explicitly, first in the mission statement, and second in the
goals and objectives of the department. Clearly, providing the drug
without the information needed to ensure its appropriate use is as
unacceptable as delivery of the information without any contact with the
drug product. A mission statement as well as a very detailed strategic and
tactical plan should be developed and should be continually monitored
and revised.
b. Defining the short-term and long-term goals of the pharmacy,
based on the new mission statement
Goals and plans are closely related. While goals are the desired ends,
plans are the means that will be used to bring about the desired goals.
Clear goals provide a framework on which to design the pharmaceutical
care practice model. Pharmaceutical care practices with different goals
8
may have completely different components and structures.

c. Defining the job responsibility for the pharmacist based on the

standards of practice expected for each patient admitted into the
hospital
All pharmacists should understand clearly and define explicitly the
service that will be offered to patients. This is the most important step and
impacts on all subsequent decisions. Pharmacists must be fully aware of
the integrated framework outlined above and must, change the way they
think about their business enterprise.
d. Designing an organizational structure that supports the drug
delivery and clinical service functions
This organizational structure also needs sufficient supportive staff
(technicians and secretaries) to facilitate the provision of these services.
The support staff are responsible for facilitating the patient care process,
including patient flow, work flow, and meeting any other needs to
facilitate the provision of pharmaceutical care. Additionally, the
organizational structure should reflect a consistent distribution of
authority, that is, decision-making capability. This suggests that a
decentralised decision-making structure is necessary for the delivery of
8
clinical pharmaceutical services.

e. Resources required in delivering the pharmaceutical care

including physical, financial, human resources
Clinical pharmaceutical services in general must have the same level of
financial support as the drug delivery area of pharmaceutical services.

g. The evaluation and reward systems

These should be consistent with the philosophical framework that
integrates effective delivery of the drug product with pharmaceutical
care at the departmental level, and further integration of the pharmacy
activities with the entire health system.

Pharmaceutical Care: The Right of the Patient

Patients' Bill of Rights
Health care involves a partnership between patients and health care
professionals including pharmacists. Open communication, respect for
personal and professional standards, and understanding of differences
are important for the best possible patient care. Today, consumers are
more responsible for their own decisions - especially when it comes to
taking care of their health. The American Hospital Association presents
“A Patient's Bill of Rights” from which many health care facilities have
adopted. Another person chosen by the patient can exercise these rights
on the patient's behalf. A proxy decision maker can exercise these rights
if the patient lacks decision-making ability, is legally incompetent, or is a
minor. This bill is stated as follows:9
· “The patient has the right to considerate and respectful care.

· The patient has the right to and is encouraged to obtain from

doctors and other direct caregivers appropriate, current, and
understandable information about diagnosis, treatment, and
prognosis. Except in emergencies when the patient lacks
decision-making ability and the need for treatment is urgent, the
patient is entitled to the chance to discuss and request
information about the specific procedures and/or treatments, the
risks involved, the possible length of recuperation, and the
medically reasonable alternatives and their risks and benefits.
The patient has the right to know the identity of doctors,
pharmacists, nurses, and others involved in their care, as well as
when those involved are students, patients, or other trainees.
The patient also has the right to know the immediate and long-
term financial implications of treatment choices, insofar as they
are known.

· The patient has the right to make decisions about the plan of care
before and during treatment. The patient has the right to refuse a
recommended treatment or plan of care to the extent allowed by
law and hospital policy and to be informed of the medical
consequences of this action. In case of refusal, the patient is
entitled to other appropriate care and services that the hospital
 provides or transfers to another hospital.

· The patient has the right to have an advance directive (such as a

living will, health care proxy, or durable power of attorney for
health care) concerning treatment or designating a surrogate
decision maker with the expectation that the hospital will honor
the intent of that directive to the extent permitted by law and
hospital policy.

· The patient has the right to every consideration of privacy. Case

discussion, consultation, examination, and treatment should be
conducted so as to protect each patient's privacy.

· The patient has the right to expect that all communications and
records related to his/her care will be treated as confidential by
the hospital, except in cases such as suspected abuse and
public health hazards when reporting is permitted or required by
law.

· The patient has the right to review the records about his/her care
and to have the information explained or interpreted as
necessary, except when restricted by law.

· The patient has the right to expect that, within its capacity and
policies, a hospital will make reasonable response to a patient's
request for appropriate and medically indicated care and
services. The hospital must provide evaluation, service, and/or
referral as indicated by the urgency of the case. When medically
appropriate and legally permitted, or when a patient has
requested, a patient may be transferred to another facility. The
institution to which the patient is to be transferred must first have
accepted the patient for transfer. The patient must also have the
benefit of complete information and explanation concerning the
 need for, risks, benefits, and alternatives to such a transfer.

· The patient has the right to ask and be informed of business

relationships among the hospital, educational institutions, other
health care providers, or payers that may influence the patient's
treatment and care.

· The patient has the right to consent to or decline to take part in

research studies or human experimentation affecting care and
treatment or requiring direct patient involvement, and to have
those studies fully explained prior to consent. A patient who
declines to take part in research or experimentation is entitled to
the most effective care that the hospital can otherwise provide.

· The patient has the right to expect reasonable continuity of care

when appropriate and to be informed by doctors and other
caregivers of available and realistic patient care options when
hospital care is no longer appropriate.

· The patient has the right to be informed of hospital policies and

practices that relate to patient care treatment, and
responsibilities. The patient has the right to be informed of
available resources for resolving disputes, grievances, and
conflicts, such as ethics committees, patient representatives, or
other mechanisms available in the institution. The patient has the
right to be informed of the hospital's charges for services and
available payment methods.”

Patients' Responsibilities

There is a responsibility for every right one enjoys. The partnership

nature of health care requires that patients, or their families/surrogates,
take part in their care. The effectiveness of care and patient satisfaction
with the treatment depends, in part, on the patient fulfilling certain
responsibilities. The following are patient responsibilities in their care:9

· “Patients are responsible for providing information about past

illnesses, hospitalizations, medications, and other matters
related to health status. To participate effectively in decision-
making, patients are responsible for asking for additional
information or explanation about their health status or treatment
when they do not fully understand information and instructions.

· Patients are also responsible for ensuring that the health care
institution has a copy of their written advance directive if they
have one.

· Patients are responsible for telling their doctors and other

caregivers if they expect problems in following prescribed
treatment.

· Patients should be aware of the hospital's duty to be reasonably

efficient and fair in providing care to other patients and the
community. The hospital's rules and regulations are intended to
help the hospital meet this responsibility. Patients and their
families are responsible for making reasonable
accommodations to the needs of the hospital, other patients,
medical staff, and hospital employees.

· Patients are responsible for giving necessary information for

insurance claims and for working with the hospital to make
payment arrangements, when necessary.

· A person's health depends on much more than health the care

services. Patients are responsible for recognizing the impact of
their lifestyle on their personal health.”

Meeting patients' right to pharmaceutical care

Pharmaceutical care represents professional aspiration for pharmacy
and a measure of quality service to the patient. Hepler has suggested
that pharmacists who fail to provide pharmaceutical care to their patients
be charged quality tax.10 Pharmaceutical care is both a clinical and an
ethical system, which is characterized by the therapeutic dyad of trust
and care. Providers of pharmaceutical care must be conscious of ethical
principles such as autonomy relating to the patients' rights and
preferences, informed consent, confidentiality, trust and commitment.
For pharmacists that were already rendering clinical pharmacy
functions, they need a change of attitude in order to make a shift towards
pharmaceutical care. However those engaged in traditional dispensing
and inventory management need to acquire additional knowledge and
skills as well. Provision of pharmaceutical care to patients takes more
than mere interest. Three basic requirements are: a practitioner,
patients, and a system of documentation.11 Similarly, building a practice
has three components: assessment of patient needs; development of a
care plan; and follow up evaluation.11

Key Learning Points

· The problem of drug related morbidity and mortality is
now so great, and the cost of treatment failure and adverse
reactions so staggering that someone would have to
address these issues. There are so many new drug
products that need individualised attention and require
follow-up evaluation.
· The pharmaceutical care practitioner would provide the
rational decision making processes for drug therapy that
medicine, nursing, the pharmaceutical manufacturer and
the patient were lacking. The pharmaceutical care
practitioner would be a key component in primary health
care in the near future.
· Patient needs determine the type of pharmaceutical care
services that pharmacists should provide.
· The pharmacist is responsible for achieving the desired
outcome of drug therapy at all levels of the pharmaceutical
care system.
· Levels of pharmaceutical care are organized according to
level of care, namely primary, secondary and tertiary
· Primary pharmaceutical care is practiced in outpatient
pharmacies in hospitals and community pharmacies
· Secondary pharmaceutical care begins with the initial drug
therapy for a more complex medical condition than in
primary care

References
1. Strand LM, Morley PC, Cipolle RJ, Ramsey R, Lamsam GD
(1990). Drug-related problems: their structure and function.
DICP Ann Pharmacother; 24:1093-1097.
2. Hepler C, Grainger-Rousseau, T (1995). Pharmaceutical care
versus traditional drug treatment: is there a difference?'' Drugs;
49:1-10.
3. Smith WE, Benderev K. (1991). Levels of pharmaceutical care:
a theoretical model. Am J Hosp Pharm 48: 540-546.
4. Cipolle RJ, Strand LM and Morley PC (1998). Pharmaceutical
care practice. McGraw-Hill, NY; 76-83.
5. Al-Shaqha WM, Zairi M (2001). Pharmaceutical care
management: a modern approach to providing seamless and
integrated health care. Int J Health Care Quality Assur 14(7):
282-301.
6. Smith W (1988). Excellence in the management of clinical
pharmacy services. Am J Hosp Pharm; 45: 319-325.
7. Charns, M.P. and Mschaefer, M.J. (1983), Healthcare
Organisations: A Model for Management, Prentice-Hall,
Englewood Cliffs, NJ; 118-120.
8. Phillips J., Strand L., Chesteen, S, Morley P (1987). Functional
and structural prerequisites for clinical pharmacy services, Am J
Hosp Pharm; 44: 1598-1606.
9. American Hospitals Association (AHA, 2002). Patient Bill of
Rights. Available at www.aha.org. (Accessed 7 May 2002).

10. Hepler CD (2003). Pharmaceutical care research the next

generation. Pharm J; 270: 370 375.

11.Strand L (1998). Building a practice in pharmaceutical care.
Pharm J; 260:874-878.
 CHAPTER FOUR

PHARMACEUTICAL CARE AS A MEASURE OF QUALITY

Azuka C Oparah
Learning Objectives
At the end of this chapter, you should be able to:
i. Understand that pharmaceutical care is a measure of quality of
pharmacists' contributions to patient care.
ii. List structure and process criteria for pharmaceutical care
iii. Discuss economic, clinical, and humanistic outcomes in
pharmaceutical care

Introduction
Quality is defined in terms of the values of individuals and society.1 For
now, PC appears to be the appropriate perspective for defining quality in
pharmacy because of the importance of individual maximal benefits. PC
represents the highest quality care that pharmacists seek to provide to
patients.2 Hepler is of the opinion that pharmacists who fail to provide
pharmaceutical care to their patients should pay quality tax to
compensate for the denial.3

Donabedian (1966) first identified the now well-established framework of

SPO (Structure-Process-Outcome) that provides guidance in quality
assessment in medical research.4 The basic paradigm is that structure
influences process and potentiates the probability of producing quality
medical care. A similar assumption exists for the link between process
and outcome: better process leads to better outcomes.4 An
 2
interpretation of later article of Donabedian (1990) on the seven pillars
of care indicates that PC appears to be consistent with the quality
6
characteristics of efficacy and acceptability. Furthermore, the
effectiveness, cost-effectiveness, and efficiency of PC should be firmly
established by its practitioners, as barriers are eliminated/or overcome;
the pillars of optimality, equity, and legitimacy seem to be overlooked
under the current definition of PC. Farris and Kirking contend in their
interpretation that PC assumes an individualist definition of quality
2
because; PC by definition is a covenantal relationship with a patient.

An assessment of pharmacy services must employ items pertaining to

the model of pharmacy practice, traditional pharmacy practice or
pharmaceutical care, if the assessment is to be valid. The SPO model
represents a good theoretical model for such assessment.

Structure
Structure represents the stable, physical structure and capabilities of an
4
institution or healthcare setting. In addition to the physical and
operational structure criteria for PC, the number and
qualifications/training of pharmacists in the healthcare setting warrant
vital attention. Many pharmacists do not possess the knowledge and
7
skills to provide a level of care outlined by Hepler and Strand. It is
uncertain whether we can identify the specific knowledge and skills that
should be imparted to pharmacists who may need additional training.
The most cost-effective mechanisms to provide additional training are
2
also undetermined. Structure has its place in quality assessment and
should be assessed periodically to ensure that validated criteria are
present because they indicate a capacity to provide quality PC.
Examples of structure criteria are provided in the Table 4.1. As
pharmacists embark upon assessing the quality of PC, they should
recall that is a relevant indicator of quality. Research is needed to
determine the significance of each of the criteria and to evaluate the
components carefully to determine which measures of structure are
linked to the more fundamental quality measures of process and
outcome.

Table 4.1: Structure Criteria of Pharmaceutical Care5

Number of licensed pharmacists

Qualifications/experience of pharmacists
Presence of appropriate drug information references
Sufficient inventory
Record-keeping capabilities (e.g., computer)
Pharmacy computer systems
Usable space of pharmacy counter
Trained and/or certified technicians
Designated area for compounding
Pharmacy business manager
Financial stability
Private patient counseling area
Nonprescription medications' proximity to pharmacists
Pharmaceutical care documentation forms

Process
The process of care occurs when patients receive care. An
example is whether a pharmacist dispenses the medication is a
process measure of pharmaceutical care. Donabedian
categorized criteria of process quality assessment into either
technical or interpersonal.4 Technical care in pharmacy
represents the procedures and tests pharmacists employ to
 ensure optimal drug use. The pharmacist's knowledge and skill
should focus on systematically identifying, resolving, and
preventing potential and actual drug and health related
problems. It is necessary for the traditional process of physically
filling the prescription should be de-emphasized to facilitate the
process of information gathering, patient counselling, drug
therapy monitoring, and communicating with physicians. The
interpersonal component of the criteria deals with the nature of
the interaction between the pharmacist/supportive personnel
and the patient. Some examples of process criteria of
pharmaceutical care are shown in Table 4.2.

Outcomes
The primary goal of pharmaceutical care is to improve patient
outcomes, hence pharmaceutical care is outcome oriented.
Outcomes are the most important to patients. In providing
pharmaceutical care, outcomes are predetermined and
assessed after implementing pharmaceutical care to a patient.
Outcomes are the results (effects) of the processes of care,
though outcome measures may be influenced by numerous
variables that may be unrelated to the process of care. Genetic
make-up, income, level of education, and family/friendly support
can all affect outcomes. Pharmaceutical care outcomes can be
ultimate/final or intermediate.
The “ECHO” model is often used to assess pharmaceutical care
outcomes. These are the Economic, Clinical, and Humanistic
Outcomes.
Economic outcomes establish the “values for money” and
include the assessment of both inputs and outcomes. The inputs
or resources consumed include the direct costs of providing care
such as cost of drugs, indirect costs, such as man hour losses, as well as
intangible costs such as pain or suffering associated with therapy. Other
measured economic costs include number of hospital admissions,
improved quality of care and reduction in the number of physician visits.

Humanistic outcomes assess the impact of pharmaceutical care on the

patient's well being, expectations and satisfaction issues, patient's
knowledge, as well as the quality of life of the patient. Self-reported
quality of life is now attracting increased attention and there are both
disease- specific and generic instruments (SF 36, SF12, SF 8), which
are standardized questionnaires for tracking a patient's quality of life.
Clinical outcomes are usually focused in therapy management. Clinical
outcomes may be ultimate (final) or intermediate. Ultimate outcomes
are long term effects which are difficult to measure as a result of
intervening variables. However intermediate outcomes are short term
goals that can be assessed during the course of therapy. For example, in
the management of hypertension, the ultimate outcomes are to reduce
cardiovascular and renovascular morbidity and mortality. The
intermediate outcomes include reduction and maintenance of blood
pressure to target levels below 140/90 mmHg or 130/80 mmHg in cases
of diabetes and chronic renal disease. Basic clinical outcomes involve
laboratory measurements e.g. blood pressure, glucose level,
cholesterol level. Table 4.3 below presents some pharmaceutical care
clinical outcomes.
 2
Table 4.3: Process criteria of pharmaceutical care

Technical
Gathering prescription information
Entering prescription into computer or typewriter
Reviewing patient profiles for drug therapy problems
Obtaining appropriate medication stock
Labelling medication container
Checking prescription label, stock bottle, and prescription
for consistency
Giving prescription to patient
Explaining drug name, indication, dosing regimen, possible
adverse effects and drug interactions.
Providing written information of indication, dosing
frequency, possible adverse effects
Documentation of drug utilization review of patient profile
Drug therapy monitoring
Telephone call for follow-up
Blood pressure check
Compliance audit documentation
Cholesterol screening
Inquiry about problem with medication
Calling prescriber with possible prescribing error or
recommendation
Answering patient queries
Answering physician queries
Interpersonal
Willing to listen
Empathetic
Friendly
Concerned
Considerate
Table 4.4: Outcome criteria of pharmaceutical care5

Cure of disease
Reduction or elimination of target symptoms
Slowing down disease process
Prevention of diseases and symptoms
Increased patient knowledge of disease
and drug treatment
Improved medication compliance
Improved medication therapy
Improved prescribing, dispensing,
and medication administration
Improved drug monitoring
Decreased drug interactions
Decreased adverse drug reactions
Decreased sub optimal therapy
Improved identification of drug allergies
Improved identification of drug intolerances
Reduced medication intolerance
Decreased misuse/abuse
Patients attitudes towards disease condition
Patient expectation from treatment
Patient expectations from the pharmacist
Patient satisfaction with treatment
Patient satisfaction with pharmacy profession
 Key Learning Points
· Pharmaceutical care is a measure of quality of
pharmacists'contributions to patient care.
· The Structure Process- Outcome (SPO) model is a good
indicator of quality
· Pharmaceutical care focuses on outcomes
· Pharmaceutical care outcomes are in three domains:
Economic, Clinical, and Humanistic
· Economic outcomes establish the “values for money” and
include the assessment of both inputs and outcomes.
· Humanistic outcomes include patient attitudes,
expectations, satisfaction, patient's knowledge, as well as
the quality of life of the patient.
· Clinical outcomes include cure of disease, reduction in
target symptoms, health promotion, adherence, drug
interactions and adverse drug reactions

References
1. Enright SM (1988). Assessing patient outcomes. Am J Hosp
Pharm; 45:45:1376-1378.

2. Farris KB, Kirking D (1993a). Assessing the quality of

pharmaceutical care I: One perspective of quality. Ann

Pharmacother ; 27:68 73.

3. Hepler CD (2003). Pharmaceutical care research the next
generation. Pharm J; 270: 370 375.
4. Donabedian A (1966). Evaluating the quality of medical care.
Milbank Mem Fund Q ;44:166-203.
5. Farris KB, Kirking D (1993b). Assessing the quality of
pharmaceutical care II: Application of the concepts of quality
assessment from medical care. Ann Pharmacother ; 27:215 223.
6. Donabedian A (1990). The seven pillars of quality. Arch Pathol
Lab Med;114:1115-1118.

7. Hepler CD, Strand LM. (1990) Opportunities and responsibilities

in pharmaceutical care. Am J Hosp Pharm; 47,533-543.

 CHAPTER FIVE

BASICS OF PHARMACOECONOMICS
Waka A Udezi
Learning objective
At the end of this chapter you should be able to:
I. Define pharmacoeconomics and explain the concepts of costs,
inflation, discount and outcomes
II. Know when to apply pharmacoeconomic techniques of cost-
minimization, cost-benefit analysis, cost-effectiveness analysis
and cost-utility analysis.
III. Make simple pharmacoeconomic calculations and appreciate
the role of a decision tree in economic evaluations.

Introduction
Would you have bought this book if the benefit (knowledge) you hope to
gain from reading it is less than what you paid? Certainly not! You have
placed a value on the knowledge which you consider higher or at least
equal to the price and then convinced yourself that you have a good
bargain before you paid. Whenever possible, you would want to haggle
in order to further bring down the the price or cost of goods and services
that you consume. The reason why you just do not pay right away is
because your resources are limited and many needs are competing for
the little money you have. As a result, you want to ration your scare
resources to purchase goods and services that you consider to be more
beneficial to you at any point in time.
The above applies to healthcare worldwide. Many healthcare
technologies including pharmaceutical products and intervention
programmes are competing for the limited resources that are available.
Decision makers (and policy makers) are therefore faced with the
dilemma of deciding which drugs (or healthcare
intervention/programme) will benefit the patient (or populace) more at a
cost that will enable more patients to be treated. If a pharmacy manager
identifies such a drug, then it should be in the hospital formulary and a
healthcare policy maker will want it to be in the essential drugs list of the
country. A pharmaceutical company will be glad to know that a newly
discovered compound will be of greater benefit to the society than
existing molecules, even if the cost of getting it to the market is slightly
higher. A systematic way of computing and comparing the cost and the
benefits of pharmaceuticals should be valuable in deciding which
medicines (or delivery systems) should be in an hospital formulary or
which is the best drug to develop; and if the final product is of any
economic benefit. The techniques of economic evaluation used to aid
decision making in these scenarios make up a body of scientific
knowledge referred to as pharmacoeconomics. Economic evaluation is
multi-disciplinary comprising pharmacy, economics, epidemiology,
biostatistics and medicine. All strive to promote efficient resource
allocation in healthcare.

What is Pharmacoeconomics?
Pharmacoeconomics identifies, measures, and compares the costs
(resources consumed) and outcomes or consequences (health benefits)
of pharmaceutical products and services to health care systems and
1
society. Decision makers use pharmacoeconomic methods to evaluate
and compare total costs of different treatment options and total
outcomes or benefits associated with these options to enable them
choose treatments or health programmes that will provide maximium
healthcare benefits to patients or a given population at minimal cost
under conditions of limited resources. At this point it is important to clarify
the following concepts:

Costs
Costs and benefits of drug treatment of patients have three
corresponding components namely, direct, indirect, and intangible.
Costs are calculated to estimate the resources or inputs that are used to
produce outcome. Direct medical costs are the most obvious costs to
measure. Direct costs include those costs incurred prior to diagnosis
and hospitalization, during hospitalization, during convalescent care
and during continued medical surveillance. Rice et al suggested that
these costs include “expenditures for prevention, detection, treatment,
rehabilitation, research, training and capital investments in medical
facilities as well as professional services, drugs, medical supplies and
2
non personal health services.” Indirect costs are difficult to measure.
These are the result of earnings and man-hour losses without treating
the patients. Such costs or rather opportunity costs include wage and
productivity losses resulting from death, absenteeism, and low
productivity (lack of motivation to work on the part of the victim).
Intangible costs include costs of pain, suffering, anxiety, or fatigue that
occur because of the disease or its treatment. It is difficult to measure or
assign values to intangible costs. In practice, since costs are
denominated in currency, which is prone to inflation the aspect of time
value of money is incorporated in pharmacoeconomic evaluations.

Inflation
This is a sustained increase in the level of prices. The rate of inflation is
the percentage change in average prices from one year to the next. The
medical care component of the consumer price index (CPI) is used to
adjust costs of drugs and healthcare services. An index of hourly wages
is used to adjust salaries in economic evaluation. When projecting costs
into the future from current prices no adjustment is made for inflation. If
prices are collected in different time periods say 2008, 2009, 2010 and
2011 the prices need to be adjusted to a uniform price to account for
inflation. Suppose you want to use information from a published
manuscript that listed the cost of chloroquine induced pruritus to be
NGN200.00 in 2009, given that the CPI in 2009 is 50 and today it is 100,
how would you adjust this amount to current day value? (NGN=Nigerian
naira)

Solution:
Current day cost of pruritus = 200 X 100/50 = NGN400.00
T
Ct
PV = å
t =1 (1 + r ) t
Where 1/(1+r)2 = discount factor, C = cost (or benefit) in time t (in years)
and r = discount rate.
For example, if a healthcare intervention programme generates
NGN10million in the first year and NGN12million in the second year
given a discount rate of 5% then the present value of the intervention is:

1 2
PV= 10/(1+0.05) + 12/(1+0.05) = 9.52 + 10.88 = NGN20.4million.

Perspective of a Pharmacoeconomic Evaluation

The budget holder or person's point of view from which an economic
evaluation is conducted should be given an important consideration
because it will affect the type of cost data that will be incorporated into
4
the evaluation. Basically, there are three perspectives; that of the
patient, hospital or health service and that of society. All the cost
incurred by a patient is used when we view the intervention from a
patient's perspective. Only direct costs are used if the evaluation is from
a hospital perspective while both direct and indirect costs are used if a
societal perspective is adopted. A societal perspective is considered the
most appropriate but a decision maker or healthcare manager faced
with limited resources has a strong incentive to concentrate entirely on
5
the costs that fall on his budget.

Outcomes
An outcome is the therapeutic (or life style modification) objective that
gave rise to a healthcare intervention. An outcome may be clinical (eg
reduction of plasma glucose concentration), economic (reduction of
treatment or healthcare intervention cost) or humanistic (increase in
quality and quantity of life).

Models of Pharmacoeconomic Analysis

Four types of Pharmacoeconomic analyses, which measure costs or
inputs in currency e.g. NGN or USD (US dollars), and assess the
4,5
outcomes associated with these outcomes, are employed. These
models of analyses are categorized by the method used to assess
outcomes of using drugs. If outcomes are assumed to be equivalent, the
study is called a cost minimization analysis; if the outcomes are
measured in currency the study is called a cost- benefit analysis; if the
costs are measured in natural units (CD4+ counts, adverse reactions,
years of life), the study is called a cost- effectiveness analysis; if
outcomes consider patient preferences or utilities, the study is called a
cost-utility analysis. Each of these analyses includes measurement of
cost in monetary terms eg NGN or USD, followed by measurement of
4,5
outcomes as illustrated below:
Methodology Cost Measurement Outcome Measurement
Unit Unit
Cost-minimization analysis (CMA) monetary Assumed to be
equivalent/comparable groups

Cost-benefit analysis (CBA) monetary monetary

Cost- effectiveness analysis (CEA) monetary Natural units (life-

years gained, CD4+ counts)

Cost-utility analysis (CUA) monetary Quality-adjusted life

year (QALY) or other utilities.
Assessment of Outcomes
Cost-Minimization Analysis (CMA)
Here, costs are measured in currency (NGN), and outcomes are
assumed to be equivalent. A typical example is the measurement and
comparison of costs for two therapeutically equivalent antiretroviral
medicines. All the outcomes e.g. efficiency, incidence of adverse drug
reactions are assumed to be equal but the costs are not. Some
researchers criticize this method for being pseudo- pharmacoeconomic
because although costs are measured, outcomes are not measured.
Others claim that the strength of CMA depends on evidence from
published data or expert opinions that the outcomes are equal and
hence the simplicity of the analysis becomes an obvious advantage
compared to other methods of analysis.
Cost-Benefit Analysis (CBA)
A cost-benefit analysis measures both inputs and outcomes in monetary
terms. One advantage of this approach is that treatment options with
different outcomes can be compared since each outcome is converted to
the same unit of currency. In doing the analysis, the sum of estimated
benefits is divided by the sum of the estimated costs to produce a cost-
benefit ratio. If this ratio is more than 1.0, the choice is considered
beneficial. Alternatively, the total cost is subtracted from the total benefit
to produce a net benefit and a positive net benefit signifies a cost
beneficial choice.
By way of a very simple illustration, consider yourself to be the personnel
manager in charge of healthcare in a small firm with 100 staff. A
pharmaceutical representative has approached you with a typhoid fever
vaccine that costs NGN3,000 with an efficacy of 80%. Since the firm
pays all healthcare bills for its workers you have the following data:
number of typhoid cases in the last 12months was 50 and it costs
NGN15,000 to treat each staff. Productivity loss due to sick leave per
staff was NGN2,000. Assuming that the rate of typhoid fever infection
remains unchanged will you recommend the vaccine?

Solution:
Net Benefit = Total Benefits Total Costs
Total Benefits = number of typhoid cases avoided X cost
= 50(80/100) X (15,000+2,000) = 680,000
Total Costs = cost of vaccination + [number of cases
(cost of treatment + loss productivity)]
= (100 X 3,000) + (10 X (15,000 + 2,000)) = 470,000
Net Benefits = 680,000 470,000 = NGN210,000

This value is positive and obviously if you divide the Total benefits with
the Total Costs your Cost Benefit Ratio will be greater than one. Based
on this analysis, you should recommend the vaccine.

Cost-Effectiveness Analysis (CEA)

This method measures costs in currency e.g. NGN and outcomes in
natural health units such as lives saved, reduction in CD4+ counts. An
advantage of this method is that practitioners are conversant with health
outcomes and these outcomes do not need to be converted into
monetary units. On the other hand, the alternatives used in comparison
must have outcomes that are measured in the same units and if more
than one unit of outcome is important when conducting the comparison,
a cost- effectiveness ratio should be calculated by dividing cost by
6
effectiveness for each type of outcome. The example at the end of this
chapter is a simple illustration of a CEA.
A randomized double blind clinical trial is the gold standard used in
evaluating new medicines to find out if they can actually treat a disease.
However, the patients in a clinical trial are selected based on some
inclusion criteria. They are also closely monitored based on an agreed
protocol that ensures rates of compliance that do not capture what really
happens in real-world medical practice. As a result, the fact that the
medicine in question was able to relief symptoms in a clinical trial in all
enrolled patients does not mean it will have the same high level of
success in a real-world clinical setting where patients have different
characteristics and co-morbidities (that were not present in clinical trial
patients) with a reduced rate of compliance. Therefore, while a clinical
trial confirms the efficacy of a drug (its ability to treat a disease in a tightly
controlled experimental environment) pharmacoeconomics confirms its
effectiveness, which is the ability of the drug to treat the disease in the
real-world.

Cost-Utility Analysis (CUA)

This method considers patients' preferences (utilities) when measuring
health consequences. Diseases affect the quality of life of patients in
three dimensions namely, physical, mental, and social well being. For
instance, since HIV/AIDS does not yet have a known cure, improvement
of the patient's quality of life appears to be the most attractive outcome.
The most common unit in conducting CUAs is the Quality Adjusted Life
Years (QALYs). This unit incorporates both the quality and quantity of
life and hence it is possible to compare different types of health
outcomes. In calculating QALYs, one year of life in perfect health is
given a score of 1.0 QALY. The impact of HIV/AIDS on health related
quality of life is a reduction in this score. The unit allows comparison
between mortality (score 0) and morbidity. The summated rating scale
whereby patients score their state of health is commonly employed.
Thus a score of 70 on a scale of 0 to 100 indicates 0.7 QALYs. There are
general and specific instruments for measuring quality of life. The SF-36
Health Survey, and Health Status Profile SF- 12 are examples of general
assessment instruments. HIV-PARSE Baseline Questionnaire, Health-
related quality of life measures from HIV Cost and Services Utilization
Study, and Questionnaire for Persons with HIV (MQOL-HIV) are some of
the specific instruments. Others are EORTC quality of life questionnaire
for cancer patients, HYPER 31 for hypertensive patients and DHP 1 for
patients living with diabetes.

Sensitivity analysis
Construction of models using hypothetical cohorts is often used in
pharmacoeconomic evaluation. In such situations, data used in model
construction may be obtained from medical literatures, expert opinion
and clinical trials. These data from various sources may have different
levels of uncertainty which can affect the results of an economic
evaluation. Sensitivity analysis is therefore conducted by varying the
value of each variable used in model construction and examining how it
affects the value of interest. If a selected treatment option remains
dominant over a plausible range of input data values, then the model is
said to be robust and the results are reliable.
How to Conduct a Pharmacoeconomic Evaluation
§ Establish the perspective
§ Describe all the treatment or intervention options under
consideration
§ For each alternative, specify the possible outcomes and the
probability of their occurrence
§ Specify and monitor the health-care resource consumed in each
alternative
§ Assign monetary (e.g. NGN, USD) values to each resource
consumed
§ Specify and monitor nonmedical resources consumed by each
alternative
 § Specify the unit of outcome measurement
§ Specify other noneconomic attributes of the alternatives, if
appropriate
§ Analyze the data
§ Conduct a sensitivity analysis
§ Write and submit your report to the budget holder (decision
maker) or for publication

Decision Tree
A decision tree is a graphical representation of the decision process
indicating competing options or treatment alternatives, their probabilities
of occurrence and costs, benefits or loss. It consists of a network of
nodes and branches. Decision nodes are represented by a square and
chance or event nodes are represented by circles. The general approach
in decision tree analysis is to work backward through the tree from right
to left, computing the expected value. This is known as roll back.
Steps in decision tree analysis:7
§ Systematically identify the decision points and the alternative
courses of action at each point
§ Determine the probability and the payoff associated with each
course of action
§ Starting from the extreme right, compute the expected payoffs or
cost for each course of action
§ Choose the course of action that yields the best payoff or cost for
each of the decisions
§ Repeat the above for each decision point
§ Finally, identify the course of action to be adopted under different
possible outcomes for the situation under consideration
Advantages of decision tree approach
§ Helps decision-making in an orderly, systematic and sequential
manner
§ It helps the decision maker to examine all possible outcomes,
whether desirable or undesirable
§ It communicates the decision making process in an easy and
clear manner to others
§ It displays logical relationship (of event occurrence in sequence)
between the parts of a complex problem
§ It is particularly useful where the initial decision and its outcome
affect subsequent decisions
§ It can be applied in various fields such as introduction of a new
product, marketing, investment etc
Disadvantages of the decision tree approach
§ The diagrams become complicated as decision alternatives and
variables increase in number
§ It becomes complicated when there is interdependence between
the alternatives
§ It yields an “average” value solution

Example
35% of patients on chloroquine that cost NGN15.00 for a complete
treatment got well. The others have to take an ACT that cost NGN450.00
for 98% of them to get well. The rest died. Another group of patients took
SP with a treatment cost of NGN120.00. 68% of them got well. The rest
took an ACT with a similar cost and outcome with the chloroquine group.
Assume that death cost the society NGN250,000.00. With the aid of a
decision tree, calculate the cost effectiveness of the options. As a policy
maker which of the drugs should be first line? Explain your answer.
 Solution: First construct the tree below with the aid of Vanguard
Studio 5.0.
Chloroquine
Well = 35 x 15 = 525
SICKact = 65 x (450 + 15) = 30,225
WELL1 = (65 x 98/100) x 0 = 0
DIED = (65 X 2/100) X 250,000 = 325,000
Total cost for 100 patients = 525 + 30,225 + 0 + 325,000 =
NGN355,750
Cost of using chloroquine as first line treatment for malaria per
patient = 355,750/100 = NGN3,557.50

As a practice example repeat the above calculations for SP and answer

the question completely.

WELL
35% 0
CHLOROQUINE 15 WELL1
15 98% 0
3557.5 SICKact 465
65% 450
5465 DIED
2% 250000
Root 250465
0
3557.5 died
2% 250000
sickACT 250570
32% 450
SP 5570 Well
120 98% 0
1864 well 570
68% 0
120
 Key Learning Points
· Resources are limited hence healthcare budget holders
need evidence to help them allocate scarce funds to
treatments and interventions, that will produce maximum
health in a given population.

· To achieve this, costs and outcomes must be identified,

measured and compared for all competing interventions in
a transparent way as to simplify the decision making
process for the budget holder.

· Pharmacoeconomic techniques such as CMA, CBA, CEA

and CUA are the tools at the disposal of decision makers to
help them achieve this goal.

References
1. Townsend RJ. Postmarketing drug research and development.
Drug Intell Clin Pharm 1987:21(1):134-6
2. Rice DP, Hodgson TA, Kopstein AN. The economic cost of
illness: a replication and update. Health Care Finance Rev.
1985; 7(1): 61-80
3. Weinstein MC, Siegel JE, Gold ME, Kamlet MS, Russell LB.
Recommendations of the Panel on Cost-Effectiveness in Health
and Medicine. JAMA 1996;276:1253-8
4. Bootman JL, Townsend RJ, McGhan WF. Principles of
rd
Pharmacoeconomics. 3 Edition. Cincinnati: Harvey Whitney
Books, 1996.
5. Walley T, Haycox A, Boland A, eds. Pharmacoeconomics.
London: Churchill Livingstone, 2004.
6. Muennig P. Designing and Conducting Cost-Effectiveness
Analysis in Medicine and Health Care. San Francisco: Jossey-
Bass. 2002.
7. Gupta PK, Hira DS. Decision Theory, Games, Investment
Analysis and Annuity. In: Operations Research. New Delhi: S.
Chand and Company, 2007: 708-883.
 CHAPTER SIX

DRUG THERAPY PROBLEMS

Azuka C Oparah
Learning Objectives
At the end of this chapter, you should be able to:
I. Define a drug therapy problem
ii. Classify drug therapy problems
iii. Identify the causes of drug therapy problems
iv. Know a scheme to identify drug therapy problems
Introduction
It should be acknowledged and appreciated that without drug therapy
problems; there would be no need for pharmaceutical care. The result of
fragmented delivery of pharmaceutical services without collaboration
with the patient and other caregivers is a number of drug related
problems including: high rate of medication error; excessive rate of
adverse drug reactions; drug-drug interaction; drug admixture
incompatibilities; drug induced disease; inefficient use of health
manpower; drug-laboratory test interactions; physician contribution to
medication errors; drug waste; high cost of the hospital medication
system.1
What is a drug therapy problem?
A drug therapy problem is any undesirable event experienced by the
patient that involves or is suspected to involve drug therapy and that
actually or potentially interferes with a desired patient outcome. The term
is used to denote a drug- related event amenable to detection, treatment
or prevention. A drug therapy problem may be potential (likely to occur)
or actual (patient is already experiencing it).
A drug therapy problem is also a situation that if left unresolved prevents
a patient from realizing the full benefits of their drug therapy. To be
recognized as a drug therapy problem, the patient, the physician and the
pharmacist must all agree there is a problem and therapy is changed as a
result. Pharmaceutical care is a multidisciplinary process. In other
words, the pharmacist works in collaboration with the patient and other
caregivers while taking responsibility for meeting the patients drug
related needs. Drug therapy problems are not medical problems but they
arise in the course of treating medical problems and hence compound
the problems being treated. The different classes of drug therapy
problems are presented in Table 6.1

Table 6.1: Classes of drug therapy problems

· Unnecessary drug therapy (e.g. duplicate therapy)
· Wrong drug (including dosage form)
· Dosage too low (dose, frequency, duration)
· Dosage too high (dose, frequency, duration)
· Adverse drug reaction
· Drug interaction (pharmaceutic, pharmacodynamic,
pharmacokinetic)
· Inappropriate adherence
· Additional drug therapy (untreated indication)

2
Cipolle et al. have elaborated on categories of drug therapy problems
(Table 6. 2). An understanding of the categories is imperative in the
systematic implementation of the pharmaceutical care process.
 2
Table 6.2: Explanation of the categories of drug therapy problems

1. The patient is taking a drug therapy that is unnecessary given

his or her present condition.

2. The patient has a medical condition for which the wrong drug is
being taken.
3. The patient has a medical condition for which too little of the
correct drug is being taken (dose, frequency, and duration).
4. The patient has a medical condition for which too much of the
correct drug is being taken.
5. The patient has a medical condition resulting from an adverse
drug reaction.
6. The patient has a medical condition resulting from clinically
significant drug interactions.
7. The patient has a medical condition resulting from not taking the
drug appropriately (explore missed doses and reasons).
8. The patient has a medical condition that requires the initiation of
new or additional therapy (untreated indication).

Causes of drug therapy problems

The causes of drug-related problems are multi-factorial and their
assessment has been based on factors such as inappropriate
prescribing, inappropriate delivery, inappropriate patient behavior,
patient idiosyncrasy, and inappropriate monitoring.3 Tomechko et al.4
have pointed out five drug related needs of patients namely: appropriate
indication, effectiveness, safety, adherence/compliance, and untreated
indication that have resulted in drug therapy problems. These
researchers present seven classes of drug related problems and their
causes; it will be logical to have drug interaction under a separate class.
The problems resulting from unmet drug-related needs of patients are
illustrated in Table 6.3 while the possible causes of the problems are
presented in Table 6.4.

Table 6.3: Problems resulting from unmet drug-related needs4

Drug related need Drug therapy problem

Appropriate indication 1. Unnecessary drug therapy
Effectiveness 2. Wrong drug
3. Dosage too low
Safety 4. Dosage too high
5. Adverse drug reactions
6. Drug interaction
Adherence 7. Inappropriate adherence
Untreated indication 8. Needs additional drug therapy

Table 6.4: Causes of Drug Therapy Problems4

Drug therapy problem Cause
Unnecessary drug therapy No medical indication
Addiction/recreational drug use
Non-drug therapy more appropriate
Duplicate therapy
Treating avoidable adverse reaction

Wrong drug Dosage form inappropriate

Contraindication present
Condition refractory to drug
Drug not indicated for condition
More effective drug available

Dosage too low Wrong dosage

Frequency inappropriate
Duration inappropriate
Incorrect storage
Incorrect administration
Drug interaction
Dosage too high Wrong dose
Frequency inappropriate
Duration inappropriate
 Drug interaction

Adverse drug reaction Unsafe drug for patient

Allergic reaction
Incorrect administration
Drug interaction
Dose increased/decreased too
quickly
Undesirable effect

Inappropriate adherence Drug product not available

Cannot afford drug product
Cannot swallow/ administer drug
Does not understand instructions
Patient prefers not to take drug

Needs additional drug therapy Untreated condition

Synergistic therapy
Prophylactic therapy

Identifying Drug Therapy problems

Pharmacists should acquire the skills to identify potential and actual
drug therapy problems better than anyone else. Relevant patient data
must be acquired and critical thinking skills are applied. Compare all
medications with the medical conditions/complaints to ascertain that
every medication is treating a condition and that every condition is being
treated with or without a medication:
Ø Is there a need for a medication? i.e. indication. If no,
unnecessary drug therapy (A)
Ø If yes, is the medication safe and efficacious for the condition? If
no, wrong drug (B)
Ø If yes, are the dose, frequency and duration appropriate? If no,
dosage too low (C) or dosage too high (D)
Ø If yes, is the patient likely to experience adverse drug reaction? If
yes, adverse drug reaction (E)
 Ø Is there a likelihood of drug interaction? If yes, drug interaction
(F)
Ø Is patient adherence appropriate? If no, inappropriate
adherence (G)
Ø Is there any condition/complaint that requires a medication but
receiving none? If yes, untreated indication/additional drug
therapy (H)

Pharmaceutical Care and Cost Reduction

Cost savings that arise from pharmacist drug-therapy intervention have

been increasingly documented in the literature. Studies indicate an
enhanced quality of life for patients and an improved profit potential for
5
the pharmacy. A large study conducted by Rupp and colleagues (1992)
noted that roughly 2% of prescriptions examined contained one or more
prescribing errors. They found that pharmacist interventions produced
6
an added value of $2.32 to each prescription filled. The value-added
determination was based on the estimated direct cost of medical-care
expenditures due to the participating pharmacists' interventions. Expert
evaluators were asked to determine the medical care that would
necessarily be required to treat the patients. Each level of medical care
was assigned an economic value. The total potential avoided expenses
were then divided by the number of prescriptions to obtain the value-
added amount per prescription.

A Minnesota study by Iverson also found that 2% of prescriptions

needed dosage corrections or other actions.7 Iverson concluded that the
cost savings amounted to $16.74 per prescription. Another study by
Rupp found that $123 in medical-care costs were avoided through
pharmacist interventions.8 Rupp and DeYoung found that prescribing
errors on the part of physicians represented the most common errors
detected in the prescribing process.9 Elsewhere, the influence of
pharmacists has produced lower drug expenditures and, in some cases,
10
the administration of fewer doses. In managed care settings,
pharmacist interventions have been calculated to save $24 per
11
intervention. In another study, Harrington and associates described
cost savings associated with educating physicians and influencing
prescribing patterns for NSAIDs, anti-ulcer medications, lipid- lowering
12
agents, and antibiotics. They found that pharmacists saved an average
of $6200 per intervention over several months through working in a
12
nonthreatening collaborative mode with primary care physicians.

Key Learning Points

· Pharmaceutical care philosophy of practice emerged to

reduce the burden of drug therapy problems (DTPs) in the
health care system

· DTPs are negative patient care outcomes that can cause

death, increase direct cost of therapy, induce/prolong
hospitalization, reduce the quality of life and patient
satisfaction.

· Potential or actual drug therapy problems may be classified

into:

ü Unnecessary drug therapy

ü Wrong drug
ü Dosage too low
ü Dosage too high
ü Adverse drug reaction
ü Drug interaction
ü Inappropriate adherence
ü Additional drug therapy
· DTPs are not medical problems but they arise
 from patients unmet drug related needs for:
ü Appropriate indication
ü Effectiveness
ü Safety
ü Adherence
ü Untreated indication
· Critical thinking skills are required to identify drug
therapy problems
· Correlate each medication with medical
condition/complaint
Assess for appropriate indication, safety, efficacy,
adherence and need for additional therapy/untreated
indication.

References

1. Smith W (1988). Excellence in the management of clinical

pharmacy services. Am J Hosp Pharm; 45: 319-325.
2. Cipolle RJ, Strand LM and Morley PC (1998). Pharmaceutical
care practice. McGraw-Hill, NY; 76-83.
3. Plumridge RJ, Worjnar-Horton RE (1998). A review of the
pharmacoeconomics of pharmaceutical care.
Pharmacoeconomics; 14 (2): 175-189.
4. Tomeckho MA, Strand LM, Morley PC, Cipolle RJ (1995). Q and
A from the pharmaceutical care project in Minnesota. Am Pharm;
NS35(4):30-39.
5. Bootman JL (1986): Application of cost benefit analysis to
community pharmacy practice. Can Pharm J; 119:295-303

6. Rupp MT, DeYoung M, Schondelmeyer SW (1992): Prescribing

problems and pharmacist interventions in community practice.
Med Care; 30:926-940.
7. Iverson PS (1992): Pharmacists' interventions. Minn
Pharmacist; 8:11-14.

8. Rupp MT (1992): Value of community pharmacists' interventions

to correct prescribing errors. Ann Pharmacother; 26:1580-1584.

9. Rupp MT, DeYoung M (1991): Reactive pharmacist

interventions: Results from a spontaneous reporting program. J
Pharmacoepidemiol; 2(1): 35-49.

10. Bussieres JF, Lepage Y (1991). Reduction of costs and drug

consumption in prolonged care through the impact of a
pharmacist. Can J Hosp Pharm; 44:121-129

11. Davis KR, Allen KL (1990). Poster Presentation: Financial impact

of routine pharmacist intervention in a managed care system.
Abstracts from the proceedings of the American Society of
Health-System Pharmacists (ASHP) 25th Midyear Clinical
Meeting, Las Vegas, Nev., p 6.

12. Harrington CA, Lennard EL, Fink CM (1994). Cost savings due to
the prescription drug education project. Abstracts from the
proceedings of the American Pharmaceutical Association
(APhA) Annual Meeting and Exposition, Seattle, Wash., Abstract
141:111.
 CHAPTER SEVEN

PATIENT DATA COLLECTION, EVALUATION AND CARE PLANING

Azuka C Oparah and Valentine U Odili

Learning Objectives
At the end of this chapter, you should be able to:
i. Know how to conduct patient interview
ii. Know the application of physical assessment skills in the
delivery of pharmaceutical care
iii. Describe patient data evaluation process
iv. Apply critical thinking and problem solving skills to
implement pharmaceutical care
v. To design an effective pharmaceutical care plan

Subjective Patient Data Collection: Patient Interview

Patient interview provides subjective data necessary for treatment
evaluations and decisions, which may reduce the need for extensive
physical examination of the patient.
Patient interview begins a professional relationship, and effective
communication skills are necessary to achieve the goal of an interview
session. The principles of the interview process are the same regardless
of whether it is a medication history or a comprehensive overview of the
patient's medical condition.

Preparation
Review existing patient records: case notes, laboratory report, treatment
chart, nursing chart etc. This provides background information on the
patient.
The communication Process
Communication is a social behaviour. Social behaviour is made up of
linguistic and non-linguistic components. Linguistic component is
concerned with vocals i.e. how something is said as opposed to what is
said, and verbal message. Whereas, non-linguistic component is
concerned with non-verbal communication issues such as body
contact, interpersonal space, body movement, and appearance. An
average person speaks for only some few minutes daily, with the
remainder of communication by nonverbal means. About 55% to 95 %
of social meanings (attitudes, feelings and emotions) are conveyed
1
non-verbally. When contradiction exists between verbal and non-
verbal messages, non-verbal communication is believed because
action speaks louder than words. It is difficult to lie non- verbally
because when being deceitful we emit signs of “social leakage” such as
2
excessive feet and hand movement, less eye contact etc. The following
are some nonverbal techniques employed in patient interview:
· Squarely face the patient and maintain eye contact 60 %
to 70 % of the time
· Use hand gestures when you speak
· Sit or stand comfortably; do not appear anxious to leave the
room or disinterested in what the patient has to say.
· Position yourself at patient's eye level when possible.
· Create an open posture by leaning toward the patient and
uncrossing your arms and legs.
· Wear clean, neat, comfortable professional clothing
· Use silence to allow the patient to compose his or her story
· Relax

Verbal communication
Here, effective use of words, questioning skill, and listening skill are very
essential. The process enables the pharmacist to investigate patients'
needs and the patients to negotiate their needs.
Questioning skills
This is the ability to make effective use of open ended, close ended and
probing questions to elicit appropriate patient response.
Listening skills
There are many talkers but few listeners. Listening demands full
attention and self-discipline, and avoidance of premature judgement.
We have to listen both to verbal and nonverbal messages. It should be
realized that while hearing is a physical activity, listening is a mental
process. Just as we see with our eyes but we read with our brains,
likewise we hear with our ears but listen with our brains. It is not
necessary to learn how to see but we learn how to read. Similarly, it is not
necessary for us to learn how to hear but we need to learn how to listen.
The pharmacist interviewing a patient must listen “actively” i.e. by
displaying appropriate verbal and non-verbal behaviour to show he is
paying attention.

Beginning the interview

Greet and introduce yourself by name and profession, and state the
purpose and duration of the interview; request for patient's time to be
interviewed. If the time is not convenient, reschedule it. It is better to
have continual sessions than a prolonged session. Begin with open
ended questions and then get more specific, to allow the patient to follow
a train of thought. The following seven screening questions, (Table 7.1)
for specific information about a symptom or problem plus three
questions developed by US Public Health Service useful in determining
how well patients understand their drug therapy provide the pharmacist
3-4
with considerable patient-specific information. Effective
communication skills are necessary for the delivery of pharmaceutical
care. The tips for good interview are presented in Table 7.2.

Using Data Collection Forms

The pharmacist should fill part of these forms during interview and
complete details immediately after the interview. A well-designed form
will include space for a pharmacist to collect information related to:
· Basic patient demographics,
· Prescription and nonprescription drug use,
· Social and family history,
· Medical history
· Complaints or symptoms that indicate how well drug therapy
is working,
· Possible adverse effects or potential untreated conditions
that will require the pharmacists' intervention or referral to a
physician.

A comprehensive pharmaceutical care documentation format, which is

based on the pharmaceutical care (PC) steps, is shown in Appendix 7.1
at the end of this chapter.
This format prompts the pharmacist to acquire the relevant subjective
and objective data as well as to complete other steps involved in
5
pharmaceutical care process. Two types of PC intervention
documentation forms are adopted. Page A prompts the pharmacist to
collect and record the patients' demographics, social, medical,
medication and compliance histories. Page B prompts recording
important laboratory findings and physical observations relevant to
pharmacotherapy. Page C provides space for the drug therapy problem
list and PC plan and Page D is blank for notes. The second form is a one-
page pad (Page E), which pharmacists in the outpatient pharmacy units
use to document their PC activities. As not all the patients would require
detailed data collection and evaluation, the form is therefore designed for
quick PC intervention and documentation.

Table 7.1: Patient interview screening questions3-4

1. Location: “Where is the symptom/problem?”

2. Quality: “What is it like?”
3. Quantity: “How severe is it?”
4. Timing: “How long or how often has it been present?”
5. Setting: “How did it happen?”
6. Modifying Factors: “What makes it better or worse?”
7. Associated symptoms: “What other symptoms do you have”
8. What did your physician tell you this medication was for?
9. How did your physician tell you to use this medication?
10. What did your physician tell you to expect from this medication?

Table 7.2: Tips for Good Patient Interview6

1. Greet the patient, smile, make introductions, establish friendly
eye contact
2. Explain the interviewing process while communicating warmth
and welcome
3. Direct the patient to the consultation area in an assertive non
threatening way
4. Detail the interview process, why information is needed and how
it will be used
5. Indicate duration of interview be sure schedule is convenient to
patient
6. Use words and manner that convey professionalism
7. Pay attention to body language: eye contact, facial expression,
body position etc
8. Ask open-ended questions. Begin with broad questions and then
 get more specific
9. Give patient adequate time for responses
10. Use good listening skills
11. To avoid having to think about what to say while patient speaks, use
a list of questions as a prompt.
12. Ask the patient to restate any unclear information.
13. Communicate at the appropriate educational level and avoid
medical jargon.

Objective Patient Data Collection: Physical Assessment

Information can be obtained as needed but it should be noted that this is
an area pharmacists need to improve upon. This information may be
collected through record review or by performing an actual physical
assessment on the patient using the appropriate assessment skills. Also
laboratory tests such as blood glucose testing, blood pressure
monitoring, cholesterol screening at your practice site may be required.
The incorporation of the pharmaceutical care model into the provision of
pharmacy services requires that practitioners have the ability to assess a
patient and his or her likely response to therapy. Patient assessment in
pharmacies, however, is not new.
Community pharmacists are commonly asked for and routinely provide
recommendations for minor health problems. This level of patient
assessment often involves obtaining subjective data through the
completion of a health history, medication history, or a patient interview.
In addition, physical assessment of the patient is one of the most
valuable tools the pharmacist can have for gathering information to
make an informed decision about a patient's health-related problems.

Physical assessment in the delivery of pharmaceutical care can be

defined as "the systematic acquisition of physical data and
symptomatology of patients for the purpose of initial evaluation and care
recommendations, in-process case management, medical referral, or
outcomes assessment." The basic physical assessment skills and their
definitions are presented in Table 7.3.
Too often, when pharmacists face the idea of performing physical
assessment, images of invasive examinations enter their mind. It is
important to remember that evaluation of physical data by the pharmacist
is not intended to replace that of a primary practitioner; rather it is
intended to augment the management of a patient's medical problems. In
fact, patients who are checking their blood pressures at home are
performing physical assessment. Physical assessment skills can play a
vital role in providing quality pharmacist care; however, when it comes to
incorporating these skills into daily pharmacy practice, it is often hard to
visualize their application and this need not be so. Tables 7.4 and 7.5
illustrate the use of physical assessment in OTC medication selection
and identification of drug therapy problem (adverse drug reactions)

7
Table 7.3: Definitions of Basic Physical Assessment Skills

Skill Definition

The observation of physical signs displayed by the patient, depends to a large

Inspection
extent upon the knowledge of the examiner.

Palpation Various ways of perceiving by the sense of touch.

Procedure used to evaluate structures lying no deeper than 4-5 cm under the
Percussion
skin.

Process of listening to sounds originating within an organ or body cavity and is

Auscultation usually augmented by use of an acoustically well-built, personally fitted
stethoscope.
Table 7.4: Physical Assessment in OTC Drug Product
Chief
Differential PA Skill
Complaint Specific Findings

Skin rash 1. Drug reaction 1. Pruritic, symmetrical, most likely on the Inspection
trunk, most commonly urticarial, maculopapular
vesicular, bullous, photosensitive, vascular,
exfoliative, pigmented, acneiform, fixed

2. Contact 2. Allergen: erratic distribution of lesions, linear

dermatitis: streaking, erythema, raised lesions, vesicles,
allergen (poison bullae; Irritant: red, oozing blisters, ulcers
ivy); irritant
(chemical)

3. Disease 3. Systemic lupus erythematous (butterfly

process rash), shingles, chicken pox

Ear ache 1. Otitis media 1. Effusion behind the eardrum, bulging, bright Inspection, Palpation
red membrane, light reflex absent, discharge, Otoscopic
fever examination

2. Otitis externa 2. Inflammation, erythema, possible discharge

3. Ear wax 3. Red-orange pastelike discharge

Sore throat 1. Bacterial 1. Rapid onset, very sore, large, tender lymph Interview questions,
(Strep) nodes, exudates on tonsils and posterior Inspection: tongue
pharyngeal wall, fever depressor, flashlight

2. Virus 2. Slower onset, less sore, enlarged but not

tender lymph nodes

Itchy scalp 1. Head lice 1. Nits, yellowish or greyish white colour, are Inspection
attached to the hair shaft

2. Dandruff 2. Scaling around the hair shaft, diffuse, thin,

white or greyish flakes

3. Psoriasis 3. Red, patchy plaques, erythematous, dry

silvery scales, small area of bleeding after
scale removal

Chest pain 1. Angina Interview questions

2. Gastro Intestinal
3.Musculoskeletal
Table 7.5: Physical Assessment in Identifying Adverse Drug

Medication Areas affected Potential Findings PA Skill

Steroids 1. Thinning, bruising, delayed

1. Skin Inspection
wound healing

Ophthalmoscopic
2. Eyes 2. Cataracts
examination

3. Face, neck 3. "Moon face," buffalo hump Inspection

4.
Musculoskeletal 4. Osteoporosis Inspection
system

5. Oropharynx 5. Fungal infection Inspection

B-blockers Palpation,
Cardiovascular Bradycardia, hypotension
Auscultation

Phenytoin 1. Eyes 1. Nystagmus Inspection

2. Gums 2. Hyperplasia Inspection

Oral
Skin Melasma (pregnancy mask) Inspection
contraceptives

Extrapyramidal side effects

Central nervous
Antipsychotics (dystonia, pseudoparkinsonism, Inspection
system
tardive dyskinesia)
Critical Thinking and Problem Solving Skills in Data Evaluation
Pharmaceutical care is service oriented and to deliver it, the pharmacist
needs some skills. The previous sections considered communication
skills and physical assessment skills, which are relevant in the
acquisition of patient-specific data. The evaluation of the acquired data
and identification of health and drug therapy problems involve critical
thinking and problem solving skills.
Critical thinking involves the following steps:9
• Collecting relevant information
• Evaluating the information
• Making a judgment about the information
• Forming an opinion, and
• Making a decision.

The pharmacist needs a systematic approach in order to identify the

drug related problems, briefly describe, and categorize them. One model
of problem solving, the “IDEAL” approach, is intended to ensure
efficiency and accuracy during the resolution process through five
cognitive steps:10-11
• Identification - Establish the existence of a potential or actual
drug therapy problem
• Definition - Define the drug therapy problem by categorizing it
into one of the eight classes previously listed
• Exploration Ascertain evidence based therapeutic alternatives
to resolve the problem
• Action Make recommendations then develop and implement
therapeutic and monitoring plans in collaboration with the patient
and physician
• Looking and learning Determine the outcome of the
implemented plans
Care Planning
Pharmaceutical care is all about caring for the drug related needs of
patients. Caring has three components that should be satisfied:
· An assessment of the patient's needs

· A care plan to meet those needs

· And a follow-up evaluation to determine the progress the patient

is making toward meeting the goals of therapy

The pharmaceutical care plan is a written, individualized,

comprehensive medication therapy plan based on clearly defined
therapeutic goals. The pharmaceutical care plan, which is available to all
pharmacists caring for a patient, is updated with each major change in
patient status. It is important that the physician be informed about the
care plan to ensure common goals. Patients should also be informed
about the general content of the care plan as means of gaining their
agreement regarding drug therapy. In most clinical practices, care plans
are organized by medical condition. In pharmaceutical care, care plans
are organized by indications for drug therapy (i.e., pain management,
sinusitis, prevention of osteoporosis). This structure allows the
practitioner to be constantly aware of the indications the patient has for
drug therapies and how best to manage each of them.

Therapeutic goals must be established for each drug-related problem so

that the pharmaceutical care planning process can be effective.
Therapeutic goals should be definite, realistic and, if possible,
measurable. Most therapeutic goals relate to:

• Approach normal physiology (i.e., normalize blood pressure

below 140/90 mmHg).

• Slow progression of disease (i.e., slow progression of cancer).

• Cure upper respiratory tract infection

 • Alleviate symptoms (i.e., optimize pain control).

• Prevent adverse effects.

• Control medication costs.

• Educate the patient about his or her medication.

The general steps involved in creating a pharmaceutical care plan are

• Create comprehensive patient database.

• Assess for actual and potential drug-related problems.

• Establish therapeutic goals.

• Specify monitoring parameters with end points and frequency.

• Document the patient's progress towards therapeutic goals.

Pharmaceutical Care Cycle

Pharmaceutical care is an on-going process of satisfying patients' drug

related needs. Once a drug therapy has been identified, goals are set
and care plans or interventions are developed and implemented. The
process is monitored and followed up until the problem is resolved. The
care cycle is illustrated in Figure 7.2.

Figure 7.2: Pharmaceutical Care Cycle

When pharmacists first perform a work-up for their patients, it becomes
obvious that many patients have multiple medical conditions and more
than one drug therapy problem and these may become impracticable to
resolve immediately or at once. Therefore, the pharmacist needs to
develop an organized, patient-specific plan. Creating such a plan
9
requires the following steps:
• Generate a problem list
• Prioritize drug therapy problems
• List interventions to resolve each problem
• Determine desired outcomes for each problem and intervention
• Determine monitoring parameters/evaluating ongoing
treatment.
An efficient patient care tool, the “SOAP”, which is already being used by
physicians, is useful (Table 7.6).

Table 7.6: SOAP format9

Subjective data: Any information that a patient provides, such as

complaints or symptoms, as well as the pharmacist's perceptions of the
situation. The primary means of gathering this information is by talking to
the patient.

Objective data: Any patient vital signs, laboratory test results, and
physical examination findings. The pharmacist should select the
pertinent objective data needed to follow a specific drug therapy. Current
medication can also be included.

Assessment: The pharmacist's opinion of the patient's drug therapy. By

assessing the patient's therapy, the pharmacist determines what drug
therapy problems exist. The assessment should be based on the data
contained in the subjective and objective components of the SOAP note.
Plan: The pharmacist discusses the goals of therapy, the action that has
already been taken to resolve the drug therapy problem, and any further
recommendations or interventions. The pharmacist also discusses the
monitoring plan and any follow-up schedule needed with the patient. The
pharmacist should list the parameters that will be monitored, the intervals
of measurement, and the subjective data being taken into consideration,
as well as any educational interventions needed to ensure patient
adherence

S = Subjective; O = Objective; A = Assessment; P = Plan

Key Learning Points

· Interpersonal communication skills are required in providing
pharmaceutical care
· These skills include use of open ended questions, active
listening, empathic responding, use of feedback and
understanding of non-verbal communication
· Patient interview begins a professional relationship towards
acquisition of subjective data
· A good interview depends on preparation and a clear focus on
relevant information
· Objective patient data may be acquired through review of
existing patient records, physical assessment, and laboratory
tests
· A number of adverse drug reactions can be identified using
physical assessment skills of inspection (observation),
palpation, percussion and auscultation
· Identification of drug therapy problems requires cognitive and
critical thinking skills
· Critical thinking involves:
 ü Collecting relevant information
ü Evaluating the information
ü Making a judgment about the information
ü Forming an opinion,
ü Making a decision
· Problem solving skills are applied to resolve drug related
problems
· A model of problem solving involves identification,
definition, exploration, looking and learning (IDEAL)
· General steps in creating a care plan are:
ü Create comprehensive patient database.
ü Assess for actual and potential drug-related
problems.
ü Establish therapeutic goals.
ü Specify monitoring parameters with end points and
frequency.
ü Document the patient's progress towards therapeutic
goals
· Pharmaceutical care cycle involves: identification of
drug therapy problems, setting therapeutic goals,
developing and implementing care plans and
monitoring/follow-up

References
1. Pytos F (1983). New Perspectives in Nonverbal Communication.
New York Pergamon Press; 50-58.

2. Tindall WN, Beardsley RS, Kimberlin CL (1994). Communication

Skills in Pharmacy Practice. 3rd ed. Philadelphia: Lea & Febiger;
138-145.
3. Boyce RW, Herrier RN (1991). Obtaining and using patient data.
Am Pharm; NS31:517-523.
4. de Bitter MR, Michocki R (1996). Establishing a pharmaceutical
care database. J Am Pharm Assoc; NS36: 60-69.
5. Oparah CA, Enato EFO, Odili VU, Aghomo OE (2002). Activities of
community pharmacy counter staff in Benin City, Nigeria. J Soc
Admin Pharm; 19(4):141-144.
6. Rovers JP, Currie JD, Hagel HP, McDonough RP, Sobotka JL
(2003) Ed. A practical guide to pharmaceutical care 2nd ed.
Washington DC: American Pharmaceutical Association; ISBN: 1-
58212-049-8.
7. Longe RL, Calvert JC, Young LY (1994). Physical Assessment: A
Guide for Evaluating Drug Therapy. Ann Arbor, MI: Applied
Therapeutics, Inc; 2: 1-12.

8. Rospond RM, Tice A, Tice B (2003). Physical assessment for

community pharmacists, part one. Online Continuing Education for
Pharmacists.

9. McDonough RP. (1996) Interventions to improve patient

pharmaceutical care outcomes. J Am Pharm Assoc; 536,453-466.
10. Bransford JD, Sherwood R, Vyne N, et al (1986)., Teaching thinking
and problem solving. American Psychologist. 41:1078-1089.
Bransford, JD, Stein BS (1984). The IDEAL problem solver. New
York: Freeman
 CHAPTER EIGHT

OPTIMIZING ADHERENCE TO PHARMACEUTICAL

CARE PLANS

Azuka C Oparah
Learning Objectives
At the end of this chapter, you should be able to:
I. Explain the role of adherence in achieving therapeutic goals
ii. List factors that promote or reduce patient adherence
iii. Discuss methods of assessing patient adherence
iv. Design patient specific strategies to promote adherence
v. Distinguish between medication information and education
vi. List patient medication counselling points

Introduction
Pharmaceutical care plans are the pharmacist's interventions that
address the identified health and drug related problems. The
interventions can be patient focused (health), and or drug focused (drug
therapy). Adherence is an intermediate pharmaceutical care clinical
outcome, the level may be predetermined and assessed, and efforts
made to improve the level of adherence. Medication non-adherence is
most simply defined as the number of doses not taken or taken
1
incorrectly that jeopardizes the patient's therapeutic outcome. Non-
adherence can take a variety of forms, including not having a prescription
filled, taking an incorrect dose, taking a medication at the wrong time,
2
forgetting to take doses, or stopping therapy too soon. Medication non-
adherence is a major public health problem that has been called an
 3-4
"invisible epidemic”. Non-adherence to pharmacotherapy has been
5
reported to range from 13% to 93%, with an average rate of 40%. The
problem encompasses all ages and ethnic groups. It has been estimated
that 43% of the general population, 55% of the elderly are non-adherent.

The major risk factors for non-adherence include: asymptomatic

conditions; chronic conditions; cognitive impairment, especially
forgetfulness; complex regimens; multiple daily doses; patient fears and
concerns related to medication effects; poor communication between
patients and practitioners; psychiatric illness; and patients' inability to
6
afford medication.
The factors that promote and reduce adherence are presented in Tables
8.1 and 8.2 respectively.

Table 8.1: Factors that promote adherence6

Disease-related factors
· Perceived or actual severity of illness
· Perceived susceptibility to the disease or developing
complications
Treatment-related factors
· Perceived benefits of therapy
· Written and verbal instructions
· Convenience of treatment
· Medication provides symptomatic relief
Patient-related factors
· Good communication and satisfactory relationship with physician
· Participation in devising the treatment plan
· Confidence in the physician, the diagnosis, and the treatment
· Support of family members and friends
· Knowledge about the illness
 6
Table 8.2: Factors that reduce adherence
Disease-related factors

· Chronic disease
· Lack of symptoms

Treatment-related factors

· Treatment requires significant behavioural changes

· Actual or perceived unpleasant side effects
· Regimen complexity and duration
· Medication takes time to take effect

Patient-related factors

· Sensory or cognitive impairments

· Physical disability or lack of mobility
· Lack of social support
· Educational deficiencies (literacy problem) or poor English
fluency
· Failure to recognize the need for medication
· Health is a low priority
· Conflicting health beliefs
· Economic problems
· Negative expectations or attitudes toward treatment

Methods of Assessing Adherence

This starts with a systematic assessment of predisposing risk factors.
Then, the level of adherence is assessed and intervention strategies
adopted to improve adherence; there should also be a follow-up
evaluation to determine the outcome of such interventions.
Direct methods
Direct and objective methods of assessing adherence include blood-
level monitoring and urine assay for the measurement of drug
metabolites or marker compounds. Collecting blood or urine samples
can be expensive and inconvenient for patients, and, moreover, only a
limited number of drugs can be monitored in this way. The bioavailability
and completeness of absorption of various drugs, as well as the rate of
metabolism and excretion, are factors that make it difficult to correlate
drug levels in blood or urine with adherence. The ability of direct methods
to identify non-adherence also depends on the accuracy of the test and
the degree to which the patient was non-adherent before the urine or
6
blood sample was taken.

Indirect methods
Indirect methods of assessing adherence include patient interviews, pill
counts, refill records, and measurement of health outcomes. In one
study, the use of patient interviews identified 80% of non-adherent
7
patients, as verified by pill counts. The interview method is inexpensive
and allows the pharmacist to show concern for the patient and provide
immediate feedback. A drawback of this method is that it can
overestimate adherence, and its accuracy depends on the patient's
cognitive abilities and the honesty of his or her replies, as well as the
interviewer's correct interpretation of responses. Pill counts provide an
objective measure of the quantity of drug taken over a given time period.
However, this method is time-consuming and assumes that medication
not in the container was consumed. The refill record provides an
objective measure of quantities obtained at given intervals, but assumes
that the patient obtained the medication only from the recorded source.

The patient's health beliefs and the degree of support available from
friends and family should also be assessed.8 Interviewing patients to
detect non-adherence is most effective when indirect probes are used.
Table 8.3 gives examples of specific probes that the pharmacist can use
to assess whether or not a patient has been or is likely to be adherent.

Table 8.3: Probes Pharmacists Can Use to Assess Adherence6

Assessing the patient's medication knowledge or medication-taking

behaviour
· What is the reason you are taking this drug?
· How do you take this medication?
· Are you taking the medication with food or fluid?
· Where did you receive information about this medication?
· Are you taking non-prescription drugs while on this
medication?
· Do you use any memory aids to help you remember to take
your medication?
· Do you depend on anyone to help you remember to take
your medication or to assist you in taking it?

Assessing attitudes, values, and beliefs regarding medication-taking

behaviours
· What results do you expect to receive from this medication?
· What are the chief problems that you feel your illness has
caused you?
· Do you have any concerns about your illness and its
treatment?
· Are you satisfied with your current treatment plan?
· How well do you usually follow a treatment plan?
· What is the main concern you have about your medication?
· Do you feel comfortable asking your physician or pharmacist
questions about your medications?
Assessing whether the patient has the proper skills and is motivated
or willing to follow through on the therapy plan
· Have you encountered any problems with your medication-
or pill-taking procedure?
· Are you confident that you can follow your treatment plan?
· What might prevent you from following the recommended
treatment plan?
· How likely is it that you will ask your physician or pharmacist
about your medications?
· Can you explain how you remind yourself to take your
medication on schedule?
· Do you normally write down questions to ask your physician
or pharmacist before an appointment?

Designing Patient-Focused Interventions for Non-adherence

Strategies to improve adherence should target the specific risk factors

and causes identified during the patient assessment. Adherence aids
may be used alone or in combination, but should be tailored to the
individual patient.6 Once the initial adherence plan is implemented,
follow-up is important to gauge how well the plan is working and whether
changes are needed. Most studies have reported that almost all
adherence strategies, regardless of their initial acceptability, will decline
in responsiveness over time.5 Therefore, the pharmaceutical care plan
must include periodic reinforcement strategies for long-term success.
The plan should also be re-evaluated from time to time to assess its
effectiveness and determine how well it meets patient expectations.
Strategies for Enhancing Adherence to Pharmacotherapy
Although pharmaceutical care plans should be individualized, some
adherence-promoting strategies tend to be helpful in the majority of
patients. Whenever possible, the pharmacist should strive towards:6
Promotion of self-efficacy

Patients are encouraged to assume an active role in their own treatment

plans. Involving patients in decisions about their care is important for
promoting self-efficacy. For example, a study by Nessman et al9 showed
that patients with hypertension who were highly involved in decisions
about their therapy and trained to take their own blood pressure had
significantly better health outcomes than patients who did not have
these characteristics.

Empowerment of patients to become informed medication

consumers

Pharmacists should provide both written and oral information to address

such basic questions as: What is the disease? Which treatments have
been prescribed or recommended and why? What is the patient's role in
managing the disease? Which adverse effects may occur? The amount
of factual information that a patient has about his or her medication is not
highly correlated with adherent behavior.5 Instead, the patient's
functional knowledge - that is, information that is directly useful and
meaningful to the patient - and clear instructions for medication use are
more significant.10

Avoiding fear tactics

Scaring patients or giving them dire warnings about the consequences

of less-than-perfect adherence can back fire and may actually worsen
11
adherence. A more constructive approach is to help the patient focus
12
on ways to integrate medication taking into his or her daily routine.

Helping the patient to develop a list of short-term and long-term

goals

These goals should be realistic, achievable, and individualized. The

pharmacist can also make "contractual" agreements with the patient to
encourage development of constructive behaviours, such as getting
more exercise or beginning a smoking cessation program.

Regular follow-up plan

The pharmacist should plan to interact with the patient at regular, usually
brief intervals to reinforce the adherence plan. The plan should be
adapted to the patient's lifestyle and be re-evaluated from time to time to
adjust for life changes, such as aging or a change in work or school
schedules. If possible, the time for counselling on adherence should be
6
separated from the dispensing and pick-up functions.

Implementing a reward system

Giving prescription coupons or specific product discounts for

successfully reaching a goal in the treatment plan can help to increase
6
adherence, particularly in patients with low motivation.

Medication education/Counseling
Inappropriate medication use behaviour has increasingly become a
public health problem. The prevention or recognition and management
of problems resulting from drug use are the main reasons for developing
and providing drug education programs. Educational efforts continue to
remain the strategy for alleviating the problem from the products of our
own technology. The primary importance of drug education is its benefit
to the drug users (patients or consumer) by improving the
appropriateness of drug taking behaviours in order to achieve optimal
health and well being. A number of approaches have been developed
for designing drug information and educational programs in medical
settings. It should be remembered, however, that these techniques and
strategies, and their basic principles are applicable to educating patients
about medicines or providing educational programs in any context.
However, in the context of our present concern it is patient's medication
on one-on-one basis in their clinical interactions that is considered here.

Any medicine however good that is not accompanied by adequate

spoken or written information is liable to become a problem drug in the
patient's hands. A study on patients' experience of medication
information that health professionals in three health care facilities in
Benin City, Nigeria deliver to them indicates the need for a uniform
guideline. Patients' recall of specific medication information showed that
pharmacists did not give the name, indication, duration, and action to
13
take if a dose was missed.
In discussing an illness or drug therapy, a distinction should be made
between “Information” and “Education”. Patients may receive
information but not understand how to use it correctly, whereas
education implies understanding and behavioural change. The goal of
patient education is to provide information that patients are able to
understand and use. The educator needs to go beyond sender-
message-receiver communication models and to adopt a problem
solving approach.
14
Falvo has summarized the components of patient education as follows:
· Patient education is an active process involving the patient as a
mutual participant
· Patient education must contain an assessment component
through which patient's individual needs are identified.
· To facilitate the process of patient education, the health
professional must develop rapport with the patient.
· Emotional support must be provided
· Patient education must be directed not only toward helping the
patient gain knowledge, but also toward helping the patient
improve decision-making and coping skills mutual process
 · A system for evaluating and monitoring the degree of behaviour
change should be established.
· The patient education plan should be reassessed and altered,
as needed, depending on information gained through the
evaluative process.

Many factors influence the effectiveness of educational efforts and a

patient's development of compliant behavior. Decision must be made as
to what information should be provided to a patient about her illness and
drug therapy and such information should be properly presented. It
must be recognized that when the information is too comprehensive or
detailed or is presented inappropriately, the patient actually may be
discouraged from taking the medications. Thus, compliance may be
compromised rather than being enhanced. The anticipated benefits of
the therapy should be explained, as should, the importance of complying
with the provided instructions. Complex terms, unnecessary jargons
that can interfere with patient understanding should be avoided. Patients
should repeat the instructions for administering their medications to
show that they understand and they also should be encouraged to ask
questions. National Council for Patients' Information and Education
(NCPIE) USA recommends a minimum list of items that should be
discussed with patients during medication education. This minimum list
of items is given Table 8.4.
2
Table 8.4: Minimum list of items for medication education

(I) The name and purpose of medication

(ii) How much of the medication that should be taken, when
to take it and how long to take it.
(iii) How to administer medicines
(iv) Prescription refill information
(v) What to do when a dose is missed
(vi) Important side effects e.g. causes dizziness, stomach
irritation etc.
 (vii) Precautions e.g. causes sleep do not drive, avoid
exposure to sunlight when on this medication.
(viii) Interaction with foods, beverages and other medicines.
(ix) How to store medicines at home e.g.
(i) Store all drugs in a cool place, protected from heat and
light
(ii) Keep similar drugs together (classified as pain-killers,
antidiarrhoeals etc)
(iii) Keep capsules and tablets in tightly closed containers
(iv) Keep oral suspension and paediatric drops in a
refrigerator (but not freeze)
(v) Discard all outdated preparations
(vi) Do not have drugs on bedside tables or in other open
places
(vii) Do not store too many drugs
(viii) Do not keep unlabeled preparations
(ix) Do not take drugs without medical advice

Hermann and Hexheimer presented a list of the main categories of

15
behavior required for proper medication utilization. This is based on
behaviorally defined objectives. The approach asks what are the exact
medication related behaviors that patients need to exhibit for proper use
of medication. When the list of behaviors has been constructed, it can
then be used as a basis of deciding what information will be required for
the patient to be able to show these behaviors. Medication education is
then directed along that line:
(a) To know how to take the drugs
(I) To take a specific dose
(ii) To take a dose in a specified manner
(iii) To take a dose at a specified time
(b) To know how to store the drug
(i) To store the drug properly
(ii) To recognize the desired effect and act upon its
absence
(c) To know how the drug is expected to help
(i) To recall the basic facts about the complaint
(ii) To recognize the desired effect and act upon its
absence
(d) To recognize problems caused by the drug
(i) To recognize unwanted effects if they do occur
(ii) To recall that certain effects may only be detected by
clinical examination or tests.
(iii) To recall circumstances indicating a need for a
change of treatment and act if they occur
(Iv) To act if overdose occurs

Key Learning Points

· Adherence is an intermediate clinical outcome

· Medication non-adherence is a major public health
problem that has been called an "invisible epidemic”
· The major risk factors for non-adherence include:
asymptomatic conditions; chronic conditions; cognitive
impairment, especially forgetfulness; complex
regimens; multiple daily doses; patient fears and
concerns related to medication effects; poor
communication between patients and practitioners;
psychiatric illness; and patients' inability to afford
medication
· An assessment of adherence starts with a systematic
assessment of predisposing risk factors. Then, the
 level of adherence is assessed and intervention
strategies adopted to improve adherence; there should
also be a follow-up evaluation to determine the outcome
of such interventions
· Direct and objective methods of assessing adherence
include blood-level monitoring and urine assay for the
measurement of drug metabolites or marker compounds
· Indirect methods of assessing adherence include patient
interviews, pill counts, refill records, and measurement of
health outcomes
· Strategies to improve adherence include:
ü Promotion of self-efficacy
ü Empowerment of patients to become informed
medication consumers
ü Avoiding fear tactics
ü Helping the patient to develop a list of short-term
and long-term goals
ü Regular follow-up plan
ü Implementing a reward system
ü Use of medication reminders
· Any medicine however good that is not
accompanied by adequate spoken or written
information is liable to become a problem drug in
the patient's hands
· Patients may receive information but not understand how
to use it correctly, whereas education implies
understanding and behavioural change.
· The goal of patient education is to provide information
that patients are able to understand and use. The
educator needs to go beyond sender-message-receiver
communication models and to adopt a problem solving
approach.
 References
1. Smith DL. (1989) Patient Compliance: An Educational Mandate.
McLean, Va: Norwich Eaton Pharmaceuticals, Inc. and
Consumer Health Information Corp; 1989; 53-58.

2. National Council on Patient Information and Education ( NCPIE,

1997). The Other Drug Problem: Statistics on Medicine Use and
Compliance. Bethesda, Md; 1997 Available at:
www.talkaboutrx.org/ compliance.html#problem. Accessed May
8, 2000.

3. Smith MC (1996). Predicting and detecting noncompliance. In:

Smith MC, Wertheimer AI, eds. Social and Behavioral Aspects of
Pharmaceutical Care. New York, NY: Pharmaceutical Products
Press, Inc; 118-125.

4. Fincham JE, Wertheimer AI (1985). Using the health belief model

to predict initial drug therapy defaulting. Soc Sci Med; 20(1):101-
105.

5. Bond WS, Hussar DA (1991) . Detection methods and strategies

for improving medication compliance. Am J Hosp Pharm;
48:1978-1988.

6. Nicholas- English G, Poirier S (2000). Optimizing adherence to

pharmaceutical care plans. J Am Pharm Assoc; 40(4):475 485.
7. Stewart M (1987). The validity of an interview to assess a
patient's drug taking. Am J Prev Med; 3(2):95-100.

8. Felkey BG (1995). Adherence screening and monitoring. Am

Pharm; NS35:42-51.

9. Nessman DG, Carnahan JE, Nugent CA (1980). Increasing

compliance. Patient-operated hypertension groups. Arch Intern

Med; 140:1427-1430.
10. Hulka BS, Kupper L, Cassel JC, et al (1975). Medication use
and misuse: Physician-patient discrepancies. J Chron Dis; 28:7-
21.

11. Rudd P (1992). Maximizing compliance with antihypertensive

therapy. Drug Therap; 22:25-32.

12. Mullen PO, Green LW, Pessinger GS (1985). Clinical trials of

patient education for chronic conditions: a comparative meta-
analysis of intervention types. Prev Med; 14:753-757.

13. Enato EFO, Eferakeya AE, Oparah CA (2003). Patients'

experience of the medication information that health
professionals deliver to them. J Soc Admin Pharm; 20(2):59-63.
14. Flavo D (1994). Effective patient education. Gaithersburg:
Aspen Publishers; 190-195.

15. Hermann F, Herxheimer S, Lionel N DW (1978). Package

inserts for prescribed medicines: what minimum information do

patients need? BMJ; 2:1132 1135.

 CHAPTER NINE

HEALTH PROMOTION: A COMPONENT OF

PHARMACEUTICAL CARE
DAVID U ADJE
Learning Objectives
At the end of this chapter, you should be able to:
i. Define health promotion
ii. Justify pharmacists' involvement in health promotion activities
iii. Identify activities in pharmacy practice that constitute health
promotion
iv. Understand how to implement and evaluate health promotion
activities in various pharmacy practice settings
v. Identify benchmarks for practice of health promotion in
pharmacy

What is health promotion?

The World Health Organization defines health promotion as the process
of enabling people to increase control over and improve their health.1
Health promotion involves encouraging people to adopt healthy
lifestyles and behaviors and creating supportive social, economic and
environmental conditions that improve health. It also involves fostering
and strengthening community action geared towards improved people's
health.
Health promotion can be carried out at the basic level of the individual
person or patient but for health promotion to have meaningful and far
reaching impact, the health promoter must from a collaborative
relationship with other partners including community groups, health
organizations, relevant government agencies and other health
professionals. His effort should be targeted more at groups of people
and the community. This would make it possible for health promotion
efforts to affect and influence the larger society. The health promoter
must also seek for avenues to influence public policy in such a way as to
help reduce health inequalities and improve access to health care for
vulnerable, poor and disadvantaged groups. It can be seen from the
above definition that the scope of health promotion activities is wide
indeed. Table 9.1 gives a brief overview of health promotion activities.

Table 9.1 Overview of health promotion activities3-5

Educate and Inform Individuals and communities about ways in which
their behaviors and lifestyle affect their health. Inform them about
preventive measures they can take to avoid ill health and to reduce risk
factors for disease as well as improve and enhance health for
themselves, their families and the community. Encourage them to adopt
healthy behaviors including proper nutrition, responsible sexual habits,
medication adherence and physical activity.
Influence Public policy in areas of better housing, safer living and
working environment, access to health and measures to reduce health
inequalities.
Individuals to stop harmful behaviors adopt and maintain healthy
lifestyles.
Increase Awareness Of individual and communities about social,
economic and environmental policies as well as individual actions that
are not conducive to good health. For example housing, food, work
condition.
Also about simple preventive measures that can be adopted to avoid or
reduce the impact of chronic disabling, potentially fatal diseases. For
example screening, vaccination, breast self examination, digital rectal
examination etc.
Empower Individuals and communities to take charge of their health
and take actions to control modifiable determinants of health. Actions
could include self care, self monitoring of illness and other measures
that can help improve their quality of life.

In other to accommodate this broad concept, other definitions have

emerged. For example O'Donnel defines health promotion as “The art
and science of helping people change their lifestyle to move towards a
2
state of optimal health.” Optimal health here means a balance between
physical, emotional, social, spiritual and intellectual health. Lifestyle
changes involve enhancing awareness, behavior change and creating
an environment that supports good health practices. A supportive
environment results in the greatest health impact as it fosters longer
lasting changes in people.

Note from the WHO definition that health promotion is a process. As such
it is continuous and ongoing. Actively promoting health provides the
reinforcement needed to produce sustainable positive changes in
individuals and communities.

CLARIFYING CONCEPTS
Health promotion is all about working with people to improve their health
and empowering individuals and communities to have increased control
over factors that influence their health.. Many theories and models of
health promotion have been proposed to explain health behavior and
predict likelihood of behavior change. This includes among others, the
Health belief model, stages of change model, the social learning theory,
3-5
and the theory of reasoned action. These models not only emphasize
the multidimensional nature of health promotion but also show that
health promotion goes beyond health education to include health
protection, disease prevention and allied concepts. For example the
social learning theory explains behavior change as a dynamic
interaction of personal factors and environmental influences.3 Ewles and
Simnett have proposed a framework for health promotion comprising
health education preventive health services , community based work,
healthy public policy, environmental health measures and economic and
regulatory activities.6 In view of the many different concepts involved in
health promotion, a clarification of terms is important in order to properly
appreciate the concept of health promotion. The following terms can
sometimes be confusing and a clarification is appropriate here.
Health education
Health education is an aspect of health promotion that involves learning
and increasing awareness. It can be defined as a deliberate opportunity
for learning, involving some form of communication designed to improve
health literacy, modify belief or induce change in behavior. Health
education is a combination of learning experiences designed to facilitate
voluntary action conducive to health. On the other hand, health
promotion embraces anything which is done to improve individual and
community health.
Health protection
Health protection is illness and injury specific. It involves intervention at
the primary, secondary or tertiary levels of prevention.
Health gain
Health gain is any measurable improvement in health status of
individuals and communities attributable to earlier intervention.
Intervention can take the form of treatment, care or health promotion. All
forms of health promotion should produce health gain but health
promotion is not the only means of producing health gain 66666
The pharmacist and health promotion
Health promotion is an integral part of pharmaceutical care irrespective
of the practice setting. Whenever and wherever a pharmacist takes
actions or provides services that actively improve the health of
individuals and communities thereby empowering them to have
increased control over their health, he is involved in health promotion. In
a broader sense health promotion in pharmacy practice has been
defined as: “A style of pharmacy practice in which the pharmacist teams
7-8
up with individuals and communities, to improve their health status.”
9
This definition is consistent with Walkers postulations. He argued that
for pharmacists to impact positively on people's health, they need to do
more than information dispensing at the micro level. They must key into
the wider national public health agenda and work with communities and
other stakeholders in a collaborative relationship. Pharmacy practice
affords a wide range of opportunities for health promotion irrespective of
practice setting. Health promotion activities may sometimes be
medicine related but the majority of activities do not necessarily have to
do with medications.
As the most easily accessible health care provider, who in many cases
is the first point of contact with the health care system, the pharmacist is
especially suited for health promotion activities. In the U.S. there are an
estimated 1.8 million visits to pharmacies daily for prescription filling,
buying of medicines and health advice. The pharmacist enjoys the
confidence of members of the public as many persons both healthy and
sick consult pharmacists on daily basis for advice on a wide range of
10
health issues including medication related problems. The long
opening hours, even on weekends and availability of the pharmacist at
all times are also factors that make the pharmacy a suitable place for
health promotion activities. Also studies have shown that pharmacists
have a positive attitude towards health promotion and are willing to
devote extra time to carrying out health promotion activities. In a cross
sectional study of community pharmacists in two Nigerian cities, ninety
percent respondents agreed to participate in health promotion activities
irrespective of whether there is reimbursement for services provided or
11
not. As the last port of call for persons who visit hospitals, the hospital
pharmacy is a suitable place for delivering health improvement
messages that patients can more readily remember after leaving the
hospital.
Historically, health promotion activities in pharmacies were necessitated
by a need for the profession to redefine itself following the shift from
extemporaneous drug compounding to pre-packaged ready-to-use
products as a result of the therapeutic revolution which made possible
large scale production of medicines. Leaflets, posters and brochures
designed to educate the public were the early tools of health promotion
12
activities by pharmacists. Health promotion activities have since
broadened to include a wider range of health improvement actions.
These actions have gone beyond the core function of the pharmacist
(supply and management of medicines) to include management of
chronic disease conditions, promoting healthy lifestyle, Provision of
health advice and targeted interventions.
Health promotion activities in the pharmacy
Health education
Health education by pharmacists can be planned or opportunistic. It can
be done on a person to person, face to face basis or through an
electronic medium. It can be verbal or through a printed material. When a
verbal approach is employed, the pharmacist must adequately deploy
appropriate communication techniques in order to be able to achieve a
positive outcome. Confidentially, courtesy and a non-threatening
environment are all essential for success. Written materials should be
well designed and easy to understand. Reinforcement of health
education messages is also essential if people are to make lifelong
positive changes. Written material should be displayed in an area of the
pharmacy where they can be clearly visible to all.
Health screening
Screening is the process of looking for signs of disease in healthy
symptom-free persons so that prompt action can be taken to avoid
serious problems in the future. Screening activities in pharmacies
usually involve minimally invasive or non-invasive procedures.
Screening has been successfully done in pharmacies for the following
13-15
conditions:
· Diabetes
· Hypertension
· Osteoporosis
· Hyperlipidemia
· Chlamydia
· Vaccination Status
Pharmacists should observe appropriate precautions when handling
body fluids where legal requirements allow them to do so. Opportunistic
referral for screening can be done for conditions where legal restrictions
or complexity of procedure makes screening impractical. For example
HIV, mammography, and pap smear tests. Pharmacists should also
have in place that a network of physicians and other experts to whom
referrals can be made whenever the need arises.

Health improvement
Health improvement services are those activities targeted at reducing
risk factors for development of chronic diseases among specified
population groups. Intervention studies can be carried out in hospital
and community pharmacies in any of the listed areas. Many of such
studies have demonstrated the benefits of pharmacists'
13,22 9
interventions. These areas include the following:
§ Weight management services
§ Smoking cessation services
 § Substance abuse reduction services
§ Services designed to enhance proper diet and nutrition
§ Services designed to promote increased physical activity.
§ Services designed to improve child, maternal and teenage
health.
§ Chronic diseases management especially as it relates to
drug therapy and lifestyle management.

Promoting self care

Self care is a process whereby people take responsibility for managing
their health. Self care enables individuals and families to stay healthy by
managing minor conditions and chronic illness by themselves. Self care
is personal health maintenance culture. Therefore any activity that
individuals, families and communities engage in with the intention of
improving and restoring health can be described as self care.16-17 Self
care includes all decisions people make for themselves and their families
to get and stay healthy physically and mentally. Activities such as
exercising, eating well, good hygiene, treating, managing and
preventing illness as well as avoiding health hazards can be properly
classified as self care. Self care is not ignorant and presumptuous
tinkering with health but is based on sound knowledge and information.
Self care is carried out in conjunction with and under the guidance of a
physician or other competent health care professional Self care is a
proactive processes that epitomizes the essence of health promotion
Self care mainly makes use of over-the-counter medications and other
products that are readily available to the consumer (responsible self
medication). When properly practiced, self care eliminates the need for
unnecessary hospital visits thereby reducing the pressure on over
stretched health care facilities. For chronic conditions, proper self care
results in the patient becoming an expert in managing his condition. The
expert patient is able to take more control of his health thereby making it
possible for physicians to use their time more productively in attending to
issues that demand their expertise. Conditions for which self care is
appropriate include yeast infection, allergies, uncomplicated malaria,
rashes, cold/flu, constipation, heartburn, headaches, mild hypoglycemic
episodes in diabetes, heartburn, nausea, some types of pain including
dysmenorrhea, halitosis and various skin infections.
In order to promote self care, efforts have been made in the United
Kingdom to increase access of people to medicines by re-classifying
some prescription medicines as OTC products. This includes Ibuprufen
and Loperamide (1983) hydrocortisone (1985), Nicotine patches (1991)
Clotrimazole (1992) Acyclovir (1993) Cimetidine (1994) Fluconazole
(1995) and most recently simvustatine.16,18

Developing competence in self care requires the expertise and support

of health professionals. Since medicine use is an integral part of
responsible self care, the pharmacist is particularly suited to provide
such guidance. Type 2 diabetes is a special area of focus for self care
initiatives involving chronic conditions. Diabetes requires a high degree
of self management in order to achieve treatment goals. Pharmacists
can play a vital role in empowering this group of patients by educating
them so they can develop skills that can equip them to be able to monitor
their treatment, set treatment goals and achieve better glycemic control.
The pharmacist's accessibility, availability and willingness to spend time
with people are an invaluable asset in promoting self care in all its
ramifications.

Management of prescribed medicines

Activities that help people and communities to avoid harm from
medicines and to optimize gain from use of medicines can be properly
classified as health promotion. The pharmacist is ideally suited to carry
out health promotion activities relating to use of medicines. Medicine
related health promotion activities include the following:
· Safe drug storage
· Promoting adherence
· Promoting safe use of medicines
· Safe disposal of waste/unneeded medicines
· Identifying and preventing medication errors
· Injury and poison prevention
· Optimizing health benefits/reducing harm from use of
complimentary/ alternative medicines etc
Caregiver education
Caregivers are an important resource in helping physicians and other
health professionals meet treatment goals. Caregivers can be parents,
spouses, older siblings or other relatives living in the same house with
sick persons. Proper caregiver education can equip them to provide
support and care that can promote adherence, help manage
complications, monitor therapy, recognize danger signals and help the
sick person live comfortably with his illness. Caregiver education is
especially important in chronic disease conditions. Pharmacists can play
a very important role in helping caregivers increase their knowledge of
disease conditions, understanding dosage schedules and in coping with
issues that the sick person may find difficult to contend with. The
accessibility, availability, knowledge base and openness of the
pharmacist make him uniquely suited to fill this health promotion role.
Targeted health promotion
Health promotion activities are likely to be more meaningful if
pharmacists target their activities at various population groups. The
activities listed in Table 9.2 can be appropriate subjects for targeted
health promotion activities among various population groups.
Table 9.2 Pharmacy health promotion activities among
different population groups 12, 18
Population Group Health Promotion Activities

Infants and Pre- Promoting and encouraging immunization/ immunization advocacy.

School Determination of immunization status, identifying unmet
immunization needs. Promoting proper handling and storage of
vaccines. Ensuring availability of good quality vaccines.
Immunization delivery/vaccine admi nistration. Promoting breast
feeding, resolving obstacles to adoption of breast feeding by
mothers, resolving problems associated with breast feeding.
Resolving teething problems. Providing guidance on infant feeding,
formula feeding, weaning diet, proper infant nutrition, and safe use
of medicines.

School Age, Promoting dental health, promoting good nutrition at home and in
Adolescents & Teens school, promoting sugar -free products. Encouraging increased
physical activity. Determination of adolescent immun ization status
and promoting appropriate immunization in this age group.
Promoting safe sex practices including abstinence. Providing and
encouraging emergency contraception. Substance abuse reduction.
Stop smoking services. Chlamydia screening and treatme nt.
HIV/AIDS education - encourage screening, counsel cases,
promote adherence to HAART where appropriate.

Female Population. Promoting breast feeding, folic acid supplementation, family

Child bearing age, planning.
others
Encourage breast self examinatio n, breast cancer awareness,
calcium/Vitamin D supplementation, pap screening (Cervical
smear), osteoporosis awareness.

Elderly Encourage self care, Teach self management of chronic diseases

in collaboration with physicians. Promote adherence to medicatio n.
Increase awareness of and provide mobility aids, incontinence aids
etc. Promote proper nutrition.

General Population Obesity management, promote healthy eating, increased physical

activity. Teach stress reduction techniques. Promote, advocate
adult imm unization. Vaccinate adults. Education on travel health.
Sign posting to other health care experts/services
Health Promotion Resources for Pharmacists
Health promotion resources for pharmacists can be in the form of:
· Printed materials
· Health promotion products
· Health promotion devices
Printed materials
Printed materials in the form of leaflets, brochures, handouts and
newsletters make a lasting impression on people and can continue to
speak long after the initial contact. They can also be of benefit to
persons other than the primary targets as others can pick them up and
also get the message. The message on printed materials should be
15, 20
brief, credible, easy to understand and straight to the point.
In designing a printed message, three requirements are critical
· Know the topic
· Know the audience
· Know the purpose
This requires that the pharmacist researches the topic thoroughly so he
can use evidence-based information (information that has been peer-
reviewed and critically evaluated for validity) in preparing the material.
He must also define the purpose of writing as this can affect the content.
The purpose can be to inform, to influence, to educate or to motivate.
Regarding the target audience, he should ask himself these key
13,20
questions:
· Who is the audience?
· What does the audience want to know?
· What does the audience need to know?
· Why should the audience read this?
· What is the expertise of the audience?
· What decision will the audience make based on what is
read?
 · What are the biases of the audience?
The draft should be revised, rewritten and perused repeatedly until a
final copy is produced. Pre-testing a proof copy on a sample of the target
population can help the pharmacist detect and correct flaws before the
final print- out. The finished copy should have a good layout and should
be so attractive as to easily catch people's attention when displayed.

Health promotion literature should be displayed if possible near relevant

products in community pharmacies. For instance, breast cancer
awareness literature can be displayed in a section for sanitary pads in
the pharmacy. Point of sales and dispensing counters in hospital
pharmacies are also good places to display such literature.
Health promotion products/Devices
Health promotion products are items stocked by pharmacies that can
help people take better control of their health and make them cope better
with limitations resulting from ill health. Table 9.3 outlines some health
promotion products and population groups to which they are applicable.

Table 9.3 Health promotion products and devices stocked by

pharmacists. 21,23
Age Group Products Uses

Newborn & Sugar free medicines Reduce incidence of dental

Children caries and periodontal disease.
Cow milk based infant formulas
Breast milk substitutes
Whey protein based formulas
Protein supplementation and
Soy beans formulas weaning. Reduce incidence of
Soya beans based feeds malnutrition.

Adolescents Condoms Reduce incidence of teen

pregnancies, STDs and its
Chlamydia test kit complications
Emergency contraceptives

Combined oral contraceptives

Women (Breast Breast pump Promote breast feeding
feeding)
Nipple shield Ease problems associated with
breast feeding e.g. sore nipples
etc

Women Pregnancy test strips , Address pre-conception

issues/post menopausal
(Others) Ovulation prediction kits problems
(strips/ovulation microscope)

Folic acid tablets 0.4 mg

Calcium/Vitamin D preparations

Aged Mobility aids Ease problems associated with

Population aging. Promote independence
- Walkers
- Wheelchairs
Incontinence aids
Improved adherence to
- External catheters medication
- Leg bags
- Adult sanitary pads
- Urinal/bed pans
Pill boxes/adherence aids

Hypertensive Sphygmomanometer (digital, aneroid self- Screening, monitoring therapy.

population taking) cholesterol test kits, low do ses Aid to reducing cardiovascular
risk factors and maintaining
Diabetes Glucose meters Monitoring diabetes therapy.

Sugar free medicines Adjunctive therapy to help

improve glucose level control
Antioxidants/micronutrients e.g.
Chromium, selenium, zinc etc

Asthmatics Peak flow meters Monitor asthma control, predict

impending attack

Smokers Nicotine patch, gum, spray etc Smoking cessation aids

General Fluoride tooth paste, Reduce dental diseases

population
Strontium containing tooth paste, Improve dental health

Dental floss, tooth picks, diet sugar, tooth

brushes, mouthwashes
Developing health promotion competency for pharmacists
Effective health promotion requires development of appropriate
competencies by pharmacists. Competences should be developed
along the line of factors involved in maintaining good health. Pharmacists
should therefore be thoroughly familiar with the major determinants of
health and variables that affect health. The major determinants of health
are illustrated in Fig. 9.1.

& Une
in g n g mp
L iv o rk i it io n lo ym
ent
W nd
Co
t
en
v ir rk
m

W
En W o
on

Sa
a t it a t i
er on
n

H eal th car e
S erv ice
n
c a t io

Age, Sex,
Edu

Heriditary
Factor
od
c & io n

H ou
Fo
Ag duct

s in g
pro
r i

Fig. 9.1 Major determinants of health.22

Understanding the interrelationship between the various determinants of

health can help pharmacists develop programs to promote health in
various practice settings. Pharmacists also have to be familiar with the
various models of behavior change since health promotion is about
changing harmful habits and adopting healthy lifestyles. The health
action model and the stages of change or trans-theoretical models are
popular models of behavior change.
The health belief model is based on the theory that persons with high self
esteem and positive self concept are more likely to make positive
changes and that attempts to change behavior will be more successful if
people are made to feel good about themselves and acquire skills that
can boast their self esteem. The theoretical basis for the stages of
change model is that behavior change does not occur in one single big
step but goes through the Pre-contemplation Contemplation
Commitment Action Maintenance Relapse Cycle. Behavior change is
most likely to be successful if changes are initiated at the contemplation
stage. Depending on various factors, a person could go through this
cycle a number of times before finally exiting the cycle and achieving
maintenance of safe and healthy lifestyle. Familiarity with these
concepts can help pharmacists design and implement successful
behavioral change programs.

Planning, documentation and evaluation of health promotion

activities
Step 1 - Choose a health problem
Planning health promotion activities starts from identifying unmet needs
and priorities of your target population or community. Choice of project
will depend on experience gathered from interaction with patients and
the community over time. The pharmacist should also be sufficiently
interested in the project to commit time and resources to it.
Step 2 Research the topic
The next step is to research the topic. This helps the pharmacist to be
familiar with the fine details of the problem and information gathered at
this stage can come in handy if there is the need to design an intervention
program.
Step 3 Determine your objective
Your Objective can be any of the following- promoting changes in
behavior, empowering individuals and community to act, to informing or
educating people so as to help them make informed and better health
choices.
Step 4 Determine available options to meet objective
Options could include
· Public enlightenment talks, printed materials, radio programs
· Mobilization of individuals, organizations or communities
 · Intervention among specific population groups e.g. children,
pregnant women, adolescents, diabetes and hypertensive
patients.

Step 5 Choose the best option

A search for similar projects can help identify methods that have proved
successful in other places. This can influence your choice of a particular
option.
Step 6 Identify available resources and determine how to deploy
them
The pharmacist should be as pragmatic as possible. Even though
financial resources are important, they are by no means the only
resources available. Local agencies, NGO's and focal persons within the
community are important resources that can help the pharmacist meet
his objectives.
Step 7 Prepare for action
This involves getting all your resources ready including the tools for
health promotion activity (leaflets, documentation forms etc). You then
set measurable targets including a time line for the intended activity, and
getting the cooperation of key actors and stakeholders in the project.

Implement plan
Plan implementation requires patience since intended changes may not
come as fast as expected.
Evaluation
Evaluation criteria should be set at the planning stage. Evaluation is an
ongoing process. Objective outcome measures should be used e.g. kg
weight lost, mmHg blood pressure drop, Hb AIC values or mm/liter drops
in blood sugar level, percentage changes in number of people exercising
three or more times a day are good examples of suitable outcome
measures.
Documentation
Documenting health promotion activities is a very important final step in
the health promotion process because as the saying goes “if it is not
documented, it is not done”. Documentation provides evidence base on
which further studies or interventions can be based. Documentation
forms either in soft or hard copies are a very good means of documenting
health promotion activities. Forms should be designed for each and
every health promotion activity carried out by the pharmacist.
Documented information must be specific, measurable and amenable to
appropriate statistical analysis and tests so that scientific conclusions
can be drawn from the data generated. Documentation forms should
contain the following information:
· Patient/community data
· Date/location of activity
· Type of activity, staff involved, topic discussed, target
audience
· Baseline values of evaluation parameters
· Periodic values of evaluation parameters at
predetermined time intervals
· Final values of evaluation parameters at the end of health
promotion activity
· Provision for ongoing contact with target audience or
community focal persons e.g. email, phone, fax number.
This ensures that changes are monitored even after the
end of health the promotion activity.
· Any other relevant parameters.

Networking
Networking with appropriate partners, agencies, organizations and
specialists is very important if health promotion activities by pharmacists
are to have a meaningful impact. Pharmacists involved in health
promotion activities should endeavor to reach and collaborate with other
agencies and persons. Examples of possible partnership agencies
include:
· Physicians, health practitioners and other specialists in practice
area
· Other colleagues
· Public health organizations e.g. pharmacy heath link, public
health departments in local government offices
· Print and electronic media houses
· Non-governmental organizations
· Professional bodies
· World health organization agencies
· Religious institutions
 · Schools/universities
· Hospitals/clinics
· Community groups e.g. market women association, road
transport workers union
· Government agencies ministry of health, ministry of agriculture,
ministry of housing/transportation, local government authorities,
and prison services etc.

Benchmarks for health promotion pharmacy

24
The document choosing health through pharmacy identifies what can
be described as health promoting pharmacy benchmarks but locates
them in the future 2015. The document identifies the following
activities for the health promoting pharmacy in 2015.

The health-promotion pharmacy in 2015

§ Is a primary source of information and advice on health issues
and local services for the community that helps reduce health
inequalities, and is part of a strong local network of health
improving services.
§ Provides directly, or makes space available for, a range of health
improvement services in particular for disadvantaged people,
older people, children and young people, and focusing on
specific services such as stop smoking, sexual health,
substance misuse and abuse, weight management and
immunization.
§ Identifies people with risk factor for disease and provides
appropriate advice, including support for self care.
§ Works in partnership with the local authority and voluntary
organizations to improve the wider determinants of health, such
as poverty, housing, education and employment.
§ Is linked with schools, workplace and other local setting,
including people's homes to provide health information and
advice.
§ Helps people to take control of their own health and to shape the
devices they need by being a trusted health advocate, visible
and active beyond the pharmacy and working closely with local
community leaders and volunteers.
§ Improves the health of people with long-terms condition by
helping them with their medicines, promotion healthy lifestyles,
supporting self care, signposting to other services and working
closely with community matrons and case managers.
§ Makes best use of the extended pharmacy teams with active
links to training, research and public health networks
§ Works in partnership with health organizations and the wider
public health community across primary, community, social care
hospital settings.
§ Uses a wide range of modern IT and communication technology
to provide electronic health information to the public and to
access electronic health records shared with patients.

Key Learning Points

· Health promotion is feasible in all pharmacy practice

settings. It should be regarded as an integral part of
pharmaceutical care. A wide variety of health promotion
activities can be carried out by pharmacists. Pharmacists
should form collaborative relationships with relevant
persons, agencies and organizations in carrying out health
promotion activities. Health promotion is an ideal way of
increasing the visibility, reach and relevance of the
practicing pharmacist.
· Health promotion is the process of empowering individuals
and communities to have increased control over their
health and improve their quality of life. It is
multidimensional and involves health protection, health
improvement, .health education and health maintenance.
· Health promotion is an integral part of pharmaceutical
care
· Whenever and wherever a pharmacist takes actions or
provides services that result in health gain or that
empowers individuals and communities to have
increased control over their health, he is involved in health
promotion
· Health education, health screening, health improvement
 services promotion of self care, management of
prescribed medicines, caregiver education,, stocking and
increasing access to health promotion products are
activities that constitute pharmaceutical health
promotion..
· In view of their location in the community, low barrier
access, high frequency of contact with all kinds of persons
in the community, and easy accessibility, pharmacists are
uniquely positioned to carry out health promotion
activities.
· Pharmacist must be thoroughly familiar with determinants
of health, behavior change theories and models as well as
available resources at their disposal in order to
successfully plan and execute health promotion activities
· Proper documentation of health promotion activities and
networking are critical if pharmacists are to impact
positively on the larger society.

References
1 World Health Organization Ottawa Charter for Health Promotion
1986. Geneva.
2 O'Donnel M (1989). Definition of health promotion part 111
expanding the definition. American Journal of Health Promotion.
3(3): 5-9.
3 Public Health agency (2008) Health promotion Theories and
models sourced from http.www.publicealthhschi.net on 20/9/09.
4 Green L, Kreteur M (1990) Health promotion as a public health
strategy for the 1990s Annual Review of Public health Vol. II pp
313-334.
5 Pendar NJ, Mardaugh CL, Parsons MA (2002). Health promotion
th
in nursing practice. 4 Ed Practice Hill, London.
6 Ewles L, Simnelt I (2003). Promoting health a practice guide 5th
Ed. Bailliere Tindal N.Y.
7 WHO (1997) The Jakarta Declaration on leading health
st
promotion into the 21 century, Geneva
8 Pharmaceutical Society of Australia (2006). Professional
Practice Standards p. 113-119.
9 Walker R (2000). Pharmaceutical Public health: the end of
pharmaceutical care? The pharmaceutical Journal 264 (7035):
340 341.
10 Knapp KK, Paavola FG, Maine LL, Sorefman E, Politzer RM
(1999). Availability of primary care provider and pharmacists
in the U.S.
11 Oparah AC, Okojie OO (2005). Health promotion perceptions
among pharmacists in Nigeria. Int J Pham Practice13: 1-9.
12 Anderson S (2007). Community pharmacy and public health in
Great Britain 1936-2006. How a phoenix rose from the Ashes. J.
Epidemiol Community Health; 61:844-848.
13 The Royal Pharmaceutical Society (1998). Guidance for
development of health promotion by community pharmacists.
Pharm. J 261: 771-774.
14 Bisselp JJ (2006). Public health and pharmacy a critical review.
Critical Public Health 11:159-169.
15 Moody MM (1998). Health promotion and health education in:
nd
Winfield AJ, Richards RM (Eds). Pharmaceutical Practice 2
Edition Churchill Livingstone London.
16 PA G B (2008) Self Care. Accessed for
http/www/pagb.co.uk/.pagb/primary sections/self care/selfcare
html on 3/4/08
17 PAGB (2009). Self care in practice Accessed from
http/www/pagb.co.uk./pagb/primary sections/self care/self
care html on 20/08/2009
18 RPSGB (2008) RPS e-PIC References on : Prescription only
medicines reclassified to pharmacy only medicines pp1-62
19 Houge M D ,,Grabestein JD ,Foster SL, Rothholz MC (2008).
Pharmacists involvement with immunization, A decade of
professional advancement J Am pharm Assosc, 46(2) 168-
182.
20 Montero J (1998). Effective drug information dissemination
and presentation in chapter 11: Millares M (Ed). Applied
drug information-- strategies for information management.
Applied therapeutics, Vancouver.
21 Martin J (Ed) (1991) Handbook of Pharmacy health education.
Pharmaceutical press, London .
22 RPSGB & Pharm. Health Link (2003). Public Health A Practical
Guide for Community Pharmacists. Royal Pharmaceutical
Society of Great Britain.
23 Harman R J (1990) Handbook of pharmacy health care-
diseases and patient advice. The pharmaceutical press.
London.
24 Department of Health (2005) Choosing health through
pharmacy-. A program for pharmaceutical public health 2005
2015. J. Am. Pharm Assoc; 39:127-135.
Accessed from http.www.dh.gor.uk/pub 0n 6/3/2009
 CHAPTER TEN

BARRIERS TO THE IMPLEMENTATION OF P

HARMACEUTICAL CARE

Azuka C Oparah

Learning Objectives

At the end of this chapter, you should be able to:

I. Know attitudinal and other barriers to pharmaceutical care

ii. Discuss strategies to overcome barriers toward the

implementation of pharmaceutical care

iii. Discuss learning methods to improve attitudes of pharmacy

students toward pharmaceutical care

Pharmacists' attitudes

Since pharmaceutical care is practitioner driven, barriers pertaining to

the pharmacist are the most important. These include: knowledge,
attitudes, skills, understanding of pharmaceutical care, orientation
towards traditional dispensing (some may argue that their choice of
pharmacy as a career was informed by its product oriented nature),
interests, lack of time, inertia, and personal energy. Attitude factors may
represent key obstacles in realizing pharmacists' contribution to society.1

Setting

Though the practice of pharmaceutical care as espoused by Strand

(1998) is dependent on the practitioner and not the setting, an
appropriate setting would facilitate the process. From literature reports,
pharmaceutical practice model developed in Minnesota was packaged
for community pharmacies. Many view lack of patient data and access to
prescribing physician as potential barriers. Other constraints in this
setting include lack of trained supportive personnel/delegation of
2
dispensing tasks, and lack of a counseling area. A counselling area
should be a minimum requirement within the pharmacy. In a country like
Nigeria where collaboration between physicians and pharmacists is
poor, the community pharmacy setting provides good opportunity for the
practice of pharmaceutical care. Pharmaceutical care is also practiced in
the hospital, GP surgeries, and Managed Care Organizations. Have
described a practice in a physician office and the setting eliminated or
diminished some of the barriers. The USA home and hospice settings
provide avenues for collaboration among health professionals.

Public attitudes and expectations

The assignment of roles to a profession depends on the public's

perceptions of the profession and hence, professions have anticipatory
social roles. There are places where the public does not expect certain
health care roles from the pharmacist and this can be a de-motivating
factor. For instance, health promotion is an integral part of
pharmaceutical care. A survey of consumers' views in UK indicated that
many consumers did not perceive a role for community pharmacists in
3
health promotion contrary to the professions presumptions. In Nigeria
where self medication with both OTC and prescription drugs is high,
patients' expectations of pharmacists to manage their drug therapies
may be quite high. Consumer perceptions and expectations change
based on prior experience. There is indication that patient expectations
of pharmacy improve with the delivery of pharmaceutical care as the
4
pharmacist increases his interaction with patients.
Lack of standards
Pharmaceutical care will fail if each pharmacy organisation or individual
pharmacists are allowed to define pharmaceutical care for their own
agenda.5 Perhaps the most important next step facing us is to agree on a
standardised method for pharmaceutical care. It is important to decide
what method pharmacists will use to collect the patient information used
to identify and resolve drug-related problems, as well as documenting
the practice. In our opinion creating a system of documenting
pharmaceutical care will remove some inertia to implement
pharmaceutical care to patients. Use of terms and terminologies make a
profession unique. Drug therapy problems are the focus of
pharmaceutical care; however, one finds varying nomenclature or
taxonomy in this area among others. In UK, they talk about medicines
management and pharmaceutical care, where lies the difference?
Systems related barrier
A major system-related barrier in healthcare settings is the lack of a
comprehensive, ongoing process for defining the appropriate outcomes
of drug therapy.6 For employers and other purchasers to understand the
quality of the health care for which they are paying, defining the quality
and appropriateness of outcomes is needed. Physical facilities limit the
ability of pharmacists to provide pharmaceutical care. Dedicated areas,
in which the pharmacist can provide patient consultations or drug
therapy information, are often lacking. Pharmacists are also isolated
from the place where diagnosis and drug therapy decisions are made.
This physical isolation limits involvement in such drug therapy decisions,
and results in an increased reliance on retrospective, often adversarial,
interactions with physicians and other clinicians. This physical barrier
also creates the perception among patients that the physician or other
clinicians are the sole providers of care.5 In Nigeria, physicians “own”
patients on one to one basis and as such any other person trying to help
the patient is viewed as an intruder who must clear with them. This
attitude is a major barrier to implementation of pharmaceutical care in
hospitals and hence the community pharmacy, where the pharmacist is
a “sole administrator” is viewed as an attractive setting with both
challenges and opportunities. A comprehensive listing of barriers to the
implementation of pharmaceutical care is presented in Table 9.1. These
barriers vary from one country to another, and also from one practice
setting to another.

OVERCOMING BARRIERS TO PHARMACEUTICAL CARE

If pharmaceutical care is to be implemented widely, it is imperative to
overcome the barriers however, those contemplating to deliver
pharmaceutical care need not wait until all barriers are overcome,
neither will this ever be possible, as new barriers will continue to emerge.
Of particular importance is the need to nurture positive attitudes
regarding pharmaceutical care among practitioners and future
practitioners.

Mission statement
The mission statement of pharmacy profession i.e. pharmacists'
responsibility to the society should be defined in terms of drug supply
management (traditional product-oriented role) and pharmaceutical
care - drug use (patient-oriented role). As the barriers to pharmaceutical
care are gradually overcome and changes in health care environment
provide more opportunities for pharmaceutical care, more pharmacists
will shift toward pharmaceutical care model of practice.
Positive attitudes
Positive attitudes of pharmacists could be fostered through
pharmaceutical care competency based training and retraining
educational programmes. Studies indicate that pharmaceutical care can
be decomposed into two components namely managing therapy and
communication. Therefore, development of therapeutic skills, physical
assessment skills, critical thinking skills, problem solving skills, and
communication skills among others will enhance self efficacy of
pharmacists to deliver pharmaceutical care. For pharmacists whose
practice is predominantly drug dispensing and inventory management,
they need a change in knowledge base as well as skills. However, those
already practising clinical pharmacy require a change in orientation and
enhanced skill acquisition. Both cases learn to do by doing.

The need to teach students the concept of pharmaceutical care and the
importance of applying this concept has been documented.7-9 The factors
influencing students' attitudes toward pharmaceutical care have been
investigated. That study found that among American students in the
second semester of their first professional year at a pharmacy school,
those who had pharmacy practice work experience had more positive
attitudes toward pharmaceutical care than did other first-year students.10
This indicates that for enhanced attitudes toward pharmaceutical care
can be developed and fostered if students should be exposed to the
principles and practices of pharmaceutical care early in their pharmacy
education.
Several other approaches have been reported to improve students'
attitudes toward pharmaceutical care. There are reports indicating the
need to teach pharmacy students the concept of pharmaceutical care
and the importance of applying this philosophy of practice to the benefits
of patients.7-10 McDonough et al. strongly recommended that students
interact with patients early in their academic careers to improve
interpersonal communication and empathy skills.11
The opportunity for students to interact with patients and develop
practical concepts about the importance of performing pharmaceutical
care occurs traditionally in the latter stages of the pharmacy curriculum
during the experiential component. However, introducing students to
patients early in the pharmacy curriculum demonstrates the importance
of performing pharmaceutical care. Additionally, these early
experiences may help students develop positive attitudes regarding
pharmaceutical care activities. Such attitudes will hopefully motivate
students to incorporate these concepts into practice.10

Another approach is to encourage pharmacy practice experience early

in students' pharmacy education. In fact, obtaining pharmacy practice
experience before the pharmacy professional curriculum is begun and
during the period of pharmacy education may result in more positive
attitudes toward pharmaceutical care.

The effectiveness of using actual patients in the classroom to develop

positive students' attitudes toward pharmaceutical care has been
demonstrated (Chisholm and Wade, 1999). A patient centered
intervention programme has also been described and demonstrated to
improve students' attitude toward providing care for HIV/AIDS patients.

Pharmaceutical care shadowing experience has been applied to

improve the pharmacy students' attitudes toward good professional
practices. During the pharmaceutical care shadowing experience, the
students gain exposure to relevant ethical and practical issues of
pharmacy practice and are expected to share their experiences with
fellow classmates and faculty members in a formalized setting.

The establishment of student-driven, faculty observed pharmaceutical

care clinics within schools and colleges of pharmacy can help to
effectively prepare students for the challenges of an active patient care
practice. Another study has determined whether completion of a patient
counselling course improved pharmacy students' perceptions of the
importance of pharmaceutical care and whether there was a difference in
students' perceptions of pharmaceutical care provided in retail settings
compared with that provided in clinical settings. This report indicates that
teaching the concept of pharmaceutical care and incorporating it into a
patient counselling course is more instructive when a clinical setting is
used.

Educational interventions
Several practice-based intervention projects to implement
pharmaceutical care have recognized the importance of pharmacists'
skill levels and work environments. These initiatives have focused on
increasing the application of pharmacists' clinical knowledge via
problemsolving and critical thinking as well as changing workflow
12
patterns. One initiative in Canada focused exclusively on the practice
environment. This approach is termed practice change model and
13
requires technical support from the academia. One other project used
social-learning theory to provide a framework for its practice
14
enhancement program.
Generally, in addressing the barriers pertaining to the pharmacist's
knowledge, skills and attitudes, an educational intervention has often
been resorted to. The pharmacist's cognitive and affective abilities are
intermediate outcomes in an educational intervention programme.
Time constraint as a barrier to pharmaceutical care is often viewed as the
time for pharmacists to deliver pharmaceutical care bearing the
competition between the pharmacist's dispensing roles and patient care
expectations. As a result of that, a usually suggested remedy is the
utilization of pharmacy technicians in order to free time for the
pharmacist. A neglected component of that time is the time for
pharmacists who lack the relevant knowledge and skill to undergo an
educational intervention programme. Such programmes must consider
that many pharmacists lack the time for this training, before the training
can be thought to change their orientation towards pharmaceutical care.
As such pharmaceutical care educational interventions should
endeavour to consider this aspect of time constraint and tailor
programmes to suit it. One approach is the onsite training of
pharmacists.

Berger and Grimley examined pharmacists' readiness to render

pharmaceutical care using the trans-theoretical model, which suggests
that five stages of voluntary behaviour change exist from the pre-
15
contemplation, contemplation, preparation, action, and maintenance.
Classification into a particular stage indicates specific behaviour change
16
strategies that are necessary to achieve behaviour change. For
example action oriented strategies such as pharmacists' workshops to
learn about developing pharmaceutical care plans will not be effective in
individuals who are in the pre-contemplation stage, where they are
unwilling or too discouraged to change their practice behaviour.
Structure criteria
These include having an adequate number of pharmacists and
supporting staff with relevant training. Practice settings with few
pharmacists will be overwhelmed by dispensing roles and inventory
management, thus creating inertia to contemplate the practice of
pharmaceutical care. A documentation system, both manual and
electronic is necessary for pharmaceutical care. This provides a
direction and helps to standardize the practice within a setting.

Inter-professional collaboration
Patient care is a collaborative process because no single professional in
the health care team has all the knowledge, attitudes and skills required
to optimise the process. However, there appears to be mutual distrust
among players in the team. Members of the team have a common
enemy to fight i.e. diseases and not themselves. Pharmaceutical care in
philosophy and practice is collaborative in nature. Collaboration
between pharmacists and physicians or pharmacists and nurses, should
be pursued through education and practice where pharmacists actively
demonstrate the value of pharmaceutical care to the health care system.
Professional relationships evolve over a period of time through mutual
understanding and respect for each other's competences. McDonough
and Doucette suggest a staged approach to developing pharmacists-
physician collaborative working relationship namely:17
• professional awareness
• professional recognition
• exploration and trial
• professional relationship expansion
• commitment to the collaborative working relationship
Marketing Pharmaceutical Care: Pharmaceutical care is a service and
hence requires marketing skills to promote its acceptance to patients,
healthcare workers and policy makers. Most importantly,
pharmaceutical care should be promoted to patients who are the focus
of the care. When pharmacists supply the service, they should at the
same time create a demand for it. Marketing skills that are to be applied
Table 9.1: Barriers to implementation of pharmaceutical care18

A. Pharmacists attitude D. Systems Related Constraints

1. Reimbursement
1. Lack of comprehension 2. Patient Demand
2. Misconceptions 3. Acceptance by physicians & nurses
3. Fear of change 4. Access to patient records
4. Lack of motivation
5. Inertia
6. Personal energy

E. Inter-professional Obstacles
B. Lack of pharmaceutical care skills
1. Lack of collaboration
2. Boards of Pharmacy
1. Therapeutics
(Pharmacists Council)
2. Clinical Problem Solving
3. Faculties of Pharmacy
3. Communication Skills
4. Documentation
5. Drug information

C. Resource Related Constraints F. Academic Obstacles

1. Time 1. Lack of role models

2. Finance 2. Curricula not focused on pharmaceutical
3. Space care
4. Personnel
5. Management

Key Learning Points

· Negative attitude of pharmacists is a major barriers to

pharmaceutical care
· Acquiring clinical knowledge and developing therapeutic skills,
physical assessment skills, critical thinking skills, problem solving
skills, and communication skills among others will enhance self
efficacy of pharmacists to deliver pharmaceutical care
· Changing the practice of pharmacists to pharmaceutical care
requires technical support of the academia
· Onsite training of pharmacists on pharmaceutical care helps to
remove time constraint to go for training and also develop the
practice site
· Pharmacists need to create demand for pharmaceutical care at the
same time that they supply the service
· Learning methods to foster positive attitudes of pharmacy students
(future practitioners) include:
ü Early introduction of pharmaceutical care in the
curriculum and focusing pharmacy education on
pharmaceutical care
ü Using actual patients to teach in the classroom
ü Pharmaceutical care shadowing experience with
practitioners
ü Establishing student-driven, faculty observed
pharmaceutical care centres in Faculties of Pharmacy
ü Teaching pharmaceutical care in a clinical setting such as
hospital and community pharmacy rotations
· Stages in developing collaborative working relationship
are:
ü professional awareness
ü professional recognition
ü exploration and trial
ü professional relationship expansion
ü commitment to the collaborative working relationship
References

1. Knapp DA (1979). Barriers faced by pharmacists when a

ttempting to maximize their contribution to society. Am J Pharm

Educ; 43: 357-359

2. Farris KB, Schopflocher DP (1999). Between intention and

behaviour: an application of community pharmacists'

assessment of pharmaceutical care. Soc Sci Med; 49:55-66.

3. Anderson C (1998). Health promotion by community

pharmacists: consumers' views. Int J Pharm Pract; 6:2-12.

4. Erstad BL, Draugalis JR, Waldrop SM, Scheurer L, Namanny MD
(1994). Patients' perceptions of increased pharmacy contact.
Pharmacother; 14(6):724 728.
5. Al-Shaqha WM, Zairi M (2001). Pharmaceutical care
management: a modern approach to providing seamless and
integrated health care. Int J Health Care Quality Assur 14(7):
282-301.
6. May JR. (1993) Barriers to pharmaceutical care in the acute care
setting. Am J Hosp Pharm; 50: 1608-1611.
7. Adamcik BA (1992). Teaching pharmaceutical care: removing
the fences. Am J Pharm Educ; 56:434-441.
8. Berardo DH (1992). Teaching pharmaceutical care: a
methodology to change. Am J Pharm Educ; 56:430-434.
9. Schommer JC, Cable GL (1996). Current status of
pharmaceutical care practice: strategies for education. Am J
Pharm Educ; 60:36-42.
10. Chisholm MA, Wade WE. (1999) Factors influencing students'
attitudes towards pharmaceutical care. Am J Health- Systems
Pharm; 56,2330- 2335.
11. McDonough RP, Pithan ES, Doucette WR, Brownlee MJ (1998).
Marketing pharmaceutical care services. J Am Pharm Assoc
38(6):667-679.

12. Farris KB, Schopflocher DP (1999). Between intention and

behaviour: an application of community pharmacists'
assessment of pharmaceutical care. Soc Sci Med; 49:55-66.
13. McDonough RP. (1996) Interventions to improve patient
pharmaceutical care outcomes. J Am Pharm Assoc; 536,453-
466.
14. Volume CI, Farris KB, Kassam R, Cox CE, Cave A (2001).
Pharmaceutical care research and education project: patient
outcomes after provision of pharmaceutical care. J Am Pharm
Assoc (Wash); 41(3):411 - 420
15. Berger BA, Grimley D (1997). Pharmacist readiness for
rendering pharmaceutical care. A Paper Presented at the Annual
Meeting of the American Pharmaceutical Association. Los
Angeles, CA.
16. Prochaska JO, Velicier WF, Rossi JS, Goldstein MG (1994).
Stages of change and decisional balance for 12-problem
behaviors. Health Psychology 13, 39-46.
17. McDonough RP, Doucette WR (2001). Developing collaborative
working relationships between pharmacists and physicians. J Am
Pharm Assoc; 41(5):682-692.

18. Rovers JP, Currie JD, Hagel HP, McDonough RP, Sobotka JL
(2003) Ed. A practical guide to pharmaceutical care 2nd ed.
Washington DC: American Pharmaceutical Association; ISBN: 1-
58212-049-8.
 CHAPTER ELEVEN

MARKETING PHARMACEUTICAL CARE

Azuka C Oparah and Uche M Ochei
Learning Objectives
At the end of this chapter, you should be able to:
i. Explain the concept of relationship marketing
ii. Characterise pharmaceutical care service as a product
iii. List and explain pharmaceutical care marketing mix
iv. Explain the concepts of target markets and marketing
cycle in pharmaceutical care.

Introduction
Marketing process is an essential element of novel service delivery.
Pharmaceutical care requires higher than usual marketing skills
because it is a service unlike the case of a tangible product which
attributes have face values or create impressions in the minds of the
consumers or potential consumers. Marketing may be defined as a set of
activities that directs the flow of goods and services from the producer to
the end user. Kotler and Armstrong see marketing as the business
function that identifies customer needs and wants, determines which
target market the organization can serve best, and designs appropriate
products, services, and programs to serve this market.1 Marketing
should be seen beyond its functions, it is a philosophy that guides the
entire organization. As part of this philosophy, pharmacists should
accept a responsibility to educate prescribers, patients and payers about
the extent and value of pharmaceutical care services. In short,
pharmacists should build the demand for pharmaceutical care service at
the same time that they create a supply.2
Pharmacists need to become more assertive in communicating patient
information and recommending clinical interventions to physicians.
Face-to-face visits between pharmacists and physicians are especially
important when initiating a professional relationship. Once physicians
become familiar with the pharmacists and trust their clinical
competence, personal visits become less important, but should
continue periodically. Pharmacists also need to determine the frequency
and type of communications (e.g., telephone call) a particular physician
prefers.
In marketing pharmaceutical care, the following should be considered:
• Consumers of pharmaceutical care services- patients,
physicians and other health care providers, third party payers of
health care services (health insurance), policy makers and
government etc.
• Marketing tools required to reach pharmaceutical care
consumers- marketing mix.

Marketing Mix
The marketing mix consists of four basic elements (4Ps) namely
product, price, promotion and place. A fifth 'P'- positioning is often
included. The principles of relationship marketing are applied to these
marketing mix elements. Relationship marketing is defined broadly as a
practice that encompasses "all marketing activities directed toward
3
establishing, developing, and maintaining successful relationships. In
the pharmacy setting, relationship marketing refers to attracting,
maintaining, and enhancing patient relationships to create mutual
4
benefit for the pharmacist and patient.

The focus of relationship marketing is on developing long-term

relationships with a targeted group of patients and other partners. Hepler
and Strand introduced the concept that the therapeutic relationship
between pharmacist and patient was an integral component of
pharmaceutical care. They saw pharmaceutical care as "a covenantal
relationship between a patient and a pharmacist in which the pharmacist
performs drug use control functions (with appropriate knowledge and
skill) governed by the awareness of and commitment to the patient's
5-7
interest.
Given the ongoing nature of chronic drug therapy and the opportunity for
repeated interactions between pharmacists and patients, identifying and
targeting groups of patients who could benefit from developing long-term
therapeutic relationships with pharmacists makes sense both
professionally and economically. In addition, relationship marketing
emphasizes the value of lasting bonds, making this approach well suited
to promoting pharmacy services to patients who have chronic conditions
and require long-term follow-up to ensure that their therapeutic goals are
met. The majority of pharmaceutical care services are for patients with
chronic diseases, such as asthma, diabetes, hypertension, or
dyslipidemia, or who require long-term support for efforts such as
smoking cessation or weight loss. Relationship marketing offers a more
focused and efficient approach to recruit and retain patients from these
8
populations.
The philosophy and practice of relationship marketing offer new insights
and strategies for building a successful pharmacy practice. This
approach emphasizes the importance of developing and maintaining
lasting relationships with patients and other partners, such as
physicians, through the provision of high-quality clinical services.
Relationship marketing requires thoughtful use of market segmentation
and niche marketing techniques to identify selected groups of patients
who are most likely to benefit from specific pharmacy services. Each
interaction with these patients should be deliberate, with the dual
purpose of improving health and building a rewarding, long-lasting
professional relationship. By developing pharmacy services that meet
patients' needs and deliver on promises, pharmacists can build lasting
relationships that are the foundation of a successful and rewarding
9
practice.
Product
This refers to the goods (tangible products) and services (intangible
products) that are being offered to the consumer. Pharmacists should
understand the differences between tangible and intangible products
because this affects their marketing activities. Pharmaceutical care is a
service and has the following characteristics:
• Intangible- pharmaceutical care is not physical so patients
cannot see or touch the services but must experience the services in
other to derive the benefits and appreciate their values which are
expressed in terms of patient care outcomes such as curing their
disease, reducing target symptoms, patient satisfaction and enhanced
quality of life.
• Inconsistent- pharmaceutical care is a covenantal relationship
between the pharmacist and the patient. In the philosophy of
practice, a pharmacist establishes a personalised therapeutic
relationship. Therefore, the outcomes of such pharmacist-
patient interaction vary over time, and from one pharmacist to
another who may have different levels of competences and
barriers.
• Inseparable- a service cannot be separated from its provider.
Pharmaceutical care services have two behavioural
components namely: the technical component (managing drug
therapy) and interpersonal component (communication) both of
which depend on the pharmaceutical care practitioner or
provider.
• Non- Inventoried- services cannot be stored the way tangible
 products are stored. However, pharmaceutical care services
once delivered and consumed should be documented as
evidence of service delivery, furthermore, the outcome of such
services should also be documented.

Price
Traditionally, pharmacists fixing the price of a dispensed product find it
easy because of the mark-up system that is based on the cost price. As
pharmacists move from product-focused services to patient-care
services, personal and professional success will depend upon the
practitioner's ability to determine the cost of providing these services and
determine an appropriate price. The definition of a "good price" for
provision of cognitive services is described as the point where the value
10
of these services to the consumer equals the value to the producer.
The use of this process occurs almost daily in most people's lives when
goods or services are purchased. A purchase is likely to be made when
the consumer desires a product or service and feels that the price of this
product or service is a good value. In setting a good price, the value to the
consumer and value to the producer have to come into balance. This
sometimes is associated with negotiation between these parties.

Determination of the price for a service is related to the cost of providing

this service; however, alternative objectives come into play in deciding
the price charged to the consumer. These alternative pricing objectives
include profit maximization and market penetration. However, pricing
pharmaceutical care may pose a big challenge in practice settings where
patients do not pay for pharmacist cognitive services and hence would
object to extra charge outside cost of medication. Other factors, which
are unrelated to the cost, that go into determining a price include the
demand for the service, competition, and the image that you wish to
project.
9
Principles of pharmaceutical care pricing
• The price of a pharmaceutical care service should include the
costs of providing that service and contribute to the overall profit.
Service costs can be divided into 2 major categories: direct costs and
indirect costs. Direct costs are further broken down into variable costs
and fixed costs. Direct costs are those costs that would not be incurred if
a service were not performed. Fixed direct costs are unrelated to the
volume of use of the service. Variable direct costs change in direct
proportion to the service provided. Indirect costs occur even if a service
was not performed. These costs are commonly referred to as overhead.

• Personnel time is the single most important direct cost of

most pharmaceutical care services. The hourly rate at which
pharmacists are compensated becomes the major determinant
of the price of a service. Recognizing this is important in
determining work assignments for pharmacy technicians and
employing the availability of pharmacy students or pharmacy
residents to provide these services.
• The full cost of a service is equal to the direct costs plus a fair
share of the indirect costs. Indirect costs are usually allocated by
1 of 2 means. The first, and most common, is as a percentage of
floor space. The second is as a percentage of sales. In either
case, the method selected should be logical and causally related
to costs.
• Discounts on usual and customary pricing should be carefully
considered and economically justified. For example, a volume
discount may be justified if a third-party payer selects your
pharmacy as a sole provider for asthma education services.
 Again, recognition of the costs associated with providing this
service and break-even point determination will determine if a
discounted price is economically justified.
• Satisfied patients are most likely to become regular patients. In
order to maintain patient satisfaction, it is important to discuss all
aspects of the service with the patient. This will include the
specific benefits you are offering as well as the costs to the
patient, whether you will bill the patient's third-party carrier, and
making it known that the patient will be responsible for any unpaid
portion of the claim you have submitted. This should be done
prior to initiating any pharmacist care services. A useful approach
is to develop a brochure with a clear description of costs and
services provided.
• The manner in which the price is presented is as important as the
price. You could apologetically say, "We offer blood pressure
check, but the price is NGN 20." An alternative and better
approach might be, "We offer blood pressure check at any time
that is convenient for you, and the cost is only NGN 20." This is
referred to as the power of presentation. It is important for
patients to appreciate the value of the services you are providing.

Promotion

Promotional strategies for pharmaceutical care include a combination of

advertising, publicity, public relations, direct mails, sales promotion and
personal selling. Advertising could be through radio, television and
newspapers, however, professional ethics, cost and target audience
reach should be considered. Direct mail options include use of letters,
newsletters and brochures which are directed at targeted patients.
Presentation at special events such as community awareness programs
may be used. Personal selling of pharmaceutical care to patients and
patrons of the pharmacy, whereby the pharmacy staff educate the
visitors on available services and their benefits in addition to notices
displaying the services within the pharmacy appears most feasible.

Place (Distribution)

Place refers to where and how a pharmaceutical care service will be

delivered. It should be made available in the right place at the right time
that are convenient and acceptable to patients. Patients can access
pharmaceutical care services in the clinic, at the pharmacy or in their
homes or offices as suitable. The outlook of the pharmacist and
pharmacy needs to evoke a professional image, where a specialized
healthcare service is obtained rather than where goods are sold. The
pharmacist as the personage of the environment should be easily
identified by his professional dressing (white overall), while the
pharmacy should have consultation areas or counseling rooms for
patient confidentiality.

Position

Positioning refers to creating a favorable image of the pharmacy practice

in the minds of potential target audiences and stakeholders, so that they
11
will want and use your services. For example, a pharmacy can position
itself as a practice, staffed by knowledgeable, caring pharmacists that
provide a full range of quality services. Another pharmacy may position
itself as a place where a wide range of good quality and moderately
priced drugs are available.Pharmacist needs to position his image, the
practice, and environment of practice to be consistent with the
aspirations of pharmaceutical care.

Target Markets and Marketing Cycle

Target Markets

Target markets are groups of consumers whose behavior shows similar

 11
patterns or who share similar characteristics. The concept of target
market is important because it is neither efficient nor cost effective to
market pharmaceutical care to the general public.

Pharmaceutical care services are novel and would unlikely appeal to all
the clients of the pharmacy department especially at the initial stage.
Therefore, there is need to identify those who are most likely to benefit
and are willing and able to access the services. Consumers can be
categorized based on their willingness to adopt new product or services
1
into:

• Innovators (below 5 %)- First to try new product or service if they

believe it meets their needs. They are considered to be risk
takers and venturesome.
• Early adopters (10 15 %) Opinion leaders who evaluate new
ideas and services carefully. They may need to hear a marketing
message several times but will try a new product or service early
in the marketing efforts.
• Early majority (30 35 %) More deliberate in their decision than
opinion leaders. Usually needs to hear a marketing message a
number of times before trying a new product or service. They
adopt new products are services earlier than the average
consumer.
• Late majority (30 35 %) Tend to be skeptical about new products
and services and eventually adopt them after the majority of
consumer have already done so.
• Late adopters (15 20%) Remain suspicious of innovation and
adopt a new product or service only after it has a well proven
record.

Identifying and focusing initial marketing efforts on the innovators and

early adopters within the target market for a pharmaceutical care service
can help the pharmacy establish a business base and facilitate later
marketing efforts. Target markets for pharmaceutical care include the
elderly and those having chronic ailments such as hypertension,
asthma, diabetes mellitus, rheumatoid arthritis, and HIV/AIDS. A patient
survey is a tool that can be useful for gauging patients' interest in a
proposed or existing pharmacy service. A survey can provide additional
information about patient demographics, the types of services that may
interest patients, patients' willingness to pay for such services and their
satisfaction with the services.

Marketing Cycle
12
A seven step model marketing cycle has been proposed to include:

i. Analyzing the market by accessing the internal environment,

external competition, patient needs and future opportunities.
Market analysis identifies opportunity and constraint to
successful pharmaceutical care services. A common technique
employed is the SWOT analysis i.e. Strengths, Weaknesses,
Opportunities and Threats.

ii. Developing the marketing plan by defining clear goals and

objectives. Goals are general statements that outline what a
practice intends to accomplish. Objectives are the steps needed
to meet the goal. Each goal should have its own set of objectives.
Objectives should be SMART i.e. Specific, Measurable,
Achievable, Realistic and Time bound.
iii. Selecting and developing promotional tools such as personal
selling (face to face contact, and display of notices).
iv. Testing and refining marketing materials using input from the
target audience
v. Implementing the plan - in a timely manner.
vi. Evaluating the effectiveness of the plan at defined time
intervals.
vii. Applying the findings and feedback into a new market analysis.
The marketing cycle is a continuous process.

Key Learning Points

· Marketing as the business function that identifies

customer needs and wants, determines which target
market the organization can serve best, and designs
appropriate products, services, and programs to serve
this market. It is a philosophy that guides the entire
organization.

· Pharmacists should build the demand for

pharmaceutical care service at the same time that they
create a supply.
· The marketing mix consists of four basic elements
(4Ps) namely product, price, promotion and place. A
fifth 'P'- positioning is often included.

· The principles of relationship marketing are applied to

these marketing mix elements. In the pharmacy setting,
relationship marketing refers to attracting, maintaining,
and enhancing patient relationships to create mutual
benefit for the pharmacist and patient.

· Pharmaceutical care is a service and has the following

characteristics:
ü Intangible
ü Inconsistent
ü Inseparable
 ü Non- Inventoried
· Determination of the price for a service is related to the
cost of providing this service and other factors such as
demand for the service, competition, and the image
that you wish to project.

· Personal selling of pharmaceutical care to patients and

patrons of the pharmacy, whereby the pharmacy staff
educate the visitors on available services and their
benefits in addition to notices displaying the services
within the pharmacy should be employed.

· Place (distribution) refers to where and how a

pharmaceutical care service will be delivered. It should
be made available in the right place at the right time
that is convenient and acceptable to patients.

· Positioning refers to creating a favorable image of the

pharmacy practice in the minds of potential target
audiences and stakeholders, so that they will want and
use your services.

· Initial marketing efforts should focus on the innovators

and early adopters within the target market

· Target markets for pharmaceutical care include the

elderly and those having chronic ailments such as
hypertension, asthma, diabetes mellitus, rheumatoid
arthritis, and HIV/AIDS.

References

1. Kotler P, Armstrong G. Principles of marketing. Upper Saddle

River, NJ: Prentice Hall; 1996.
2. Rovers JP, Currie JD, Hagel HP, McDonough RP, Sobotka JL.
A Practical Guide to Pharmaceutical Care. Washington, DC:
 American Pharmaceutical Association; 1998: 136-150.
3. Morgan RM, Hunt SD. The commitment-trust theory of
relationship marketing. J Marketing. 1994;58(July):20-38.
4. Berry LL. Relationship marketing. In: Berry L, Shostack GL,
Upah GD, eds. Emerging Perspectives on Services
Marketing. Chicago, Ill: American Marketing Association;
1983:25-8.
5. Hepler CD. The third wave in pharmaceutical education and
the clinical movement. Am J Pharm Ed. 1987;51:369-85.

6. Hepler CD, Strand LM. Opportunities and responsibilities in

pharmaceutical care. Am J Hosp Pharm. 1990;47:533-43.

7. Cippole RJ, Strand LM, Morley PC. Pharmaceutical Care

Practice. New York, NY: McGraw-Hill Co.; 1998.

8. Doucette WR, McDonough RP. Beyond the 4Ps: Using

Relationship Marketing to Build Value and Demand for
Pharmacy Services. J Am Pharm Assoc 42(2):183-194, 2002.
9. ASHP Conference Report Reimbursement for Pharmaceutical
Care Annual Meeting 2000, Philadelphia, Pennsylvania --
June 4-7, 2000
10. Rupp M. Pricing pharmacist care services. Int Pharm
Abstracts. 37;9:811.
11. Schwartz A, Sogol E. Developing a marketing plan. Drug
Topics. 1987; 6: 69 - 75.
12. Shepard MD. Defining and Marketing Value Added Services.
Monograph 16. In: Value Added Services: The Dynamics of
Pharmaceutical Care. Washington, DC: APhA; 1995.
 CHAPTER TWELVE

PHARMACEUTICAL CARE IN ELDERLY PATIENTS

Azuka C Oparah and Ifeanyi E Chiazor

Learning Objectives

At the end of this chapter, you should be able to:

i. Discuss the need for individualized pharmaceutical care i

n the elderly population
ii. Explain strategies to optimize adherence in elderly patients

Introduction
Aged persons are described in different terminologies such as
geriatrics, elderly, older people, senior citizens or seniors. They are
usually 65 years and over in developed countries with high life
expectancy or 60 years and over in developing economies. As one ages,
the health declines and consequently the need for medication
increases. Too often, illness in older people is misdiagnosed,
overlooked or dismissed as part of the normal aging process, simply
because health professionals are not trained to recognize how diseases
1
and drugs affect geriatrics. A “one drug fits all” approach does not work
for elderly patients because they are exposed to unique health variables
that are rare in younger patients. When these factors interact in an older
patient, individualized drug therapy is required, and restricted drug
2
access could lead to ineffective or negative health outcomes.

As the population ages, the level and pattern of demand for health care
are likely to change, and difficulties in financing care will increase. Older
persons, for example, tend to consume more health care than those in
younger age cohorts, as well as different types of care (for example more
long-term care). By the same token, older persons (who are often retired)
tend to have less income than those in younger age cohorts.3 A
consequence of this is that they are less able to meet the costs of health
care directly (i.e. out of pocket) or contribute through direct taxation to
meeting the costs of publicly funded health care. These two factors of
growing demand and diminishing income among those for whom
demand is expanding will present challenges to the future finance and
delivery of care.4

Pharmacists are committed to optimizing therapies for each patient to

improve clinical/humanistic outcomes and reduce costs. They are
making significant contributions to the profession through specialized
pharmaceutical care. Medications are probably the single most
important healthcare technology in preventing illness, disability and
health in the geriatric population. New products provide pharmacists with
valuable tools for promoting quality of life but also confer upon them the
more difficult task as well as the greater responsibility of balancing
clinical effects to provide the highest possible quality of life for their
patients.1 Drug therapy is the most common medical treatment for the elderly
and the elderly are subject to complex health variables. When these factors
interact in an older patient, individualized pharmaceutical care is required.

Need for individualized pharmaceutical care in the elderly

population
Multiple Diseases
Comorbidity, or the simultaneous presence of two or more chronic
diseases, is common in the elderly and is an important reason why
treatment must be tailored to the needs of individual patients. The rate of
comorbidity in the elderly population has increased steadily since the
early 20th century. This increase may be attributed to a rise in the number
5
of diagnoses and to increased longevity. As people age, the incidence
and impact of comorbidity increase, resulting in a decline in well being
6
and functional abilities. Just as certain individual diseases are more
common in the elderly, there are also frequently occurring disease pairs.
The simultaneous presence of arthritis and high blood pressure is one
such pair common in older people; more than 24% of people older than
60 suffer the effects of both diseases. Such comorbidity requires careful
selection of drug therapy to ensure safe and effective drug combinations.

7
Verbrugge and colleagues determined that a person over age 55 has an
average of 3 chronic conditions, and Hobson cited an average of 5
coexisting conditions in patients 65 years and older. MCgee and
8
colleagues found an average of 8 conditions in a population that aged 55
years and above. The common thread through almost all comorbidity
studies is that the number of diseases per person increases with age. By
the seventh decade of life, three out of four people suffer from at least
5-7
one chronic disease and more than half have two or more diseases.
Some common disease conditions occurring in the elderly population
are:
• Arthritis
• Hypertension
• Congestive heart failure
• Diabetes mellitus
• Stroke
Polypharmacy
A study has indicated that an elderly population group (55 years and
8
over) received an average of 7.72 medications a day. The elderly tend to
utilize numerous health care providers and medical specialists. Because
their prescribers generally do not confer with one another, polypharmacy
is a frequent problem. Also, elderly patients without prescription drug
benefits often patronize several pharmacies in search of the best price.
Another reason for polytherapy in the elderly population is the nature of
their chronic conditions, each of which would require multiple therapy to
control and with comorbidities, the number of necessary medications
also increases. Therefore, the elderly are at increased risk of adverse
drug reactions and drug interactions. When treating elderly patients with
multiple conditions, there is a higher risk of an adverse drug reaction (ADR). An
ADR can result in mild to serious injury to the patient. Patients taking five or
fewer drugs have a four percent chance of an ADR. With six to 10 medications,
the risk increases to 10 percent and at 11 to 15 medications, the risk of an ADR
skyrockets to 28 percent. ADRs can result from drug-drug interactions, drug-
disease interactions, and synergism.9
Further, the side effects of medications in geriatrics often are more
severe. Hospital admissions among the elderly due to drug
misadventures are six times that of the general population.

Physiological Changes
An older body reacts to medications quite differently from a young one
due to physiological changes that accompany aging; metabolism rates
change, organ function declines and sensitivity to some drugs can be
altered. Age-related physiological changes affect the outcomes of drug
therapy. As a group, the elderly span the continuum from near perfect
health to extreme physiological decline. With so much variation, many
drug options are necessary to meet the health needs of specific elderly
individuals and groups safely and effectively.

Pharmacodynamic and Pharmacokinetic Variations

With age, organ systems can be more sensitive to drugs and their effects can
be enhanced or diminished. Some drug side effects can be used to a patient's
advantage, while other side effects may not be desirable, but can be tolerated.
Three types of drug side effects that are particularly significant for elderly
patients are effects on the brain, digestive, and cardiovascular systems, these
9
effects may not be experienced by younger persons at all.

Drug dose should be reduced in elderly patients because of a general

decline in body function with age. Altered medication absorption in the
elderly include: delayed gastric emptying, decreased splanchnic blood
flow, elevated gastric pH and impaired intestinal motility. Although the
rate of drug absorption is rarely affected. The lean body mass decreases
and body fat increases by almost 100% in elderly persons as compared
to adults. Because of smaller volume of body water, higher peak alcohol
levels are observed in elderly than in young adults. Volume of distribution
of a water soluble drug may decrease and that of a lipid soluble drug like
diazepam increases with age. Drugs that are highly bound to albumin
(e.g. warfarin, phenytoin) may have a greater free concentration because
albumin is decreased in the elderly.

Age related changes in hepatic and renal function greatly alter the
clearance of drugs. Serum creatinine may not be a good predictor of renal
functions, as creatinine production declines with age. Decline in cardiac
output with age results in decrease of renal perfusion by 40% to 50%.
Due to progressive decrease in renal function, the dosage regimen of
drugs that are predominantly excreted unchanged in urine should be
reduced in elderly patients. A reduction in phase 1 reactions (oxidation,
reduction and hydrolysis) can occur. This results in prolonged elimination
half lives of benzodiazepines and certain analgesics
(dependent on phase-1 metabolism). This may result in drug
10
accumulation and possible adverse effects.
Psychotropic medications have been consistently and significantly
associated with an increased risk of falls in the elderly. The tricyclic
antidepressants serotonin reuptake inhibitor, antidepressants,
benzodiazepines and antipsychotic need to be monitored closely in the
geriatric population with regard to falls. Studies have consistently
shown a significant association between multiple medication use and
11
risk of falling in the elderly. Elderly patients are particularly vulnerable
to the sedative effects of psychotropic drugs, resulting in cognitive
impairment and motor in coordination with an increased risk of falls and
hip fracture. Discomfort, pain or difficulty swallowing medication is a
problem faced by many elderly patients. Dysphagia is seen in patients
with Parkinson's disease, altered mental status or as a result of a
cerebal vascular accident. For an example when a solid dosage form is
reduced to a powder (crushed or opened), the surface area is greater
and the substance usually dissolves more readily making it more easily
absorbed. This may result in an increase in the rate of side effects or
toxicity. This is especially true in the elderly with impaired renal or
11-13
hepatic function.

Non-Adherence
In a study it was found that 60% of geriatric patients do not take their
medications as prescribed and many self medicate as often as once a
week. Elderly patients can have some diseases that make adherence
to drug therapy difficult, such as; conditions that affect vision, e.g.
macular degeneration or cataract formation, can make reading
prescription labels and medication instruction difficult. Hearing loss can
prevent patients from understanding health care professionals'
instructions and medication information. Arthritis and parkinsonism can
1
add to the difficultly of opening medicine bottles. Depression and
memory loss are possible factors for non-adherence.
Furthermore, non-adherence in older persons may be due to
polypharmacy, adverse drug reactions, and social conditions such as
living alone and inability to afford medication.

Optimizing Drug Therapy of Elderly Patients

Pharmacist's coordinating and optimizing drug therapy to improve
outcomes by reducing costs:
• Designing patient specific strategies to improve adherence
• Targeting patients taking unnecessary multiple prescriptions
(often duplicate or triplicate therapies) that can cause serious
harm and waste valuable resources.
• Reducing the number of serious at risk for side effects of drugs
considered inappropriate for use in the elderly
• Working with physicians to optimize drug therapies by
increasing the use of medications considered to be best for
individuals practices
• Providing therapeutic interchange for certain drugs to provide
equal or better clinical outcomes.
· The elderly have a higher prevalence of multiple diseases, and thus
receive more prescriptions and see more physicians who must then
coordinate care,

· An older body can react very differently to medicines than a younger

one due to physiological changes, such as changes in metabolism and
organ function, and

· There is wider variation in the pharmacological actions of a drug in

elderly individuals
 Key Learning Points

· As one ages, the health declines and consequently the

need for medication increases. Too often, illness in older
people is misdiagnosed, overlooked or dismissed as part
of the normal aging process.

· Medications are probably the single most important

healthcare technology in preventing illness, disability and
health in the geriatric population. New products provide
pharmacists with valuable tools for promoting quality of life
but also confer upon them the more difficult task as well as
the greater responsibility of balancing clinical effects to
provide the highest possible quality of life for their patients.

· Need for individualized pharmaceutical care in the elderly

population arises from:

ü Multiple Diseases

ü Polypharmacy
ü Physiological Changes

ü Pharmacodynamic and Pharmacokinetic

Variation

ü Non-Adherence

References

1. Roy V, Varsha R (2005). Pharmacists in Geriatric Care: A

Challenging Service. Health Administrator; 19(1): 76-82.

2. Nash BD, Koenig JB, Chatterton ML (2000). Why the Elderly

Need Individualized Pharmaceutical Care. Office of Health
Policy and Clinical Outcomes, Thomas Jefferson University.
3. United Nations. Demographic Yearbook, Series R (United
Nations Publication, E/F.98.XIII.1),1996.
4. McAlister DA, Hughes CM, Fleming I, O'Neill C. Costs of
pharmacological care of elderly patients. Reviews in Clinical
Gerontology 2005 14; 7178. United Kingdom, Cambridge
University Press.

5. Guralnik JM, LaCroix A, Everett D,Kovar M. Aging in the

eighties:The prevalence of comorbidity and its association with
disability. National Center for Health Statistics. 1989; 170:1-8.

6. Stewart AL, Greenfield S, Hays RD,Wells K, Rogers WH, Berry

SD, et al. Functional status and well-being of patients with
chronic conditions. JAMA 1989; 262:(7)907-913.

7. Verbrugge L, Lepkowski J, Imanaka Y. Comorbidity and its

impact on disability. The Milbank Quarterly 1989; 67 (3-4) 450-
484.

8. MCgee KH, MClaughlin CE, Ashton HA, Thames JN.

Pharmaceutical care model for elderly patients in South
Carolina. Am J Health-Syst Pharm. 2003; 60:2350-2351

9. National Pharmaceutical Council (NPC). Elderly Patients

Require Individual Pharmaceutical Care White Paper Finds
Efforts to Restrict Drug Options Can Have Negative Health
Outcomes 2003.

10. Hassan AA. Geriatric care and the role of pharmacist.

Professional Pharmacist 2005; 4: 2-4.

11. Leipzig RM, Cumming RG, Tinatti ME Drugs and falls in older
people :a systematic review and meta-analysis II, Cardiac
and analgesic drugs, J Am Geriatrics Society 1999; 47(1), 40-
50.

12. Goodman LS, Goodman and Gilman's The Pharmacological

Basis of Therapeutics, 7th ed. New York MacMillan, 1980:1-7,
28.

13. Osol A, Remington's Pharmaceutical Sciences, 17th ed.

Eaton, PA: Mack; 1985: 655-656, 728-730, 762-763.
 CHAPTER THIRTEEN

PAEDIATRIC PHARMACEUTICAL CARE

Azuka C Oparah

Learning Objectives

At the end of this chapter, you should be able to:

i. Define pharmaceutical care in relation to the paediatric

population
ii. Justify the need for pharmaceutical care in paediatric patients
iii. Discuss peculiar pharmaceutical care activities in paediatrics,
such as paediatric dosage, medication use and administration,
off-label medications, and drug information.
iv. Apply the steps in providing pharmaceutical care to the
paediatric population.

Introduction
Modern medicines are effective and specific in action. Of all modern
therapeutic treatments available, only medicines are primarily self-
administered. Success depends upon the active participation of patients
and objective information if they are to derive maximum therapeutic
benefit and avoid unwanted side effects from courses of treatment. This
ensures that both patient care and economic aspects are considered
and are correctly balanced in the interests of the patient. Patient care
consists of integrated domains of care, including medical care, nursing
care, and pharmaceutical care.1
The paediatric population represents a heterogeneous group consisting
of infants (birth-1 year), and children (1-12 years). Neonates are those
aged from birth-4 weeks. Paediatric pharmacy is relatively new and
hence paediatric pharmaceutical care.

What is paediatric pharmaceutical care?

Paediatric pharmaceutical care is pharmaceutical care applied in the
paediatric population. PC is the responsible provision of
pharmacotherapy for the purpose of achieving definite outcomes that
improve or maintain a patient's quality of life. It is a collaborative process
that aims to prevent or identify and solve medicinal product and health
related problems. This is a continuous quality improvement process for
1
the use of medicinal products.
Pharmaceutical care in the adult population provides new thinking to
pharmacy practice and it aims to reduce the burden of drug therapy
problems. The paediatric population is a more vulnerable group than the
adults. Though this population suffers similar adverse drug reactions as
in adults, the prevalence is higher and detection of adverse drug reaction
in children is more difficult because infants cannot communicate their
problems and hence the health behaviour is dependent on the mother.
Furthermore, as a result of immature organ systems, there is high
variability in pharmacodynamic and pharmacokinetic profiles of drugs.
Changes that occur with age include volume of distribution, protein
binding, metabolism and renal excretion, muscle mass and fluid
requirements. Disease-specific conditions that might affect drug choice
or administration include pharmacogenetic variations such as G6PD
deficiency, short-gut syndrome and lactose intolerance.

Paediatric pharmaceutical care activities

Prior to the delivery of pharmaceutical care, the pharmacist should
ensure that the paediatric patient has received the relevant medicines
and appropriate drug information. These pose challenges to paediatric
pharmaceutical care for the following reasons:

Paediatric dosage
One of the challenges in paediatric pharmacy practice is providing a
drug product that is suitable for administration to infants and small
children, because many commercial products are not. This may entail
preparing a liquid formulation from a solid dosage form or instructing the
caregiver on how to extract the contents out of a liquid-containing
capsule as well as improving the palatability of the formulations and
splitting of single dosage units can lead to a reduction in drug effect and
increase in toxicity.

Dosage calculation errors are the most common type ofmedication error
encountered in paediatric pharmacy practice. It is imperative that the
pharmacist verifies the dosages for all medication orders with
appropriate dosage references. Establishing basic procedures for the
processing of paediatric medication orders can reduce the risk for
2
medication errors.
A lack of availability of commercially prepared dosage forms, combined
with the documented risk of calculation errors, requires the use of
comprehensive unit dose drug distribution systems and intravenous
admixture services for paediatric patients. Appropriate dosage
standardization in both oral and parenteral drug distribution systems
3
may facilitate the provision of the services.

Medication use and administration

The fear of receiving an injectable medication is often paramount on a
young child's mind when seen in a clinic setting or upon hospital
admission. When possible such as non-emergency cases, the potential
for this discomfort should be addressed with the patient and caregivers.
Medication products (local anaesthetics) are available for this use.
These products should be readily available and offered to children and
caregivers. Nondrug methods to reduce discomfort and anxiety may also
be helpful and they should additionally be offered to children and
4
caregivers when feasible.

Off-label medications

Few medications routinely prescribed for children have actually been

studied for paediatric use. Off-label drug use ranges from 25% of
prescriptions in a study conducted in hospital wards, to 90% on a
5
neonatal intensive care unit. Medications that are safe for adults may
have detrimental effects on children. However, the trend of forgoing
paediatric drug research continues. The lack of paediatric data leads to
"off-label" prescribing by health care providers. This is a situation
whereby children are commonly treated with drugs that have not been
approved for paediatric use. The continued “off-label” use of medications
by practitioners for paediatric clients can lead to dangerous outcomes.
Examples of poor outcomes due to the absence of paediatric data
include tetracycline-induced dental dysplasia and neonatal deaths due
6
to chloramphenicol-induced “gray baby” syndrome. Other instances of
paediatric side effects have included colonic strictures in paediatric
cystic fibrosis patients receiving high-dose pancreatic enzymes and
7
kernicterus from sulfa drugs.
It is estimated that approximately 80% of drugs approved by the FDA
contain a labelling disclaimer for children. Every pharmacist should strive
to familiarize themselves with the common “off-label” use of drugs and
must decide what is safest for the patient depending on community
standards and practices. Pharmacists are required to counsel patients
about adverse effects and precautions. How does a pharmacist
accurately discuss paediatric implications with a family when the drug
8
has not been researched in controlled paediatric studies?.

Drug Information
Drug information services should provide the pharmacist practicing in
the paediatric setting with information unique to the paediatric
population. References should include paediatric medical texts and
current information on paediatric dosages, extemporaneous
formulations, drug compatibilities and stability, poison control, and drug
effects during pregnancy and lactation. Drug information should be
available in areas where decisions are being made about drug therapy.
Literature supporting the use of drugs for unlabeled uses in paediatric
3
patients should also be available.

Pharmacists should provide other health care professionals with

information on new and investigational drugs, adverse effects of and
contraindications to drug therapy, compatibility and stability
information, dosage computations, pharmacokinetics, and drug
interactions. This may be accomplished through educational
presentations, seeing patients in conjunction with other care- givers
(ground ward round), and printed materials (e.g., newsletters).
Examples of references include, but not limited to the Nelson Textbook
of Paediatrics, Neonatology, Pathophysiology and Management of the
Newborn, the Neofax, the Paediatric Dosage Handbook, the Harriet
Lane Handbook, the Teddy Bear Book: Paediatric Injectable Drugs, and
4
Drugs in Pregnancy and Lactation.

Providing pharmaceutical care to the paediatric population

Providing pharmaceutical care to the paediatric population follows the
same systematic step wise approach. However, there are some
peculiarities. Pharmaceutical care is patient-centered and the
pharmacist is expected to interact with one patient at a time. Depending
on the age of the paediatric patient, a professional relationship may be
established directly with them or with their guardians or both. Outcome
assessment in the paediatric population should focus on clinical and
economic domains since children often cannot clearly report their state
of well being; humanistic outcomes are patient reported. A follow-up
indicates the need to modify care plans and lessons for the future.

Orientation, training, and staff development programs for pharmacists

providing services to paediatric patients should emphasize dosage
calculations, dosage-form selection appropriate to the patient's age and
condition, and specialized drug preparation and administration
techniques. Pharmacists should be familiar with the pharmacokinetic
and pharmacodynamic changes that occur with age. Sensitivity to the
nature, frequency, and severity of medication-related errors in the
paediatric population is important in paediatric pharmaceutical care.

Key Learning Points

· The paediatric population represents a heterogeneous group
consisting of infants (birth-1 year), and children (1-12 years).
Neonates are those aged from birth-4 weeks. Paediatric
pharmacy is relatively new and hence paediatric
pharmaceutical care.

· Paediatric pharmaceutical care is pharmaceutical care applied

in the paediatric population.

· The paediatric population is a more vulnerable group than the

adults.
 · The population suffers similar adverse drug reactions as in
adults, the prevalence is higher and detection of adverse
drug reaction in children is more difficult because infants
cannot communicate their problems.

· This age group shows high pharmacodynamic,

pharmacokinetic and pharmacogenetic variability.

· Challenges of paediatric pharmaceutical care include:

ü Paediatric dosage
ü Medication use and administration
ü Off-label medications
ü Drug Information

· Providing pharmaceutical care to the paediatric population

follows the same systematic step wise approach but there are
some peculiarities.

References

1. FIP (1998) Statement of professional standards pharmaceutical

care.

2. Young SL (1996). Providing Pharmaceutical Care to the Pediatric

Patient. Journal of Pharmacy Practice, 9(1): 3-13 (1996).
3. American Society of Hospital Pharmacists. ASHP Statement on the
use of medications for unlabeled uses. Am J Hosp Pharm. 1992;
49:20068.)

4. Paediatric Pharmacy Advocacy Group (PPAG)- Comments on

ASHP Guidelines on
Providing Paediatric Pharmaceutical Services, 2005.

5. Baber and Pritchard, (2003). Dose estimation for children. Br J Clin

Pharmacol. 56(5): 489493.
6. Cote CJ, Kauffman RE, Toendale GJ, Lambert, GH. Is the
therapeutic orphan about to be adopted? Paediatrics 1996;98:118-
12.

7. Fed Regist: Department of Health and Human Services:

Regulations requiring manufacturers to assess the safety and
effectiveness of new drugs and biological products in paediatric
patients. Washington, DC: U.S. Government Printing Office,
August, 1997.

8. Rapkin K R (Paediatric "Off-Label" Prescribing: What Every APN

Should Know . The Internet Journal of Advanced Nursing Practice.
1999 Volume 3 Number 1)
 CHAPTER FOURTEEN

PHARMACEUTICAL CARE IN HYPERTENSION

Azuka C Oparah

Learning Objectives

At the end of this chapter, you should be able to:

i. Define hypertension and classify it based on the JNC 7

guideline
ii. Outline the goals of antihypertensive therapy
iii. Explain patient focused interventions in hypertension
iv. Discuss the rationale for pharmacotherapeutic options in the
evidence-based management of hypertension
v. List pharmaceutical care outcomes in hypertension
vi. Write a pharmaceutical care plan for hypertension

Introduction
Blood pressure (BP) is the pressure at which the heart pumps blood
through the blood vessels. There are two components of blood pressure:
the resistance and volume components, and hence, BP = total peripheral
resistance x cardiac output (heart rate x stroke volume = cardiac output)
Hypertension or the preferred term high blood pressure is a common
cardiovascular disease and risk factor to other cardiovascular diseases
worldwide. Hypertension affects approximately 50 million individuals in
the United States and approximately 1 billion worldwide. As the
population ages, the prevalence of hypertension will increase even
further, unless broad and effective preventive measures are
implemented. Recent data from the Framingham Heart Study suggest
that individuals who are normotensive at age 55 have a 90 percent
lifetime risk for developing hypertension. The relationship between BP
and risk of CVD events is continuous, consistent, and independent of
other risk factors. The higher the BP, the greater is the chance of heart
attack, heart failure, stroke, and kidney disease.

Definition and classification

Hypertension is the persistent elevation of arterial blood pressure
(diastolic and or systolic) equal to or above 140/ 90 mmHg (BP = 140/90
mmHg) in an adult of 18 years or above. The Seventh Report of the Joint
National Committee on Prevention, Detection, and Treatment of High
Blood Pressure (JNC 7) classification of BP for adults ages 18 and older,
based on the average of two or more properly measured, seated BP
readings on each of two or more office visits is given in Table 14.1:

Table 14 .1 Classification of blood pressure for adults1

Blood Pressure Systolic BP Diastolic BP

Normal < 120 mmHg and < 80 mmHg
Prehypertension 120 – 139 mmHg or 80 – 89 mmHg
Stage 1 140 – 159 mmHg or 90 – 99 mmHg
Stage 2 – 160 mmHg
< or – 100 mmHg
<

Etiology
In 95 % or the majority of the cases, the cause of the high blood pressure
is unknown. This class is referred to as primary or idiopathic
hypertension. Some cardiovascular risk factors (modifiable and non-
modifiable) have been identified in primary hypertension and they are
shown below. Some 5 % or minority of the cases of hypertension can be
traced to an identifiable cause. This class is referred to as secondary
hypertension and its possible causes are indicated below:
Risk factors in primary hypertension
• Hypertension
• Cigarette smoking
• Obesity (body mass index = 30 kg/m2)
• Physical inactivity
• Dyslipidemia
• Diabetes mellitus
• Microalbuminuria or estimated GFR < 60 mL/min
• Age (older than 55 for men, 65 for women)
• Family history of premature cardiovascular disease
• (men under age 55 or women under age 65)
• Salt intake
• Stress
Identifiable causes in secondary hypertension
• Sleep apnea
• Drug-induced or related causes
• Chronic kidney disease
• Primary aldosteronism
• Renovascular disease
• Chronic steroid therapy
• Cushing's syndrome
• Pheochromocytoma
• Coarctation of the aorta
• Thyroid or parathyroid disease

Drugs associated with secondary hypertension

Prescription drugs
• Corticosteroids
• Estrogens (usually oral contraceptives with high estrogenic
activity)
• Nonsteroidal anti-inflammatory drugs, a COX-2 inhibitors
• Phenylpropanolamine and analogues
• Cyclosporine and tacrolimus
 • Erythropoetin
• Sibutramine
• Antidepressants (especially venlafaxine), bromocriptine,
buspirone,
• carbamazepine, clozapine, desfulrane, ketamine,
metoclopramide
• Clonidine (rebound hypertension)

Hard Drugs and Other Natural Products

• Cocaine
• Marihuana ”herbal ecstasy,” and other phenylpropanolamine
analogues
• Nicotine
• Anabolic steroids and withdrawal
• Narcotic withdrawal
• Methylphenidate, phencyclidine, ketamine, ergotamine and
other
• Ergot-containing herbal products, St. John's wort
Food Substances
• Sodium
• Ethanol
• Licorice
• Tyramine-containing foods if taking a monoamine oxidase
inhibitor

Chemical Elements and Other Industrial Chemicals

Lead, mercury, thallium and other heavy metals, lithium
Signs and Symptoms

Hypertension is usually found incidentally - "case finding" - by

healthcare professionals during a routine checkup. The only test for
hypertension is a blood pressure measurement. Hypertension in
isolation usually produces no symptoms (“silent killer”) although some
people report headaches, fatigue, dizziness, blurred vision, facial
flushing or tinnitus.

Malignant hypertension (or accelerated hypertension) is distinct as a

late phase in the condition, and may present with headaches, blurred
vision and end-organ damage.

Hypertension is often confused with mental tension, stress and anxiety.

While chronic anxiety and/or irritability is associated with poor outcomes
in people with hypertension, it alone does not cause it. Accelerated
hypertension is associated with somnolence, confusion, visual
disturbances, and nausea and vomiting (hypertensive encephalopathy).
Hypertensive urgencies and emergencies
Hypertensive crises are clinical situations where BP values are greater
3-4
than 180/120mmHg. They are categorized as either a hypertensive
emergency or hypertensive urgency. Hypertensive emergencies are
extreme elevations in BP that are accompanied by acute or progressing
target-organ damage. Examples of acute target-organ injury include
encephalopathy, intracranial hemorrhage, acute left ventricular failure
with pulmonary edema, dissecting aortic aneurysm, unstable angina,
and eclampsia or severe hypertension during pregnancy. Hypertensive
emergencies require an immediate but gradual reduction in BP over a
period of several minutes to several hours using intravenous
antihypertensive agents. A reasonable goal is to gradually lower DBP to
<110 mm Hg.7 Abrupt BP reductions should be avoided. Hypertensive
urgencies are high elevations in BP without acute or progressing target-
organ injury. These situations require BP reductions with oral
antihypertensive agents to stage 1 values over a period of several hours
to several days.
Complications of hypertension
Uncontrolled high blood pressure can damage target organs of the body
and this damage manifests as follows:

Target organ damage in hypertension

Heart
Left ventricular hypertrophy (cardiomegaly)
Angina or prior myocardial infarction
Prior coronary revascularization
Heart failure
Brain
Stroke (Cerebrovascular accident)
· Transient ischemic attack
Kidney
· Chronic kidney disease
· Chronic renal failure
Eye
· Retinopathy

Peripheral arterial disease

Treatment

Goal of therapy
The ultimate public health goal of antihypertensive therapy is the
reduction of cardiovascular and renal morbidity and mortality. Since most
persons with hypertension, especially those age > 50 years, will reach
the DBP goal once SBP is at goal, the primary focus should be on
achieving the SBP goal. Treating SBP and DBP to targets that are <
140/90 mmHg is associated with a decrease in CVD complications. In
patients with hypertension and diabetes or renal disease (estimated
GFR < 60 mL/min, serum creatinine > 1.3 mg/dL in women or > 1.5
mg/dL in men, or albuminuria > 300 mg/day or = 200 mg/g creatinine),
the BP goal is < 130/80 mmHg.

Patient focused interventions

Patients should receive adequate education on the under listed lifestyle
management themes. Table 14.2 presents the outcomes of lifestyle
management measures.
· Education the condition is high blood pressure and
should not be confused with mental tension, stress and
anxiety. It is asymptomatic so the patients appear healthy
and look like any other person. With appropriate
management, hypertensive patients can live good
quality life. The patient plays an active role through
adherence to drug therapy and lifestyle changes and
treatment is life-long.

· Weight reduction and regular aerobic exercise (e.g.

jogging, brisk walking) are recommended as the first steps in
treating mild to moderate hypertension. Regular mild exercise
improves blood flow and helps to reduce resting heart rate and
blood pressure. These steps are highly effective in reducing
blood pressure, although drug therapy is still necessary for many
patients with moderate or severe hypertension to bring their
blood pressure down to a safe level.

· Reducing sodium (salt) diet is proven very effective: it

decreases blood pressure in about 60% of people. Many people
choose to use a salt substitute to reduce their salt intake.

· Additional dietary changes beneficial to reducing blood

pressure include the DASH diet (Dietary Approaches to Stop
Hypertension), which is rich in fruits and vegetables and low fat
or fat-free dairy foods. In addition, an increase in daily calcium
intake has also been shown to be highly effective in reducing
blood pressure. Fruits, vegetables, and nuts have the added
benefit of increasing dietary potassium, which theoretically can
offset the effect of sodium and act on the kidney to decrease
blood pressure.

· Cessation tobacco smoking and moderation of alcohol

have been shown to lower blood pressure. The exact
mechanisms are not fully understood, but blood pressure
(especially systolic) always transiently increases following
alcohol and/or nicotine consumption. Besides, abstention from
cigarette smoking is important for people with hypertension
because it reduces the risk of many dangerous outcomes of
hypertension, such as stroke and heart attack. Note that coffee
drinking (caffeine ingestion) also increases blood pressure
transiently.

· Relaxation therapy, such as meditation, that reduces

environmental stress, high sound levels and over-illumination
can be an additional method of ameliorating hypertension.
Biofeedback is also used particularly device guided paced
breathing. Obviously, the effectiveness of relaxation therapy
relies on the patient's attitude and compliance.
 Table 14.2: Outcomes of lifestyle management1

Modification Recommendation Approximate SBP Reduction

(Range)
Weight reduction Maintain normal body weight 5 20 mmHg/10 kg weight loss
(body mass index 18.5 24.9
kg/m2).

Adopt DASH eating plan Consume a diet rich in fruits, 8 14 mmHg

vegetables, and low fat dairy
products with a reduced content
of saturated and total fat.

Dietary sodium reduction Reduce dietary sodium intake to 2 8 mmHg

no more than 100 mmol per day
(2.4 g sodium or 6 g sodium
chloride).

Physical activity Engage in regular aerobic 4 9 mmHg

physical activity such as brisk
walking
(at least 30 min per day, 3-5
days of the week).

Moderation of alcohol Limit consumption to no more 2 4 mmHg

consumption than 2 drinks (1 oz or 30 mL
ethanol; e.g., 24 oz beer, 10 oz
wine, or 3 oz 80-proof whiskey)
per day in most men and to no
more than 1 drink per day in
women and lighter weight
persons.

Drug focused interventions

There are excellent clinical outcome trial data proving that lowering BP
with several classes of drugs, including angiotensin converting enzyme
inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers
(BBs), calcium channel blockers (CCBs), and thiazide-type diuretics, will
all reduce the complications of hypertension. Thiazide-type diuretics
have been the basis of antihypertensive therapy in most outcome trials.
In these trials, including the recently published Antihypertensive and
Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
diuretics have been virtually unsurpassed in preventing the
cardiovascular complications of hypertension.
The exception is the Second Australian National Blood Pressure trial,
which reported slightly better outcomes in White men with a regimen that
began with an ACEI compared to one starting with a diuretic. Diuretics
enhance the antihypertensive efficacy of multidrug regimens, can be
useful in achieving BP control, and are more affordable than other
antihypertensive agents. Despite these findings, diuretics remain
underutilized. Thiazide-type diuretics should be used as initial therapy
for most patients with hypertension, either alone or in combination with
one of the other classes (ACEIs, ARBs, BBs, CCBs) demonstrated to be
beneficial in randomized controlled outcome trials.
The guidelines for selecting drugs in the treatment of hypertension are
shown in Table 14.3.
5
Table 14.3 Guidelines for selecting treatment of hypertension
Drug Compelling Possible Compelling Possible
indications indications contraindications contraindications
low dose thiazides - heart failure - diabetes mellitus - gout - dyslipidaemia
and thiazide-like - elderly patients - symptomatic
drugs orthostatic
- systolic
hypertension hypotension

beta blockers - angina - pregnancy - asthma and COPD - dyslipidaemia

- acute myocardial - diabetes mellitus - heart block - athletes and
infarct physically active
- tachyarrhythmias patients
- heart failure - PVD

ACEI - heart failure - pregnancy

- left ventricular - hyperkalaemia
dysfunction - bilateral renal
- acute myocardial artery stenosis
infarct
- diabetes mellitus
calcium channel - angina - PVD - heart block congestive heart
blockers - elderly patients failure
- systolic
hypertension
alpha-blockers - prostatic - glucose - orthostatic
hypertrophy intolerance hypotension
- dyslipidaemia
angiotensin II - ACEI cough - heart failure - pregnancy
receptor blockers - type 2 diabetes - bilateral renal
artery stenosis
- hyperkalaemia

ACEI = Angiotensin converting enzyme inhibitor; PVD = Peripheral vascular

disease; COPD = Chronic obstructive pulmonary disease.
Thiazides

In general, low-dose thiazides or thiazide-like diuretics should be

considered first line for the majority of uncomplicated patients.

Bendrofluazide 2.5 mg OR Chlorthalidone 12.5 mg orally daily OR

Hydrochlorothiazide 12.5 to 25 mg daily OR Indapamide 2.5 mg orally,
daily (or 1.5 mg as a slow-release formulation)

Loop diuretics should not be used as chronic therapy for hypertension

except in severe refractory disease in combination with first-line drugs.
Indapamide is a reasonable alternative to thiazides but trial evidence of
an effect on cardiovascular event rates is lacking.

Measure sodium and potassium after 3 to 6 weeks of diuretic therapy.

Hypokalaemia and hyponatraemia are uncommon at the above doses. If
necessary, the diuretics may be given in combination with potassium
supplements or with a potassium-sparing diuretic such as amiloride 2.5
to 5 mg orally, daily (combination products are available for this purpose)

Angiotensin converting enzyme inhibitors (ACEIs)

ACE inhibitors are particularly useful in patients with systolic (and

probably diastolic) dysfunction and/or clinical heart failure. ACE
inhibition has also been shown to decrease cardiovascular risk in
patients with high risk due to multiple risk factors, particularly
hypertension and diabetes, or pre-existing vascular disease,
irrespective of the level of blood pressure prior to treatment.

A large number of ACEIs are now available. The benefits are likely to be
class effects. For most patients, it is advisable to measure electrolytes
and creatinine shortly after commencing therapy, especially in renal
disease, diabetes mellitus and the elderly. ACE inhibitors have a range of
desirable or apparently desirable secondary effects (e.g. regression of
left ventricular hypertrophy, preservation of renal function in diabetics),
but no clear incremental outcome benefit compared to other agents.
However, the combination of low doses of an ACE inhibitor and a
thiazide diuretic (combination products are available) is highly effective
in blood pressure lowering, Table 14.4.
5
Table 14.4 Dosing regimens for ACEI in hypertension

Drug Patients not Patients Maintenance dose

sensitive to sensitive to
ACEI initial ACEI - initial
dose dose

Captopril 12.5 mg twice 6.25 mg daily 25 to 75 mg twice daily

daily

Enalapril 5 mg daily 2.5 mg daily 5 to 40 mg daily

Fosinopril 10 mg daily 5 mg daily 5 to 40 mg daily

Lisinopril 2.5 mg daily 2.5 mg daily 5 to 40 mg daily

Perindopril 2 mg daily 2 mg daily 4 to 8 mg daily

Quinapril 5 mg daily 2.5 mg daily 5 to 40 mg daily

Ramipril 2.5 mg daily 1.25 mg daily 5 to 10 mg daily

Trandolapril 1 mg daily 0.5 mg daily 1 to 4 mg daily

Angiotensin II receptor blockers

Angiotensin II receptor blockers probably have similar effects to ACEI in

heart failure, after myocardial infarction, in dyslipidaemia and in renal
disease. Further outcome data in heart failure and other indications are
awaited.

Angiotensin II receptor blockers have been shown to be well tolerated

and the adverse effect of cough seen with ACEI is not common. As with
ACE inhibitors, measure electrolytes and creatinine in all patients 1 to 2
weeks after commencing therapy. This is especially important in patients
with renal disease, in patients with diabetes mellitus, and in the elderly:
candesartan 4 to 16 mg orally, daily OR irbesartan 75 to 300 mg orally,
daily OR eprosartan 400 to 800 mg orally, daily OR telmisartan 40 to 80
mg orally, daily.

Calcium channel blockers

Drugs within the group known as calcium channel blockers vary in their
properties, depending particularly on whether they are dihydropyridines
or nondihydropyridines. Neither subclass has particular advantages in
outcomes compared to diuretics.

Nondihydropyridine calcium channel blockers have negative cardiac

inotropic and chronotropic actions as well as modest vasodilatation.
Diltiazem controlled-release 180 to 360 mg orally, daily OR verapamil
sustained-release 160 to 480 mg orally, daily

Short-acting dihydropyridine calcium channel blockers may have

adverse effects on mortality in patients with coronary heart disease,
especially in the context of acute coronary syndromes. Hence longer-
acting preparations that may be given once daily are preferred.
Dihydropyridine calcium channel blockers have a predominantly
vasodilator action: amlodipine 5 to 10 mg orally, daily OR felodipine
sustained-release 2.5 to 10 mg orally, daily OR nifedipine controlled-
release 30 to 60 mg orally, daily OR lercanidipine 10 to 20 mg orally,
daily.

Beta-adrenoceptor blockers

These drugs are particularly useful in patients with both coronary heart
disease and hypertension, and also in patients with heart failure. Use
atenolol 25 to 100 mg orally, daily OR metoprolol 50 to 100 mg orally,
twice daily.

Alternative drugs
Alpha-blockers

Prazosin 0.5 mg orally, daily, up to maintenance dose of 1 to 10 mg daily.

Prazosin has a first-dose effect causing postural hypotension, so it is
important to commence or resume therapy at the lowest dose and warn
patients of this effect.

Centrally acting antiadrenergic agent therapy

Methyldopa 125 mg orally, twice daily, up to 500 mg 3 times daily OR

Clonidine 75 to 150 micrograms orally, twice daily. Clonidine should not
be stopped suddenly as there is a risk of severe rebound hypertension.

Direct acting vasodilators

Hydralazine 12.5 mg orally, twice daily, up to 150 mg per day in divided

doses. Higher doses may be used in fast acetylators only.

Treatment of chronic hypertension in pregnancy

It is important to differentiate preeclampsia from chronic, transient, and
gestational hypertension. Preeclampsia can lead rapidly to life-
threatening complications for both mother and fetus and usually
presents after 20 weeks' gestation in primigravid women.
The diagnosis of preeclampsia is based on the appearance of
hypertension (> 140/90 mmHg) after 20 weeks' gestation with
proteinuria. Chronic hypertension presents before 20 weeks' gestation.
It is controversial whether treating elevated BP in patients with chronic
hypertension in pregnancy is beneficial. Women with chronic
hypertension prior to pregnancy can develop preeclampsia. Table 14.5
summarizes drug treatment of chronic hypertension in pregnancy.

Table 14.5 Treatment of Chronic Hypertension in Pregnancy2

Drug/Class Comments
Methyldopa Preferred agent based on long-term follow-up
data supporting safety
â-Blockers Generally safe, but intrauterine growth
retardation reported
Labetolol Increasingly preferred over methyldopa
because of fewer side effects
Clonidine Limited data available
Calcium channel
Blockers Limited data available; no increase in major
teratogenicity with exposure

Diuretics Not first-line agents but probably safe in low

doses
ACE inhibitors &
angiotensin II
receptor blockers Contraindicated; major teratogenicity
reported with exposure (fetal toxicity and
Death)
Pharmaceutical care outcomes

Pharmaceutical care as an essential element in patient care addresses

the question of how well medicines are prescribed and used in any given
patient population. Pharmaceutical care optimizes drug use in
healthcare delivery systems through identification, prevention, and
resolution of potential or actual drug therapy problems.6
In primary care, pharmaceutical care is focused on the management of
common clinical conditions. Hypertension is a good example of chronic
disease management and repeat prescribing, a common situation in
which patients often have more regular contact with their pharmacists
than with their physicians or any other health manager.7
A convincing evidence base that links the successful management of
hypertension to increased survival, reduced morbidity and, therefore
improved quality of life has been established. It therefore follows that
attention to the drug therapy problems (patient concordance, recognition
of unwanted effects, optimization of dosage, and appropriate
individualization of treatment) can be expected to improve outcomes.7

Why is pharmaceutical care needed in hypertension

· Hypertension is a chronic condition
· Prevalence/ disease burden is high in the society
· Known interventions improve outcomes
 Pharmaceutical care outcomes in hypertension
· Maintain target blood pressure
· Improve patient adherence to medication, clinic
appointments, and lifestyle modifications
· Improve quality of life
· Improve disease knowledge and its management
· Develop positive attitudes toward hypertension
· Improve patient satisfaction with treatment and
pharmacy
· Reduce adverse drug reactions
· Reduce cost of medication

Table 14.6 Select monitoring for antihypertensive medication2

Class Parameters
Diuretics Blood pressure,
BUN at 1-2 weeks ( 8-25 mg/dl )/serum
creatinine (0.5-1.3 mg/dl),
Serum electrolytes at 3-6 weeks,
(mEq/L):
Potassium (3.5- 5.0),
Sodium (135- 145),
Uric acid (for thiazides) (3.0- 7.0 mg/dl)
Aldosterone
Antagonists Blood pressure, BUN/serum creatinine,
serum potassium
â-Blockers Blood pressure, heart rate
ACE inhibitors Blood pressure, BUN/serum creatinine,
serum potassium
Angiotensin II
receptor
blockers Blood pressure, BUN/serum creatinine,
serum potassium
Calcium channel
Blockers Blood pressure; heart rate

Specific patient counselling points

• Diuretics should be taken in the morning and afternoon if a
second dose is needed to avoid nocturnal diuresis
• ACEIs may produce disturbing dry cough especially in smokers
and the obese
• Methyldopa may cause postural hypotension so patients should
not get up suddenly from bed
• Cardioselective â-Blockers, Mixed á- and â-blockers and
clonidine cause rebound hypertension and should not be
discontinued abruptly

Key Learning Points

· High blood pressure is a major public health chronic disease as
well as cardiovascular risk factor in several other cardiovascular
conditions worldwide.
· It is now known that in people 50 years or older, systolic
hypertension represents a greater risk than diastolic blood
pressure.

· A goal BP of less than 140/90mmHg is appropriate for most

patients. For patients with diabetes or chronic kidney disease, a
goal BP of less than 130/80 mm Hg is appropriate.
· Lifestyle modifications should be prescribed in all patients with
hypertension and pre-hypertension. However, they should
 never be used as a replacement for antihypertensive drug
therapy in patients with hypertension.
· Thiazide diuretics are first-line agents for the management of
hypertension in most patients. This recommendation is
supported by clinical trials showing reduced morbidity and
mortality with these agents.
· ARBs, as with ACE inhibitors, measure electrolytes and
creatinine in all patients 1 to 2 weeks after commencing therapy.
This is especially important in patients with renal disease, in
patients with diabetes mellitus, and in the elderly
· All patients with diabetes and hypertension should be managed
with either an angiotensin-converting enzyme (ACE) inhibitor or
an angiotensin II receptor blocker (ARB), typically in combination
with one or more other antihypertensive agents.
· Most patients require combination therapy to achieve goal BP
values. Combination regimens should include a diuretic,
preferably a thiazide. If a diuretic was not the first drug, itshould
be the second drug add-on therapy.

References
1. The Seventh Report of the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment of High
Blood Pressure. (JNC 7, 2003).
2. DiPiro JT et al., (Ed. 2005). Pharmacotherapy- A
Pathophysiologic Approach, McGraw Hill Medical Publishing
Division.
3. Kaplan NM. Kaplan's Clinical Hypertension, 8th ed.
Philadelphia, Lippincott Williams & Wilkins, 2002:1550.
4. Bales A. Hypertensive crisis: How to tell if it's an emergency or
an urgency. Postgrad Med 1999;105:119126, 130.
5. Therapeutic Guidelines of Australia July 2007 version.
6. Strand LM, Morley PC, Cipolle RJ, Ramsey R, Lamsam GD
(1990). Drug-related problems: their structure and function.
DICP Ann Pharmacother; 24:1093-1097.
7. Hudson S, Mc Anaw J, McGlynn S and Boyter A (1998).
Essential hypertension. Pharm J; 260 (6986): 411-417.
 CHAPTER FIFTEEN

PHARMACEUTICAL CARE IN CARDIAC FAILURE

Azuka C Oparah and Evbade Arigbe-Osula

Learning Objectives

At the end of this chapter, you should be able to:

i. Define heart failure and explain the compensatory mechanisms

in cardiac failure

ii. Outline the signs and symptoms of cardiac failure

iii. Discuss lifestyle changes and the pharmacotherapy of cardiac

failure

iv. List drugs that can worsen cardiac failure

v. Outline outcomes and monitoring indices in the pharmaceutical

care of patients with cardiac failure.

Introduction

The heart performs a mechanical pumping function. The inability of the

heart to pump sufficient blood to meet tissue metabolic requirements is
referred to as heart failure. Heart failure may be acute (high output) or
chronic (low output). It is not to be confused with "cessation of
heartbeat", which is known as asystole, or with cardiac arrest, which is
the cessation of normal cardiac function with subsequent hemodynamic
collapse leading to death. Because not all patients have volume
overload at the time of initial or subsequent evaluation, the term "heart
failure" is preferred over the older term "congestive heart failure". When
the heart is placed under increased load, there are several
compensatory mechanisms that occur to try to maintain adequate heart
function. These are often successful for quite a while. When they are no
longer successful, heart failure ensues.

Compensatory mechanisms in heart failure

Autonomic nerves

Increased sympathetic adrenergic activity and reduced vagal activity to

the heart: The most immediate compensatory mechanism to maintain
cardiac output is sympathetic nervous system output. Any decrease in
blood flow will trigger the release of adrenaline and noradrenaline, which
serve to increase heart rate and the force of contraction. All of these
effects help to maintain adequate perfusion of tissues, but they also
increase myocardial oxygen consumption and ultimately lead to
worsening of heart failure.

Cardiac

Frank Starling mechanism: Here the contractile myofilaments tend to

overlap and there is ventricular hypertrophy with or without chamber
dilatation due to fluid retention. Increased venous return increases the
ventricular filling (end-diastolic volume) and therefore preload, which is
the initial stretching of the cardiac myocytes prior to contraction.
Myocyte stretching increases the sarcomere length, which causes an
increase in force generation. This mechanism enables the heart to eject
the additional venous return, thereby increasing stroke volume. This
phenomenon is described in mechanical terms by the length-tension
and force-velocity relationships for cardiac muscle. Increasing preload
increases the active tension developed by the muscle fiber and
increases the velocity of fiber shortening at a given afterload and
inotropic state.
Hormones

Activation of the renin angiotensin - aldosterone system, increased

release vasopressin (antidiuretic hormone), circulating catecholamines,
and natriuretic peptides: The net effect of these hormones is to produce
arterial vasoconstriction in order to maintain arterial pressure, venous
constriction (to increase venous pressure), and increased blood volume.
When blood flow to the kidneys is reduced, the kidneys are stimulated to
save fluid. In addition, renin is released which leads to the production of
Angiotensin II, a potent vasoconstrictor that causes the release of
aldosterone. Angiotensin II and aldosterone both lead to sodium and
water retention. Initially the additional fluid does increase cardiac output.
However, the overall effect is deleterious as the heart now has even
more fluid to pump.

Signs and symptoms

Symptoms

The symptoms depend largely on the side of the heart which is failing
predominantly. If both sides are functioning inadequately, symptoms and
signs from both categories may be present.

The left ventricle pumps blood from the lungs to the organs, left
ventricular failure leads to congestion in the lungs, as well as reduced
supply of blood to the tissues. The predominant respiratory symptom is
dyspnea on exertion or in severe cases at rest. Other symptoms include
easy fatigueability, orthopnea, paroxysmal nocturnal dyspnea which is a
nighttime attack of severe breathlessness (cardiac asthma), usually
several hours after going to sleep. Poor circulation to the body leads to
dizziness, confusion, diaphoresis and cool extremities at rest.

The right ventricle pumps blood returned from the tissues to the lungs for
oxygenation, hence, failure of the right ventricle leads to congestion of
peripheral tissues. This may lead to peripheral edema (anasarca) and
nocturia (frequent nighttime urination when the fluid from the legs is
returned to the bloodstream). In more severe cases, ascites (fluid
accumulation in the abdominal cavity) and hepatomegaly (painful
enlargement of the liver) may develop.

A failing heart may decompensate easily; this may occur as the result of
any intercurrent illness (such as pneumonia), but specifically myocardial
infarction (heart attack), anaemia, hyperthyroidism and arrhythmias.
These place additional strain on the heart muscle, which may cause
symptoms to rapidly worsen. Excessive fluid or salt intake (including
intravenous fluids for unrelated indications), and medication that causes
fluid retention (such as NSAIDs and thiazolidinediones), may also
precipitate decompensation.
Signs

In examining a patient with possible heart failure, a health professional

would look for particular signs. General signs indicating heart failure are
a laterally displaced apex beat or point of maximal impulse (as the heart
is enlarged) and a gallop rhythm (additional heart sounds) in case of
decompensation. Heart murmurs may indicate the presence of valvular
heart disease, either as a cause (e.g. aortic stenosis) or as a result (e.g.
mitral regurgitation) of the heart failure.

Predominant left-sided clinical signs are pulmonary edema (abnormal

lung sounds due to fluid accumulation), evidence for pleural effusions
(fluid collection in the pleural cavity), and cyanosis (due to poor
absorption of oxygen by fluid-filled lungs).

Right-sided signs are peripheral edema, ascites and hepatomegaly, an

increased jugular venous pressure and hepatojugular reflux and
parasternal heave. The clinical presentation of heart failure is illustrated
in Table 15.1
Table 15.1 Clinical presentation of heart failure

General

Patient presentation may range from asymptomatic to cardiogenic

shock.

Symptoms

· Dyspnea, particularly on exertion

· Orthopnea
· Paroxysmal nocturnal dyspnea
· Exercise intolerance
· Tachypnea
· Cough
· Fatigue
· Nocturia
· Hemoptysis
· Abdominal pain
· Anorexia
· Nausea
· Bloating
· Ascites
· Mental status changes
· Low personal energy

Signs

• Pulmonary rales
• Pulmonary edema
• S3 gallop
• Pleural effusion
• Cheyne-Stokes respiration
• Tachycardia
Diagnosis

Imaging

Echocardiography is commonly used to support a clinical diagnosis of

heart failure. This modality uses ultrasound to determine the stroke
volume (SV, the amount of blood in the heart that exits the ventricles with
each beat), the end-diastolic volume (EDV, the total amount of blood at
the end of diastole), and the SV in proportion to the EDV, a value known
as the ejection fraction. Normally, the EF should be between 50% and
70%; in systolic heart failure, it drops below 40%. Echocardiography can
also identify valvular heart disease and assess the state of the
pericardium (the connective tissue sac surrounding the heart).
Echocardiography may also aid in deciding what treatments will help the
patient, such as medication, insertion of an implantable cardioverter-
defibrillator or cardiac resynchronization therapy.

Chest X-rays are frequently used to aid in the diagnosis of CHF. In the
compensated patient, this may show cardiomegaly (visible enlargement
of the heart), quantified as the cardiothoracic ratio (proportion of the heart
size to the chest). In left ventricular failure, there may be evidence of
vascular redistribution ("upper lobe blood diversion"), Kerley lines, cuffing
of the areas around the bronchi, and interstitial edema.
Electrophysiology

An electrocardiogram (ECG/EKG) is used to identify arrhythmias,

ischemic heart disease, right and left ventricular hypertrophy, and
presence of conduction delay or abnormalities (e.g. left bundle branch
block).
Blood tests

Blood tests routinely performed include electrolytes (sodium, potassium),

measures of renal function, liver function tests, thyroid function tests, a
complete blood count, and often C-reactive protein if infection is
suspected. A specific test for heart failure is B-type natriuretic peptide
(BNP), which is found to be elevated in heart failure. BNP can be used to
differentiate between causes of dyspnea due to heart failure from other
causes of dyspnea. If myocardial infarction is suspected, various cardiac
markers may be used.
Angiography

Heart failure may be the result of coronary artery disease, and its
prognosis depends in part on the ability of the coronary arteries to supply
blood to the myocardium. As a result, coronary catheterization may be
used to identify possibilities for revascularisation through percutaneous
coronary intervention or bypass surgery.

Classification

There are many different ways to categorize heart failure, including:

· the side of the heart involved, (left heart failure versus right heart
failure or biventricular)

· whether the abnormality is due to contraction or relaxation of the

heart (systolic dysfunction versus diastolic dysfunction)

· whether the abnormality is due to low cardiac output or high

systemic vascular resistance (low-output heart failure versus
high-output heart failure)

The degree of functional impairment conferred by the abnormality (as in

the New York Heart Association functional classification). The classes (I-
IV) are:

· Class I: no limitation is experienced in any activities; there are no

symptoms from ordinary activities.

· Class II: slight, mild limitation of activity; the patient is

comfortable at rest or with mild exertion.
 · Class III: marked limitation of any activity; the patient is
comfortable only at rest.

· Class IV: any physical activity brings on discomfort and

symptoms occur at rest.

Causes and contributing factors to congestive heart failure

Left-sided: hypertension, aortic and mitral Right-sided: pulmonary

valve diseases, aortic coarctation hypertension (e.g. due to
chronic lung disease),
pulmonary or tricuspid
valve disease

May affect both sides: Ischemic heart disease (due to insufficient

vascular supply, usually as a result of coronary artery disease); this
may be chronic or due to acute myocardial infarction, chronic
arrhythmias (e.g. atrial fibrillation), cardiomyopathy of any cause,
cardiac fibrosis, chronic severe anaemia, thyroid disease
(hyperthyroidism and hypothyroidism)

Treatment

Although heart failure is a serious condition that progressively gets worse

over time, certain cases can be reversed with treatment. Even when the
heart muscle is impaired, there are a number of treatments that can
relieve symptoms and stop or slow the gradual worsening of the
condition.

The goals of therapy are to:

· Relieve disabling symptoms and improve quality of life

· Slow disease progression

· Reduce the need for emergency room visits and hospitalization

 · Prolong life

Treating the Underlying Causes

A number of conditions can contribute to heart failure. Treatment of

these other factors may range from surgery or angioplasty to open
clogged blood vessels in patients with coronary artery disease to
medications prescribed to control high blood pressure, diabetes,
anaemia or thyroid disease. In addition, it is particularly important to treat
arrhythmias in patients with heart failure.

Lifestyle changes

Patients with CHF are educated to undertake various non-

pharmacological measures to improve symptoms and prognosis. Such
measures include:

· Moderate physical activity, when symptoms are mild or

moderate; or bed rest when symptoms are severe.

· Weight reduction through physical activity and dietary

modification, as obesity is a risk factor for heart failure and
ventricular hypertrophy.

· Monitor weight - Weight gain of more than 0.9 kg is associated

with admission to the hospital for heart failure

· Sodium restriction excessive sodium intake may precipitate or

exacerbate heart failure, thus a "no added salt" diet (60100 mmol
total daily intake) is recommended for patients with CHF. More
severe restrictions may be required in severe CHF.

· Fluid restriction patients with CHF have a diminished ability to

excrete free water load. They are also at an increased risk of
hyponatremia due to the combination of decreased sodium
intake and diuretic therapy. Generally water intake should be
 limited to 1.5 L daily or less in patients with hyponatremia,
though fluid restriction may be beneficial regardless in
symptomatic reduction.

· Cessation of smoking and avoidance of passive smoking

· Avoiding or limiting caffeine intake.

· Stress reduction

· Moderation of alcohol intake or avoidance

· Regular checkups to monitor the condition.

Medications

There is a significant evidencepractice gap in the treatment of CHF;

particularly the underuse of ACE inhibitors, â-blockers and
aldosterone antagonists, which have been shown to provide mortality
benefit. Treatment of CHF aims to relieve symptoms, maintain a
euvolemic state (normal fluid level in the circulatory system), and to
improve prognosis by delaying progression of heart failure and reducing
cardiovascular risk. Drugs used include: diuretics, vasodilators, positive
inotropes, ACE inhibitors, beta blockers, and aldosterone antagonists
(e.g. spironolactone). It should be noted that while intuitive, increasing
heart function with some drugs, such as the positive inotrope Milrinone,
leads to increased mortality.

Angiotensin-modulating agents

ACE inhibitor (ACEI) is the recommended initial therapy for all patients
with systolic heart failure, irrespective of symptomatic severity or blood
pressure. Asymptomatic patients should also receive an ACEI if there is
significant left ventricular dysfunction (i.e. left ventricular ejection
fraction is < 40 %). ACE inhibitors improve symptoms, decrease
mortality and reduce ventricular hypertrophy. Angiotensin II receptor
antagonist therapy (also referred to as AT1-antagonists or angiotensin
receptor blockers), particularly using candesartan, is an acceptable
alternative if the patient is unable to tolerate ACEI therapy, Table 11.2.

Table 15.2 Dosing regimen for ACEIs in heart failure

Drug Starting dose Target maintenance

dose
Captopril 6.25 mg twice daily 50 mg 3 times daily
Enalapril 2.5 mg daily 10 to 20 mg twice daily
Fosinopril 5 mg daily 20 to 40 mg daily
Lisinopril 2.5 mg daily 20 to 40 mg daily
Perindopril 2 mg daily 4 to 8 mg daily
Quinapril 2.5 mg daily 20 to 40 mg daily
Ramipril 1.25 mg daily 5 to 10 mg daily
Trandolapril 0.5 mg daily 2 to 4 mg daily

Diuretics

Diuretics should be added to ACEI therapy to control congestive

symptoms and signs. Close monitoring of weight, renal function and
electrolytes is required.

Loop diuretics (high-ceiling) are commonly used, particularly for heart

failure of moderate severity: Frusemide 20 to 40 mg orally, daily OR
bumetanide 0.5 to 1 mg orally, daily OR ethacrynic acid 50 mg orally,
daily.

Thiazide and related diuretics (low-ceiling) produce a gradual diuresis

and are effective for mild heart failure: bendrofluazide 2.5 to 5 mg orally,
daily, OR hydrochlorothiazide 25 to 50 mg orally, daily OR chlorthalidone
25 to 50 mg orally, daily OR indapamide 1.5 to 2.5 mg orally, daily

Caution: When thiazide and loop diuretics are combined there is a

considerable synergistic effect and the combination should be reserved
for severe heart failure.

In patients with normal renal function, receiving the combination of ACEI

and diuretic, a potassium-sparing diuretic or potassium supplement will
occasionally be needed: amiloride 5 to 10 mg orally, daily OR potassium
chloride sustained release 600 to 3600 mg orally in divided doses OR
spironolactone 25 to 100 mg orally, daily.

In patients with renal impairment, when diuretics are used with an ACEI,
potassium-sparing diuretic or potassium supplementation is usually not
necessary and may cause life-threatening hyperkalaemia.

If hypokalaemia proves difficult to correct, hypomagnesaemia may be

present. Use magnesium aspartate 1 to 3 g orally, daily in divided doses.

If the response to standard doses of ACEI and diuretic is inadequate,

increase the doses of ACEI and diuretic.

Beta blockers

Until recently, â-blockers were contraindicated in CHF, owing to their

negative inotropic effect and ability to produce bradycardia effects which
worsen heart failure. However, current guidelines recommend â-
blocker therapy for patients with systolic heart failure due to left
ventricular systolic dysfunction after stabilization with diuretic and
ACEI therapy, irrespective of symptomatic severity or blood
pressure. As with ACEI therapy, the addition of a â-blocker can
decrease mortality and improve left ventricular function. Several â-
blockers are specifically indicated for CHF including: bisoprolol,
carvedilol, and extended-release metoprolol.

Patients with systolic heart failure are often very sensitive to beta-
blockers. Major complications include worsening of heart failure, severe
hypotension and bradyarrhythmias. These complications are due to beta
blockade leading to withdrawal of sympathetic nervous system support
for the failing heart. These complications may be minimised by:

· starting therapy with extremely low doses

· increasing the dose very gradually

· monitoring the patient frequently, with daily weighing

· adjusting the dose of other medications such as diuretics and

ACEI to compensate for any tendency to increased heart failure

· avoiding simultaneous addition of vasodilator drugs

· excluding patients with extremely severe heart failure and those

whose heart failure is not well controlled on other therapy.

The best advice is to start low and go slow. Use: bisoprolol 1.25 mg
orally OR carvedilol 3.125 mg orally, twice OR metoprolol 12.5 mg orally,
twice daily

Beta-blocker therapy in patients with heart failure can be extremely

difficult to manage. The initiation and up-titration should be undertaken in
consultation with a specialist.

Positive inotropes

Digoxin, once used as first-line therapy, is now reserved for control of

ventricular rhythm in patients with atrial fibrillation; or where adequate
control is not achieved with an ACEI, a beta blocker and a loop diuretic.
There is no evidence that digoxin reduces mortality in CHF, although
some studies suggest a decreased rate in hospital admissions. It is
contraindicated in cardiac tamponade and restrictive cardiomyopathy.
The inotropic agent dobutamine is advised only in the short-term use of
acutely decompensated heart failure, and has no other uses.
Alternative vasodilators

The combination of isosorbide dinitrate/hydralazine is the only

vasodilator regimen, other than ACE inhibitors or angiotensin II receptor
antagonists, with proven survival benefits. This combination appears to
be particularly beneficial in CHF patients with an African American
background, who respond less effectively to ACEI therapy.

Drugs that May Precipitate or Exacerbate Heart Failure

A list of such agents that may precipitate or exacerbate a heart failure is

shown in Table 15.3

Table 15.3 Drugs that May Precipitate or Exacerbate Heart

Failure

Negative Inotropic Effect

Antiarrhythmics (e.g., disopyramide, flecainide, and others except

amiodarone)
â-Blockers (e.g., propranolol, metoprolol, atenolol, and others )
Calcium channel blockers (e.g., verapamil and others)
Itraconazole
Terbinafine

Cardiotoxic

Doxorubicin
Daunomycin
Cyclophosphamide

Sodium and Water Retention

NSAIDs
COX-2 inhibitors
Rosiglitazone and pioglitazone
Glucocorticoids
Androgens
Estrogens
Salicylates (high dose)
Sodium-containing drugs (e.g., carbenicillin disodium, ticarcillin
Disodium)

Surgery
Surgical options to treat underlying causes of heart failure include:

§ Coronary artery bypass graft (CABG or "cabbage") or

angioplasty to prevent and treat heart failure caused by blocked
arteries.

§ Implantation of pacemakers and other devices such as artificial

heart valves

§ Repairing congenital heart defects

Surgical treatments for heart failure itself include:

§ Heart Transplantation -- Although a heart transplant may be

the best option for patients with the most severe types of heart
failure, this treatment is available to only a small number of
people due to a shortage of donor hearts. Recent advances may
make artificial heart transplantation an option in the future.

§ Left Ventricular Assist Devices (LVAD) These may be

implanted in the chest to increase heart-pumping action. Until
recently, LVADs required that the patient be hooked up to a
large, hospital-based console while awaiting a transplant.
Miniaturized battery-powered LVAD units, however, are allowing
many patients to leave the hospital. The devices may be used as
a primary treatment or as a bridge to heart transplant in adults.

Heart Reconstruction The electrical signals that cause the heart to

contract move in a spiral pattern. Ideally the heart is an elliptical shape,
like a football, for this makes it easier to receive the electrical signals that
trigger heartbeats. In heart failure, the heart often enlarges and become
spherical, more like a basketball, which no longer "fits" the electrical
pattern and makes the heart less efficient. A number of promising
surgical procedures are being investigated to address this problem by
reconstructing parts of the heart to normalize its shape.

Pharmaceutical Care Interventions and Outcomes

Why is Pharmaceutical Care needed in Congestive Heart Failure?

• Chronic diseas
• CHF mainly affects elderly people
• Usually intercurrent with other diseases
• Multiple/complex drug therapy is involved
• Patient lifestyle management which is a vital component is
challenging
• Adherence issues arise
• Disabling symptoms and impact heavily on quality of life
• Morbidity is high with aging population and unhealthy lifestyle
of young people.
• Mortality rate is also high
• Cost of therapy is high especially with the progressive mature
• Collaborative care has been shown to improve outcomes

Therapeutic interventions with diuretics, vasodilators, and angiotensin-

converting enzyme (ACE) inhibitors improve quality of life by reducing
symptoms. However, the prognosis depends not only on the disorder's
severity but also on patients' compliance with prescribed therapy (Cahill,
1987). For optimal treatment, drugs alone are not sufficient (Goodyer et
al., 1995); patients must take some responsibility by making necessary
changes in lifestyle (e.g., controlling sodium and fluid intake, exercising,
complying with treatment). Pharmacists' specific interventions to
improve outcomes in congestive heart failure include the following
areas:
 • Optimization of drug treatment
• Patient knowledge of drug therapy
• Patient education
• Self-monitoring of symptoms by patients

Clinical and humanistic outcome parameters that are predetermined

and assessed after delivery of pharmaceutical care include:

• Improvement in heart failure symptoms - orthopnoea at

rest, paroxysmal nocturnal dyspnea, palpitation, chest
pain at rest and during exercise,
• Adherence to drug therapy and lifestyle changes
• Improvement in health related quality of life can be
assed using a disease specific instrument such as
Minnesota Living with Heart Failure (MLHF)
questionnaire
• Forced vital capacity (FVC) pulmonary function test
(assesses pulmonary oedema using a spirometer
• Two - minute walk test (measure distance covered)
including time to walk 25 m and 50 m - An objective
measure of functional status and exercise tolerance
• Body weight changes indicate fluid shifts
• Pulse rate a correlation between heart rate and
atherosclerosis progression exists, in that an increase in
heart rate of five beats per minute corresponds to an
increase in the atherosclerosis progression score of
0.21 and an increase in the stenosis progression score
of 0.27 (Ferrari et al., 1999)
• Blood pressure to guard against symptomatic
hypotension
 • Reduction in hospitalization (frequency and length of
stay) and
• Avoidance of emergency hospital visits

Monitoring in heart failure therapy

• Routine monitoring of serum electrolytes and renal function is

required in patients with heart failure. Assessment of serum
potassium is especially important because hypokalemia is a
common adverse effect of diuretic therapy and is associated
with an increased risk of arrhythmias and digoxin toxicity. Serum
potassium monitoring is also required because of the risk of
hyperkalemia associated with ACE inhibitors, ARBs, and
aldosterone antagonists.

• Assessment of renal function (BUN and serum creatinine) is

also an important end point for monitoring diuretic and ACE
inhibitor therapy. Common causes of worsening renal function in
patients with heart failure include overdiuresis, adverse effects
of ACE inhibitor or ARB therapy, and hypoperfusion.

Key Learning Points

· Heart failure is the failure of the compensatory mechanisms

that sustain cardiac function in a weak heart.
· These compensatory mechanisms are:
ü Increase in adrenergic neurone activity leading to positive
ionotropic and chronotropic effects
ü Frank Starling: overlapping of the myocontractile filaments to
enhance end diastolic volume
ü Left ventricular hypertrophy (increase in muscle mass) with or
without chamber dilatation (due to oedema)
 ü Activation of the rennin-angiotensin-aldosterone system
leading to production of angiotensin II and aldosterone that
lead to fluid retention
· The goals of therapy are to:

ü Relieve disabling symptoms and improve quality of life

ü Slow disease progression
ü Reduce the need for emergency room visits and hospitalization
ü Prolong life

· For optimal treatment, drugs alone are not sufficient. Patients must
take some responsibility by making necessary changes in lifestyle
e.g. controlling sodium and fluid intake, exercising, and complying
with treatment.

· There is a significant evidencepractice gap in the treatment of CHF;

particularly the underuse of ACE inhibitors, â-blockers and
aldosterone antagonists, which have been shown to provide
mortality benefit. Diuretics should be added to ACEI therapy to
control congestive symptoms and signs.

· Digoxin, once used as first-line therapy, is now reserved for control of

ventricular rhythm in patients with atrial fibrillation; or where
adequate control is not achieved. There is no evidence that digoxin
reduces mortality in CHF, although some studies suggest a
decreased rate in hospital admissions.

· Outcome criteria include: target symptoms, forced vital capacity, two

minute walk test, body weight, pulse rate and blood pressure.

· Routine monitoring of serum electrolytes and renal function is

required in therapy.
 References

1. Aguwa CN (2004). Congestive Heart Failure. In:

rd
Therapeutic Basis of Clinical Pharmacy in the Tropics 3
ed. Aguwa CN (Ed.) SNAAP Press Ltd; Enugu Nigeria.
2. Jackson G, Gibbs CR, Davies MK, Lip GYH (2000). ABC of
heart failure. BMJ; 320:167 170.
3. Klabunde RE (2007). Cardiovascular physiology concepts.
Available @ www.cvphysiology.com Accessed 5/11/07.
4. Therapeutic Guidelines of Australia July 2007 version.
5. UCSF (2007). University of California, SanFrancisco
Medical Center. Heart failure treatment available online.
Accessed 5/11/07.
6. Wikipedia, the free encyclopedia. Heart Failure. Available online.
Accessed 5/11/07.
 CHAPTER SIXTEEN

PHARMACEUTICAL CARE IN ACUTE

MYOCARDIAL INFARCTION
Azuka C Oparah and Evbade M Arigbe-Osula

Learning Objectives
At the end of this chapter, you should be able to:
i. Explain ischaemic heart diseases and know modifiable and
non-modifiable risk factors in myocardial infarction (MI)
ii. Identify treatment goals in myocardial infarction therapy
iii. Discuss initial and hospital management of acute myocardial
infarction
iv. Outline Pharmaceutical care role in the prevention of myocardial
infarction
v. List criteria for evaluating therapeutic outcomes in MI

Introduction
Ischemic heart disease (IHD), also known as coronary artery disease
(CAD) is caused primarily by coronary atherosclerosis, and results in an
imbalance between myocardial oxygen supply and demand with
resulting ischemia. IHD may present as an acute coronary syndrome
(ACS), which includes unstable angina, nonST-segment-elevation
myocardial infarction (NSTEMI), and ST-segment-elevation myocardial
infarction (STEMI), and myocardial infarction (MI) diagnosed by
biomarkers only, chronic stable exertional angina pectoris, and ischemia
without clinical symptoms or owing to coronary artery vasospasm
(variant or Prinzmetal's angina). Some useful definitions are given in
Panel 16.1.
 Panel 16. 1: Definitions
• Coronary heart disease - pathological definition:
"The narrowing or blockage of the coronary arteries by
atheroma, leading to angina, coronary thrombosis or
heart attack, heart failure and/or sudden death
• Coronary heart disease - epidemiological
definition: Fatal or non-fatal myocardial infarction or
incident angina
• Cardiovascular disease - Coronary heart disease plus
stroke, peripheral vascular disease and heart failure

Definition and causes of acute myocardial infarction

Acute myocardial infarction (heart attack) is a common cause of death.

Most of the deaths are due to ventricular fibrillation occurring soon after
the onset of ischaemia. Acute myocardial infarction (MI) is defined as
death or necrosis of myocardial cells. It is a diagnosis at the end of the
spectrum of myocardial ischemia or acute coronary syndromes.
Myocardial infarction occurs when myocardial ischemia exceeds a
critical threshold and overwhelms myocardial cellular repair
mechanisms designed to maintain normal operating function and
hemostasis. Ischemia at this critical threshold level for an extended
period results in irreversible myocardial cell damage or death.

An interruption in the supply of myocardial oxygen and nutrients occurs

when a thrombus is superimposed on an ulcerated or unstable
atherosclerotic plaque and results in coronary occlusion. A high-grade
(more than 75%) fixed coronary artery stenosis caused by
atherosclerosis or a dynamic stenosis associated with coronary
vasospasm can also limit the supply of oxygen and nutrients and
precipitate an MI.

Conditions associated with increased myocardial metabolic demand

include:

• extremes of physical exertion

• severe hypertension

• severe aortic valve stenosis.

Risk factors

Six primary risk factors have been identified with the development of
atherosclerotic coronary artery disease and myocardial infarction:
hyperlipidemia, diabetes mellitus, hypertension, smoking, male gender,
and family history of atherosclerotic arterial disease. The presence of
any risk factor is associated with doubling the relative risk of developing
atherosclerotic coronary artery disease.

High Blood Cholesterol Level

Elevated levels of total cholesterol and low-density lipoprotein (LDL) are

associated with an increased incidence of atherosclerosis and MI.

Diabetes Mellitus

Patients with diabetes (both Type 1 and 2) have a substantially greater

risk of atherosclerotic vascular disease in the heart as well as in other
areas of their vasculature. Diabetes increases the risk of MI because it
increases the rate of atherosclerotic progression and adversely affects
blood cholesterol levels.

Hypertension

High blood pressure (BP) has consistently been associated with an

increased risk of MI. This risk is associated with systolic and diastolic
hypertension. The control of hypertension with appropriate medication
has been shown to reduce the risk of MI significantly.
Tobacco Use

Certain components of tobacco and tobacco combustion gases are

known to damage blood vessel walls. The body's response to this type
of injury elicits the formation of atherosclerosis and its progression,
thereby increasing the risk of MI.

Male Gender

The incidence of atherosclerotic vascular disease and MI is higher in

men than women in all age groups. This gender difference in MI
incidence, however, narrows with increasing age. Premature
menopause poses a risk in women.

Family History

A family history of premature coronary disease increases an individual's

risk of atherosclerosis and MI. The cause of familial coronary events is
multifactorial and includes other elements, such as genetic components
and unhealthy lifestyles.

Signs and Symptoms

• Chest pain: three quarters of patients present with
characteristic central or epigastric chest pain radiating to the
arms, shoulders, neck, or jaw. The pain is described as sub-
sternal pressure, squeezing, aching, burning, or even sharp
pain. Radiation to the left arm or neck is common. Chest pain
may be associated with sweating, nausea, vomiting, dyspnoea,
fatigue, or palpitations.
• Shortness of breath: may be the patient's anginal equivalent or
a symptom of heart failure.
• Atypical presentations are common (especially women, older
men, people with diabetes,) e.g. abdominal discomfort or jaw
pain; elderly patients may present with altered mental state.

An MI may occur at any time of the day, but most appear to be clustered
around the early hours of the morning, are associated with demanding
physical activity, or both. Approximately 50 % of patients have some
warning symptoms (angina pectoris or an anginal equivalent) before the
infarct.

Diagnosis

MI usually presents as a medical emergency. Once a patient's clinical

picture raises a suspicion of a MI, several confirmatory tests can be
performed. These tests include electrocardiography, blood testing, and
echocardiography.

Electrocardiography

The first test is electrocardiography, which may demonstrate that a

myocardial infarction is in progress or has already occurred. Practice
guidelines on MI management consider patients whose ECG does or
does not show ST-segment elevation separately. As noted earlier, the
former is referred to as STEMI (ST-elevation MI) and the latter as
NSTEMI (nonST-elevation MI).

Blood Tests
Living heart cells contain enzymes and proteins (e.g., creatine
phosphokinase, troponin, myoglobin) When a heart muscle dies, cellular
membranes lose integrity and intracellular enzymes and proteins slowly
leak into the bloodstream. These enzymes and proteins can be detected
by a blood sample analysis. The concentration of enzymes in a blood
sampleand more importantly, the changes in concentration found in
samples taken over timecorrelate with the amount of heart muscle that
has died. The analytes that rise are: Total creatinine phosphokinase
(CPK), CK, MB fraction, CK, MB fraction (% of total CPK), CK, MB2
fraction, Troponin I, and Troponin T
Echocardiography
An echocardiogram may be performed to compare areas of the left
ventricle that are contracting normally with those that are not. The
presence of wall motion abnormalities on the echocardiogram may be
the result of an acute MI or previous (old) MI or other myopathic
processes. Thus, the usefulness of echocardiography for the diagnosis
of MI is limited.

Goal of treatment
Early treatment aims to reduce the extent of myocardial damage. As
the myocardium is damaged by a diminished oxygen supply due to
the obstructed coronary artery, infarct size can be reduced in two
ways:

• dissolution of the thrombus to restore coronary blood flow

• decreasing myocardial oxygen consumption

Aspirin

All patients with a suspected myocardial infarction should be given

aspirin. It is a powerful antiplatelet drug, with a rapid effect, which
reduces mortality by 20%.1 Aspirin, 150-300 mg, should be swallowed as
early as possible.
Analgesia

Pain and anxiety relief should be treated with intravenous morphine

titrated slowly, starting at 2.5 mg. Oxygen (90 %) therapy is thought to be
beneficial, although there have been no trials to confirm this.

Restoration of blood flow

This has become the main aim of treatment as it reduces the mortality
1-2
significantly. Blood flow is normally restored using drug therapy -
fibrinolytic agents (e.g. streptokinase, tissue plasminogen activator),
antiplatelet agents (e.g. aspirin) and antithrombins (e.g. heparin).
Recently, coronary angioplasty (PTCA) has been used to restore flow
mechanically.The speed at which the flow is restored is important. For
every hour of delay, the effect of therapy diminishes and mortality
increases.

Fibrinolytic therapy
The mainstay of treatment is fibrinolytic therapy. This is given to
dissolve the thrombus in the artery and restore flow. Two fibrinolytic
drugs commonly used are streptokinase and tissue plasminogen
activator (tPA).

Fibrinolytic therapy should be given to all patients with appropriate

indications and no contraindications (Panel 16.2).

The indications for fibrinolytic therapy are symptoms of myocardial

ischaemia, of less than 12 hours' duration, with ECG changes of ST
elevation or left bundle branch block. Patients without these ECG
changes should not be given fibrinolytic therapy.3

Panel 16.2 Indications and contraindications for

fibrinolytic therapy
Indications
• within 12 hours of onset of chest pain lasting for at least
30 minutes
• ECG changes of ST elevation of at least 1 mm in two or
more contiguous leads, or left bundle branch block
Contraindications
• cerebral event within 6 months
• major trauma including surgery within 1 month
• bleeding peptic ulcer within 2 months
• uncontrolled hypertension
Non-compressible vascular puncture
Streptokinase

Streptokinase produces generalised systemic fibrinolysis. Despite

1-2
reducing mortality by 25% , only about 30% of patients have their
coronary flow restored to normal within 90 minutes of treatment. This
4
increases to over 50% by 3 hours and up to 80% by 5-7 days. An
intravenous infusion of 1.5 million units is given over 30-60 minutes.
Most patients will develop hypotension if streptokinase is given quickly,
but this is usually easily overcome by slowing the infusion and giving
fluid.

Streptokinase is derived from Streptococci and will produce an antibody

reaction. These antibodies appear after 2-3 days and persist for some
years. The presence of antibodies reduces the efficacy of subsequent
doses of streptokinase and increases the potential for anaphylaxis. The
present consensus is that streptokinase should be used only once per
patient.5 All patients should be informed about being treated with
streptokinase and ideally given a card or other form of record so that this
information is available should they have another infarction.

Tissue plasminogen activator (tPA)

As tPA specifically binds to thrombus, it produces local fibrinolysis. It

does not have the same systemic effects as streptokinase. tPA is given
as 15 mg bolus and a maintenance dose of 0.75 mg/kg over 30 minutes
without exceeding 50 mg, then 0.5 mg/kg over 60 minutes. Clot
dissolution occurs more promptly with tPA than streptokinase restoring
patency at 90 minutes in 55% of patients.4 However, by 3 hours and 5-7
days there is no major difference in patency in patients treated with
streptokinase or tPA. This improved early patency results in slightly
improved mortality. Compared with streptokinase, tPA appears to cause
more bleeding and, in particular, produces a higher incidence of cerebral
bleeding and stroke.
Heparin

Heparin is an antithrombin agent. It has been utilised with both

fibrinolytic drugs and given subcutaneously and intravenously.
Intravenous heparin is given as a 5000 unit bolus followed by 1000 units
per hour intravenously, adjusted after 24 hours according to the
activated partial thromboplastin time (APTT). (APTT measurements are
little use in the first 24 hours as streptokinase also raises the APTT.)

Heparin and streptokinase

There is contention about the routine use of heparin with streptokinase.

There has been no apparent benefit on mortality of subcutaneous versus
no heparin7 and no benefit of intravenous heparin versus subcutaneous
heparin.6 Equally, the addition of routine intravenous or subcutaneous
heparin does not appear to do any harm. Not giving routine heparin has
the benefit that clotting studies are not necessary and this may be
particularly advantageous in smaller hospitals without 24-hour
laboratory facilities. However, heparin may be required for clinical
reasons e.g. large infarcts, ongoing ischaemia.

Heparin and tPA

Currently, it is believed that heparin should be given with tPA. The

standard regimen is an initial bolus of 5000 units, followed by an infusion
of 1000 units per hour adjusted after 6 hours for APTT.

Decreasing myocardial oxygen consumption

The benefit of therapy aimed at decreasing myocardial oxygen

consumption is considerably less than the benefit of restoration of flow.
Decreased oxygen consumption is achieved by lowering heart rate,
blood pressure and cardiac filling pressures. Beta blockers, glyceryl
trinitrate and possibly ACE inhibitors work in this way.

ACE inhibitors

ACE inhibitors reduce the mortality of myocardial infarction and this

benefit is seen within the first 30 days. Captopril 6.25 mg, or equivalent
low doses of another ACE inhibitor, should be used as a first dose and, if
tolerated, the dose increased to at least 25 mg twice daily of captopril or
the equivalent dose of the alternatives. Current consensus is that they
should be given as early as feasible when the patient is
haemodynamically stable.

Beta blockers

Intravenous beta blockers such as atenolol, metoprolol and timolol

reduce the incidence of arrhythmias, infarct size and mortality. As the
effect is relatively small, they are not widely used. Beta blockers can be
given if the patient is haemodynamically stable with a heart rate above 50
beats per minute and systolic blood pressure above 100 mmHg. The
standard regimen is atenolol 5 mg intravenously over 5 minutes followed
10 minutes later by a further 5 mg. Oral beta blockade is commenced 30
minutes later. Many centres use only oral beta blockade (atenolol 50 mg,
metoprolol 50 mg) commenced as soon as possible after admission.

Glyceryl trinitrate

Intravenous glyceryl trinitrate reduces preload and afterload and may

help to keep the coronary vessels open. Intravenous glyceryl trinitrate
can be used routinely or only for ongoing chest pain or left ventricular
failure (the standard dose is 5 microgram/minute and this can be titrated
against the blood pressure). Oral nitrates should not be used routinely as
they are of no benefit.

Primary and Secondary Prevention of Myocardial Infarction

The implementation of educational interventions, lifestyle modification

and drug treatment to prevent the development of symptoms of CHD
(angina or MI) in high-risk individuals is termed primary prevention. The
use of similar measures in patients already presenting with angina or MI
is referred to as secondary prevention. Primary prevention includes a
range of health promotion initiatives coupled with targeted
pharmacological and non-pharmacological interventions. Reported
health screening and intervention initiatives with pharmacist
participation have typically focused on lipid management, blood
pressure monitoring, antiplatelet therapy and smoking cessation.

Pharmacists are in a position to reinforce the implementation of a variety

of clinical guideline treatment goals (systolic BP < 140 mmHg and
diastolic BP < 90 mmHg, total cholesterol < 5mmol/L, and HbA1c < 7 per
cent). The use of pharmacy patient records to help identify and monitor
patients who are candidates for primary and secondary CHD prevention
has not been explored in health services research, and would seem
worthy of investigation and development. The identification of high-risk
individuals and slowing of the progression of CHD is becoming
increasingly important as a public health priority.

Low dose aspirin

In the absence of contra-indications, low dose aspirin is recommended

as antiplatelet therapy for patients who have a CHD risk greater than or
8
equal to 15 per cent and are aged greater than or equal to 50 years.
Patients with hypertension should have their blood pressure controlled
to minimise the risk of antiplatelet therapy contributing to risk of
cerebrovascular bleeding. For those patients allergic to or intolerant of
aspirin, clopidogrel 75 mg daily is recommended

Lipid lowering drugs

Lipid lowering drugs are recommended in patients with hyper-

cholesterolaemia and a greater than or equal to 30 per cent CHD risk.
Dietary modification lowers plasma cholesterol on average by only 5 per
9
cent; therefore, in most patients drug therapy is necessary to reduce
plasma cholesterol.
Evaluation of Therapeutic Outcomes
• Baseline renal and hepatic function assessment affecting the
use of ACE inhibitors and statins
• Monitoring of laboratory markers and investigations, especially in
the elderly and for initiation of ACE inhibitor therapy (eg,
creatinine, potassium, urea, LDL and total cholesterol monitoring
· Subjective measures of drug response include the number of
painful episodes, amount of rapid-acting nitroglycerin consumed,
and patient-reported alterations in activities of daily living (e.g.,
time to walk two blocks, number of stairs climbed without pain).
· Objective clinical measures of response include heart rate, blood
pressure, and the diastolic pressure as a measure of MVo2.
Nitrates may increase heart rate but lower SBP, whereas calcium
channel blockers and β blockers reduce the diastolic pressure.
· Objective assessment also includes the resolution of ECG
changes at rest, during exercise, or with ambulatory ECG
monitoring.
· Monitoring for major adverse effects should be undertaken; they
include headache and dizziness with nitrates; fatigue and
lassitude with β blockers; and peripheral edema, constipation,
and dizziness with calcium channel blockers.
· The ECG is very useful, particularly if the patient is experiencing
chest pain or other symptoms thought to be of ischemic origin.
ST-segment deviations are very important, and the extent of their
deviation is related to the severity of ischemia.
· ETT may also be used to evaluate the response to therapy, but
the expense and time needed to perform this test preclude its
routine use.
· Cardiac catheterization, radionuclide scans, and
echocardiography are used primarily for risk stratification and
selecting patients for more invasive procedures rather than for
monitoring therapy.
· A comprehensive plan includes ancillary monitoring of lipid
profiles, fasting plasma glucose, thyroid function tests,
hemoglobin/hematocrit, and electrolytes.

Key Learning Points

· Acute myocardial infarction (MI) is defined as death or

necrosis of myocardial cells. It is a diagnosis at the end
of the spectrum of myocardial ischemia or acute
coronary syndromes.

· Major risk factors that can be altered include dyslipidemia,

smoking, glycemic control hypertension, and adoption of
therapeutic lifestyle changes.

· Early treatment aims to reduce the extent of myocardial

damage. Infarct size can be reduced in two ways: dissolution
of the thrombus to restore coronary blood flow and
decreasing myocardial oxygen consumption.
· Initial management consists of administration of aspirin
before transporting the patient for emergency hospital
care.
· Blood flow is normally restored using drug therapy -
fibrinolytic agents (e.g. streptokinase, tissue plasminogen
activator), antiplatelet agents (e.g. aspirin) and antithrombins
(e.g. heparin).

· The benefit of therapy aimed at decreasing myocardial

oxygen consumption is considerably less than the benefit of
restoration of flow. Beta blockers, glyceryl trinitrate and
possibly ACE inhibitors are used.

· Health screening and intervention initiatives with pharmacist

participation have typically focused on education, lipid
management, blood pressure monitoring, antiplatelet therapy
and smoking cessation.
 · Objective assessment also includes the resolution of ECG
changes at rest, during exercise, or with ambulatory ECG
monitoring.

References
1. ISIS-2 (Second International Study of Infarct Survival)
Collaborative Group. Randomised trial of intravenous
streptokinase, oral aspirin, both, or neither among 17,187 cases
of suspected acute myocardial infarction: ISIS-2. Lancet
1988;2:349-60.
2. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto
miocardico (GISSI). Effectiveness of intravenous thrombolytic
treatment in acute myocardial infarction. Lancet 1986;1:397-402.
3. Fibrinolytic Therapy Trialists' (FTT) Collaborative Group.
Indications for fibrinolytic therapy in suspected acute myocardial
infarction: collaborative overview of early mortality and major
morbidity results from all randomized trials of more than 1000
patients [published erratum appears in Lancet 1994;343:742].
Lancet 1994;343:311-22.
4. The GUSTO Angiographic Investigators. The effect of tissue
plasminogen activator, streptokinase, or both on coronary-artery
patency, ventricular function, and survival after acute myocardial
infarction [published erratum appears in N Engl J Med
1994;330:516]. N Engl J Med 1993;329:1615-22.
5. Thrombolysis '93. Canberra, Australia. 1-3 July 1993. Aust NZ J
Med 1993;23:727-78.
6. The GUSTO Investigators. An international randomized trial
comparing four thrombolytic strategies for acute myocardial
infarction. N Engl J Med 1993;329:673-82.
7. ISIS-3 (Third International Study of Infarct Survival) Collaborative
Group. ISIS-3: a randomised comparison of streptokinase vs
tissue plasminogen activator vs anistreplase and of aspirin plus
heparin vs aspirin alone among 41,299 cases of suspected acute
myocardial infarction. Lancet 1992;339:753-70.
8. 18. British Cardiac Society, British Hyperlipidaemia Association,
British Hypertension Society, endorsed by the British Diabetic
Association. Joint British recommendations on prevention of
coronary heart disease in clinical practice. Heart 1999;80
(suppl 2):S1-S29.
9. 16. Tang J, Armitage J, Lancaster T, Silagy C, Fowler G, Neil H.
Systematic review of dietary intervention trials to lower blood
total cholesterol in free-living subjects. BMJ 1998;316:1213-20.
 CHAPTER SEVENTEEN

PHARMACEUTICAL CARE OF PATIENTS WITH ASTHMA

Azuka C Oparah and Ifeanyi E Chiazor

Learning Objectives
At the end of this chapter, you should be able to:
I. Describe asthma and its clinical presentation
ii. List the goals of asthma therapy
iii. Discuss non-pharmacologic and pharmacologic therapy of
asthma
iv. Describe the technique of proper inhaler use
v. Explain specific pharmaceutical care roles in asthma
management.
Introduction

Asthma is a common disease with high morbidity and mortality, which

has been associated with inadequate treatment and underuse of
objective measurement of severity. Asthma simply means shortness of
breath. The Global Initiative for Asthma (GINA) 2003 guideline describes
asthma as a 'chronic inflammatory disorder of the airways in which many
1
cells and cellular elements play a role. The chronic inflammation causes
an associated increase in airway hyper-responsiveness that leads to
recurrent episodes of wheezing, breathlessness, chest tightness and
coughing, particularly at night or in the morning. The episodes are
usually associated with widespread but variable airflow obstruction
which is often reversible either spontaneously or with treatment'. Many
of the symptoms overlap with other diseases (e.g. chronic obstructive
pulmonary disease - COPD). Therefore, asthma largely remains a
clinical diagnosis.
Common risk factors include exposure to allergens such as domestic
dust, animal fur, cockroach, pollens and molds; occupational irritants;
tobacco smoke; air pollution; respiratory infections; exercise, strong
emotional expressions, chemical irritants and drugs (such as aspirin and
beta adrenoceptor blockers). There is good evidence that asthma
occurs in families.

Clinical Presentation
Chronic Asthma
· Classic asthma is characterized by episodic dyspnea associated
with wheezing, but the clinical presentation of asthma is diverse.
Patients may also complain of chest tightness, coughing (particularly at
night), or a whistling sound when breathing. These often occur with
exercise but may occur spontaneously or in association with known
allergens.
· Signs include expiratory wheezing on auscultation, dry
hacking cough, or signs of atopy (e.g., allergic rhinitis or
eczema).

· Asthma can vary from chronic daily symptoms to only

intermittent symptoms. There are recurrent
exacerbations and remissions, and the intervals
between symptoms may be weeks, months, or years.

· The severity is determined by lung function and

symptoms prior to therapy as well as by the number of
medications required to control symptoms. Patients can
present with mild intermittent symptoms that require no
medications or only occasional use of short-acting
inhaled â2 agonists, to severe chronic asthma symptoms
despite receiving multiple medications.
Acute Severe Asthma
· Uncontrolled asthma can progress to an acute state
where inflammation, airway edema, excessive
accumulation of mucus, and severe bronchospasm
result in profound airway narrowing that is poorly
responsive to usual bronchodilator therapy.

· Patients may be anxious in acute distress and complain

of severe dyspnea, shortness of breath, chest tightness,
or burning. They may be able to say only a few words with
each breath. Symptoms are unresponsive to usual
measures.

· Signs include expiratory and inspiratory wheezing on

auscultation, dry hacking cough, tachypnea,
tachycardia, pallor or cyanosis, and hyperinflated chest
with intercostal and supraclavicular retractions. Breath
sounds may be diminished with very severe obstruction.

Classification of Asthma Severity

Asthma severity varies among individuals and this changes with time.
Severity does not necessarily relate to frequency or persistence of
symptoms and is the basis for treatment decisions. Asthma severity can
be intermittent, persistently mild, moderate or severe, Table 17.1.
Table 17. 1 Classification of asthma severity based on symptoms
and lung function2

Symptoms Lung Functiona

Step 1 Daytime ? 2 times/wk FEV1 OR
PEF ? 80%
Mild Intermittent Asymptomatic between exacerbations
Exacerbations brief (from a few hours to a few days);
intensity may vary
Nocturnal ? 2 times/mo

Step 2 Daytime ? 2 times/wk but < 1 time/day FEV1 or PEF ?

80%
Persistent Exacerbations may affect activities
Nocturnal ? 2 times/mo

Step 3 Daily symptoms FEV1 or PEF?

60% to < 80%
Moderate Persistent Daily use of inhaled, short-acting â 2 -agonist
Exacerbations affect activity
Exacerbations ? 2 times/wk; but may last days
Nocturnal ? 1 time/ wk

Step 4 Continual symptoms FEV1 or PEF ? 60%

Limited physical activity PEF Availability ?
30%
Frequent exacerbations
Nocturnal frequent
a
The presence of one of the features of severity is sufficient to place a patient in that categor
y. An individual should
be assigned to the most severe grade in which any feature occurs. The characteristics noted are general and may
overlap because asthma is highly variable. Furthermore, an individual’s classification may change over time.
Patients at any level of severity can be mild, moderate, or severe exacerbations. Some patients with intermittent
asthma experience severe and life -threatening exacerbations separated by long periods of normal lung function
and no symptoms.

Goal of therapy

The aims of asthma management are to achieve good long-term asthma

control. Features of good asthma control include:
Absent or minimal daytime symptoms and no nocturnal symptoms
• normal (> 80% of predicted) or near best lung function (best
achievable by the patient)
• good exercise performance, which is unimpaired by asthma
• minimal need for short-acting â2 agonists as required (i.e. rarely
needed other than before exercise)
 • absence of exacerbations
• no need for emergency visits for medical help.
• provide optimal pharmacotherapy with minimal or no adverse
effects
• meet patients' and families' expectations of satisfaction with
asthma care.

Good asthma control is likely to achieve:

• avoidance of permanently impaired lung function

• reduced risk of death from asthma
• avoidance of unnecessary medication adverse effects.

Acute Severe Asthma

The goals of treatment are as follows:
• Correction of significant hypoxemia
• Rapid reversal of airway obstruction (within minutes)
• Reduction of the likelihood of recurrence of severe airflow
obstruction
• Development of a written action plan in case of a future
exacerbation.

Nonpharmacologic Therapy
• Patient education and the teaching of self-management skills
should be the cornerstone of the treatment program. Self-
management programs improve adherence to medication
regimens, self-management skills, and use of health care
services. Education of patients and their families should include
the following information:
Patient education on asthma

i. Nature of asthma a chronic disease, not sporadic.

ii. Preventive measures/avoidance of triggers

iii. Drugs and their side effects

iv. Proper use of inhaled drugs

v. Proper use of peak flow meter

vi. Knowledge of difference between relieving and

preventive medications

vii. Rescue medications (â2 agonists) should not be used for

long term therapy to avoid tolerance development, and
they do not treat underlying inflammation

viii. Recognition of symptoms of worsening asthma (increase

in bronchodilator requirement, development of nocturnal
symptoms, reducing peak flow rates)

ix. Self management plans for selected motivated patients.

An asthma action plan gives guidance on taking the
medicines properly, avoiding factors that worsen asthma,
tracking the level of asthma control, responding to
worsening asthma, and seeking emergency care when
needed.

· Objective measurements of airflow obstruction with a

home peak flow meter may not necessarily improve
patient outcomes. The National Asthma Education and
Prevention Program (NAEPP) advocates routine use of
peak flow meters only for patients with moderate and
severe persistent asthma.
· Avoidance of known allergenic triggers can improve
symptoms, reduce medication use, and decrease
bronchial hyper-responsiveness (BHR). Environmental
triggers (e.g., animals) should be avoided in sensitive
patients, and those who smoke should be encouraged to
stop.

· Patients with acute severe asthma should receive

supplemental oxygen therapy by mask or nasal cannula
titrated to maintain Sao2 normal for altitude (greater than
95% at sea level). Significant dehydration should be
corrected; urine specific gravity may help guide therapy
in young children, in whom assessment of hydration
status may be difficult.

· The steps for proper use of inhalers are illustrated

3
below:
Drug therapy
There are two major classes of drugs to treat asthma:
1. Bronchodilator drugs to relieve bronchospasm and improve
symptoms.
• â2 agonists such as salbutamol, terbutaline, fenoterol,
and salmeterol (long acting). Inhaled â2 agonists are first
line drugs
• Anticholinergics ipratropium bromide (inhalation)
• Methylxanthines (available as oral and parenteral forms)
- aminophylline
2. Anti-inflammatory drugs to treat the airway inflammation and
bronchial hyperresponsiveness, the underlying cause of asthma,
i.e. to prevent attacks.
• Corticosteroids beclomethasone dipropionate
(inhalation), prednisolone (oral and parenteral),
hydrocortisone (parenteral).
• Sodium cromoglycate (inhalation), which is of great
benefit in young atopic patients.
• Leucotriene receptor antagonists - zafirlukast,
montelukast

Life Saving Message!!

All asthmatic patients should carry a quick-relief inhaler

(rescue medication) with them at all times in case they need it.
If your child has asthma, make sure that anyone caring for him
or her and the child's school has the child's quick-relief
medicines. They should understand when and how to use
them and when to seek medical care for your child.
Mild intermittent asthma: Mild intermittent asthma in adults can often
be adequately treated with inhaled short-acting â2 agonists as required.
Use salbutamol 100 to 200 micrograms metered dose inhaler (MDI) by
inhalation, as required OR terbutaline 500 micrograms by inhalation, as
required.

Persistent asthma

In adults, persistent asthma requires a long-term preventive medication

to maintain good control; it can be classified as mild, moderate or severe.
Patients should also use inhaled short-acting â2 agonists as required.
Mild persistent asthma can be well controlled by low-dose inhaled
corticosteroids.

In moderate persistent asthma, a long-acting â2 agonist should be used

in combination with medium-dose inhaled corticosteroids. Evidence
shows that adding a long-acting â2 agonist to inhaled corticosteroids
produces a greater beneficial effect than doubling the dose of inhaled
corticosteroids.

In patients established on inhaled corticosteroids and long-acting â2

agonists, using combination products may aid adherence and reduce
costs. However, there is no evidence that taking the combination of
drugs in the same device is significantly more efficacious than taking the
drugs from separate devices.

If symptoms persist despite treatment, check patient adherence and

device use. If these are adequate, review the diagnosis. If the diagnosis
is correct, treat as severe persistent asthma.

Adults with severe asthma should be referred to a specialist with

expertise in the area. They may require high doses of inhaled
corticosteroids in addition to a long-acting â2 agonist. As in all types of
persistent asthma, patients should also use short-acting â2 agonists as
necessary (see Mild intermittent asthma). Some patients may require
high doses of short-acting â2 agonist from an MDI when their asthma is
uncontrolled; this can be administered by 6 to 8 doses.

Leukotriene receptor antagonists are oral preparations that may have a

role as corticosteroid-sparing drugs; however, patient response to them
is unpredictable, and their precise role in asthma management is yet to
be defined.

Severe asthma, resistant to treatment with optimally administered

inhaled corticosteroids, may require the addition of long-term
prednisolone (oral), which should be used in the smallest doses
possible. Alternate-day prednisolone is preferred if long-term use is
clinically indicated. Referral to a specialist is indicated.

Pregnant women who have asthma need to control the disease to

ensure a good supply of oxygen to their babies. Poor asthma control
raises the chance of a preterm baby and low birth weight. Poor asthma
control may even result in foetal death.

Acute Severe Asthma

Uncontrolled asthma, with its inherent variability, can progress to an
acute state where inflammation, airways edema, excessive
accumulation of mucus, and severe bronchospasm result in a profound
airways narrowing that is poorly responsive to usual bronchodilator
4
therapy.
The principal goals of treatment include:
• Correction of significant hypoxemia
• Rapid reversal of airflow obstruction
• Reduction of the likelihood of recurrence of severe airflow
obstruction
• Development of a written action plan in case of a further
exacerbation
Acute severe asthma is a medical emergency. These goals are best
achieved by early initiation of treatment and close monitoring of
objective measures of oxygenation and lung function.

Oxygen therapy: If available, oxygen must be administered. SaO2

should be maintained above 94%.

Bronchodilator therapy: Use a short-acting â2 agonist plus ipratropium

bromide.

If inhaled therapy is not feasible or if there is no response to nebulised

therapy, intravenous salbutamol can be considered in a highly
monitored situation; however, there is no evidence that it is better than
inhaled salbutamol.

Care must be taken to monitor potassium levels.

For anaphylaxis or imminent cardiorespiratory arrest, use

adrenaline.

Corticosteroids: Use either oral or intravenous corticosteroids.

Prevention of Exercise Induced Asthma

Physical activity is an important part of a healthy lifestyle. Adults need

physical activity to maintain good health. Children need it for growth and
development. In many people, however, physical activity may set off
asthma symptoms. The following medicines may help to prevent asthma
5
symptoms due to physical activity:

• Short-acting â2 agonists taken shortly before physical activity

can last 2 to 3 hours and prevent exercise-related symptoms in
most people.

• Long-acting â2 agonists can be protective up to 12 hours.

However, with daily use, they will no longer give up to 12 hours of
 protection. Also, frequent use for physical activity may be a sign
that asthma is poorly controlled.

• Leukotriene modifiers. These regimens are taken several hours

before physical activity. They help relieve asthma symptoms
brought on by physical activity in up to half of the people who take
them.

• Cromolyn or nedocromil. These medicines are taken shortly

before physical activity to help control asthma symptoms.

• Long-term control medicines. Frequent or severe symptoms due

to physical activity may indicate poorly controlled asthma and the
need to either start or increase long-term control medicines that
reduce inflammation. This will help prevent exercise-related
symptoms.

• Easing into physical activity with a warm-up period also may be

helpful.

Medications for allergy-induced asthma

These agents decrease the body's sensitivity to a particular allergen or

prevent the immune system from reacting to allergens. Allergy
treatments for asthma include:6

• I m m u n o t h e r a p y. A l l e r g y - d e s e n s i t i z a t i o n s h o t s
(immunotherapy) are generally given once a week for a few
months, then once a month for a period of three to five years.
Over time, they gradually reduce your immune system reaction
to specific allergens.

• Anti-IgE monoclonal antibodies, such as omalizumab

given parenterally every two to four weeks.
Evaluation of Therapeutic Outcomes
Chronic Asthma
• Control of asthma is defined as achieving minimal need for
rescue short-acting â2 agonists (ideally none), no acute
episodes, no limitation of activity, no emergency care visits, no
nocturnal symptoms, normal pulmonary function, minimal or no
medication side effects, and satisfaction of the patient and family
with care.

•
· Monitoring consists of quantifying the use of inhaled short-acting
inhaled â2 agonists, days of limited activity, and number of
symptoms (especially nocturnal).

· Patients should be encouraged to keep a symptom diary.

• In moderate to severe persistent asthma, once-daily (on

awakening) peak flow monitoring is recommended. The NAEPP
recommends yearly spirometric assessment.

• Patients should also be asked about exercise tolerance and

nocturnal symptoms.

• All patients on inhaled drugs should have their inhalation

technique evaluated monthly initially and then every 3 to 6
months.

· • After initiation of anti-inflammatory therapy or an increase in

dosage, most patients should begin experiencing a decrease in
symptoms within 1 to 2 weeks and achieve maximum
symptomatic improvement within 4 to 8 weeks. Improvement in
baseline FEV1 or peak expiratory flow (PEF) should follow a
similar time frame, but a decrease in bronchial
hyperresponsiveness as measured by morning PEF, PEF
variability, and exercise tolerance may take longer and improve
over 1 to 3 months.
Acute Severe Asthma
• Patients at risk for acute severe exacerbations should monitor
morning peak flows at home.

• In young children, increased respiratory rate and heart rate and

inability to speak more than one or two words between breaths
are signs of severe obstruction.

• Lung function, either spirometry or peak flows, should be

monitored 5 to 10 minutes after each treatment.

• Oxygen saturation by pulse oximetry and peak flows should be

measured in all patients not completely responding to initial
intensive inhaled â2-agonist therapy.

• Peak flow meters, uses and techniques are shown in the panel.
7

Peak Flow Meters: Uses and Techniques

• Lung function measurements assess airflow

limitation and help diagnose and monitor the course
of asthma.

• To assess the level of airflow limitation, two

methods are used. Peak flow meters measure peak
expiratory flow (PEF), and spirometers measure
forced expiratory volume in 1 second (FEV1) and its
accompanying forced vital capacity (FVC). The
accuracy of all lung function measurements
depends on patients' efforts and correct techniques.

• Several kinds of peak flow meters and spirometers are

 available, and the technique for use is similar for all. To use a
peak flow meter:

- Stand up and hold the peak flow meter without

restricting movement of the marker. Make sure
that the marker is at the bottom of the zero scale.

- Take a deep breath, put the peak flow meter in your

mouth, seal your lips around the mouthpiece, and
breathe out as hard and as fast as possible. Do not put
your tongue inside the mouthpiece.

- Record the result and return the marker to zero.

- Repeat twice more. Choose the highest of the three

readings.

•
· Daily PEF monitoring for 2 to 3 weeks is useful, when it is
available, for establishing a diagnosis and treatment. If
during 2 to 3 weeks a patient cannot achieve 80 % of
predicted PEF (predicted values are provided with all
peak flow meters), it may be necessary to determine a
patient's personal best value, e.g. by a course of oral
pednisolone.

• Long term PEF monitoring is useful, along with review of

symptoms for, for evaluating a patient's response to therapy.
PEF monitoring can also help detect early signs of worsening
before symptoms occur.
Pharmaceutical Care Role in Asthma

Asthma is a common chronic disease with significant morbidity and

mortality. Despite widely disseminated evidence-based guidelines, most
patients still receive sub-optimal treatment.
The SCIAD report has identified numerous areas where improvements
could be made. These include improved patient education, ensuring
appropriate use of inhaler devices, encouraging the use of peak
expiratory flow rate (PEFR) monitoring and identifying those patients
who overuse their inhaled â2 agonists.8-9 Pharmaceutical care has an
important role to play in improving patient care in these and other areas:

• Educating patients and family members about the disease,

medications, and proper inhaler techniques
• Designing patient specific medication regimens
• Monitoring asthma control
• Referral of severe cases for appropriate treatment
• Monitoring the individual medication regimen for
appropriateness of medications and doses over time
• Screening for the development of adverse drug reactions and
drug interactions
• Assessing the quality of life of the patients using generic and
disease specific instruments such as SF 36 and Asthma Quality of
Life Questionnaire
• Assessing patient knowledge of asthma and its management
• Assessing patient satisfaction with care
• Assessing adherence intervening with creative approaches to
improve adherence
Medication adherence ranges from 20% to 70% for chronic conditions,
10
such as asthma. Pharmacist-provided education can improve
11
adherence rates and patient understanding. The National Asthma
Education and Prevention Program recognizes the need for
pharmaceutical care and recommends that asthma education be
12
integrated throughout asthma care. Most patients do not know a
correct inhaler technique, which may lead to less than optimal delivery
and suboptimal efficacy of the medication
Important Points to Cover in the use of metered dose inhaler have been
13
identified:

DIPS [Dosage, Instructions, Priming, Special Instructions] is an

easy-to-remember acronym that covers most of the important parts
regarding correct use of inhalers.

DIPS

D. Is the patient going to be using 1 or 2 inhalations? Will the dosage be

scheduled or as needed? This is also an easy transition to discuss the
indication of the medicationrescue, longterm control, or combination
product. If a bronchodilator and maintenance medications are
prescribed, the patient needs to use the bronchodilator first, wait 5
minutes, and then use the maintenance inhaler.

I. The instructions can vary according to which delivery system is being

used. Metered dose inhalers (MDIs) require coordination, which can be
difficult for small children and the elderly. The patient needs to breathe
out and press down on the canister while breathing in. Patients should
hold this breath for up to 10 seconds, or as long as they are comfortable.
The patient needs to shake the inhaler and wait approximately 1 minute
between inhalations, if multiple inhalations are prescribed. Most
companies can provide placebo versions of their inhalers upon request.
The use of a placebo inhaler can be very helpful when demonstrating
correct inhaler technique. The patient should subsequently be able to
demonstrate the technique, as most people do not have questions or do
not discover problems until the first use of a product.
Dry powder inhalers may be more patient-friendly and do not require the
patient to coordinate breathing and product delivery. The patient does
need to keep the inhaler parallel to the ground after the dose has been
released to keep the powder in the delivery channel before inhalation.
Be sure to warn the patient that humidity, including patient breath, can
cause the powder to clump together. Patient exhalation into the device
prior to inhalation can also cause that dose to exit the device.

P. MDIs require priming (i.e., 2 to 4 sprays in the air) before use if the
product is new or unused for a certain amount of time (Check
manufacturers leaflet for appropriate priming time). If the patient does
not prime the device, less than the desired dose of active ingredient may
be received. Educate patients that this is an important part of inhaler use,
especially if they use their rescue albuterol inhaler infrequently. Dry
inhalers require no such priming.

S. Inhalers are like no other delivery device and have special

instructions for each type of device. Some relatively new inhaler devices
require special instructions (e.g., some are breath-actuated, and some
require capsules to be inserted into the device). For inhalers that require
capsules, patients need to be aware that the capsule is not to be
ingested and needs to be replaced with each use. For MDIs, the correct
amount of medication in each canister is measured in a certain amount
of actuations. After that specific number of actuations, even though the
canister does not feel completely empty, the canister should be
discarded. Placing an inhaler in water to see if it floats does not indicate if
the canister is emptythis is no longer considered appropriate or
accurate.

Patients need to rinse and spit following the inhalation of corticosteroids

to prevent systemic absorption and because MDIs may also lead to
oropharyngeal deposition, which can cause hoarseness and thrush.
One can use a spacer or holding chamber to avoid thrush. A spacer or
holding chamber may be attached to the inhaler when taking medicine to
keep the medicine from landing on the mouth or on the back of the throat.
Spacers should not be used with dry powder inhalers. Cleaning of
inhalers is not necessary; wiping with a moist, clean rag is sufficient.

Areas of Patient Confusion

"My asthma medication is not working" is a common statement

pharmacists should expect to hear. This statement should lead
pharmacists to check patient inhaler technique and use open-ended
questions to discover the problem.14

Language Barrier

Patients and health care providers have different definitions for

commonly used medical terminology.15 A patient may define controller or
long term controller as a medication that controls symptoms, and he or
she will use this medication when symptoms occur that need to be
controlled. Rescue medication can have different meanings to the
patient and provider. The phrase "rescue medications open the airways"
is often used to describe the mechanism of action of the rescue
medication. The patient may misunderstand that the force of the product
exiting the inhaler inflates the lungs.

Expectations

Patients' expectations also affect how they view the efficacy of their
medication. Patients may expect to feel or taste the medication when
they inhale, and if correct technique is used this should not occur.
Patients may anticipate feeling systemic side effects, such as heart
palpitations or excitation.
To correct or prevent incorrect inhaler technique, ask patients to
describe under what circumstances they use each medication,
provide verbal and written education, and demonstrate proper
techniques

Key Learning Points

· Asthma is a chronic inflammatory disorder of the airways with
associated increase in airway hyperresponsiveness that leads
to recurrent episodes of wheezing, breathlessness, chest
tightness and coughing, particularly at night or in the morning
· The clinical presentation of asthma is diverse and can vary
from chronic daily symptoms to only intermittent symptoms.
There are recurrent exacerbations and remissions, and the
intervals between symptoms may be weeks, months, or years
· Asthma severity forms the basis of treatment and can be
intermittent or persistent (mild, moderate or severe)
· The aims of asthma management are to achieve good long-
term asthma control which includes:
ü Normal or near best lung function
ü good exercise performance
ü minimal need for short-acting â2 agonists
ü absence of exacerbations
ü no need for emergency visits
ü provide optimal pharmacotherapy
ü meet satisfaction with asthma care

· Bronchodilator drugs (â2 agonists, ipratropium, and

methyxanthines) are used to relieve bronchospasm and
improve symptoms. Corticosteroids are used for long term
therapy to treat the airway inflammation and bronchial
hyperresponsiveness.
· If a bronchodilator and corticosteroid inhaler are prescribed,
the patient needs to use the bronchodilator first, wait for 5
 minutes, and then use the corticosteroid inhaler
· MDIs require priming (i.e., 2 to 4 sprays in the air) before use if
the product is new or unused for a certain amount of time. Dry
inhalers require no such priming
·· Specific pharmaceutical care roles include:
ü Educating patients and family members about the
disease, medications, and proper inhaler techniques
ü Monitoring outcomes such as asthma control, quality of
life and patient knowledge
ü Designing specific strategies to enhance patient
adherence

References

1. Global strategy for asthma management and prevention:

Global initiative for asthma (GINA); 2003

2. Kelly WH, Sorkness CA. Asthma in: Pharmacotherapy a

Pathophysiologic Approach, DiPiro JT et al (Ed.) McGraw Hill
Publishers USA, 2005: 503 - 535.
3. National Asthma Education and Prevention Program. Expert
panel report: guidelines for the diagnosis and management of
asthma: update on selected topics - 2002. J Allergy Clin
Immunol. 2002;110(suppl 5):141-219. Available at:
www.nhlbi.nih.gov/guidelines/asthma/asthmafullrpt.pdf
4. eTG Complete Therapeutic Guidelines of Australia March 2008
5. NHLBIWHO. Global initiative for chronic obstructive lung
disease (GOLD): Global strategy for the diagnosis,
management, and prevention of chronic obstructive pulmonary
disease. Bethseda, MD; 2008.
6. Mayo Clinic Staff (2009). Asthma. Available @ www.
mayoclinic.com Accessed 12/02/09.
7. Global Strategy for Asthma Management and Prevention
(2002)
8. Bucknall CE, Slack R, Godley CG, Mackay TM, Wright SC on
behalf of SCIAD collaborators. Scottish Confidential Inquiry
into Asthma Deaths (SCIAD), 1994-6. Thorax 1999;54:978-84.
9. Boyter A, Currie J, Dagg K, , Groundland F, Hudson S.
Pharmaceutical Care - Asthma. The Pharmaceutical Journal
2000; 264 (7091): 546-556.
10. Boulet LP. Perception of the role and potential side effects of
inhaled corticosteroids among asthmatic patients. Chest.
1998;113:587-592.
11. Stiegler KA, Yunker NS, Crouch MA. Effect of pharmacist
counseling in patients hospitalized with acute exacerbation of
asthma. Am J Health Syst Pharm. 2003;60:473-476.
12.
13. Knudsen DS, Asthma Patient Counseling: Join the Pharmacist
Revolution. Pharmacy Times 2007
14. Lewis RK, Lasack NL, Lambert BL, Connor SE. Patient
counselling - a focus on maintenance therapy. Am J Health Syst
Pharm. 1997; 54:2084-2098.
15. Rubin BK. What does it mean when a patient says, "My asthma
medication is not working?" Chest. 2004;126:972-981.
 CHAPTER EIGHTEEN

PHARMACEUTICAL CARE IN DIABETES MELLITUS

Valentine U Odili
Learning Objectives
At the end of this chapter, you should be able to:

i. Describe diabetes and its diagnostic criteria, clinical staging

and complications.
ii. Discuss the role of self-care, oral hypoglyceamic agents and
insulin in the management of diabetes.
iii. Describe the systematic process and functions in the
pharmaceutical care of patients with diabetes.

Introduction

The term diabetes mellitus (DM) describes a metabolic disorder of

carbohydrate, fat and protein metabolism. The disorder is characterized
by chronic hyperglycemia resulting from defects in insulin secretion,
insulin action, or both. Diabetes mellitus may present with characteristic
symptoms such as polyuria, polyphagia, polydypsia, blurring of vision,
and weight loss. In its most severe forms, ketoacidosis or a non-ketotic
hyperosmolar state may develop and lead to stupor, coma and, in the
absence of effective treatment, death. Often, symptoms are not severe,
or may be absent, and consequently hyperglycemia sufficient to cause
pathological and functional changes may be present for a long time
before the diagnosis is made. The effects of diabetes mellitus include
long-term damage, dysfunction and failure of various organs. The long-
term effects of diabetes mellitus include progressive development of the
specific complications of retinopathy with potential blindness,
nephropathy that may lead to renal failure, and/or neuropathy with risk of
foot ulcers, amputation, Charcot joints, and features of autonomic
dysfunction, including sexual dysfunction. People with diabetes are at
increased risk of cardiovascular, peripheral vascular and
cerebrovascular disease.

Several pathogenetic processes are involved in the development of

diabetes. These include processes which destroy the beta cells of the
pancreas with consequent insulin deficiency, and others that result in
resistance to insulin action.

The prevalence of diabetes for all age groups world- wide has been
estimated to be 2.8 % in 2000 and projected to be 4.4 % by 2030. The
total number of people with diabetes has been projected to rise from 171
1
million to 366 million by 2030. In Nigeria the number of persons with
diabetes was 1.7 million in 2000 and it is estimated that in 2030 will rise to
4.8 million.
Diagnosis

The diagnosis of diabetes in an asymptomatic subject should never be

made on the basis of a single abnormal blood glucose value. For the
asymptomatic person, at least one additional plasma/blood glucose test
result with a value in the diabetic range is essential, either fasting, from a
random (casual) sample, or from the oral glucose tolerance test (OGTT).
If such samples fail to confirm the diagnosis of diabetes mellitus, it will
usually be advisable to maintain surveillance with periodic re-testing
until the diagnostic situation becomes clear. In these circumstances, the
clinician should take into consideration such additional factors as
ethnicity, family history, age, adiposity, and concomitant disorders,
before deciding on a diagnostic or therapeutic course of action. An
alternative to blood glucose estimation or the OGTT has long been
sought to simplify the diagnosis of diabetes. Glycosylated haemoglobin,
(HbA1C) reflecting average glycemia over a period of weeks, was thought
to provide such a test. Although in certain cases it gives equal or almost
equal sensitivity and specificity to glucose measurement , it is not
commonly available in many parts of the world including Nigeria and is
not well enough standardized for its use to be recommended at this time.2
Diagnostic Criteria
1 A casual (random) plasma glucose > 200mg/dl (11.1 mmol/L),
and the symptoms of diabetes. Random is defined as any time of
day without regard to time since the last meal. The classic
symptoms of diabetes include polyuria, polydypsia and
unexplained weight loss.
OR
2 Fasting Plasma Glucose concentration (FPG) = 126mg/dl (7.0
mmol/L). Fasting is defined as no caloric intake for at least 8
hours.
OR
3 2-hour plasma glucose concentration of = 200mg/dl (11.1
mmol/L) during an OGTT. The test should be performed using 75
g anhydrous glucose load dissolved in water.

The Expert Committee on the Diagnosis and Classification of Diabetes

2-3
mellitus recognized an intermediate group of subjects whose glucose
levels, although not meeting criteria for diabetes are nonetheless too
high to be considered normal. This group is defined as those who have
fasting plasma glucose (FPG) levels = 100 mg/dl (5.6 mmol/L) but < 126
mg/dl (7.0 mmol/L)
OR
2-hr values in the oral glucose tolerance test (OGTT) of = 140 mg/dl (7.8
mmol/L) but < 200 mg/dl (11.1 mmol/L)

The subjects who have a FPG of 100-125mg/dl (5.6-6.9 mmol/L) are said
to have impaired fasting glucose (IFG). While those with 2-hr postload
glucose of 140-199mg/dl (7.8-11.1 mmol/L) have impaired glucose
tolerance (IGT)
Patients with IFG and /or IGT are referred to as having “pre- diabetes”
indicating the relatively high risk of development of diabetes in these
patients.

Urine Glucose
Urine glucose measurement may be used to screen people for diabetes.
However its presence is not diagnostic because glucosuria may occur
when the renal threshold for glucose is decreased just as it is in
pregnancy, there may also be other sugars and substances that can
cause interference in the urine. Conversely, in the elderly where the renal
threshold is increased the absence of sugar does not rule out diabetes.

Classification of Diabetes
The recent classification of diabetes encompasses both clinical stages
and etiological types of diabetes mellitus. The clinical staging reflects
that diabetes, regardless of its etiology, progresses through several
clinical stages during its natural history. Moreover, individual subjects
may move from stage to stage in either direction. For example a woman
who has gestational diabetes mellitus (GDM) may be labeled to have
Type 2 diabetes if she continues to have hyperglycemia after delivery. On
the other hand, someone who has drug induced diabetes
(hyperglycemia) due to say large doses of glucocorticoids may become
normoglycemic once the glucocorticoids are stopped, but then may
develop diabetes many years later after recurrent episodes of
pancreatitis. Another example would be a person treated thiazides that
develops diabetes years later. Note that thiazides in themselves seldom
cause severe hyperglycemia, such individuals probably have Type 2
diabetes that is exacerbated by the drug. Persons who have, or who are
developing, diabetes mellitus can be categorized by stage according to
the clinical characteristics, even in the absence of information
concerning the underlying etiology. The classification by etiological type
4
results from improved understanding of the causes of diabetes mellitus.
CLINICAL STAGING OF DIABETES MELLITUS AND OTHER
CATEGORIES OF GLUCOSE TOLERANCE

Figure 18.1: Disorders of glycemia: etiological types and

clinical stages. (Adapted from a report of a WHO consultation
on Definition, Diagnosis and Classification of Diabetes Mellitus
and its Complications WHO/NCD/NCS/99.2
(http://www.staff.ncl.ac.uk/philip.home/who_dmg.pdf)
Diabetes mellitus, regardless of the underlying cause, is sub-divided
into:
· Insulin requiring for survival (corresponding to the
former clinical class of "Insulin Dependent Diabetes
Mellitus - IDDM"), e.g. C-peptide deficient;
 · Insulin requiring for control, i.e. metabolic control,
rather than for survival, e.g. some endogenous insulin
secretion but insufficient to achieve normoglycemia without
added exogenous insulin; and

· Not insulin requiring, i.e. those who may be controlled

satisfactorily by non-pharmacological methods or drugs
other than insulin. Together, the latter two sub-divisions
constitute the former class of NIDDM.

Etiological Classification of Glycemic Disorders

Type 1
There is beta-cell destruction, usually leading to absolute insulin
deficiency. It may be autoimmune or idiopathic.
Type 2
This may range from predominantly insulin resistance with relative
insulin deficiency to a predominantly secretory defect with or without
insulin resistance.

Other specific types

· Genetic defects of beta-cell function
· Genetic defects in insulin action
· Diseases of the exocrine pancreas
· Endocrinopathies
· Drug- or chemical-induced
· Infections
· Uncommon forms of immune-mediated diabetes
· Other genetic syndromes sometimes associated with
diabetes
Gestational diabetes

This includes the former categories of gestational impaired glucose

tolerance and gestational diabetes. As additional subtypes are
discovered it is anticipated that they will be reclassified within their own
specific category.

Symptoms and Signs

Diabetes mellitus has diverse initial presentation. Type 1 usually

presents with symptomatic hyperglycemia or DKA Type 2 DM may
present with symptomatic hyperglycemia or NKHHC (non ketotic
hyperglycemic-hyperosmolar coma). Type 2 DM is frequently diagnosed
in asymptomatic patients during routine medical examination or when
patients present with late complication.

Following the acute onset of Type 1 DM there is substantial secretion of

insulin. Type 1 DM patients may experience a 'honey moon period'
characterized by a long phase of near normal glucose level without any
treatment.

Clinical Manifestations of Hyperglycemia

The classic symptoms of DM are easily traceable to the elevated blood

glucose levels that occur when glucose is denied entry into to cells. The
direct consequences of high blood glucose levels include: polyuria,
polyphagia, polydypsia. There may be visual disturbances, (osmotic
changes to intraocular pressure), urethritis, pruritis vulvae, balanitis
(urogenital infection). Metabolic consequences of impaired glucose
utilization include lethargy, weakness, weight loss (intracellular glucose
deficit), and ketoacidosis (due to increased fat metabolism).

Acute complications

These are diabetic ketoacidosis (DKA), nonketotic hyperosmolar coma,

and hyperglycemia. Hypoglycemia may occur due to excess insulin and
the body reacts to the stress of hypoglycemia, or treatment.
Hypoglycemia manifests as tachycardia, perspiration, tremor, and
anxiety. It can progress further to confusion, seizure, and coma if
untreated. The most common acute complications of DM are the
disturbances in glycaemic control i.e. hypoglycemia and
hyperglycemia/ketoacidosis. Hypoglycemia can be caused by excess
insulin, a high or potentiated dose of an oral hypoglycaemic agent, a
missed meal, unexpected activity (exercise), and alcohol.
Hyperglycemia can be caused by: a missed dose of insulin,
hyperglycaemic drugs, e.g. thiazides, steroids, excessive eating, and
metabolic stress e.g. infection, surgery, pregnancy.

Chronic complications

These produce microvascular and macrovascular diseases.

Microvascular diseases (diabetic retinopathy, neuropathy and
nephropathy) are due to damage to small blood vessels. Macrovascular
diseases are due to damage to the arteries through atherosclerosis and
include hypertension, coronary artery disease, angina pectoris, acute
myocardial infarction, peripheral vascular disease, and cerebrovascular
accident (Ischemic).

Long term complications of hyperglycemia and hyperlipidaemia result in

vascular disease, heart disease, renal disease, neuropathy, eye
disease, infections, arthropathy (stiffness). Diabetic retinopathy is an
important cause of blindness and occurs as a result of long term
accumulated damage to the small blood vessels of the retina. After 15
years of diabetes about approximately 2 % of people become blind, and
about 10 % develop severe visual impairment. Diabetic neuropathy is
damage to the nerves as a result of diabetes, and affects about half of
people with diabetes. Common symptoms of diabetic neuropathy
include tingling, pain, numbness or weakness in the feet and hands.
Combined with reduced blood flow, neuropathy in the feet can increase
the chance of foot ulcers and eventual limb amputation. Diabetes
nephropathy, diabetes is the leading cause of kidney failure. 10-20 % of
people with diabetes die of kidney failure. Macrovascular complications:
coronary artery disease, cerebrovascular disease, and peripheral
vascular disease cause up to 80 % of deaths among with diabetes. For
this reason the control of blood pressure and lipid and blood glucose
levels is very important in reducing risk factors in patients with Type
1and 2 disease.

Diabetes care

Dietary management is the bedrock of treatment. All patients with

diabetes, irrespective of other treatments require some control of their
exercise and eating habits, considering total caloric intake, types of
nutrients and eating schedule. For about half of the patients, this may be
all that is required. Another 25 % would need to augment their natural
insulin with drugs while the remainder will need insulin. Younger patients
who are frequently none obese usually present as Type 1 and will
require insulin, even though there may be a honey moon (remission)
period. Older patients, who are often obese, are usually Type 2 and must
be tried first on diet alone. If diet fails then drug therapy should be added.

Exercise

Regular physical exercise is even more important for patients with

diabetes than those without the condition. Exercise improves blood
glucose and high density lipoprotein (HDL) cholesterol levels, reduces
the risk of developing coronary heart disease, decreases stress and
makes patients feel better. It also helps to prevent weight gain. Patients
should strive to exercise everyday and they must realize that exercise
reduces blood glucose levels hence they must either reduce their insulin
dosage or consume extra calories before they exercise. They should
also be aware that insulin is absorbed and peaks more rapidly during
exercise especially when injected into the leg.
Diet

All patients whether on oral hypoglycemic agents or insulin must be

advised to control their diet. Dietary recommendations include
discouraging fats while encouraging complex carbohydrates and fibers.
The overall dietary approach is now far less restrictive than before. The
recommended diet except in a few respects is now similar to the normal
healthy diet that everyone should eat i.e. regular meals, low in fats,
simple sugars and sodium and high in complex carbohydrate (starch)
and fiber.

Insulin
As beta-cell function declines over time, a large percentage of patients
with Type 2 diabetes will require insulin therapy for adequate glycemic
control.5-6 Various insulin formulations are available. Rapid or short-
acting insulin covers mealtime or bolus insulin requirements, while
intermediate or long-acting insulin provides basal insulin coverage.
Addition of bedtime basal insulin (intermediate or long acting) is a
reasonable first step in patients not controlled with oral agents. Patients
not achieving adequate response with basal insulin may be switched to
twice-daily or multiple daily injections of basal and bolus insulin.
Regimen complexity should be individualized based on functional and
cognitive status of the patient and the desired level of glycemic control.
Although short-term, sliding-scale insulin is frequently used during
hospitalization or acute illness. Routine usage should be avoided as it
provides suboptimal glycemic control and places the patient at risk of
prolonged hyperglycemia.

The main risk with insulin therapy in the elderly is hypoglycemia. As with
sulfonylureas, patients should be educated on warning signs and
symptoms and management of hypoglycemia. Another concern is the
ability of the patient to accurately draw up and administer insulin. Many
older patients have limited dexterity or poor visual acuity, which impedes
their ability to mix or inject insulin. In this instance, patients may benefit
from specialized delivery devices such as insulin pens or syringe
magnifiers. Use of premixed insulin to simplify the regimen (e.g., insulin
70/30) and prefilling of syringes are alternatives.

Human insulin is often preferred and now recommended for initiating

insulin therapy because it is less antigenic than animal derived insulin.
The pharmacokinetic profile of various insulin preparations is shown in
the table below.

Table 18.1: Pharmacokinetic profile of various insulin preparation s

Insulin preparation onset of action peak (hr) duration (hr)

Rapid acting insulin (Lispro®) 5-15 min 0.5-1.5 <5

Short acting (Regular) 30-60 min 2-3 5-8

Intermediate acting (NPH ) 2-4 hr 4-10 10-16

Long acting (Glargine®) 2-4 hr no peak 20-24

Adapted from Hirsh IB et al. A real world approach to insulin therapy in

primary care practice Clinical diabetes 23(2)78-80, 2005

Sites of Injection

Insulin can be given by intravenous, intramuscular, or subcutaneous

routes. The different sites of injection include: the abdomen, arm, buttock
and thigh. The rate of absorption is fastest from the abdomen,
intermediate from the arm and slowest from the thigh. Strenuous
exercise of an injected area within 1 hr of an injection can increase the
absorption rate of regular insulin but has little effect on intermediate
acting insulin. The abdominal injection site is least affected by exercise.
Previously patients were advised to rotate injection sites between the
aforementioned sites but this has been shown to cause altered glucose
control due rate of absorption differences. Now it is recommended that
insulin injection be rotated within the same anatomical region to avoid
this effect.

Hypoglycemia

Insulin induced hypoglycemia or what is also referred to as insulin

reaction occurs when the blood glucose is less than 3 mmol/L. Many
patients have sight problems and so it is not unusual to give excessive
insulin dose.

The clinical features of hypoglycemia include: Tremor, pallor,

unexplained sweating, shivering, palpitations, anxiety, drowsiness,
disorientation, confusion, aggression (irritability) in extreme cases it can
lead to inappropriate behavior (irrationality) apparent drunkenness,
convulsions, coma, and brain damage, and death. Others include
headache or hunger, salivation, weakness and blurred vision. These
symptoms may vary on different occasions. Hypoglycemia may be
treated with any quick sugar source such as juice, sodas (soft drinks) or
hard candies. Diet soft drinks should not be used. Since hypoglycemia
leads to an urgent need to rapidly increase a patient's blood glucose level
and because food may not always be available, it is important for patients
to always carry a ready source of sugar such as some cubes or vial of
granulated sugar or hard candy (sweets)

Oral hypoglycemic agents

Sulfonylureas

These agents reduce serum glucose concentrations by increasing

insulin secretion from pancreatic beta cells in patients with residual beta
cell function. All are well absorbed; half-life and duration of action vary.
These agents are classified as first generation (acetohexamide,
chlorpropamide, tolazamide, tolbutamide), these are not frequently
used anymore and chlorpropamide should be avoided in the elderly
because of its long half life and the attendant risk for prolonged
hypoglycemia.7 Second generation (glipizide, glyburide), and third
generation (glimepiride). All sulfonylureas have hypoglycemia and
weight gain as major adverse effects.

Glipizide

Second-generation sulfonylurea; stimulates insulin release from

pancreatic beta cells.

Dose 4mg/d PO initially in untreated patients with symptomatic

hyperglycemia; not to exceed 40 mg/d PO; daily doses >20 mg given in
divided doses bid; Glucotrol XL not to exceed 20 mg/d PO
Start at 2.5 mg/d PO for elderly patients and patients with hepatic or renal
disease; may start at higher doses in patients with severe
hyperglycemia or symptoms, if home glucose monitoring and close
follow-up can be arranged.

Interactions: Numerous possible, few clinically significant;

sulfonamides may enhance hypoglycemic effect

®
Glimepiride (Amaryl )

Third-generation sulfonylurea; increases insulin secretion from

pancreatic beta cells.

Dose Usual starting dose is 1-2 mg PO qd with breakfast; usual

maintenance dose is 1-4 mg PO qd; maximum dose is 8 mg PO qd

Interactions: NSAIDs, sulfonamides, chloramphenicol, probenecid,

warfarin, MAOIs, beta-blockers, and miconazole produce increased
hypoglycemic effects; thiazides, hydantoins, oral contraceptives,
corticosteroids, phenothiazines, thyroid estrogen, nicotinic acid,
sympathomimetics, calcium channel blockers, and isoniazid produce
decreased hypoglycemic effects; increases alcohol-related disulfiram
reactions; increases warfarin effects
Meglitinides

Like the sulfonylureas these agents are insulin secretagogues, though

short-acting i.e. they have a faster onset and a shorter duration of action.
They act on the ATP-dependent potassium channels in pancreatic beta
cells, allowing opening of calcium channels and increased insulin
release. When used alone repaglinide is more effective than nateglinide
and lowers the HbA1c by 0.5 % to 1.5 %.8 Hypoglycemia and weight gain
are the commonest adverse effects. Meglitinides should not be used in
conjunction with sulfonylureas since they have similar action and there is
an increased risk of hypoglycemia.

®
Repaglinide (Prandin )

This drug stimulates insulin release from pancreatic beta cells.

Dose 0.5-4 mg PO ac; may dose bid/qid preprandial, not to exceed 16

mg/d

Interactions: Thiazide diuretics, corticosteroids, estrogens, oral

contraceptives, nicotinic acid, CCBs, phenothiazines, and thyroid
products may lower glycemic control; toxicity increased with highly
protein-bound drugs (e.g., NSAIDs, sulfonamides, anticoagulants,
hydantoins, salicylates, phenylbutazone) CYP3A4 inhibitors (e.g.,
clarithromycin, ketoconazole, miconazole, erythromycin) decrease
metabolism, increasing serum levels and effects

Contraindications

Documented hypersensitivity; DKA; Type 1 diabetes mellitus

Precautions

Hypoglycemia, especially if carbohydrate not taken after medication;

caution in hepatic impairment

Nateglinide

This is a short-acting insulin secretagogue and its action is dependent

upon functional beta-cells in pancreatic islets. It stimulates pancreatic
insulin secretion within 20 min of oral administration.

Dose 120 mg PO tid ac; may decrease to 60 mg PO tid ac

Interactions: Metabolized by cytochrome P450 isozyme CYP2C9 (70

%) and CYP3A4 (30 %); may inhibit CYP2C9; inhibitors of CYP2C9
(e.g., NSAIDs, fluvoxamine, cimetidine) may decrease elimination;
inducers of CYP2C9 (eg, carbamazepine, phenobarbital, phenytoin)
may enhance elimination; co-administration with NSAIDs, salicylates,
MAOIs, and non-selective beta-blocking agents may potentiate
hypoglycemic effects; thiazides, corticosteroids, thyroid products, and
sympathomimetics may reduce hypoglycemic effects

Contraindications

Documented hypersensitivity; diabetic ketoacidosis

Precautions

Reduce dose in hepatic impairment; may cause hypoglycemia (monitor

glucose level); may cause GI distress; hypersensitivity reactions have
been reported.
Biguanides

These agents increase sensitivity of insulin by decreasing hepatic

gluconeogenesis (primary effect) and increasing peripheral insulin
 8
sensitivity (secondary effect). They do not increase insulin levels or
cause weight gain. Alone, they rarely cause hypoglycemia. The agents
are similar to the sulfonylureas. Metformin, one of the commonly used
biguanides when used alone reduces the HbA1c by 1 % to 2 %. In
overweight patients with Type 2 diabetes, metformin therapy has been
associated with a decrease in diabetes related end-points such as death
from hyperglycemia, fatal or non fatal myocardial infarction, or renal
failure) when compared to therapy with insulin and sulfonylureas.
Metformin together with lifestyle changes is recommended as initial
therapy for managing Type 2 diabetes.

Metformin is absorbed from intestine (bioavailability 50-60 %). It is not

bound to plasma proteins, not metabolized; rapidly eliminated by
kidneys. Levels increase markedly in renal insufficiency. Metformin
accumulates in the intestine; may decrease local glucose absorption
(may explain GI effects such as discomfort and diarrhea). At high plasma
levels (e.g., in renal failure), it accumulates in the mitochondria; inhibits
oxidative phosphorylation and causes lactic acidosis (potentiated by
alcohol). This side effect is rare, however to reduce the risk of lactic
acidosis metformin is contraindicated in females with serum creatinine
of = 1.4 mg/dl or males with creatinine of = 1.5 mg/dl.

Metformin (Glucophage®)

The drug could be used as monotherapy or with sulfonylurea,

thiazolidinediones, or insulin. It should be taken with food to minimize
adverse GI effects.

Dose Metformin immediate release: 500 or 850 mg/d PO with dinner;

increase less than q2wk to desired effect (1 g PO bid), GI effects prevent
increase, or 2550 mg/d

Interactions: Numerous possible, few (if any) clinically significant

Contraindications

Serum creatinine level > 1.5 mg/dL (men) or > 1.4 mg/dL (women);
hepatic dysfunction; acute or chronic acidosis; local or systemic tissue
hypoxia; excessive alcohol intake; drug therapy for CHF

Precautions

There may be fatal lactic acidosis if given where contraindicated (rare

without contraindication); discontinue before IV contrast enhancement,
do not restart until creatinine level returns to normal; withhold in acute
hypoxia; check renal function regularly and discontinue if abnormal;
adverse effects (including GI, especially diarrhea [30 %]), may cause
discontinuation (5 %)
Thiazolidinediones

Thiazolidinedione derivatives improve glycemic control by improving

insulin sensitivity. These drugs are selective agonists for peroxisome
proliferator-activated receptor-gamma (PPAR-gamma).9 Activation of
PPAR-gamma receptors regulates insulin-responsive gene
transcription involved in glucose production, transport, and utilization,
thereby reducing blood glucose concentrations and hyperinsulinemia. It
must be taken about 12-16 weeks to achieve maximal effect and can
reduce HbA1c by 0.5 % to 1.4 %. These agents are used as
monotherapy or with sulfonylureas, metformin, meglitinide, or insulin.

Rosiglitazone has been a subject of controversy due to concerns about

increased cardiovascular risk with this agent. Two recent meta-analyses
have suggested that rosiglitazone is associated with an increased risk of
myocardial infarction, and an interim analysis of a prospective trial was
inconclusive regarding the risk of myocardial infarction and
cardiovascular death with rosiglitazone. As a result, rosiglitazone is not
recommended for the treatment of Type 2 diabetes in the most recent
treatment algorithm.
 ®
Rosiglitazone (Avandia )

The agent is an insulin sensitizer. Its major effect is to stimulate glucose

uptake in skeletal muscle and adipose tissue. It lowers plasma insulin
levels and its used to treat Type 2 diabetes mellitus with insulin
resistance.

Dose 4-8 mg/d PO or divided bid

Interactions: With insulin or oral hypoglycemic agents (e.g.

sulfonylureas) may increase risk of hypoglycemia

Contraindications

Documented hypersensitivity; active liver disease, ALT level > 2.5 times
upper limits of normal; DKA; Type 1 diabetes mellitus; congestive heart
failure

Precautions

Caution in edema; may worsen macular edema; may decrease

hemoglobin, hematocrit, and WBC counts (dilution); may increase HDL
cholesterol, neutral effect on triglycerides; may increase risk for distal
fractures in women.

Pioglitazone

This is an insulin sensitizer. It decreases hepatic glucose output and

increases insulin-dependent glucose use in skeletal muscle and possibly
liver and adipose tissue.

Dose 15 or 30 mg PO qd; may increase prn; not to exceed 45 mg/d;

maximal effect may not be achieved for up to 12 wk

Interactions: With insulin or oral hypoglycemic agents (e.g.

sulfonylureas) may increase risk of hypoglycemia
Contraindications

Documented hypersensitivity; active liver disease, ALT level > 2.5 times
upper limits of normal; DKA; Type 1 diabetes mellitus; congestive heart
failure

Precautions

Caution in patients with edema; may worsen macular edema; may

decrease hemoglobin, hematocrit, and WBC counts (dilution); effects on
lipids neutral or beneficial (decreased triglyceride, increased HDL
levels); may increase risk for distal fractures in women.

Alpha-glucosidase Inhibitors

Acarbose and miglitol are alpha-glucosidase inhibitors that lower

postprandial glucose by inhibiting the breakdown of complex starches in
10
the intestine, thereby delaying carbohydrate absorption. They are
taken at the beginning of each meal and may reduce A1C by 0.5 % to 0.8
%. They have a high incidence of flatulence, bloating, and diarrhea.
Alpha-glucosidase inhibitors (AGIs) do not increase insulin levels or
inhibit lactase; their major effect is to lower postprandial glucose levels
(lesser effect on fasting levels). They do not cause weight gain and may
restore ovulation in anovulation due to insulin resistance.

®
Acarbose (Precose )

This agent delays hydrolysis of ingested complex carbohydrates and

disaccharides and absorption of glucose. It inhibits metabolism of
sucrose to glucose and fructose.

Dose 25 mg PO tid ac initially with first bite of food; adjust q4-8 wk based
on 1-h postprandial glucose levels and tolerance; may increase dose
prn, not to exceed 100 mg PO tid

Interactions: Hypoglycemia with insulin or sulfonylurea agents (give

glucose as dextrose, as absorption of long-chain carbohydrates is
delayed); may decrease absorption and bioavailability of digoxin,
propranolol, and ranitidine; digestive enzymes (e.g. amylase,
pancreatin) may reduce effects

Contraindications

Documented hypersensitivity; DKA; cirrhosis; IBD; colonic ulceration;

serum creatinine level > 2 mg/dl; elevated liver enzyme levels; partial or
predisposition to intestinal obstruction

Precautions

Gastrointestinal effects (e.g. flatulence, diarrhea, abdominal

discomfort) common, especially with metformin (17 % discontinue);
systemic accumulation at high doses and in renal dysfunction, with
possible drug-induced hepatitis
Dipeptidyl Peptidase IV (DPP-4) Inhibitors

These agents block the action of DPP-4, which is known to degrade

incretin hormones such as glucagon-like peptide 1 (GLP-1) and glucose
dependent insulinotropic polypeptide (GIP),10 thereby increasing its
concentrations. The levels of GLP-1 achieved enhance glucose-
dependent insulin secretion and suppress elevated glucagon secretion.
Examples of these agents are Sitagliptin and Saxagliptin.

Incretin Mimetics

Exenatide, an incretin mimetic indicated for Type 2 diabetes, targets

blood glucose by increasing glucose-dependent insulin synthesis and
10
release and diminishing inappropriate secretion of glucagon.
Exenatide also slows gastric emptying and increases satiety, thereby
reducing food intake. The drug is injected twice daily within the 60
minutes preceding a main meal. When used as monotherapy, exenatide
21
lowers the A1C by 0.5 % to 1 %. Because of its peptide nature patients
may develop antibodies to exenatide. In most cases, the titers lessen
over time. Patients who develop high titers of antiexenatide antibodies (3
%-9 %) may experience attenuated response to exenatide and require
alternative pharmacotherapy.

Due to delayed gastric emptying, exenatide has a high rate of nausea,

especially upon initiation of treatment. Furthermore, delayed gastric
emptying may negatively affect the absorption of oral medications, which
can be particularly concerning in older patients on multiple medications.3
During postmarketing surveillance, exenatide has been associated with
acute pancreatitis. Exenatide has the potential benefit of modest weight
loss; however, weight loss is undesirable in the frail elderly. Due to the
above concerns, the expense of the drug, and limited safety and efficacy
data in the elderly, exenatide should be reserved for those who fail to
respond to other therapies.
Amylin Analogs

These agents have endogenous amylin effects; they delay gastric

emptying, decrease postprandial glucagon release, and modulate
8
appetite. Pramlintide is a synthetic analogue of amylin, a hormone that
is co-secreted with insulin by pancreatic beta cells following food intake.
Like exenatide, pramlintide decreases postprandial glucagon secretion,
delays gastric emptying, and enhances satiety; however, it does not
promote insulin secretion. Pramlintide is indicated for Type 1 or 2
diabetes as an adjunct to mealtime insulin, and it reduces the HbA1c by an
additional 0.5 % to 0.6 %.

Pramlintide should be injected three times daily prior to major meals

(>30 g carbohydrate) and should not be mixed with insulin. Pramlintide
increases the risk of severe hypoglycemia, and it should not be
administered in patients with hypoglycemic unawareness, a condition
more likely in the elderly. To reduce the risk of hypoglycemia, the dose of
preprandial insulin should be decreased by 50 % when initiating
pramlintide. Due to delayed gastric emptying, pramlintide frequently
causes nausea and can impact the absorption of oral medications,
another important consideration in the elderly who take multiple
8
medications. Because it necessitates multiple daily injections,
increases the risk of severe hypoglycemia, and provides only modest
efficacy, pramlintide has limited utility in older patients.

Application of pharmaceutical care in diabetes mellitus

It is common knowledge now that there is a huge problem of drug related
morbidity and mortality which confronts health care systems and the
general public. This is one of the major driving forces for the
implementation of pharmaceutical care. In Nigeria, data are not readily
available but we know that in the USA, about 7,000 patients die each
year from medication errors and 65% of hospitalized patients have
dangerous life threatening reactions to prescribed medications1 what
.
these values would be in a developing country like ours is better left to
the imagination. The pharmacist as a pharmaceutical care practitioner
can play a huge role in drastically reducing drug related adverse
incidents particularly in patients with chronic diseases such as Diabetes,
hypertension, asthma, etc.
The African continent counts approximately 14 million people with
diabetes. Estimates for 2005 are likely to double and reach 27 million.
Nigeria has the highest number of people with diabetes approximately
 11
1,218,000 people are affected. These figures show clearly that there is
an explosion of patients being diagnosed with diabetes, unfortunately,
the overall care of patients with the disease remains suboptimal.
A team approach involving the patient, physician and diabetes educator
(nurse, dietitian and or pharmacist) has proven to result in a lowering of
the patient's HbA1c values, reduced acute and chronic complication
12
decreased hospitalizations and improved quality of life.
Pharmacists by applying the principles of pharmaceutical care can
work with patients with diabetes as well as collaboratively with medical
providers, often in primary care setting or in close proximity to the
13
providers' practices. Various studies have shown that patients who
receive pharmaceutical care inputs demonstrate improved glycemic
control, blood pressure, as well as low-density-lipoprotein cholesterol
levels, quality-of-life measures and meet treatment goals more often
14-19
than patients receiving standard care. In different practice settings
pharmacists help to identify, assess, monitor, educate and refer
patients thereby reducing the emergency room visits of patients and
decreasing the total health care costs of diabetes.
Why Pharmaceutical Care in Diabetes?
Diabetes is a chronic illness that is receiving much attention because
of:
· The increasing prevalence of the disease due to lifestyle
changes and better methods of detection.
· Its relationship to other co-morbid conditions such as
hypertension, dyslipidemia and obesity.
· Increased awareness of the impact of glucose control on the
disease and related conditions.
· The cost of the disease to society.
· Patients with Type 2 diabetes represent over 80 % of the
diabetes population.
 · A pharmaceutical care delivery approach focuses on
prevalent diseases and Type 2 diabetes is a good example.
· Diabetes care provides opportunity for collaborative care.
· Inclusion of pharmacists in diabetes care teams improves
patient outcomes

Role of the Pharmacist

Identification
The first thing is to identify the patients with diabetes, these may include
those already known that the pharmacist wishes to render
pharmaceutical care and those who have not been previously
diagnosed.20 This can be achieved through analyzing prescriptions and
diabetes care product sales for patients with diabetes, establishing a
data base of these patients would be a first step in establishing a
therapeutic relationship with them. This identification role is very
important particularly now that the new diagnostic criteria
recommended by the American Diabetes Association have reduced the
fasting plasma glucose level for diagnosis from 140 mg/dl to 126 mg/dl.
The vast majority of undiagnosed Type II diabetes would be among the
groups listed below. Patients with high risk of developing diabetes
include:
· Overweight patients with abdominal obesity
· Age over 40 years
· Family history of diabetes
· Patients with hypertension
· Patients with hyperlipidemia
· Individuals with birth weight of over 4.1 g
· Women who have given birth to babies over 4.1 kg
Assessment of Diabetes Care
Patient assessment can be defined as a systematic process of
acquiring, analyzing and interpreting subjective and objective patient
information to identify, resolve and prevent drug-related and disease
21
related problems.
In order to assess thoroughly the diabetes patient, the pharmacist
should obtain the following as a patient database:

· Past and current health history

· Medication history (both prescription ,OTC and herbal)
· Medication side effects/allergies/intolerances
· Information regarding hypoglycemic and hyperglycemic
reactions
· Glucose monitoring data
· Diet, smoking, alcohol, caffeine/drug use history
· Exercise history
· Information about patient's foot care and diabetes
complication.

The above information can be gathered by interviewing the patient

privately or by having the patient fill out a Diabetes Patient Assessment
12
Questionnaire. It has been shown that patients who adhere to
standards of diabetes care have improved outcomes. The pharmacist
can review the assessment form and quickly determine the patient's
level of care, identify gaps in the care plan, evaluate where the patient
falls in a diabetes medication treatment algorithm or standard treatment
guidelines and from this determine which diabetes care products should
be recommended for the patient, as well as appropriate referrals to other
health care professionals such as dieticians, dentists, ophthalmologists,
podiatrists.
Monitoring Medication Use
Drug Regimen Review
The pharmacist should note that the ideal pharmacotherapeutic
regimen comprises drugs which cover all indications identified by
detailed clinical assessment and appropriate laboratory tests. The
regimen should be well tolerated, safe and effective, devoid of significant
interactions. Unfortunately, this ideal can be difficult to achieve,
22
especially in chronic diseases such a diabetes. The fact that diabetes is
a progressive chronic illness means that patients may likely develop co-
mobidities such as hypertension, dyslipidemia, or complications which
invariably will increase the number and complexity of the patient's drug
regimen. This area of drug regimen or pharmacotherapy review is one
where pharmacists can exert a huge influence on the health of their
patients.
After obtaining the patient's past health history, the pharmacist should
review the patient medication profile to:
· Determine whether drug therapy correlate with medical
problems
· Assess the patient for drug-related problems
· Determine whether drug related problems are being treated
· Determine whether current drug therapy is appropriate
· Determine whether additional drug therapy is needed
· Determine if any of the drug-related problems may have been
caused by medication.
Performing this medication review helps the pharmacist to identify
therapeutic issues not recognized by other disciplines. Examples of
such therapeutic issues include determining medications which
increase or decrease blood glucose as shown below.

Some medications that interfere with blood sugar

Increase Glucose Decrease Glucose

Glucocorticoids Ethanol

Oral contraceptives Beta adrenoceptor Antagonists

Diuretics Salicylates (High doses)

An understanding of the types of drug related problems that may occur

facilitates the evaluation process; most drug-related problems generally
are the result of:
· Not receiving an indicated drug (or device or intervention)
· Receiving the wrong drug(or device or intervention)/ a more
efficacious choice is possible
· Receiving too little of the right drug
· Receiving too much of the right drug
· Experiencing an adverse drug reactions
· Experiencing a drug interaction
· Not receiving the prescribed drug
· Receiving a drug for which there is no valid medical indication.
After identifying the patients' drug related problems the next step would
be to develop the resolutions, prioritize and then implement them.
Establishing therapeutic goals required for the achievement of the
desired outcome for each drug related problem identified helps in the
process of resolving the drug related problems.
Drug therapy problems
Common problems in diabetes include:
· Adherence problems
· Untreated indication or additional drug therapy such
as:
· Influenza vaccine to all patients with diabetes 6 mo
and over
· Therapy for dyslipidemia
· Aspirin prophylaxis
Patient focused interventions
· Educating diabetes patients helps to empower them.
Pharmacists mandatorily have to counsel their patients
about medications but for diabetes patients, pharmacists
play a relatively unique role as educators by instructing
diabetic patients on proper use of diabetes medications,
care product etc. Other topics include, educating the
patient to self monitor blood glucose, proper foot and
dental care.
· Diabetes Mellitus is a disease that needs more
pharmacist involvement, there are a growing number of
people affected by the disease and this portends an
increase in the amount of money directly or indirectly
spent on the disease and its complications. Greater
pharmacist involvement in the screening and
management of the disease may well be the solution to
reducing costs, delaying onset, early detection, and
better monitoring as well as educating patients,
encouraging compliance and improving the overall
quality of life of patients .
Patient outcomes in diabetes management
Clinical Outcomes:
· Glycemic control, assessed by Hb A1C < 7 %, FPG <
126 mg/dl (7.0 mmol/l), Casual plasma glucose < 200
mg/dl (11.1 mmol/l). To convert mg/dl to mmol/l divide
by 18
· BP < 130/80 mmHg and Total Cholesterol level < 200
mg/dl
· Symptom control: polyuria, polyphagia, polydypsia
· Improved adherence to therapy (pharmacological and
lifestyle)
Humanistic outcomes:
· Patient knowledge of diabetes and its management.
· Attitudes about illness
· Expectations from management
· Satisfaction with treatment
· Health related quality of life physical, emotional,
social, and financial well-being
Economic outcomes:
· Decreased direct medical costs
· Increased productivity due to reduced sick time.
· Reduction in hospitalization and length of stay
· Reduction in physician visits etc.
 Key Learning Points

· The term diabetes mellitus (DM) describes a metabolic

disorder of carbohydrate, fat and protein metabolism.

· There are Type 1 (Insulin Dependent), Type 2 (Non

Insulin Dependent), and Gestational (Associated with
pregnancy).

· Acute complications of diabetes include: Diabetic

ketoacidosis (DKA), nonketotic hyperosmolar coma, and
hyperglycemia.

· Chronic complications may be microvascular (diabetic

retinopathy, neuropathy and nephropathy), or
macrovascular (hypertension, coronary artery disease,
angina pectoris, acute myocardial infarction, peripheral
vascular disease, and cerebrovascular accident -
Ischemic).
· Various forms of insulin preparations and oral
hypoglycaemic agents (Sulfonylureas, Meglitinides,
Biguanides, Thiazolidinediones, Alpha-glucosidase
Inhibitors, Dipeptidyl Peptidase IV (DPP-4) Inhibitors,
and Amylin Analogs) are utilized.

· As part of standard diabetes care the patient ought to

check the following at least 3 times a year:
Ü Random or fasting blood glucose
ü Haemoglobin AIC (<5.9 % - < 7 %)
ü Weight and height (BMI)
ü Blood pressure (should be <130/80 mmHg)
ü Feet examination
ü Cardiac status and or risk
ü Skin care
ü Analysis of daily self monitoring of blood
glucose results
ü Medication/insulin regimen
ü Other medical conditions and their treatments
ü Nutrition plan
 ü Exercise plan
ü Frequency of acute diabetes complication
ü Long-term complications, e.g. Neuropathy,
GIT problems, sexual dysfunction, infections
ü Smoking status
ü Educational needs
ü Psychological well-being
ü Aspirin use

References
1. Sarah Wild, Gojka Roglic, Anderson Green, Richard Sicree,
Hilary King (2004). Global prevalence of diabetes. Diabetes
Care 27:(5)1047-1053.
2. The Expert Committee on the Diagnosis and Classification of
Diabetes Mellitus Follow Up Report on the Diagnosis of
Diabetes Mellitus (2003). Diabetes Care 26:3160-3167.
3. The Expert Committee on the Diagnosis and Classification of
Diabetes Mellitus. Report of the expert committee on diagnosis
and classification of diabetes mellitus (1997). Diabetes Care;
20:1183-1197.
4. American Diabetes Association; Diagnosis and classification of
Diabetes mellitus (2004). Diabetes Care; 27, supp. 1; 55
5. Fonseca V (2006). The role of insulin therapy in patients with
type 2 diabetes mellitus. Insulin 1(2):51-60.
6. Hirsh IB, Bergenstal RM, Parkin CG, Wright E (Jr) Buse JB
(2005). A real world approach to insulin therapy in primary care
practice. Clinical Diabetes 23(2) 78-86.
7. Peters AC, Davidson MB (1990). Use of sulphonylureas in older
diabetic patients. Clin Geriatr Med;6(4) 903-21
8. Rosenstock J, Hassman DR, Madder RD, Brazinsky SA, Farrel
J, Khutoryyansky N, et al (2004). Rapaglinide versus
Nateglinide Monotherapy. Diabetes Care 27:1265-1270.
9. Votey SR, Peters AL, Diabetes Mellitus, Type 2 A review ,
available at http://emedicine.medscape.com; Accessed 30 Sept.
2009
10. Nathan DM (2006). Thiazolidinediones for initial treatment of
Type 2 diabetes? N Engl. J Med 355;23 2477-80.
11. Modi P (2007). Diabetes beyond insulin: Review of new drugs for
treatment of diabetes mellitus. Current Drug Discovery
Technologies; 4, 39-47
12. International Diabetes Federation 2006. The International
W o r k i n g G r o u p o n t h e D i a b e t i c
Foot.http://www.idf.org/webdata/docs/Background-info-
athens.pdf
13. Keith Campbell R, Bennett James (2002). How to assess the
health care needs of diabetes patients. The Diabetes Educator;
28;40
14. Keil DJ, Mc Cord AD (2005). Pharmacist impact on clinical
outcomes in a diabetes disease management programme via
collaborative practice. Ann. Pharmacother;39;1828-32
15. Morello CM, Zadvorny EB, Cording MA, Suemoto RT, Skog J,
Harari A (2006). Development and Clinical outcomes of
pharmacist managed diabetes care clinics. Am. J Health Syst
Pharm;631325-31
16. Scott DM, Boyd ST, Stephan M, Augustine SC, Reardon TP
(2006). Outcomes of pharmacist management diabetes care
services in a community health centre. Am J Health Syst Pham;
63:2116 212.
17. Rogucci KR, Fermo ID, Wessel AM, Chumney CG (2005).
Effectiveness of Pharmacist Administered Diabetes Mellitus
Education and Management Services. Pharmacotherapy; 25:
1809 1816.
18. Cranor CW, Bunting BA, Christensen DB (2003). The Ashville
Project: Long-term clinical and economic outcomes of a
community Pharmacy diabetes fare programme. J Am Pharm
Assoc.; 43: 173.
19. Lial S, Glover JJ, Heirier RN, Felix A (2004). Improving quality of
care in diabetes through a comprehensive pharmacist-based
disease management programme. Diabetes care; 27(12): 2983
84.
20. Campbell RK, Bennett JA (2002). Assessing diabetes patient's
Healthcare needs. The Diabetes Educator; (28): 40 50.
21. Campbell RK, (2002). Role of the pharmacist in diabetes
management Am J Health-Syst Pharm (59 ): 1, Suppl 9.
22. Davis TM, Clifford RM, Davis WA, Batty KT (2005). The role of
pharmaceutical care in diabetes management. British Journal
of Diabetes and Vascular Disease; 5; 352 356
 CHAPTER NINETEEN

PHARMACEUTICAL CARE IN RHEUMATOID ARTHRITIS

AND OSTEOARTHRITIS
Frederick O Oseji and Uche M Ochei

Learning Objectives
At the end of this chapter, you should be able to:
I. Understand the basic pathophysiology of arthritis
ii. Discuss non-drug therapy and drug therapy of arthritis
iii. Illustrate pharmaceutical care of arthritis disease
Introduction
Arthritis literally means “joint inflammation” and this can be caused by
numerous factors. Arthritis includes: rheumatoid arthritis, osteoarthritis,
psoriatic arthritis and gout. They affect patients differently and may have
significantly different complications. As such, it is necessary to know the
exact type or form of arthritis being treated. Rheumatoid arthritis (RA) is
one of the most common chronic inflammatory conditions affecting the
population worldwide. Joint pain and loss of function are the most
obvious symptoms of RA and the early symptoms are non specific,
consisting of fatigue, malaise, diffuse musculoskeletal pain and stiffness.
The peripheral joints of the hands and feet are usually involved first and
are usually symmetrical. The most serious long-term disability is
associated with damage to the larger weight bearing joints. RA patients
usually experience prolonged morning stiffness, which improves during
the day, only to return at night.
RA is a progressive disease of the synovial lining of peripheral joints
characterized by symmetrical inflammation leading to potentially
deforming polyarthritis and a wide spectrum of extra-articular features
such as anaemia, nodules, muscle wasting, dry eyes (Sjogren's
syndrome), depression, osteoporosis, epicleritis, carpal tunnel
syndrome, leg ulcers, lymphadenopathy, nail-fold vasculitis, peripheral
sensory neuropathy and rarely: pleural effusion, pulmonary fibrosis,
pericarditis, sclerotic, systemic vasculitis, mitral valve and conduction
1
defects.
In most cases, RA patients have remission and exacerbations of the
symptoms showing times when patients “feel good” and times they “feel
worse.” There will likely be times when a patient with RA “feels cured”.
Only very few patients have complete remission of the disease and it is
essential that patients do not stop an already established treatment
program.

RA is an acquired autoimmune disease in which genetic factors appear

to play a role. The presence of HLA DR4 antibody in 70 % of patients with
RA lends support to the genetic predisposition to the disease.
Rheumatoid Factors (RFs) which are antibodies to 1gG are present in 60
- 80 % of adults with RA. High titres of RFs are usually associated with
severe active joint disease, systemic involvement, and a poor prognosis
for remission.
Epidemiology
RA affects approximately 1% of the adult population worldwide, with
twice as many female sufferers as male. The prevalence of RA increases
with age in both sexes with nearly 5 % of women and 2 % of men over 55
years of age affected. The age of onset is typically around 30-50 years
and reaches its peak in the fourth decade. Some ethnic variation has
also been observed in the prevalence of RA. Among rural black Africans,
the prevalence is low, about 0.1 %, compared to 3 % in Caucasians. A
comparative study among urban and rural populations suggests that
 1
environmental factors associated with urban life may play a role.
Socio-economic impact of RA
RA has major socio-economic implications for the affected population.
The articular and extra-articular progressive nature of RA leads to both
significant patient morbidity and mortality. Patients with RA have six
times the probability of severe limitation of activity, four times as many
restricted days and 10 times the work disability rate of the general
population. Over a period of 6 years, the average earnings of a patient
with RA will be reduced by approximately 60 % and after 10 years of
disease duration, more than 50 % of patients are unable to work at all.
Survival rates among patients with RA are lower than those in the
general population. Median life expectancy is reduced by 7 years for
men and 3 years for women. These reduced survival rates are similar to
1
those observed for Hodgkin's disease, diabetes and stroke.
Etiology
The cause of RA remains unclear, though there is abundant evidence
that RA is immune-mediated, it is still not clear whether it is primarily an
autoimmune disease. It is possible that many different arthritogenic
stimuli activate the immune response in the susceptible host. Whether
the initiating agent is an infection, a self antigen or an environmental
2
factor remains unproven.
Epidemiological data support the case for both environmental and
genetic factors causing RA. Research in twins and other genetic
studies suggest the genetic component is at best 30 percent. RA may be
classified based on the clinical manifestation, Table 19.1. The presence
1
of four of the listed criteria is diagnostic of rheumatoid arthritis.
Table 19.1: Classification of RA based on clinical manifestation

1. Morning Stiffness Duration >1 hr lasting > 6 weeks

2. Arthritis of at least three areas Soft tissue swelling or exudation

> 6 weeks

3. Arthritis of hand joints Wrist, metacarpophalangeal

Joints or proximal interphalangeal
joints lasting > 6 weeks.

4. Symmetrical arthritis At least one area, lasting

> 6 weeks.

5. Rheumatoid nodules As observed by physicians

6. Serum rheumatoid factors. As assessed by a method

positive in less than 5 % of control
subjects.

7. Radiographic changes As seen on anteriposterior films

of wrists and hands.

Investigations /Differential diagnosis

The diagnosis of RA is usually made on presenting signs, symptoms
and some biochemical investigations. The most useful of these are
the inflammatory markers, such as Erythrocyte Sedimentation Rate
(ESR), C-Reative Protein (CRP) and Plasma Viscosity (PV),
Rheumatoid Factor (RF), and Antinuclear Antibodies (ANAs). A
raised inflammatory marker simply confirms the presence of an
inflammatory condition and is present in many disease states,
though a normal inflammatory marker does not necessary exclude
an active disease. Although these markers are not specific for RA,
 they may be used to assess response to drug treatment as they are
usually raised when the disease is active. Other abnormal laboratory
tests include an elevated alkaline phosphatase, an elevated platelet
count, a decreased serum albumin level and a normochromic,
normocytic anaemia.
Radiographs of the hands and feet are used in establishing the
diagnosis of RA and also to tract its progression. Erosions at joint
margins and loss of joint space due to erosion of cartilage and bone
may be identified. The synovial fluid is not routinely analyzed to
establish the diagnosis of RA but typically, it is yellow , watery and
turbid due to a high white blood cell count, and has a low glucose
content-subluxation and deformity are the dominant features of
severe long standing RA.
Therapy
Goals of therapy
The goals of therapy of rheumatoid arthritis are to:
· Relieve pain and inflammation
· Prevent joint destruction
· Preserve or improve functional ability
· Maintain a normal lifestyle
· Avoid, minimize or eliminate adverse effects resulting
from therapy
· Promote rehabilitation.

Treatment should begin as soon as possible as there is evidence that

most patients develop joint destruction within the first two years of their
3
disease. A multi-disciplinary approach to treating RA patients is
important. Physiotherapists, occupational therapists, clinical nurse
specialists, podiatrists, social workers and pharmacists, all have crucial
roles. Education of the patients and family members is important. The
patient should have a good knowledge of the disease process, the likely
prognosis, treatment strategies and the psychological aspects of the
disease. Such education is best carried out by the multi-disciplinary
team and should reinforce the importance of adherence to all aspects of
treatment plan. Each patient's treatment should be individualized based
on factors such as age, occupation, family responsibilities, severity of
the disease, joint function, and the patient's response to previous
therapy.
Selected parameters are used to assess disease severity and drug
response to RA and these may include:
· Duration of morning stiffness
· Number of painful and tender joints (severity of pain)
· Number of swollen joints
· Range of joint motion (gait changes)
· Circumference of affected joints (joint deformity
development)
· Time of onset of fatigue
· Erythrocyte Sedimentation Rate (ESR)
· Signs of depression
· Weight loss.

Non drug therapy

Nondrug therapies are widely used in all stages of RA. Patients should
be well informed of the nature and possible progression of their disease
in order to promote self-awareness, self-determination and self reliance
as well as the knowledge of when to seek help from others. Family
support is essential since negative attitudes towards the patient's
disease reduces coping and adaptation and produces more stress than
the patient experiences.
Physiotherapy
Physiotherapy is a vital part of treating RA, both in acute flares of the
disease and chronic state. Heat, cold and electrotherapy help to reduce
pain and swelling. A program of exercise and rest strengthens joints to
prevent disuse atrophy, mobilize joints to minimize deformity and
increase the range of movement and functions.

Occupational therapy
Occupational therapy educates patients to protect joints with the use of
appliances and splint. Surgical techniques, ranging from carpal tunnel
decompression to major joint replacement can be effective in relieving
pain and restoring function. Surgical intervention is becoming less
frequent with the availability of aggressive and effective drug treatments.
Occupational therapists assist in the design and use of special eating
utensils, grooming aids, working aids and other self-help aids that are
useful in maintaining patients' self-reliance. Splints may be useful in
stabilizing a weak joint, resting an active joint or possibly diminishing the
rate of joint destruction, walking aids or wheelchairs may dramatically
improve a patient's mobility and stability when mobile.
Rest
Rest serves to spare joints, decrease inflammation and ideally leads to
repair of damaged tissues. Patients with RA and fatigue should not
diminish activity completely but should be encouraged to rest on a
routine basis each day. Prolonged immobility may lead to increased
stiffness and diminished mobility of joints and strength.
Nutrition
Proper nutrition is required to help patients lose weight, if overweight and
maintain protein and calcium intake. Fish oils, certain plant seed oils and
a vegetarian diet may be of some benefit in RA.
Hot paraffin wax treatments may decrease inflammation and discomfort.
Topical ointments, creams and liniments may provide some local relief.
External application of heat by soaking hands and feet in hot water baths
may reduce joint stiffness and allow greater benefit from a passive
exercise program. Several heat applications per day may be more
effective than a single prolonged treatment.
Drug therapy
Each patient's treatment is individualized and the selection and use of
drugs may be influenced by a few general guidelines such as:
· Nature of disease. Early referral as indicated
· The phase and extent of the disease
· The presence and absence of complications such as
dyspepsia or other gastrointestinal symptoms.
· Possible prognosis and safe and effective treatment
strategies-considering convenience and cost.
· The side effects of the drug(s) in question (usually dose
related)
· Possible clinically important interactions between the
various drugs the patient may be taking.
· Individual risk factors based on age, degree of disease
activity etc, should be considered
· Possibility of multidisciplinary approach to RA care which
ensures that treatment is holistic, giving adequate
adherence to all aspects of the treatment plan.
· Some drug toxicities may be discovered by appropriate
laboratory monitoring before serious problems become
clinically apparent.

The ultimate aim of treatment is to induce disease remission. RA is

traditionally treated in a step wise, “pyramidal” manner. Analgesics and
non-steroidal anti-inflammatory drugs (NSAIDs) are the first choice for
the relief of symptoms. Where symptoms are not adequately controlled,
the second-line (e.g. sulfasalazine) and third- line (e.g. azathioprine)
agents, which are disease modifying anti-rheumatic drugs (DMARDs),
are used. DMARDs suppress markers of disease activity and improve
function but with no serious impact on long-term disability. Treatment
that suppresses underlying inflammation produces improvements in
functions and bone erosions. Reduction in previously C-reactive
protein (CRP) levels has correlated with better preservation of joint
function. Though complete disease remission is nearly impossible,
CRP assessment gives a good indication of disease activity and
correlates with preservation of function and should, as such, be kept as
near normal as possible.
First-line Agents
Simple analgesics
Acetylsalicylic acid (ASA), paracetamol, paracetamol combinations
and hydrocodeine are useful for simple pain relief. Although they have
no anti-inflammatory properties, and do not affect the disease process,
they do have a place in both early and late stages of the disease. They
may help in relieving referred pain associated with muscle weakness
and the general soreness associated with RA.

ASA is as effective as any other NSAID and is much less expensive. It

can be administered initially as an analgesic, then at higher doses as an
anti-inflammatory agent. It appears to work (at least in part), by
inhibiting prostaglandins (PGs) synthesis and release. A total daily
dose is 3.6 g 5-4 g is recommended.
ASA interferes with platelet function and can cause serious bleeding
which may persist for 4-7 days after the dose has been discontinued.4
Tinnitus and rarely hepatitis or renal damage can occur with high doses
of ASA therapy. Tinnitus is a sign to decrease dose to the minimum that
can be tolerated. However, the intolerable gastrointestinal effects
noted in some patients may be avoided or reduced by the use of
enteric-coated agents or taking the drug with or after meals followed by
a glass of water or an appropriate antacid. Reversible elevations of
liver transaminase and alkaline phosphatase are occasionally seen
with salicylate levels in the therapeutic range especially in juvenile RA
and systemic lupus erythromatosus (SLE).
Platelet aggregation is irreversibly decreased by ASA, therefore,
caution must be exercised in patients with bleeding tendencies or
coagulation defects. Serum levels of 40- 90 mg/100 ml are toxic and may
lead to hyperventilation, respiratory alkalosis, metabolic acidosis, fever,
coma and ultimately, dehydration with renal failure and condiovascular
collapse. Salicylates must be avoided or used with extreme caution in
patients with a history of recurrent urticaria, nasal polyps or asthma
because they usually show idiosyncratic reactions. Salicylates should
be used carefully in patients with hyperuricemia because low doses of
ASA (1-2 g /day) may decrease urate concentrations while large doses (>
5 g/day) induce uricosuria and lower plasma urate levels. The use of
salicylates in children or adolescents with chicken pox or influenza is
contraindicated because of the possibility of Reye's syndrome.
Paracetamol
Paracetamol (acetaminophen) a mild pain reliever, is commonly used to
treat the pain from RA and Osteoarthritis (OA), although unlike NSAIDs,
acetaminophen does not treat the inflammation. A randomized
controlled trial comparing paracetamol with ibuprofen in x-ray-proven
mild to moderate osteoarthritis or RA of the hip or knee found equal
5
benefits.
Non-steroidal anti-inflammatory drugs (NSAIDs)
The NSAIDs form the major agents for the relief of pain and inflammation
in rheumatic diseases. They have replaced the use of high-dose ASA, as
they are less toxic, longer acting and give better adherence.
The main mechanism of action of NSAIDs is believed to be the inhibition
of the enzyme cyclo-oxygenase (COX-1 and COX-2). COX converts the
fatty acid arachidonic acid into endoperoxidases, prostaglandins and
thromboxanes in a cell specific manner. These prostanoids have a
diverse variety of physiological functions including the protection of GI
tract, renal homeostasis, platelet aggregation, contraction of uterine
smooth muscles etc and are widely implicated in pathological states
associated with inflammation. The older traditional NSAIDs inhibit
COX-1 and COX-2 to similar degree. Etodolac and meloxicam inhibit
COX-2 up to 50 times more than COX-1, and the newer agents
celecoxib and rofecoxib, are even more COX-2 selective.
Patients' response to NSAIDs is highly variable, therapeutic trials with
several NSAIDs may be needed to determine the best agent. It is
estimated that 60 % of patients will respond to any one NSAID. After
one week of non-response, it should be changed, if an analgesic effect
is the desired outcome, or three weeks, if an anti-inflammatory effect is
required. There is no evidence of synergism or reduced toxicity with the
use of more than one NSAID. In fact, there is evidence that two NSAIDs
6
may increase the risk of gastrointestinal toxicity. The NSAIDs can be
divided into two broad groups with short or long plasma half-life. Only
one agent should be used at a time, although a short acting drug may be
used during the day with a longer-acting preparation at night.
The site of action for NSAIDs is assumed to be within the joint space,
and as such, synovial fluid pharmacokinetics may be more important for
efficacy than plasma kinetic profiles. Studies on synovial fluid kinetics
show that drug concentrations are more sustained and exhibit less
variability than plasma concentrations. Although the NSAIDs differ in
chemical structure, all of them have similar pharmacological properties
in terms of antipyretic, anti-inflammatory and analgesic actions and are
involved in essentially similar drug interactions. The drug interactions of
the commonly used NSAIDs are shown in the Table 19.2.
 Table 19.2: Drug Interactions of NSAIDs

Affected Drug Drug Causing effect Effect

Oral anticoagulants NSAIDs Aspirin enhances

Hypoprothrombinaemic effect

All increase risk GI bleeding,

All have antiplatelet effects.

Hypotensive agents NSAIDs Decreased hypotensive effect

Diuretics NSAIDs Decreased diuretic effects

Potassuim – Sparing drugs Indomethacin Hyperkalemia

+
e.g. ACE inhibitors, K -sparing diuretics

Lithium Most NSAIDs Increased lithium level

Methotrexate All NSAIDs Increased methotrexate level

Most NSAIDs Probenecid Increased NSAID concentration

Adverse effects
GI complications are the most important adverse reactions, with other
serious reactions including renal impairment, angiodema, urticaria,
hepatic dysfunction, hematological abnormalities and bronchospasm.
Gastric damage appears to require a direct mucosal effect as well as
inhibition of prostaglandin biosynthesis. The impairment of mucosal
defensive factors (mucus and bicarbonate secretion, mucosal blood
flow) also plays a major role. GI adverse reactions range from
superficial damage, with minor symptoms such as dyspepsia,
abdominal pain, and diarrhea, to duodenal and gastric ulceration and
potentially fatal complications. Misoprostol, omeprazole, lansoprazole
may be used to prevent NSAID induced gastric and duodenal ulcers, as
well as the reduction of serious upper GI complications.
Use of COX-2 Selective NSAIDs
These agents appear to have reduced incidence of symptomatic GI
adverse events. Newer ones like rofecoxib and celecoxib are much
more selective than the preferential COX-inhibitors meloxicam,
7
piroxicam. Current data suggest that COX-2 selective NSAIDs are not
always appropriate as first- line therapy in patients with arthritis.
Ibuprofen remains a suitable first choice. Co-prescriptions with a
gastroprotective agent is recommended for older patients with history of
GI ulceration, bleeding or perforation or on systemic corticosteroids or
anti-coagulant.
Second Line Agents
These are referred to as slow-acting anti-rheumatic drugs (SAARDs)
and disease modifying anti-rheumatic drugs (DMARDS). All DMARDs
exhibit potentially severe adverse reactions and as such, require
careful monitoring of patients. Patient information sheets/booklets are
recommended for patients taking DMARDS. Counseling should
reinforce the need for adherence to monitoring requirements, the
expected onset of action, potential toxicity and the relevant action to
take in the event of adverse effects. The precise mechanism of
DMARDs is unclear but they inhibit the release of or reduce the activity
of inflammatory cytokines (TNF, IL-1, IL-2 & IL-6). Activated T-
lymphocytes appear to be particularly important in this process and it is
known that methotrexate, leflunomide and ciclosporin all inhibit T-cells.
Leflunomide has been shown to inhibit the proliferation of B-cells with a
subsequent inhibition of antibody production. Several new biological
therapies have been designed to expressly target T- cells or specific
cytokines. The most recent of these therapies are the anti-TNF agents.
These include the monoclonal antibody, infliximab which neutralizes the
activity of TNF and the soluble TNF receptor etanercept which binds to
TNF and renders it biologically inactive. Interleukin -1 antagonists are
 1
currently being developed for use in RA. Patients with disease that
progresses to deformity may require more than one anti-inflammatory
agent. The dosage, side-effects and monitoring guideline for DMARDs
are presented in Table 19.3. Examples of second line agents include:
Antimalarials Chloroquine & hydroxychloroquine, Methotrexate,
Soduim aurothiomalate (gold salt), Azathioprine, Sulfasalazine (SSZ),
Minocycline, Cyclophosphamid, Penicillamine, Chlorambucil
Sulfasalazine is the most commonly used DMARD due to its favorable
risk-benefit ratio. It has a high continuation rate, a low rate of serious
adverse effects and has been shown to slow disease progression. Its
monitoring requirements are less arduous than most other DMARDs.
To reduce nausea, a daily dose of 500 mg should be given, increasing
weekly up to 1 g twice daily.
Methotrexate is fast becoming first-line therapy, generally given in
patients with moderate to severe disease. It is probably the most
effective DMARD, with a high 5 year continuation rate and a low
incidence of adverse effects at low weekly doses. It has a relatively
rapid onset of action of 4-6 weeks and is easy to administer as a single
weekly dose. It has a relatively high response rate of 40-50 %,
improving quality of life and reducing joint destruction.

Hepatic fibrosis and liver toxicity do occur significantly and appear to

be enhanced by high alcohol intake. Patients should be encouraged to
avoid alcohol or restrict it to only special occasions.
Liver function tests (LFT) must be frequently monitored. Severe
alveolitis can be a serious and even fatal adverse event that requires
urgent medical treatment. Patients with severe dyspnoea should stop
methotrexate and seek urgent medical help. The addition of folic acid
(vitamin B9, 5 mg weekly 5 mg daily) can be used to manage nausea
and stomatitis.
One of the greatest concerns with methotrexate therapy is the potential
for bone marrow suppression, neutropenia and thrombocytopenia
especially in over-dose or patients with too high a maintenance dose.
This can be fatal and is common with the elderly who may inadvertently
take methotrexate daily rather than on the same day each week.
Sodium-aurothiomate (gold injection) is a long established DMARD, a
very effective agent in RA management, though limited by its side-effect
profile and toxicity namely stomatitis, proteinuria, leucopenia and
thrombocytopenia.
In spite of these, injectable gold can provide benefit to some patients
with progressive disease who have failed to respond to other therapies.
Patients are advised to test their urine routinely for proteinuria and report
new side effects such as rashes or mouth ulcers. Auranofin (oral gold) is
less toxic and generally less effective. It is now seldom used.
Penicillamine is now rarely used due to its toxicity and poor long-term
efficacy which appears to have a ceiling effect. It should be taken on an
empty stomach at a daily dose of 125 mg with monthly increases (not
above 750 mg) until a response is shown. The common adverse events
include thrombocytopenia, proteinuria, taste disturbances and rashes.
Less common and rarely, autoimmune side effects such as myositis and
drug induced lupus.
Ciclosporin is an immunosuppressive agent used in RA. It is useful in
early and late disease but does not reduce joint destruction. Because of
this and the potential for toxicity, it is reserved for patients who have
failed to respond to conventional therapies. It causes hirsutism, tremor,
nephrotoxicity and hypertension with long-term consequences. The
initial treatment is 2.5 mg/kg dependent upon tolerance. Baseline blood
pressure and creatinine are determined prior to treatment.

Hydroxychloroquine and other antimalarials are the least toxic and

also the least effective of all DMARDs and are generally reserved for
less severe form of the disease, or in combination regimens.
Gastrointestinal toxicity is the main adverse effect, otherwise, it requires
little monitoring. Retinopathy may occur after high cumulative doses and
eye tests may be needed. Dose is typically 400 mg/day, increasing up to
800 mg/day to achieve efficacy.
Azathioprine is believed to have a steroid-sparing effect and is of use
when treating RA not responding to other agents. It can cause infertility
and development of malignancies.
Cyclophosphamide is a potent cytotoxic agent used orally or as
intravenous pulse therapy in the management of rheumatoid vasculitis.
Like azathioprine, it has the potential to cause infertility and
malignancies.
Combination DMARD Therapy
The evidence supporting the efficacy of combination therapy is
conflicting, though a triple regimen of hydroxychloroquine, methotrexate
and sulfasalazine has shown impressive benefits compared to
monotherapy with the individual agents. This combination regimen is
well tolerated. Also, sulfasalazine (or cyclosporin), methotrexate and
prednisolone have been used with some success.1
Table 19.3: Dosage, side-effects and monitoring guideline for DMARDs

Drug Dose schedule Adverse effects Monitoring

Sulfasalazine Initially 500 mg once Nausea, reversible male FBC fortnightly

daily, infertility,
LFTs 4 -weekly for 12
Increasing in weekly rashes, marrow weeks then 3-6 monthly
steps of 500 mg to 1g suppressions,
twice daily
hepatitis

Methotrexate 5-25 mg once weekly Rashes, nausea, stomatitis, FBC fortnightly for 12
marrow suppression, weeks then monthly
hepatitis, pneumonitis LFTs monthly

Sodium 10 mg test dose, then Rashes, stomatitis, marrow FBC and urinalysis prior
aurothiomalate 50mg weekly until suppression, proteinuria to each injection
(gold i.m) signs of remission
then reduce frequency
to monthly

Penicillamine 250-750 mg once daily Rashes, taste FBC fortnightly until

(on empty stomach) disturbance,nausea, stable dose, then
proteinuria, myasthenia, monthly Weekly
myositis, marrow urinalysis
suppression

Ciclosporin 2.5 mg/kg per day Hirsutism, gingival Fortnightly U&E, blood
hyperplasia, Hypertension, pressure and urinalysis
renal impairment for 2 months, then 1-2
monthly. Use baseline
creatinine to alter dose

Leflunomide Loading dose 100 mg Gastrointestinal disturbance, FBC, U&E, LFTs and
daily for 3 days then alopecia, liver abnormalities, BP fortnightly during first
maintenance dose of hypertension, marrow 6
10-20mg per day suppression
months then at least every
8 weeks thereafter

Azathioprine 1-5-2-5 mg/kg day Nausea, hepatitis, cholestatic FBC U&E, and LFTs
jaundice, Marrow fortnightly for 2-3
suppression months, then 1-2
monthly

Corticosteroids
These suppress cytokines and produce a rapid improvement in signs
and symptoms of the disease an immediate and dramatic anti-
inflammatory effect in RA, but they do not alter the natural progression of
the disease. Clinical manifestations of active disease commonly
reappear when the drug is discontinued.
Systemic corticosteroids can be difficult to withdraw once commenced
because the disease tends to flare up with dose reductions. To minimize
side effects, a daily maintenance dose of 7.5 mg of prednisolone or less
should be used, given as a single dose in the morning. Prophylaxis
against osteoporosis is necessary in patients on long-term therapy.
Serious problem of reaction resulting from prolonged therapy limits its
long term use. They may be used in a short-term basis to tide patients
over acute disabling episodes, to facilitate other disease measures
(physical therapy) or to manage serious extra-articular manifestations
(e.g. pericarditis, perforating eye lesions). They can also be indicated
for active and progressive disease that does not respond favorably to
conservative management and when there are contra-indications to
gold salts or therapeutic failures of gold salts.
When steroids are to be discontinued, they should be phased out
gradually on a planned schedule appropriate to the duration of the
4
disease. Intra-articular steroid administration (i.e. prednisolone
acetate, triamcinolone acetonide or triamcinolone hexacetonide) can
effectively relieve pain, increase mobility and reduce deformity in one or
more joints. The duration of response is variable and triamcinolone
hexacetonide may produce the greatest response. Intra-articular
steroids should be given oftener than 4 times a year and usually
recognized as agents of last resort.
Corticosteroids can be used:
· For acute flare-up of disease
· D u r i n g t h e i n t e r i m - b e f o r e t h e r a p e u t i c e ff e c ts o f
SAARDs/DMARDs are observed.
· In elderly patients as alternatives to the risks of a second-line
agents
· Inpatients with significant systemic RA
Long-term administration may produce GI bleeding, poor wound healing,
myopathy, cataracts, hypoglycemia, hypertension and osteoporosis.
Corticosteriods inhibit T and B cell activity. Low dose oral
corticosteroids of prednisolone (2.5 mg 15 mg/day) can improve the
sense of well being in patients treated with NSAIDs or just started on
SAARDs.

The risk of cumulative toxic effects on the skeleton, metabolism and other
organ systems limit the chronic use and dose of corticosteroids. They
may increase the incidence of peptic ulcer and GI hemrrhage,
particularly in patients receiving NSAIDs. Hypothalamic-pituitary-
adrenal suppression can be seen even with the use of low-dose
corticosteroids. Patients with RA (or asthma) often need to take a bone
strengthening drugs to counter the debilitating effects of their steroid
medications. Now, a new study has shown that a once-yearly injection of
a biphosphonate bone-building drug, Reclast, may work better than a
8
once- daily bisphosphonate pill for patients. Reclast (Zoledronic acid)
was found to hold off and /or reverse bone loss among patients taking a
glucocortiicoid medication (including prednisolone or prednisone) for
one of several inflammatory and immune-related diseases, including
asthma, lupus and rheumathoid arthritis. It did so more effectively than a
daily dose of an oral bisphosphonate, Actonel (risedronate) available as
8
a once-weekly and once-monthly pill. It was also found that both drugs
appear successful in lowering the risk of bone fracture that can result
from glucocorticoid use.
Topical Therapy
Topical capsaicin (Zostrix) is useful in symptomatic treatment of RA.
Counter irritants (e.g. Allyl isothiocyanate, methylsalicylate, menthol)
produce mild anti-inflammatory reactions when applied to the skin. Their
therapeutic benefit may be explained by the massing action that
accompanies drug application.
Surgical Therapy
Surgical therapy involves the following procedures:
· Joint replacement
· Surgical removal of the synovium-synovectomy
· Tendon rupture
· Arthroplasty: surgical remodeling of a diseased joint to prevent
the ends of the bone fusing; after an operation.
· Arthrodesis: fusion of bones across a joint space by surgery
which eliminates movement. Surgery is indicated when a joint is
very painful, highly unstable, grossly deformed or chronically
infected.

New Developments in RA
There are many limitations to the use of conventional DMARDs, despite
new approaches to their use. Over half of the patients treated with
DMARDs experience insufficient response because the response rate to
either mono or combination therapy is at best 40-60 %.1
The high rate of toxicity coupled with inadequate response of
conventional, DMARD therapy has necessitated the search for new
therapeutic strategies. Better use of mono-therapy: a greater use of
combinations and numerous new agents are now available for the
management of RA.
Leflunomide is a new, oral DMARD. It is a novel isoxazole derivative,
which exhibits both anti-inflammatory and immuno-modulatory
properties. It essentially acts by inhibiting the synthesis of DNA and RNA
in immune response cells, particularly the T cells. It also inhibits the
production of the pro-inflammatory cytokines, TNF and, interleukin-1 (1L-
1). In short-term studies, it appears to be equipotent to sulfasalazine and
methotrexate. It has shown reasonable improvements in functional
disability and quality of life and slows radiographic progression of RA.
Leflunomide has a rapid onset of action (within 4 weeks) which is
significantly faster than sulfasalazine. It appears to be well tolerated.
The commonest side effects include GI disturbances, reversible
alopecia, rash, hypertension and abnormal LFTs (liver function tests)
and these are mild to moderate and resolve without complications.
Leflunomide is likely to be useful in two groups of RA management.
Patients who cannot tolerate their current DMARDs because of serious
adverse effects and those who have either patient response or no
response to their current DMARD may benefit, as alternative or as
combination therapy.
Etanercept and infliximab: The development of TNF blockade therapy
is an attempt to antagonize the biological effects of tumour necrosis
factor (TNF) in rheumatoid arthritis. Etanercept and infliximab were the
first two of these therapies.
Etanercept is a recombinant human soluble TNF receptor. It acts by
competitive inhibition of TNF, binding to cell surface receptors and
preventing TNF-mediated cellular responses. It is administered
subcutaneously twice weekly. Generally, it is well tolerated, though
commonly, 40 % of patients develop injection site reactions which are
often mild, transient and resolve with time, without suspension of
treatment. There have been reports of demyelinating disorders and
upper respiratory tract infections in patients treated with this product.
Infliximab is a chimeric human-murine monoclonal antibody given by
slow I.V. infusion, every 4-8 weeks, at a dose of 3 mg/kg. It must be
given with oral methotrexate to prevent the development of murine
antibodies. It neutralizes the biological activity of NF. Common side
effects include headache, diarrhoea, rash, fever, chills, urticaria and
dyspnoea.
Patients treated with both agents have reported serious infections, with
some fatalities occurring in patients predisposed to infections. These
agents must therefore, not be used in patients with active infection.
The efficacy of both products is similar with response rates in the region
of 60-70 % as against 40 % with other therapies. They have been shown
to significantly reduce disease activity and to improve quality of life.
Both are expensive, costing about 1.5-2.5 million naira per patient, per
year. It is recommended that TNF blockade therapies should be used in
patients with highly active disease who have failed an adequate trial (at
least 6 months) of at least two standard DMARDs. Patients with high
risk of infection must be excluded from treatment.
OSTEOARTHRITIS (OA)
OA is a chronic disease and the most common of all the rheumatological
disorders. It is the most common joint problem in persons over 65 years
of age and the major cause of hip and knee replacements in the
developed world. It is painful and disabling-a big challenge to health
resources. OA is an active disease with great potential for treatment,
though it was previously generally considered to be an inevitable
consequence of ageing.1

Epidemiology
The prevalence of OA increases with age; uncommon in people less
than 45 years (2 % prevalence). It increases in people over 65 years to
68 % of women and 58 % of men. OA occurs in all populations, the race
climate or geographical location notwithstanding. Most forms of the
disease are more common and severe in women. Obesity has been
shown to be associated with the development of OA, especially in
women and particularly with OA of the knee.
The pattern of the disease varies with ethnic origin. For instance, hip
disease is more common in those of Western origin than in Chinese and
Asians. A strong genetic component is believed to be present,
particularly in women. Heberden's nodes are three times more common
in sisters with OA than in the general population. An inherited defect in
type 2 collagen genes is linked with the development of early onset
9
polyarticular OA.
Etiology
OA is a complex disease, involving both cartilage and bone and is
generally believed to result from an imbalance in erosive and reparative
processes. The disease process may involve inflammatory
components and not just a simple wear-and-tear mechanism. OA is
multi-factorial in etiology and a wide variety of factors predispose a
2
person to it. The predisposing factors to the development OA are
presented in Table 19.4.

Table 19.4: Predisposing factors to osteoarthritis1

· Increasing age
· Race
· Genetic disposition
· Gender <45 years, more common in males
> 55 years, more common in females
OA hip and knee, more common in females.
· Obesity
· Systemic disorders, e.g. hypertension
· Physical and occupational factors

Other etiological factors include mechanical overloading of the joints,

failure in the bones remodeling process, synovial and vascular changes,
crystal disposition and catabolic enzyme secretion.

Pathogensis
The pathogensis of OA is classified into four stages viz: initial repair,
early stage OA, intermediate stage OA and late stage OA.

· Initial repair is characterized by proliferation of

chondrocytes synthesizing the extracellular matrix of
bone
· Early stage OA results in degradation of the extracellular
matrix as protease enzyme activity exceeds chondrocyte
 activity leading to net degradation and loss of articular
cartilage.
· Intermediate OA is associated with a failure of
extracellular matrix synthesis and increased protease
activity, further increasing cartilage loss.
· Finally, late stage OA will result in extreme or complete
loss of cartilage with joint space narrowing. Bony
outgrowths (osteophytes) appear at joint margins and
there is general bone sclerosis, clinically manifesting
with pain and reduced joint movement.

Clinical manifestations
OA is characterized by joint pain, reduced joint movement, stiffness
and joint swelling. The signs and symptoms depend upon the affected
joints. The most commonly affected are the distal interphalangeal
joints, the knees, hips and the cervical lumbar spine. Muscle
weakness/wasting are usual. Loading and movement worsen pain, but
eased by rest. Pain is usually localized to the affected joint; although it
may be referred away from its origin (e.g. hip pain may be felt at the
knee). Pain is often worse at the end of the day. Stiffness and reduced
joint movement generally become worse as the day progresses, and
are particularly troublesome after a long period of rest. Swelling
(caused by synovitis or osteophyte formation) and joint deformity
restrict the range of joint movement and may lead to loss of function.
Knee and hip diseases are the most significant causes of morbidity
associated with OA. Upon passive or active movement, crepitus may
be heard.

Investigations
OA is primarily diagnosed on the clinical presentation. Radiography
can be used to achieve confirmation and evaluation. Sclerosis,
osteophyte formation and joint space narrowing are usually evident on
radiography. On athroscopy, normal cartilage is smooth, white and
glistening. OA cartilage is yellowed, irregular and ulcerated. Synovial
fluid analysis which shows crystals confirm the presence of pseudogout.
In OA, the ESR/plasma viscosity, and C-reactive protein levels are
usually normal, with no extra-articular disease.

Treatment
The goals of therapy are to: reduce pain, increase mobility, reduce
disability, minimize disease progression, and enhance the patient's
quality of life.

Non-Drug Treatment
Patient education plays a major role in OA. Advice on the protection of
joints through daily lifestyle modification and weight reduction can be of
great help. Physiotherapy may help patients regain muscle strength and
improve the range of movement of affected joints. An exercise program,
heat, cold, ultrasound, diathermy and other aspects of physical therapy
will support this strategy.
Exercise regimens should encourage “little and often” physical activity to
improve muscle strength and resting tone. Occupational therapy may
also help to protect joints and preserve function, especially with the aid of
physical aids and splints. For severe pain, transcutaneous electrical
nerve stimulation (TENS) and orthopaedic surgery (such as
arthroplasty) may be of assistance.

Drug Treatment
Damage to bone and cartilage cause pain in OA. If there is no
inflammation, simple analgesia and joint protection are often enough for
the treatment of mild to moderate disease. The American College of
Rheumatology (2000) has recommended simple analgesia as first-line
therapy in patients with OA of the hip and knee.
Paracetamol is safe and as effective as NSAIDs therapy in mild to
moderate OA. It is often taken “as required”, though a regular regimen is
frequently more successful. Addition of codeine or dextropropoxyphene
to paracetamol may result in a slight increase in benefit but this must be
assessed against an increased incidence of adverse events.
There may be an associated inflammatory component in OA. In such
cases, NSAIDs may provide more effective pain control than simple
analgesics, though evidence for the use of NSAIDs in the management
of OA is quite conflicting. NSAID treated patients have significantly
reduced pain at rest and on movement, compared to simple analgesia.
However, studies have shown that paracetamol and ibuprofen have
comparable efficacy in mild to moderate pain, with ibuprofen being
superior where there is severe pain. Thus, patients should be given a
5
trial of paracetamol as initial therapy before switching to NSAID therapy.
The choice of NSAID should be made after evaluation of the risk factors
for serving upper GI and renal toxicity. It is common knowledge that OA
patients are elderly and female and are particularly susceptible to GI side
effects. The use of NSAIDs should be reviewed regularly and if possible
restricted to short courses- a two-week trial should give an indication of
its efficacy. Gastro-protection with a proton pump inhibitor or misoprostol
is necessary in patients at high risk of GI events-patients aged > 65
years, a history of peptic ulcer or GI bleeding, concomitant steroids,
concomitant anticoagulants or the presence of co-morbidity. COX-2
selective NSAIDs have been found to be more effective in the
management of OA, compared to placebo and standard NSAIDs thus
providing alternative strategy in patients at high risk of GI events.
Topical NSAIDs, topical capsaicin or simple rubefacients may be of use
when pain is localized or if systemic therapy is not recommended
though, use of NSAIDs topically can produce systemic side-effects.
Intra-articular steroids may be of benefit in patients with acute
inflammation or joint effusion. Repeat injections should not be given
more often than every three months for a given joint. The duration of
symptomatic improvement following intra-articular injection may range
from just a few days to one month or longer. Intra-articular hyaluronic
acid derivatives (visco-supplemention) may prove useful in some
patients.
These agents have been shown to be more effective than placebo and
equivalent to intra-articular steroids and oral NSAIDs in reducing OA
pain of the knee. Visco-supplementations are expensive and are
indicated for patients who have failed non-drug treatment, simple
analgesia, NSAIDs, strong analgesia and intra-articular corticosteroids
(Fig 19.1). Tramadol is a centrally acting opioid agonist which inhibits re-
uptake of noradrenaline (norepinephrine) and serotonin. It has been
shown to be comparable to ibuprofen in OA and may be useful in adjunct
therapy in patients who are poorly NSAIDs controlled.

New developments
Numerous chondroprotective agents have been proposed for OA
management. Chondroitin and glucosamine compoumds are the most
common. There are not enough data from studies to support the use of
these agents in OA, although some studies recommend their use. A
10
recent meta-analysis. investigating the use of glucosamine in OA
concluded that while there may be some symptomatic benefit, there is
11
no evidence that glucosamine offers a long-term cure in OA. However,
in a large three-year study, glucosamine was suggested to be a safe and
12
beneficial disease-modifying agent in OA.
 Non-pharmacological methods

Paracetamol 1g qds

If acute inflammation or effusion

aspirate and inject joint with
corticosteroids

NSAID, e.g. ibuprofen/consider

COX-2 inhibitor

Stronger analgesia, e.g. tramadol

topical NSAID or topical capsaicin
Non-pharmacological methods

Intra-articular hyaluronate
Arthroscopy surgery

Fig 19.1: Algorithm of the management of osteoarthritis

Need for Pharmaceutical Care in Arthritis

A combination of pharmacological and non-pharmacological
approaches for managing RA is required, the latter including
physiotherapy, occupational therapy, podiatry, encouragement to
exercise and weight control. Concomitant disorders, polypharmacy and
repeat prescriptions, combined with possible advanced age, also
contribute to the need for individualization of care. Among the arthritic
conditions, relative consulting rates for osteoarthritis (OA), RA and gout
are 21, 4 and 2 percent respectively. Co-morbidity, especially chest
disease, cardiovascular disease, and obesity, commonly cause
complications in OA and RA. In a Scottish GP electronic questionnaire of
2646 patients in 1998, the estimated major co-morbidities reported in RA
patients were hypertension (20 %), respiratory disease (16 %),
depression (15 %), ischemic heart disease (13 %), anxiety (12 %) and
duodenal ulcer (10 %). Mortality due to co-morbid conditions may be
increased because of increased risk of infection, cardiopulmonary
disease and gastrointestinal diseases.
Pharmaceutical care activities in arthritis are presented in Table 19.5

Table 6: Pharmaceutical care of arthritis13

Stage of treatment Actions Points to consider at each stage

Treatment plan Verify the plan in Radiographic/symptomatic type of arthritis

Patient respect of: Patient's health beliefs, understanding of their
comprehension/active Patient's condition, treatment goals, complications and the
participation characteristics impact on their quality of life
Patient's characteristics Medication Health advice regarding diet, exercise, smoking,
Indication (the need for suitability alcohol consumption
each drug) Patient's needs for
Drug history education
Choice of medication Concordance and
Contraindication agreed expectations
/interaction
Conformity to guidelines Modify the plan to Motivation of the patient and their family with respect
Continuity of care address: to self care, lifestyle modification and treatment goals
Specific educational Presence of risk factors such as obesity, trauma,
needs infectious disease, diabetes
Need for Concomitant therapy or pregnancy which may
individualisation of influence drug choice
treatment plan Reasons for drugs withdrawn in the past
Selection of appropriate NSAIDs with regard to risk
factors for toxicity, such as known cardiac, respiratory
or renal disease, concomitant therapy and previous
response to NSAIDs
Need for appropriate co-prescription with misoprostol
or proton pump inhibitors
Other co-morbidities present that influence treatment
choice, eg, hypertension, upper GI disease, COPD
Renal function assessment and implications for drug
choice and dosage individualisation
Shared care arrangements and support available
Implementation Monitor the patient for: Patient compliance and the need to re-inforce health
Dose Continuing suitability of messages
Frequency drug/dose regimen Adjust choice of oral dose forms to help patients with
Timing Signs/symptoms of swallowing difficulties
Compliance effectiveness and toxicity Frequency and timing of analgesics/anti-inflammatory
Clinical signs agents
Laboratory Advice/discouragement about over-consumption of
markers OTC medicines

Adjust the process by: Achievement of regular exercise and adherence to

Further individualisation in advice on self care
response to monitoring Monitoring of laboratory (erythrocyte sedimentation
rate, C-reactive protein, creatinine, urea and
electrolytes, chest X ray) and clinical markers (cough,
fever, shortness of breath, duration of stiffness, pain,
swollen joints) in the initiation of DMARDs and NSAIDs
Ensure adequate dietary intake of calcium to protect
against osteoporosis, especially in patients receiving
corticosteroids, who may require appropriate
prophylaxis

Clinical outcome Confirm evidence of Attainment of treatment goals with pain relief, mobility,
Therapeutic treatment success: functional ability and improved quality of life
benefit Seek and provide Unwanted symptoms from medication (steroid-induced
Safety reassurance that treatment osteoporosis, worsening of sleep disturbances,
Unwanted expectations are being gastrointestinal complications, toxicity of DMARDs)
symptoms achieved
Recorded
adverse reaction Prompt a review from: Documentation of unexpected or serious adverse
Identification of treatment effects
failure Changes in the patient's needs after pharmacotherapy
Newly identified patient's Indications for treatment plan revisions, such as
needs persistent symptoms and progression of disease,
Sharing information and complicating features such as co-morbidity and
discussion of implications polypharmacy
with the prescriber and
other team members
 Key Learning Points

· RA is a chronic systemic, autoimmune, inflammatory condition

that is most apparent in its synovial joint involvement and may
extend to extra-articular sites such as tendons and organ
structures
· There are no pathognomic tests for RA; diagnosis is primarily
on the basis of clinical findings, supported by results of
laboratory tests and radiologic studies.
· Goals of therapy include: pain relief, suppression of
inflammation, avoid/minimize/eliminate adverse effects,
preserve/restore joint function, maintain patients
quantity/quality of life and rehabilitation.
· Patients with RA should be treated early and aggressively with
DMARDs. Combination therapy may be useful.
· NSAIDs are the major group of drugs used for the relief of pain
and inflammation of RA.COX-2 NSAIDs may reduce the
incidence of GI adverse events associated with these drugs.
NSAIDs should be taken with or after food.
· Osteoarthritis (OA) is uncommon in persons aged less than 45
years, but the prevalence increases up to 65 years when at
least 50 percent of the population have radiographic evidence
in a least one joint.
· Regular simple analgesics are effective. Oral NSAIDs may be
of value in some patients. Intra-articular corticosteroids and
hyaluronic acid derivatives (visco-supplementation) may be
useful in patients with OA of the knee.
· Patients with RD must be educated and counseled
appropriately about their illness and drugs therapy. PC in
rheumatoid disease ensures appropriate drug monitoring,
treatment evaluation and manipulations.
 References
1. Walker R, Edwards C (2004). Clinical Pharmacy and
Therapeutics Churchill Livingstone.3rd Ed. 791-809.
2. Brandt KD, Dieppe P, Radin E (2009). Etiopathogenesis of
osteoarthritis Med Clin North Am. 93(1):1-24.
3. Fuchs HA, Kaye JJ, Callan LF et al. (1989). Evidence of
significant radiographic damage in rheumatoid arthritis within the
2 years of disease. Journal of Rheumatology; 16:585-591.
4. Michelle AF, Larry NS (2002). Rheumatoid Arthritis In:
Comprehensive Pharmacy Review (Ed) Leon Shargel, Alen H,
Mutnice, Paul F. Larry N. Swarsin 4th Edition.
5. Hawkey CJ (1998). Progress in prophylaxis against nonsteroidal
anti-inflammatory drug-associated ulcers and erosions. Am J.
Med; 104 (3A): 67-74.
6. Corte LC, Caselli M, Castelline G et al. (1999). Prophylaxis and
treatment of NSAID-induced gastroduodenal disorders. Drug
Safety 20:527-543.
7. Silverstein FE, Faich G, Goldsteni GL et al. (2000).
Gastrointestinal toxicity with celecoxib versus nonsteroidal anti-
inflammatory drugs for osteoarthritis and rheumatoid arthritis.
The CLASS study: a randomized controlled trial. Journal of the
American Medical Association 284: 1247-1255.
8. Reid DM et al. (2009). Once-a-year drug helps counter steroid-
linked bone loss. The Lancet, April 11.
9. Valdes AM, Spector TD (2008). The contribution of genes to
osteoarthritis. Rheum Disclin North Am: 34(3):581-603.
10. Vlad SC, Lavalley MP, Mc Alindon TE, Felson DT (2007).
Glucosamine for pain in osteoarthritis: why do trial result differ
Arthritis and Rheumatism 56(7):2267-77.
11. Poolsup N, Suthisisang C, Channark P, Kittikulsuth W (2005).
Glucosamine long-term treatment and the Progression of Knee
osteoarthritis: systematic review of randomized control trials.
The Annals of Pharmacotherapy 39(6): 1080-7.
12. Mc Alindon T (2001). Glucosamine in osteoarthritis: dawn of a
new era? Lancet 357:251.
13. Bayraktar et al. (2000). Pharmaceutical care in arthritis; Pharm J
264(7078) 57-68.
 CHAPTER TWENTY

PHARMACEUTICAL CARE IN PSYCHIATRY

Ehijie FO Enato and Israel Aina

Learning objectives
At the end of this chapter, you should be able to:
i. Discuss the general considerations for managing psychiatric
disorders, and these will include:
a. General evaluation of psychiatric illness (Diagnosis and
classification of mental disorders, patient interview, mental
status examination, physical and laboratory assessments
relevant to pharmacotherapy in mental health, psychiatric rating
scale, and measurement of cognitive function)
b. Components of mental health policy
c. Special considerations in therapeutic management of
mentally ill patients (Adherence problem, stigmatization
and social distance, antipsychotic medication use during
pregnancy)
ii. Give a brief review of pharmacotherapy of
schizophrenia and mood disorders
iii. Apply pharmaceutical care model in psychiatry

Introduction
The World Health Organization report in 2001 showed that
approximately 450 million persons in the world suffer from mental or
neurological disorders or from psychological problems such as those
1
related to alcohol and drug abuse. In Africa, neuropsychiatric disorders
result in about 17.6 % of all years of life lived with disability.1 An estimated
26.2 % of Americans ages 18 years and older (about one in four adults)
suffer from a diagnosable mental disorder in a given year.2 In Nigeria,
Gureje et al.3 reported that 12.1 % of those sampled in a study conducted
in Yoruba-speaking area of the country had at least one lifetime mental
disorder and that 5.6 % had experienced at least one of the mental
disorders in the previous 12 months. As a result of the burden of mental
illness, different health professionals, including the pharmacist, are
involved in the management of the different disorders.4 Therefore, the
pharmacist being an integral member of the health care team should be
adequately equipped with the necessary knowledge and skills in the
management of psychiatric illnesses, particularly ensuring that
antipsychotic medications are optimally utilized. This need has become
more relevant today than previously acknowledged due to several
reasons, especially the increasing numbers of available antipsychotic
medications with various mechanisms of action. Other reasons include
the potentials for drug-drug, and drug-food interactions, increasing age
of the society with need for multiple drug use, and emphasis towards
community rather than institutional patient management.4
General considerations for managing psychiatric patients
As noted previously, in order for pharmacists to effectively function in a
psychiatric setting, they should understand the general approaches to
managing psychiatric illnesses, including patients' initial evaluation and
follow-up plans.
General evaluation of psychiatric illness
This includes: understanding diagnostic and classification methods for
mental disorders, patient interview, mental status examination, physical
and laboratory assessments, psychiatric rating, and measurement of
cognitive function.
Diagnosis and classification
The two most commonly used formats for diagnosis and classification of
mental illnesses include: Diagnostic and Statistical Manual of Mental
Disorders (DSM), and International Classification of Diseases and
Related Disorders (ICD). Whereas, DSM is published by the American
Psychiatric Association, ICD is primarily a document of the World Health
Organization (WHO), which is used by many European and WHO
member countries. Their current versions are: text revision of DSM IV
(DSM IV-TR), and ICD10. Both methods of classification give the
definitions of mental disorders in form of description of their clinical
features. Furthermore, by using these classification methods, specified
diagnostic criteria are presented for each mental disorder. The
diagnostic criteria provided are lists of features that should be present in
order to make a diagnosis of each of the mental disorders. By applying
these diagnostic criteria for each condition, it ensures uniformity in the
initial assessment and follow-up evaluation of psychiatric patients by
mental health professionals.

Patient interview
This is the process of evaluating patients with mental health, in order to
gather the relevant information to arrive at a diagnosis and plan
5
treatment. In addition, it is one of the primary means by which response
to drug therapy can be monitored.

First and foremost, patient interview is the bedrock from which rapport
and therapeutic relationship are developed with the mentally ill patient.
During this process, the clinician is able to elicit the relevant history of
illness. It also affords an opportunity to carry out the mental status
examination. The whole information gathered during the interview is
synthesized together through a good theoretical framework to arrive at
the psychiatric diagnosis. This helps to determine areas that require
further investigation before treatment is planned. The patient's interview
also helps to elicit the etiologic factors in each patient's case, as well as
6
determine the prognosis of the illness.
The details obtained during the patient's interview are documented in the
patient's record or case note, and this forms the basis for further
evaluation of the patient. Patient interview in psychiatry comprises two
main sections, which are: psychiatric history and mental status
examination (MSE).

Psychiatric history
This is the history of mental illness as told by the patient to the care
provider. The care provider may need to get additional information from
those closest to the patient, so as to have a comprehensive detail about
the patient and the illness with which the patient is presenting. Generally,
open-ended questions, which allow the patient to provide descriptions
and other relevant information in his or her own words, come first. This is
normally followed with questions that focus on more specifics or
7
personal data.
Psychiatric history differs from the history taken in other medical
specialties, because apart from the chronological sequence in which the
symptoms of the patient has developed, other information related to
stressful life events, which may have precipitated the illness are
7
explored. The relationships of the patients are considered important and
the roles that they play in the onset and progression of the mental illness
are evaluated. Psychiatric history also seeks to determine the
personality characteristics of the patient.
The above information is needed in psychiatry because the view of the
mental illness is not just based on a straight forward pathological etiology
as found in other aspects of medicine. Rather, theoretical framework is
the approach to etiology of mental disorders.7 This theoretical framework
has been developed by various authorities over the years. The various
sections of psychiatric history include: socio-demographic
characteristics, presenting complaints, history of present illness, past
psychiatric history, past medical history, family history, personal history,
forensic history, and pre-morbid history.

It is important to note that in some patients, assessment could be very

challenging or even the patients could be violent. Most of the time
violence is preceded by increased psychomotor agitation which is
characterized by pacing, speaking in a loud voice, or gripping the arms of
the chair. When safety is a concern, the interviewer should avoid any
behavior that could be misconstrued as threatening, such as touching or
unnecessary staring. Where possible, the interviewer should be
accompanied by another health care provider, and when the interviewer
feels unsafe, he or she should not hesitate to leave the room or call for
help.
Mental Status Examination
Mental status examination is the aspect of the patient interview, where
the psychiatrist records the direct observation made on the patient at the
time of the interview. During an episode of mental illness, the psychiatric
history of the illness remains essentially the same, but the mental status
changes from time to time.7
Mental status examination involves the psychiatrist's observation of the
patient's appearance and behavior. During the interview, the patient is
expected to communicate with the psychiatrist. Thus, parts of the
mental status examination such as the speech and thoughts of the
patient can be determined by listening carefully to what the patient says.
Other components of mental status examination are the perception,
concentration and attention. It also includes memory of the patient,
intellectual functions, judgment and insight of the patient into the illness.
The expertise of the psychiatrist is brought to bear in the mental status
examination to elicit the relevant psychopathology (abnormal signs and
symptoms of psychiatric illness) found in the patient's mental state.
The signs elicited (abnormalities) found in mental status examination
are tied up to the psychiatric history of the patient to arrive at a
diagnosis.8
The details of the relevant psychopathology in each aspect of the mental
status examination are beyond the scope of this text.
P h y s i c a l a n d l a b o r a t o r y a s s e s s m e n ts r e l e v a n t t o
pharmacotherapy in mental health
The psychiatric interview as briefly described above is relevant in
evaluating the mentally ill for establishing diagnosis, and monitoring
response to drug therapy; however, this is not complete without the
appropriate physical and laboratory assessments.

Physical assessment is the examination of the body of patients by

focusing on the various systems, such as the central nervous,
cardiovascular, respiratory, gastrointestinal, urogenital and
musculoskeletal systems. Physical examination is done through the
stages of inspection, palpation, percussion and auscultation (using the
stethoscope). Through these stages, any abnormality in any of the
systems of the body can be identified and treated.9
Mental illnesses are seen as disturbances in the psychological function.
These psychological functions include the mood, perception, speech,
and thought. These are not assessed by the physical examination,
rather by mental status examination. However, on some occasions, the
physical illness may be the cause of stress leading to a psychological
(mental) illness. Thus, it is important to examine the bodily systems to
rule out the possibility of the physical illness, which may have led to
psychological illness.7 This same reason is applicable to laboratory
assessment in evaluation of mental disorders.
Laboratory assessment in psychiatry includes: hematological tests such
as full blood count (FBC) to examine the blood cells, urinalysis to assess
the various components of the urine. Others include liver function test
(LFT), which assesses the liver- the main organ of drug metabolism, and
assay of drug concentrations in biological fluids (clinical
pharmacokinetics). Furthermore, there are lots of other laboratory
assessments that can be done depending on the judgment of the
clinician at the time of evaluation of the patient.10
With respect to making a diagnosis in psychiatry, the physical
examination and laboratory assessment only help to make diagnosis in
cases of organic psychiatric disorders e.g. delirium, by helping to
determine the underlying cause. The physical and laboratory
assessments also help to rule out an organic basis for the illness in order
to establish psychiatric diagnosis. Another important use of physical and
laboratory assessments is to evaluate the ability of the body to handle
drugs that may be needed to treat the mental illness. From time to time, it
may also be needed to monitor the serum concentrations of certain
antipsychotic medications to ensure that the serum concentrations
needed to achieve optimal therapeutic effect is attained. A few
psychotropic drugs such as lithium used in the treatment of bipolar
affective disorder have narrow therapeutic indices. It is thus required
that the serum concentrations of such drugs be monitored to avoid
toxicity.4, 10
Other psychotropic drugs may affect the blood cells e.g. clozapine has a
possible side effect leading to neutropenia (a low white blood count) and
subsequent agranulocytosis (complete absence of white blood cells).
Therefore, prior to initiation of clozapine therapy, the baseline white
blood cell count of the patient is required. It is also required that patients
on clozapine should have their white blood cell count monitored regularly
 4,10,11
in order to detect, early, any reduction in the white cell count.
It is also important that physical assessment is carried out on patients
taking lithium or clozapine therapy, as this can help to identify early
problems which may lead to life threatening side effects of the drugs. For
example mild tremor which is a mild adverse effect of lithium observed on
physical examination may herald a possible severe toxic side effect
which may manifest as marked tremor, confusion, clouding of
consciousness, etc.
Psychiatric rating scale
The rating scales used in psychiatry are methods of measuring some
characteristics of the patient's psychological functions such as the mood,
7
patient's behavior and external interaction with others.
These measurements done with the rating scale may initially appear not
to be straight forward, when compared to measurement of parameters
such as weight, height, etc. However, these rating scales have been
developed for some characteristics of the patient that have been properly
defined. For example, in the Brief Psychiatric Rating Scale, one of the
components is the presence of guilt feelings such as self blame, shame,
remorse for past behavior. This is rated from “0” to “6” in terms of not
present (0), very mild (1), mild (2), moderate (3), moderately severe (4),
severe (5) and extremely severe (6).
The essence of rating scale is that it provides an objective (measurable)
assessment of the patient health state, which can be reproduced by
another clinician. Over time, the response of the patient to treatment can
be objectively determined by a repeat measurement as the treatment
progresses.
Classification of rating scales
The classification of rating scales includes the following:
· Rating Scales can be specific (short) or comprehensive. The
specific rating scales measure discrete thoughts, moods or behavior,
such as obsessive thoughts, while the comprehensive scales measure
broad areas of abstractions such as depression and anxiety.
· Rating Scales could also be self rated or observer (clinician)
rated. The self rated scales are filled/completed by the patient
herself e.g. Beck Depression Inventory (BDI), Major Depression
Inventory (MDI), Hopkins Symptom Checklist (SCL 90), Hospital
Anxiety Inventory (HAI) etc. On the other hand, the observer
(Clinician) rated scales are those filled/completed by the
interviewer or the mental health professional from his
observation and evaluation of the patient e.g. Mini Mental State
Examination (MMSE), Neuropsychiatric Inventory (NPI),
Disability Assessment for Dementia (DAD), Brief Psychiatric
Rating Scale (BPRS), Positive and Negative Syndrome Scale
(PANSS), Hamilton Depression Rating Scale (HAM-DA).

Measurement of cognitive function

The cognitive function of an individual is a part of the mental status
examination. Some of the components of the cognitive function include
orientation to time, place and person, memory functions, reading,
writing, mathematical abilities and constructional abilities. The details of
the measurement of these cognitive functions can be elaborate.
However for the practical purpose of measurement of cognitive functions
in clinical practice, the Mini Mental State Examination (MMSE) is a useful
test.
The MMSE is a screening test to determine cognitive impairment in
patients. It could also serve as a way of tracking or following up on
changes that may come about in patient's cognitive state. It is not
suitable for making a diagnosis, but can be used to indicate the presence
of cognitive impairment such as in persons with suspected dementia
following head injury. The MMSE is far more sensitive in detecting
cognitive impairment than the use of informal questioning or overall
impression of a patient's orientation.
Small reported that the test takes about 10 minutes, but it is limited
because it will not detect subtle memory losses, particularly in well
12 13
educated patients. Tombaugh et al. reported that people from
different cultural groups, or low intelligence, or education may score
poorly on this examination in the absence of cognitive impairment. On
the other hand, it can be inferred that patients who are well educated
may score well on the MMSE despite having cognitive impairment. As a
preparation to the administration of the MMSE, rapport must be
established with the patient who should also be made comfortable.
Details of MMSE are provided in appendix 20.1 at the end of this
chapter. Furthermore, common terminologies used in mental health are
presented in appendix 20.2.

Components of mental health policy

In Africa where morbidity and mortality is still mostly due to infectious
diseases and malnutrition, mental health policy often receives little
14
attention by the government. However, mental health policy, like the
national health policy, has its basis in social justice and equity. In 1998
and 1990 the Member States in the African Region of the WHO adopted
resolutions to improve mental health services in the region, though
14
implementation has been very poor. Mental health policy guarantees
treatment of people with mental disorders. In addition, it advises that
treatment should be offered as close as possible to where the person
live and that there should be no discrimination for persons with mental
disorder. Furthermore, mental health policy conceptualizes the
integration of mental health into the general health care services. This
implies that the delivery of mental health care is to be anchored on
Primary Health Care (PHC), which every health care personnel should
promote with the active participation of the community. Therefore, all
health care personnel should receive adequate training in mental
health, along with psychosocial skills and positive attitude towards
person with mental disorders.
Special considerations in therapeutic management of mentally ill
patients
Therapeutic management of mentally ill patients requires addressing
such issues as adherence problem, stigmatization and social distance.
In addition, antipsychotic drug therapy during pregnancy and lactation
can be very challenging, and among the elderly and pediatric patients,
issues of inappropriate therapeutic response are often encountered.
Adherence problem
In mental health, medication non-adherence is a common issue, and it is
often problematic. Clinical experience from professional practice and
evidence from published literature indicate that non-adherence is one of
the major drug therapy problems often encountered by the mental
health practitioners. Though adherence has been defined as the extent
to which an individual's behavior coincides with medical or health
advice,15 the fundamental methodological problems in assessing
adherence still remains.16 The percentage judged as non-adherent
during clinical practice and research will vary depending on the criteria
used and the methods of their assessment.16 Despite the variability,
clinicians and researchers continue to document non-adherence, using
either direct or indirect methods of assessment or a combination of both
methods. These methods are listed below, and each of them has both
merits and demerits.17
· Indirect methods include
Ø Self reports
Ø Interview
Ø Therapeutic outcome
Ø Tablet count
 Ø Change in the weight of metered dose inhaler
Ø Medication-refill rate
Ø Computerized compliance monitors
· Direct methods include
Ø Biological markers e.g. Glycosylated haemoglobin in
diabetes
Ø Tracer compounds e.g. using Phenobarbital or digoxin
Ø Assay of body fluids
In practice, the easiest ways of assessing adherence are patients'
16
report and tablet count. A systematic review of literature indicates
that investigators rely heavily on self reports and other
16
subjective/indirect measures of adherence.
The prevalence and etiology of non-adherence may vary in different
mental health disorders. In schizophrenia for example, it has been noted
that neurocognitive deficits and paranoid symptoms may hamper
adherence. Therefore, identification of non-adherence by caretakers
18
and providers can be very challenging.
Stigmatization and social distance
Stigmatization is about labeling of individuals who have suffered mental
illness. Stigmatization is associated with mental disorder as well as with
its treatment. The beliefs among health professionals that people with
mental illnesses are hard to talk with, have different feelings, and are
19
unpredictable are thought to contribute to social distance.
Stigmatization often results in social distance, which can be considered
as a form of discrimination whereby the society tends to isolate the
individuals with mental disorder. Social distance has been defined as
the relative willingness to associate with or enter into relationships of
20
varying degrees of intimacy with a person. A large social distance
between health professionals and people with mental illnesses may
mean that health professionals do not understand peoples' experiences
with mental illness.
In a study on attitude of pharmacy students toward patients with mental
illness in Benin City, Nigeria, it was found that though the students had
positive attitude towards providing pharmaceutical care for these
patients; however, their efforts would be limited by their expressed
21
stigmatization and social distance for the disorder. Similar findings
19
were also reported by Bell et al. among pharmacy students and
graduates in Australia. A major approach to addressing the problem of
stigmatization and social distance is public enlightenment and health
education about mental disorder, as well a providing a comprehensive
education and training programs to improve the ability of practitioners to
19
meet the needs of people with mental illness.

Pharmacotherapy in special patient populations

In general, medication use during pregnancy raises a major concern
among clinicians and the lay public, and antipsychotic drug use is no
exception. In fact, since the advent of thalidomide tragedy in the sixties,
medication use during pregnancy has continually agitated the minds of
the general public even when there is no scientific evidence. A report by
the US Department of Health and Human Services on mental health
suggests that physicians may often under prescribe or stop
2
antidepressants at the time of conception and during pregnancy. As
over half of all pregnancies are unplanned, fetal safety should
continually be of concern to health care providers. However, estimating
fetal risk is not easy due to the fact that randomized, prospective, and
well-controlled investigational studies on the risks of exposure to
22
psychoactive drugs during pregnancy are neither feasible nor ethical.
To date, we largely derived our knowledge from case reports or
retrospective cohort epidemiologic studies. However, these types of
studies are often biased or flawed because of possible reporting bias,
and there are many confounding variables, such as multiple drug
therapies and coexisting disorders, nutritional and health status of the
pregnant women, etc. 23
Though as far back as 1979, the US Food, Drug Administration and
Control devised a system of classification of teratogenic risks of drugs
in-use during pregnancy, the clinical usefulness of such classification is
highly debatable. The FDA rating is believed to be misleading as it does
not provide sufficient useful therapeutic guidance for physicians. As a
result, this classification has been replaced with narrative statements
that summarize and interpret available data regarding hazards of
developmental toxicity and provide estimates of teratogenic risk.23
When therapeutic drug use is indicated during pregnancy, the
determination of which drug treatment to institute entails the following:
The physician/clinician and informed patient (family) riskbenefit
analysis; an assessment of risk for the fetus and the breastfed
10, 24
newborn; consideration of skip-generation or first filial (F1)
generation risk (e.g. epidemiologic evidence of the development of
vaginal cancer in the offspring of a mother exposed to
diethylstilbestrol); 25 and the family medical history, especially a history
of psychoactive drug treatment that was effective. 23
The potential adverse effects for the fetus and the neonate following
exposure to antipsychotic medications include: 25
· structural malformations
· acute neonatal effects including intoxication and neonatal
abstinence syndromes intrauterine fetal death,
· altered fetal growth, and
· neuro-behavioral teratogenicity.
To minimize the risk of fetal and neonatal toxicity, including abstinence
syndrome, it is recommended that the physician should prescribe the
lowest dosage that provides adequate control of the woman's illness.
The neonate must be monitored for evidence of persistent drug effect or
development of an abstinence syndrome.23

PHARMACOTHERAPY OF SCHIZOPHRENIA
Definition and description
The term schizophrenia was coined by Eugen Bleuler. It means a
division between thought, emotion and behavior of a patient, and is a
major psychiatric disorder. Normal individuals (mentally stable persons)
function as an integral whole, whereby there is an appropriate
integration of the patient's thoughts with his behavior and emotions.
However, in the schizophrenic patient, the normal integration of these
psychological functions (thought, emotion and behavior) is broken
down, and as such, the patient functions in a disintegrated way.27
Several symptoms have been developed for schizophrenia, and the
most common are positive (hallucination, delusion, disorganized speech
and behavior) and negative symptoms (alogia, flat affect, poor attention
and lack of motivation).11
Types of schizophrenia
The various types of schizoprenia include:28
· Paranoid: This is characterized by prominent preoccupation
with paranoid delusions and hallucination particularly of the
auditory and perceptual disturbances
· Hebephrenic Schizophrenia: Affective changes are prominent,
delusions and hallucinations are fleeting and fragmentary,
behavior is irresponsible and unpredictable, and mannerisms
are common. The mood is shallow and inappropriate and often
accompanied by giggling or self satisfied, self absorbed smiling,
or by a lofty manner, grimaces and mannerisms
· Disorganized: disorganized speech and behavior and/or flat or
inappropriate affect
 · Catatonic: prominent motor symptoms with non-reactivity to the
environment are essential features. This may alternate between
extremes such as hyperkinesis and stupor or automatic
obedience and negativism. Constrained attitudes and postures
may be maintained for long periods
· Undifferentiated: no clear prominence of a particular
constellation of symptoms
· Residual: absence of prominent symptoms but ongoing
disturbance of less magnitude for example social withdrawal,
blunted affect and apathy.

Epidemiology
The life time prevalence of schizophrenia is about 1 %. Schizophrenia is
equally prevalent in men and women; onset is however earlier in men
than women. The peak age of onset is 10 to 25 years for men and 25 35
years for women. Some geographic regions of the world like Ireland have
unusually high prevalence of schizophrenia. People with schizophrenia
have a higher mortality rate from accidents and natural cause than the
general population. Suicide rate among schizophrenia is about 15 %.29

Pathophysiology
The etiology of schizophrenia is said to be multi-factorial. Many factors
act synergistically to bring about the illness. The factors that have
interplay include the vulnerability of an individual to stress. Some
authorities have reported abnormalities in the limbic region of the brain.
Excess dopamine activity in the brain has been equally implicated.
Other neurotransmitters aside of dopamine have been implicated e.g.
excess serotonin and norepinephrine. In addition, genetic theory also
has a role in the pathogenesis of schizophrenia. Family disorders such
as marital breakdown makes the child raised in such an environment to
be prone to schizophrenia.
 Clinical presentation and diagnosis (ICD10 diagnostic criteria)
Although it has been documented that no strictly pathognomonic
symptoms can be identified for schizophrenia, some symptoms have
special importance in helping to make a diagnosis:28
a. Thought echo - patient hearing his thoughts being spoken aloud.
Thought insertion the patient feeling that thoughts are being put
into his mind from outside.
Thought withdrawal the patient feeling that his thoughts are being
removed from his mind.
Thought broadcasting the patient feeling that everyone knows his
thoughts without telling them
B. Delusion of control, influence, or passivity, clearly referred to
body or limb movements or specific thought, actions or
sensations (the patient generally feels that his actions, thoughts
feelings are under the influence of an external agent), delusional
perception.
c. Hallucinatory voices giving a running commentary on the
behavior, or discussing the patient among themselves, or other
types of hallucinatory voices coming from some part of the body.
d. Persistent delusions of other kinds that are culturally
inappropriate and completely impossible, such as religious or
political identity or super human powers and abilities (e.g. being
able to control the weather, or being in communication with aliens
from another world).
e. Persistent hallucinations in any modality, when accompanied
either by fleeting or half formed delusions without affective
content, or by persistent over-valued ideas, or when occurring
everyday for weeks or months unending
f. Breaks or interpolations in the train of thought, resulting in
incoherence or irrelevant speech, or neologisms
 g. Catatonic behavior, such as excitement, posturing, or waxy
flexibility, negativism, mutism, and stupor
h. “Negative” symptoms such as marked apathy, paucity of
speech, and blunting or incongruity of emotional response,
usually resulting in social withdrawal and lowering of social
performances. It must be clear that these are not due to
depression or to neuroleptic medication
i. A significant and consistent change in the overall quality of
some aspects of personal behavior, manifest as loss of interest,
aimlessness, idleness, a self absorbed attitude, and social
withdrawal
The ICD 10 diagnostic guidelines outlined above stipulate the normal
requirement for a diagnosis of schizophrenia. It is required that a
minimum of one very clear symptom (and usually two or more if less
clear cut) belonging to any one of the groups listed as (a) to (d) above, or
symptoms from at least two of the groups referred to as (e) to (h) should
have been clearly present for most of the time during a period of 1 month
or more.
Therapeutic Options
A summary of National Institute on Clinical Excellence (NICE) guideline
30
in the management of schizophrenia indicates that:
1. Optimism should be expressed and considered at the outset of
management of any case.
2. Help should be received early, as this improves outcome of
treatment and prognosis in each case.
3. The assessment of the patient should be done early. The
assessment should be comprehensive and address medical,
social, psychological, occupational, economic, physical and
cultural issues.
4. There should be a good working partnership between service
 users and carers, and they should be given clear intelligible
information.
5. The consent of service user is very important for any treatment
that is to be administered.
6. Health professional should provide accessible information about
schizophrenia and its treatment to service users and carers.
They should also be offered opportunity to participate in family or
carer support programs, where they exist.
7. Advance directives in which a patient gives consent ahead of
time for future treatment in case of crisis should be explored.
8. It is recommended that oral atypical antipsychotic drugs e.g.
amisulpride, olanzapine, quetiapine, risperidone and zotepine
are considered in the choice of first line treatment for individuals
with newly diagnosed schizophrenia.
9. Hospitalization may be required during an acute episode if a
patient desires a second opinion after an initial
diagnosis/treatment
10. Crisis resolution and home treatment teams should be
considered for people with schizophrenia who are in crisis to
augment the services provided by early interventions services
and assertive outreach teams.
11. Social group and physical activities are an improved aspect of
comprehensive service provision for people with schizophrenia
as the acute phase recedes and afterwards
12. If conventional antipsychotic medications are to be used for an
acute episode, the dosage should be in the range of 300 1000
mg chlorpromazine equivalent per day for a minimum of 6 weeks.
Reasons for dosage outside this range should be justified and
documented. The minimum effective dose should be used at all
times
13. The patient should be well informed about the side effect profile
of any drug to be used and his consent obtained.
14. Consideration should be given, where practicable, to
encouraging service users to write their account of the illness in
their notes.
15. Cognitive behavioral therapy (CBT) should be available as a
treatment option for people with schizophrenia
16. Family interventions should be available to the families of people
with schizophrenia who are living with or who are in close contact
with the service user.
17. Given the high risk of relapse following an acute episode, the
continuation of antipsychotic drugs for up to 1 to 2 year after a
relapse should be discussed with service users and carers,
where appropriate
18. If antipsychotics are to be withdrawn, this should be done
gradually while monitoring the patient. Following withdrawal, the
patient should be followed up for at least 2 years after the last
acute episode.
19. Everything should be done to promote recovery after the acute
episode
20. Assertive outreach team should be provided for people with
serious mental disorders, including for people with
schizophrenia, who make high use of inpatient services and who
have a history of poor engagement with services leading to
frequent relapse and/or social breakdown (as manifest by
homelessness or seriously inadequate accommodation).
21. Depot neuroleptics should be considered for patients who have
poor adherent with oral neuroleptics, beginning with a test dose,
and patients consent is important in this regard.
22. Clozapine should be considered for cases of treatment resistant
schizophrenia
 Pharmacotherapy
Available anti-psychotic drugs are classified based on their chemistry or
pharmacology. Pharmacologic classification has more clinical
relevance, which is further classified as low- and high potency, typical
and atypical antipsychotic drugs. Typical antipsychotic drugs are potent
D2 receptor blockers, while atypicals have less dopaminergic blockade
but greater serotonin 2 (5-HT2) blockade. Low-potency typicals
additionally have potent anti-histamine, antimuscarinic, and apha-1
adrenergic blockade, leading to increased sedation, anticholinergic and
cardiovascular effects with less extrapyramidal symptoms (EPS). High
potency typicals primary adverse effects are EPS. In general, typicals
are effective in treating positive symptoms, while atypicals treat both
positive and negative symptoms with minimal risk of EPS.
Examples of typicals are: chlorpromazine, thioridazine (low potency),
fluphenazine, haloperidol (high potency), etc. Their adverse effects
include: sedation, anticholinergic effects, neurologic effects (e.g.
parkinsonism[tremor, rigidity and bradykinesia], dystonic
reactions[torticollis-neck twisting, oculogyric crisis-fixed upward stare,
trismus-clenched jaw, laryngospasm difficulty breathing, speaking and
swallowing], akatisia [inability to sit, constant pacing, continuous
agitation and restless movement rocking and shifting of weight while
standing], and tardive dyskinesia [rhythmic involuntary movements of
tongue, lips, jaw, protrusion of tongue, puckering of mouth, chewing
movements, athethoid-continuous wormlike slow movements of arms.
Other adverse effects are: weight gain, sexual dysfunction, neuroleptic
malignant syndrome, endocrine effects, etc
Examples of atypicals include: Clozapine, resperidone, olanzapine,
4, 11
quetiapine, ziprasidone, aripiprazole.
PHARMACOTHERAPY OF MOOD DISORDER
Definition
Mood disorders are mental disorders where the major abnormality is in
the emotional feeling state of the patient. This may be accompanied by
abnormality in other psychological aspects of the patient and an overall
impairment in functioning. These groups of disorders are sometimes
referred to as affective disorders. Examples of mood disorder include
depression, mania, bipolar affective disorder, persistent mood disorders
such as cyclothymia, dysthymia etc. To exemplify this group of mental
disorder, depression is summarized below.

Classification
The four primary mood disorders include major depression, dysthymia,
11
bipolar disorders, and cyclothymia.
· Major depressive disorder: classic depression with symptoms
which include marked decreased in interest/pleasure in usual
activities; appetite changes and sleep disturbances. Other
symptoms include change in level of energy; and feelings of
guilt, helplessness, or worthlessness.
· Dysthmic disorder: chronic depressed mood that does not
meet the criteria for major depression
· Bipolar disorders
Ø Bipolar I: one or more manic or mixed episodes, usually
including major depressive episodes
Ø Bipolar II: one or more major depressive episodes
accompanied by at least one hypomanic episode
· Cyclothymic disorder: numerous periods of hypomania and
depression, neither of which meet the criteria for mania or major
depressive episode.
Etiology/pathophysiology
The exact cause of mood disorder remains unknown, but it is probably
multi-factorial. Biologic, psychological, and social theories abound, and
many practitioners suggest that the development of depression often is
predicated on the complex synthesis of genetic predisposition,
psychological stressors, and biologic pathophysiology. Some familial
tendencies have been documented for mood disorders. There is an
increased risk of unipolar depression in first degree relatives. In
general, affective disorders tend to have a higher concordance rate
among monozygotic twins than dizygotic twins. In addition, some
authorities had suggested the depressive personality disorder which
tends to present like depression illness.
Furthermore, psychosocial stressors also have a role to play. It was
reported that high expressed emotion (EE) increased the risks of
relapse in depressed patients. Depressives were more sensitive to
critical remarks than schizophrenics. Other psychosocial factors
include a female having three or more children at home under the age of
14 years; not working outside the home, lack of confiding relationship,
loss of the mother before the age of 11 years. Physical problems like
endocrine disorders such as hypothyroidism can also lead to
31
depression. put forward the cognitive model of depression. This was
expressed as the cognitive triad: depressed person has a negative
personal view, a tendency to interpret his or her ongoing experience in a
negative way, and a negative view of the future.

Clinical presentation and diagnosis (ICD 10 Criteria)

In typical depressive episode of all three varieties described as mild,
moderate and severe, the individual usually suffers from typical features
(1) depressed mood, (2) loss of interest and enjoyment and (3) reduced
28
energy leading to increased fatigability and diminished activity.
Other symptoms that are common include:
· Reduced concentration and attention
· Reduced self-esteem and self confidence
· Ideas of guilt and unworthiness (even in a mild type of episode)
· Bleak and pessimistic views of the future
· Ideas or acts of self-harm or suicide
· Disturbed sleep
· Diminished appetite

Mild Depression Two of the 3 typical features plus at least two of other
symptoms
Moderate Depression At least two of the 3 typical features plus at least
three (and preferably four of other symptoms)
Severe Depression All three of the typical features plus at least four of
the other symptoms. The minimum duration of the whole episode is
about 2 weeks.
Therapeutic options in the management of depression
Summary of National Institute on Clinical Excellence (NICE) guideline
on the management of depression: 30
1. Screening for depression should be undertaken in primary care
and general hospital settings in high risk groups e.g. patients
with past history of depression, significant physical illness
causing disability
2. Watchful waiting is needed for patients with mild depression who
do not want an intervention, or who in the opinion of the health
care professional may recover with no intervention. A further
assessment should be arranged normally within 2 weeks
(“Watchful waiting”)
3. Antidepressants are not recommended for the initial treatment of
mild depression, because the risk benefit ratio is poor
4. Guided self help based on cognitive behavioral therapy (CBT)
should be recommended for patients with mild depression.
5. Psychological treatment focused on depression (e.g. problem-
solving therapy, brief CBT and counseling) of 6 to 8 sessions
over 10 to 12 weeks should be considered for both mild and
moderate depression.
6. If an antidepressant should be prescribed, it should be a
selective serotonin reuptake inhibitor (SSRI) because it is as
effective as tricyclic antidepressant (TCA) and less likely to be
discontinued because of side effects.
7. Sudden discontinuation or withdrawal of antidepressant may be
associated with withdrawal/discontinuation symptoms.
8. In initial presentation of severe depression, a combination of
antidepressant and individual CBT is better and less costly than
either modality alone
9. Patients who have had two or more depressive episodes in the
recent past, with significant functional impairment should be
advised to continue antidepressant medication for 2 years.
10. For patients whose depression is treatment resistant, the
combination of antidepressant medication with CBT should be
considered.
11. CBT should be considered for patients with recurrent
depression who have relapsed despite antidepressant
treatment, or who express a preference for psychological
interventions.

Antidepressant medications
4, 24
These include the following classes:
· Tricyclic antidepressants e.g. imipramine, amitriptyline,
desipramine, nortriptyline. They work by blocking the re-uptake of 5-
 HT and norepinephrine. Their side effects include anticholinergic
effects, sedation, orthostatic hypotension and cardiotoxicity.
· Monoamine oxidase inhibitors: phenelzine,
isocarboxazid, tranylcypromine. They work by blocking
MAO, the enzyme responsible for the breakdown of certain
neurotransmitters, such as norepinephrine.
· Selective serotonin reuptake inhibitors: e.g. fluoxetine,
paroxetine, sertraline, fluvoxamine, citalopram, and
escitalopram. Common adverse effects are: GIT
complaints, insomnia, restlessness, headache, and sexual
dysfunction
· Others are: venlafaxine, trazodone, nefazodone,
4, 11
bupropion, mirtazapine, duloxetine.

Application of pharmaceutical care in psychiatry

The role of pharmacists in patient care has grown well beyond
dispensing functions Clinical pharmacists have been involved in
mental health care settings for over 30 years, in addition to their being
32-36
involved in the management of other medical disorders.
Studies have shown that services provided by pharmacists such as
medication counseling, therapeutic monitoring and medication supply
37
etc, can potentially optimize the use of medications for mental illness.
It has been reported that the provision of clinical pharmacy services to
inpatients in an acute care psychiatric facility was associated with
improvements in rating-scale scores for clinical response and for drug-
37
induced extra-pyramidal symptoms.
In both inpatient and outpatient psychiatric settings, pharmacists
routinely participate as pharmacotherapy experts and consultants,
manage individual patient drug regimens, obtain drug histories, lead
patient education discussion groups, and coordinate the use of drug
assistance programs. Given the emphasis on managing mental illness in
primary care settings, it is not surprising that psychiatric pharmacists
have expanded their practices into the primary care.
Today, pharmacy as a profession has reoriented its practice from a
38-39
clinical service model to a pharmaceutical care model - a practice
philosophy were pharmacists take active responsibilities for patients'
drug related needs. Pharmaceutical care model proclaims a commitment and
responsibility to enhance outcomes for patients through developing an
alliance between the professional and the patient. Pharmaceutical care
is uniquely focused on the pharmacists' responsibility for the patient's
drug related needs. Those needs are not limited to specific clinical
problems and goals but to all of the patient's medications, medical
conditions, and outcome parameters.39 Pharmaceutical care can be
provided in a general or disease specific approach.40 The general
guideline for providing disease specific pharmaceutical care, which has
already been provided in chapter on “pharmaceutical care” in malaria,
also applies in psychiatry. In brief, disease-specific pharmaceutical care
requires the pharmacist to gather and valuate extensive patient-related
medical information, documentation, and provision of pharmaceutical
patient care far beyond what is required of a pharmacist providing
general care.
Psychiatric illness is a major mental health disorder, and pharmacists
need to play an extended role in collaboration with other health care
professionals in ensuring that the patients derive maximal benefits from
their drug therapies. In order to effectively fulfill this role, pharmacists
should adequately equip themselves with the necessary knowledge and
skills in the management of psychiatric disorders. In particular, the
pharmacists' professional responsibilities in psychiatric setting will
include ensuring that patients derive maximal benefits from their drug
therapies.
Key Learning Points
· Psychiatric illness is a major mental health disorder
· Proper evaluation is important for both establishing diagnosis
and monitoring response to pharmacotherapy
· Evaluation psychiatric illness considers diagnostic and
classification methods, patient interview, mental status
examination, physical and laboratory assessments, psychiatric
rating, and measurement of cognitive function.
· Psychological functions such as the mood, patient's behavior
and external interaction with others are assessed using rating
scale.
· Mental health policy guarantees treatment of people with mental
disorders as an integral component of primary health care.
· Non-adherence is a major drug therapy problem often
encountered mental health care
· Hallucination, delusion, disorganized speech and behaviour are
positive schizophrenic symptoms) and negative symptoms
include alogia, flat affect, poor attention and lack of motivation.
· Typical antipsychotic drugs (chlorpromazine, thioridazine,
fluphenazine, haloperidol are potent D2 receptor blockers, while
atypicals (Clozapine, resperidone, olanzapine,) have less
dopaminergic blockade but greater serotonin 2 (5-HT2) blockade
· Pharmacists being an integral member of the health care team
should be adequately equipped with the necessary knowledge
and skills in the management of the condition
· Providing pharmaceutical care in psychiatry helps to maximize
pharmacotherapeutic outcomes, thus improving the patients'
quality of life
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Collaborative care model to improve outcomes in major
depression. Ann Pharmacother36:585-91.
37. Canales PL, Dorson PG, Crismon ML (2001). Outcomes
assessment of clinical pharmacy services in a psychiatric
inpatient setting. Am J Health-Syst Pharmacy 58:1309-16.

38. Hepler CD, Strand LM (1990). Opportunities and responsibilities

in pharmaceutical care. Am J Hosp Pharm47: 533-43.

39. Ballantyne P (2007). The role of pharmacists in primary care

needs reconsideration in light of the evidence of an unfavourable
impact on patients outcomes (Editorials). BMJ 334: 1066-1067.

40. Rovers JP, Currie JD, Hagel HP, McDonough RP, Sobotka JL
(2003). A practical guide to pharmaceutical care (Second edition).
APhA, Washington DC: 153-173
 Appendix 20.1

Mini-Mental State Examination (MMSE) Questionnaire

Orientation
· What is the year, season, date, day and month (1 point for each;
maximum total 5 points)
· Where are we: town, county, country, which hospital surgery, and
which floor (1 point for each maximum total 5 point).

Registration
· Ask the patient if you may test their memory
· Say the names of three unrelated objects (e.g. apple, table,
penny) clearly and slowly, taking about one second for each
· After you have said all three, ask the patient to repeat them
· The first repetition is considered the test of registration and
determines the patient's score out of 3, but keep saying the words
until the patient can repeat all three (up to six trials).
· If the patient does not eventually learn all three, it is unlikely that
recall can be meaningfully tested but it should still be attempted
(see below).

Attention and Calculation

· Ask the patient to begin with 100 and count backward by 7. Stop
after 5 subtractions (93, 86, 79, 72, 65)
· Score the total number of correct answers (maximum total 5
points).
· If the patient cannot or will not perform this task ask them to spell
the word “world” backwards. The score is the number of letters in
correct order e.g. dlrow = 5; dlorw = 3.

Recall
· Ask for the 3 objects repeated above (e.g. apple, table, penny).
Give 1 point for each correct object (Maximum total 3 points).

Language
· Naming: show the patient a wrist-watch and ask then what it is.
Repeat for pencil score one for each correct answer (Maximum
total 2 points).
 · Repetition: ask the patient to repeat the sentence “No ifs, ands or
buts” after you. Allow only one trial. Score 1 if the repetition is
completely correct and 0 if it is not.
· 3 stage command: give the person a piece of blank white paper
and ask then to follow a 3 stage command. “take a paper in your
right hand, fold it in half and put it on the floor” (1 point for each
part that is correctly followed) (Maximum total 3 points).
· Reading: Write “Close your eyes” in large letters and show it to the
patient. Ask him or her to read the message and do what it says
(give 1 point if they actually close their eyes)
· Writing: Give the patient a blank piece of paper and ask them to
write a sentence of their choice (do not dictate a sentence); the
sentence must contain a subject and verb and must make sense.
Spelling, punctuation and grammar are not important (1 point).
Copying: show the person a drawing of 2 pentagons which intersected
to form a quadrangle. Each side should be about 1.5cm. Ask them to
copy the design exactly as it is. All 10 angles need to be present and
the two shapes must intersect to score 1 point. Tremor and rotation
are

Total MMSE Questionnaire Score (Maximum = 30).

 Appendix 20.2

Definitions of common terminologies used in mental health

(Sadock et al; 1998).
Affect: Observed expression of emotion, possibly inconsistent with
patient's description of emotion.
Akathisia: Subjective feeling of muscular tension secondary to
antipsychotic or other medication, which can cause restlessness,
pacing, repeated sitting and standing; can be mistaken for psychotic
agitation.
Anorexia: Loss of, or decrease in, appetite
Anxiety: Feeling of apprehension caused by anticipation of danger,
which may be internal or external.
Circumstantiality: Indirect speech that is delayed in reaching the point
but eventually gets from original point to desired goal; characterized by
over inclusion of details and parenthetical remarks.
Coma: Profound unconsciousness
Compulsion: Uncontrollable impulse to perform an act repetitively
Confabulation: Unconscious filling of gaps in memory by imagined or
untrue experiences that a person believes but that have no basis in fact;
not often associated with organic pathology.
Delirium: Bewildered, restless, confused, disoriented reaction
associated with fear and hallucinations.
Delusion of control: False feeling that a person's will, thoughts, or
feelings are being controlled by external forces.
Delusion: False belief, based on incorrect inference about external
reality, not consistent with patient's intelligence and cultural background;
cannot be corrected by reasoning.
Disinhibition: Removal of an inhibitory effect that permits persons to
lose control of impulses as occurs in alcohol intoxication.
Disorientation: Disturbance of orientation in time, place, or person.
Distractibility: Inability to concentrate attention; state in which attention
is drawn to unimportant or irrelevant external stimuli.
Echopraxia: Pathological imitation of movements of one person by
another.
Formal thought disorder: Disturbance in the form of thought rather
than the content of though; thinking characterized by loosened
associations, neologisms, and illogical constructs, thought process is
disordered and the person is defined as psychotic.

Hyperphagia: Increase in intake of food

Hypersomnia: Excessive sleeping
Hypnosis: Artificially induced modification of consciousness
characterized by heightened suggestibility.
Incoherence: Thought that generally is not understandable; running
together of thoughts or words with no logical or grammatical connection,
resulting in disorganization.
Mannerism: Ingrained, habitual involuntary movement
Mental disorder: Clinical significant behavour or psychological
syndrome associated with distress or disability, not just an expected
response to a particular event or limited to relations between a person
and society.
Mood: Pervasive and sustained emotion subjective experienced and
reported by a patient and observed by others; examples include
depression, elation, and anger
Negativism: Motiveless resistance to all attempts to be moved or to all
instructions.
Neologism: New word created by a patient, often by combining
syllables of other words, for idiosyncratic psychological reasons
Overvalued idea: Unreasonable, sustained false belief maintained
less firmly than a delusion
Panic: Acute, episodic, intense attack of anxiety associated with
overwhelming feelings of dread and autonomic discharge
Perseveration: Persisting response to a previous stimulus after a new
stimulus has been presented; often associated with cognitive disorders.
Phobia: Persistent, irrational, exaggerated, and invariably
pathological dread of a specific stimulus or situation; results in a
compelling desire to avoid the feared stimulus
Psychosis: Inability to distinguish reality from fantasy; impaired reality
testing, with the creation of a new reality (as opposed to neurosis:
mental disorder in which reality testing is intact; behaviour may not
violate gross social norms, but is relatively enduring or recurrent without
treatment).
Stereotype: Repetitive fixed pattern of physical action or speech
Tangentiality: Inability to have goal-directed associations of thought;
speaker never gets from point to desired goal.
Word salad: Incoherent mixture of words and phrases.
 CHAPTER TWENTY ONE

PHARMACEUTICAL CARE IN MALARIA

Ehijie FO Enato
Learning objectives
At the end of this chapter, you should be able to discuss the following:
I. Aetiology of malaria
ii. Epidemiology and transmission
iii. Pathogenesis and clinical presentations
iv. Diagnosis
v. Prevention and control of malaria
vi. Monitoring of anti-malarial drug efficacy
vii. Pharmaceutical care plan/intervention for prevention and control
of malaria

Introduction
Malaria is a febrile illness characterized by fever and related symptoms.
Malaria has been known to mankind for a very long time, as mentions of it
are found in Egyptian, Chinese and Indian manuscripts. Its clinical
symptoms were fully described by Hippocrates 400 years before the
Christian era.1 It was initially thought that 'miasma' (bad air or gas from
swamps “mal air ia”) was responsible for the disease.
Etiology
Malaria is caused by plasmodial species of which four are important in
human disease - Plasmodium falciparum, P. vivax, P. ovale, and P.
malariae. Of these four species, P. falciparum is responsible for most
case fatality and it is the predominant species causing malaria in tropical
Africa.2
Transmission
Malaria parasites are transmitted through the bite of female anopheles
mosquitoes, the vector for human malaria, which is most active at night.
Anopheles gambiae, which is widespread in Africa is the most effective
2
vector and it is difficult to control.
During the bite of female anopheles mosquito for a blood meal, it sucks
the gametocytes (the sexual forms of the parasites) along with blood.
The blood meal is needed before the first batch of eggs can be laid.
These gametocytes continue the sexual phase of the cycle in the
mosquito to form the sporozoites. The sporozoites migrate to the salivary
gland of the mosquito from where they are inoculated into the human
blood stream during another blood meal.

3
Fig 21.1: The malaria cycle of infection.
Malaria can, however, be transmitted through other ways: by design or
by accident, through inoculation of blood from infected person to a
healthy person. By this means, the asexual blood forms continue to
develop in their own periodicities in the peripheral blood producing
attacks of fever in the recipient, without first undergoing pre-erythrocytic
schizonts stage in the liver. It is important to note that malaria
transmitted through inoculation of blood has a shorter incubation period
than sporozoite-induced infection, and relapses do not occur. However,
4
P. falciparum infections transmitted in this way can be fatal.
Several factors affect the transmission of malaria, and these include
breeding sites, parasites, climate, and population. Stagnant or slow-
flowing bodies of water such as small ponds, ditches, pits, swamps,
reservoirs, uncovered tanks, objects that collect water (e.g. empty tins,
2
containers etc) encourage breeding of mosquitoes.
Epidemiology
The epidemiology of malaria is complex and may vary considerably
even within relatively small geographical areas. The principal
determinants of the epidemiology of malaria are the number (density),
the human-biting habits, and the longevity of the anopheline mosquito
vectors. More specifically, the transmission of malaria is directly
proportional to the density of the vector, the square of the number of
human bites per day per month, and the tenth power of the probability of
the mosquito's surviving per one day. In other words, the most effective
mosquito vectors are those (such as Anophele gambiae in western
Africa) that occur in high densities, bites humans frequently, and are
5
long-lived.

Fig 21.2: The changing pattern of malaria transmission from 1946 to

1994 shows a disease burden that is increasingly being confined to
tropical regions.6
Pathogenesis
Though the pathologic changes related to malaria affect most organs
and systems of the body, the most pronounced changes involve the
blood and blood forming system, spleen and the liver. In addition,
secondary changes may occur in all the major organs, depending on
the type and severity of infection. Clinically, malaria results in chills,
fever, sweating, headache, nausea, vomiting, and in complicated
7
cases convulsion and coma.
Classification of malaria
Malaria is classified into acute uncomplicated and severe malaria. For
acute uncomplicated P. falciparum malaria, the primary objective is to
cure infection. It is important in order to help prevent progression to
severe disease and prevent additional morbidity associated with
treatment failure. The secondary objective is to prevent emergence and
spread of resistance to anti-malarial drugs, tolerability, adverse effects
and speed of response to therapy. On the other hand, in severe malaria,
the primary objective is to prevent death, for pregnant women it is to
prevent death of mother, while the secondary is prevention of
8
recrudescence and minor adverse effect.
Burden of malaria
Malaria is a major public health problem and a negative factor in the
9
socio-economic development, particularly in sub-Saharan Africa. It
results in significant medical and socio-economic burden in endemic
regions of the world. For example, it has been reported that about 300-
500 million clinical cases of malaria occur every year, resulting in over 1
million deaths, particularly in under five year old children. Over 90 % of
2, 10
malaria burden occur in sub-Saharan Africa. Malaria is one of the top
three killers among communicable diseases in tropical Africa. In
Nigeria, malaria accounts for 50 % of all outpatient visits, 10-30 % of all
 11
hospital admissions. Furthermore, in sub-Saharan Africa, over 50
million pregnancies are threatened by falciparum malaria each year.
Also, falciparum malaria is an important contributor to maternal
morbidity and perinatal morbidity and mortality. In areas of Africa with
stable malaria transmission, P.falciparum infection during pregnancy is
estimated to cause as many as 10, 000 maternal deaths each year,
contributes to approximately 2 to 15 % of maternal anaemia, 8 to 14 % of
all low birth weight infants (an important contributor to infant mortality),
12-14
and 3 to 8 % of all infant deaths.
Malaria affects the health and wealth of endemic nations and individuals
alike. In Africa today, malaria is understood to be both a disease of
poverty and a cause of poverty and it is both a major public health
15, 6
problem and a negative factor in the socioeconomic development.
Furthermore, malaria has significant measurable direct and indirect
costs, and has been shown to be a major constraint to economic
development. What this means is that the gap in prosperity between
countries with malaria and countries without malaria has become wider
6, 10, 8
every single year.

Diagnosis

Diagnosis of malaria involves the use of age-long light microscopic

examination of Giemsa-stained blood firms, which is the current
standard for definitive diagnosis and it is widely practiced. However, its
limitations include the time required for sample collection, staining and
reading, and the need for highly trained and experienced
microscopists.16

Other methods of malaria diagnosis include:

· Quantitative Buffy Coat (QBC), which is a modified method of

conventional light microscopy that uses microhaematocrit tubes
precoated with acridine orange stain, which fluorescence to highlight
malaria parasite. Advantages include less staining, and less time
requirement to perform the test. However, need for constant availability
of electricity, special samples, cost and inability to differentiate species
16
are some of the disadvantages.

· Clinical presentations of patients, though highly practiced in

many developing countries, it is devoid of specificity. Clinical
diagnostic criteria vary with prevalence of species of malaria
parasite, intensity of transmission, incidence of other conditions
with similar presentations, and experience of health-care
providers.

· Antigen detection (dipstick) method, include commercially

available kits e.g. ParaSight-F® which is based on the detection
of histiden-rich protein II (HRP II) of P. falciparum, and Optimal®
which is based on detection of lactate dehydrogenase (LDH), a
parasite specific enzyme.16

· Molecular markers, which detect parasite genetic materials

through use of polymerase-chain reaction (PCR): Though this
method is highly sensitive and specific when compared with
other diagnostic techniques, it is however a lengthy procedure
that requires specialized and costly equipment and reagents, as
well as laboratory conditions not available in many malaria
endemic countries.16

Prevention and control of malaria

The Global Malaria Control Strategy represents a concerted effort to
bring about changes in the way malaria problem is being addressed.
This strategy stresses the selective use of preventive measures
wherever they can lead to sustainable results. Such measures should
be aimed at halting the deterioration of the malaria situation,
minimizing the wasteful use of resources and contributing
appropriately to the development of health services, inter-sectoral
cooperation and community participation. The ultimate goal of malaria
control is to prevent mortality and reduce morbidity and social and
economic loss through the progressive improvement and
17
strengthening of local and national capacities.
The goal of malaria prevention and control is to prevent mortality and
reduce morbidity and socio-economic loss. Malaria control in Africa is
based on Global Malaria Control Strategy with four basic elements:
· Early diagnosis, prompt and effective treatment (PET)
· Prevention of contact between vector and human by using
insecticide treated materials and vector control
· Intermittent preventive therapy in pregnancy (IPT)
· Strengthening of local capacities for basic and applied
17
research.
Also, the United Nations (UN) has set a target of combating malaria
and other poverty-related diseases of the world. Consequently, the
Global Strategic Plan 2005 2015 (GSP) of the Roll Back Malaria
Partnership details the necessary steps for all partners to ensure a
scale-up of malaria control interventions towards 2010 and 2015
targets of the UNs' Millennium Development Goals (MDGs). The set
18
targets by MDG for malaria prevention are that:
By 2010:
· 80 % of people at risk from malaria are protected
· 80 % of malaria patients are diagnosed and treated with
effective anti-malarial medicines e.g. artemisinin-based
combination therapy (ACT) within one day of the onset of
 illness.
· In areas where transmission is stable, 80 % of pregnant women
will receive intermittent preventive therapy.
· Malaria burden is reduced by 50 % compared with 2000.
By 2015:
· Malaria morbidity and mortality are reduced by 75 % in
comparison with 2005, not only by national aggregate but particularly
among the poorest groups across all affected countries.
· Malaria-related MDG are achieved, not only by national
aggregate but also among the poorest groups, across all affected
countries.
· Universal and equitable coverage with effective interventions.

Treatment of malaria
Drug treatment option for malaria is based on whether the patient has
acute uncomplicated or severe malaria. Uncomplicated malaria is
defined as symptomatic malaria without signs of severity or evidence of
vital organ dysfunction. In acute falciparum malaria, there is a continuum
from mild to severe malaria. On the other hand, a patient with falciparum
asexual parasitaemia, presence of one or more of the following clinical or
laboratory features classifies them as having severe malaria: Clinical
Prostration, Impaired consciousness, Respiratory distress (acidotic
breathing), Multiple convulsions, Circulatory collapse, Pulmonary
oedema (radiological), Abnormal bleeding, Jaundice, Haemoglobinuria;
Laboraotry test - Severe anaemia, Hypoglycaemia, Acidosis, Renal
8
impairment, Hyperlactataemia, Hyperparasitaemia.
The recommended anti-malarial treatment for acute uncomplicated
falciparum malaria in Nigeria is artemisinin-based combination therapy
11
(ACT). This is because of high level of treatment failures due to growing
resistance to the limited number of anti-malarial drugs available. This
concept is similar to other areas in medicine e.g. tuberculosis, leprosy,
etc
Artemisinin-base combination therapy takes advantage of the rapid
blood schizontocidal properties of artemisinin and the long half - life of
the partner drug. In addition, ACTs have been shown to be safe and
19
effective in endemic countries.
For children and adult non-pregnant patients, the recommended ACTs
are: Artemether (20 mg)/Lumefantrine (120 mg), a 3-day six-dose
regimen, based on body weight: 5- <15 kg, one tablet (20 mg
artemether and 120 mg lumefantrine) per dose, those weighing 15-<25
kg two tablets per dose, those weighing 25-<35 kg will receive three
tablets per dose, and those weighing 35 kg and more will receive four
tablets per dose (WHO, 2006). Atemether-lumefantrine should be
taken with fatty meal to ensure maximal bioavailability. Atesunate plus
amodiaquine, artesunate 4 mg/kg and amodiaquine 10 mg/kg body
weight for 3 consecutive days.
For pregnant women, the treatment guideline recommends oral quinine
(10 mg/kg, 8-12hr for 5-7days) in the management of acute
11
uncomplicated falciparum malaria.
Other ACTs which are available in Nigeria pharmaceutical market and
are used in the management of acute uncomplicated malaria include
artesunate/mefloquine (4 mg/kg body weight of artesunate given once
a day for 3 days and 25 mg base/kg body weight of mefloquine usually
split over 2 or 3 days), and artesunate/sulfadoxinepyrimethamine (4
mg/kg body weight of artesunate given once a day for 3 days and a
single administration of SP [25/1.25 mg base/kg body weight] on day 1)
For severe malaria, intravenous quinine or artesunate is
recommended. The regimen for quinine is 20 mg/kg loading dose,
followed by 10 mg/kg, maintenance dose, given over 4 hrs, every 8
hourly until the patient is able to tolerate oral dose to complete the 7
days treatment course. For artesuate, the regimen is 2.4 mg/kg bolus
intravenously, then 12 hrs later 1.2 mg/kg, finally 1.2 mg daily for 6 days.
The dose of artesunate should be changed to oral, once the patient can
11
tolerate oral preparation.
Therapeutic efficacy
Regular monitoring of efficacy of anti-malarial drugs is important in
order to ensure that patients continue to receive the best available
medications. It has been noted that resistance to anti-malarial drugs is
one major factor that impact negatively on early diagnosis, prompt and
effective treatment as a malaria control strategy. Resistance to anti-
malarial drug has been defined “as the ability of a parasite strain to
survive and/or to multiply despite the administration and absorption of a
drug given in doses equal or higher than those usually recommended,
21
but within the limits of tolerance of the subject. ” Anti-malarial drug
resistance is worldwide in distribution; however, the intensity varies
from one country to another.
Anti-malarial drug resistance can be detected using in vivo, in vitro
20
methods, animal studies and molecular techniques. However, other
methods such as case reports, case series, or passive surveillance,
which are less rigorous, have also been used. The primary objective of
monitoring drug resistance is to evaluate the therapeutic efficacy of the
recommended treatment option for malaria in any country or locality.
This is necessary because of the changing patterns of drug resistance.
Through series of inter-regional and inter-country workshops organized
by the World Health Organization, the protocol for in vivo assessment of
therapeutic efficacy of anti-malarial drugs for uncomplicated falciparum
in areas of intense transmission was developed in 1996. This earlier
protocol has been modified based on consultations jointly organized by
the Emerging Public Health Risks including Resistance, Communicable
Disease Surveillance and Response (CSR/EPH) and Roll Back Malaria
(RBM). Consequently, the classification of anti-malarial sensitivity as
recommended is given as: early treatment failure (ETF), late treatment
failure (LTF), and adequate clinical and parasitological response
21
(ACPR).
Intermittent preventive treatment (IPT)
This is based on the use of anti-malarial drugs given in treatment doses
at predefined intervals after quickening (after 16 weeks gestation or first
noted movement of the foetus). The World Health Organization
recommends that in areas of stable malaria transmission, IPT with an
effective, preferably one-dose, anti-malarial drug be provided as part of
antenatal care, starting after quickening. Sulphadoxine/pyrimethaminen
(S/P) is currently the most effective single-dose anti-malarial drug for
prevention of malaria during pregnancy in areas of Africa where
transmission of P. falciparum malaria is stable and resistance to S/P is
13
low. At least two doses of S/P should be given. There is no evidence
that receiving more than three IPT doses of S/P during pregnancy offers
additional benefit; however, there is similarly no evidence that receiving
three or more IPT doses of S/P will result in increased risk of adverse
13 13,
drug reactions. IPT should not be given more frequently than monthly.
22
Studies in Kenya and Malawi have shown that IPT with S/P has a
beneficial impact on maternal and infant health. IPT with S/P, when
delivered as part of antenatal care significantly reduces the prevalence
23
of maternal aneamia and the incidence of low birth weight infant.
However, issues relating to implementation of intervention need to be
addressed.
 Intermittent preventive therapy

Teratogenicity

Fig 21.3: Recommended schedule for intermittent preventive therapy in

pregnancy
Insecticide-treated bed nets (ITNs)
Use of ITNs during pregnancy in areas of stable transmission provides
24, 3,
significant protection against maternal anaemia and low birth weight.
13
In addition, ITN use benefits the infant who sleeps under the net with
the mother by decreasing exposure to malaria infection, the incidence of
anaemia, and the risk of death, while enhancing development.
Furthermore, insecticide-treated materials, e.g. caves-strips, curtains,
hammock, nets, raffia foldable shields and fly curtains, have been
shown to successfully control malaria morbidity and mortality in a range
of environment throughout the African and Western Pacific regions
2
(WHO, 2000). This approach will expand the acceptability and flexibility
of impregnated materials. Of major concern is the mechanism to ensure
that these materials are available to all who need them, in particular the
underprivileged.
The role of pharmacists in malaria prevention and control
Generally, the role of the pharmacists has increased over the last
decade in many countries, thus resulting in their increasing involvement
in patient care and active participation in public health care programs.
These activities are described in pharmaceutical care (PC), which is the
new philosophy of pharmacy practice, were pharmacists assume
greater responsibilities in patient drug related needs.

Disease-specific PC requires the pharmacist to gather extensive

patient-related medical information and documentation of such
information. These services are far beyond what is required for
pharmacist providing general PC. The general guideline for developing
25
disease-specific PC services has been well described in Hagel et al. A
summary is provided in this chapter; however, readers who are
interested in additional information should consult the above reference
for details.
When preparing for disease-specific PC, the pharmacist should
consider the following points:
· Identify all potential stakeholders for the disease services that
she is considering
· Gather data about the patient she serves, the medications that
they use, and prescribing pattern of the physicians for specific
therapeutic categories
· Do research to determine the patients' needs that are not being
consistently met.
· Talk to key decisions makers among prescribers, employers, etc
· Put together a list of the types of services most likely to be
purchased by prospective customers/ and or payers
· Formulate mission statement, goals, and objectives for the new
disease-specific program, which can be financial, patient-
related or personal
· Identify outcomes of disease-specific services, which can be
 clinical, economic or humanistic outcomes
· Develop disease-specific tools and methods such as protocols,
patient education materials and forms for communicating with
providers.

Malaria is a major public health problem in Nigeria and indeed many

other sub-Saharan African countries, for which concerted efforts among
all stakeholders including the pharmacist is needed. The role of
pharmacist in treatment, control and prevention of malaria can never be
overemphasized. The hospital, community, academic and
administrative pharmacists all have important roles to play in ensuring
that the unacceptable burden of malaria is reduced drastically in our
environment.
Pharmacists who are interested in providing malaria-specific PC
services should:
· Have a thorough understanding of the medical and socio-
economic problems associated with the disease, including the
vulnerable groups (e.g. pregnant women and children) that need special
attention
· Know the various diagnostic methods, their advantages and
disadvantages
· Have and familiarizes herself with the various national and
international anti-malarial treatment guidelines and protocols
· Have in-stock the recommended good quality anti-malarial
medications, such as ACTs, insecticide-treated nets (e.g. long
lasting insecticide-treated bed nets), etc
· Have sufficient public health care focus in her practice in order to
fully appreciate the problem, and also be ready to provide wide
scale community-based malaria-related services.
Interventions for effective control and prevention are available. The
pharmacist, being a member of health care team, has a unique role to
play in ensuring that these interventions are effectively delivered,
particularly to the vulnerable groups (pregnant women and under five
year old children). It is also the responsibility of the pharmacist to ensure
that good quality anti-malarial drugs are available and that they are
rationally administered to patients at every level of health care.

Key Learning Points

· Malaria is a febrile illness characterized by fever and related
symptoms, which has been known to mankind for a very long time.
· Of the fours species responsible for human malaria, P. falciparum is
the most dangerous, and is the predominant species causing in
sub-Saharan Africa.
· Malaria is transmitted through the bite of female Anopheles
mosquito, which is most active at night.
· Malaria parasites attack and destroy red blood cells, resulting in the
clinical manifestation of chills, fever, etc.
· Various diagnostic methods are available, each having advantages
and disadvantages. However, nowadays emphasis is on the use of
malaria parasite genetics through polymerase chain reaction, which
is yet to be adapted to laboratory conditions available in many
African countries.
· Malaria control strategies is hinged on early diagnosis, prompt and
effective therapy; intermittent preventive therapy for pregnant
women, prevention of contact between human and mosquitoes
through the use of insecticide treated bed nets, and
environmental management.
· Artemisinin-based combination therapy is the recommended ant-
malarial drug for acute uncomplicated falciparum malaria in Nigeria,
 due to the problem of malaria parasite resistance to older anti-
malarial drugs.
· The pharmacist has a great role to play in prevention and control of
malaria in endemic regions, through the regular supply of good
quality drugs, ITNs etc, efficacy monitoring, awareness campaign
and other malaria related public health care program.

References
nd
1. Bruce-Chatt LJ (1986). Chemotherapy of malaria (2 edition).
World Health Organization.

2. WHO (2000). Expert Committee on malaria. WHO Technical

Report Series 892, 12th Report: 3 6, Geneva, WHO, Geneva.

3. JHPIEGO (2008). Prevention and control of malaria during

pregnancy. Reference manual for health care providers (second
edition).

4. Manson-Bahr PEC, Bell DR (1987). Manson's tropical diseases.

ELBS, London. 5-50.

5. White NJ, Breman JG (1998). Malaria and other diseases

caused by red blood cells parasites. In: Fauci AS, Braunwald E,
Isselbacher KJ et al (eds). Harrison's principles of internal
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medicine (14 edition). McGraw-Hill, New York. 1180-1189.

6. Sachs J, Malaney P (2002). The economic and social burden of

malaria. Nature. 415: 680 685.

7. Louis H, Barruch DI, Marsh K, Doumbo OK (2002). Pathogenic

basis of malaria. Nature. 415: 673-679.

8. WHO (2006). Guideline for the treatment of malaria.

WHO/HTM/MAL/2006.1108. WHO, Geneva.
9. Enato EFO, Mens PF, Okhamafe AO, Okpere EE, Schallig HD,
Pogoson EE (2009). Plasmodium falciparum malaria in
pregnancy: Prevalence of peripheral parasitaemia, anaemia,
and malaria care-seeking behaviour among pregnant women
attending antenatal clinics in Edo State, Nigeria. J Obst and
Gynaecol. 29 (4): 301-306.

10. Breman JG, Egan A, Keusch G (2001). The intolerable burden of

malaria: a new look at the numbers. Am J Trop Med Hyg; 64 (1-2
Suppl): iv vii.

11. FMoH (2004). Federal Ministry of Health national malaria control

policy for Nigeria. National Malaria and Vector Control Division,
Lagos, Nigeria.

12. Steketee RW, Nahlen BL, Parise M, Menedez C (2001). The

burden of malaria in pregnancy in malaria endemic areas. Am J
Trop Med Hyg. 64 (1-2 Suppl): 28-35.

13. WHO (WHO/AFRO) (2004) A strategic framework for malaria

prevention and control during pregnancy in the African region.
World Health Organization Regional Office for Africa, Brazzaville
AFR/MAL/04.01

14. Menendez C, D'Alessandro U, ter Kuile FO (2007). Reducing the

burden of malaria in pregnancy by preventive strategies. Lancet
Infect Dis. 7: 126-135.

15. Greenwood B, Mutabingwa T (2002). Malaria in 2002. Nature.

415: 670-672.

16. WHO (1999). New perspectives. Malaria diagnosis. Report of a

Joint WHO/USAID Informal Consultation 25-27 October, WHO,
Geneva.

17. WHO (1993). Implementation of the global malaria control

strategy. Reports of the World Health Organization Study Group
 on The Implementation of the Global Plan of Action for malaria
control 1993 2002. WHO Technical Report Series 839, WHO,
Geneva.

18. Roll Back Malaria (RBM) 2005 2015 (2005). Global Strategic
Plan. Roll Back Malaria Partnership, WHO, Geneva.

19. WHO (2001). Antimalarial drug combination therapy. Report of

the World Health Organization Technical Consultation, WHO,
Geneva.

20. Bloland PB (2001). Drug resistance in malaria. World Health

Organization. WHO/CDS/CSR/DRS/2001.4.

21. WHO (2003). Assessing and monitoring of anti-malarial drug

efficacy for the treatment of uncomplicated falciparum malaria.
WHO, Geneva.

22. FMoH (2005). Federal Ministry Health national guidelines and

strategies for malaria prevention and control during pregnancy,
Lagos, Nigeria.

23. van Ejik AM, Ayisi JG, ter Kuile FO (2004). Effectiveness of
intermittent preventive treatment with sulphadoxine-
pyrimethamine for control of malaria in pregnancy in western
Kenya: a hospital-based study. Trop Med Inter Health. 9 (3): 351-
360.

24. Dolan G, ter Kuile FO Jacoutot V,Jacoutot V, White NJ,

Luxemburger C, Malankirii, Chongsuphajaisiddhi T, Nosten F
(1993). Bed nets for the prevention of malaria and anaemia in
pregnancy. Trans R Soc Trop Med Hyg. 87 (6): 620-626.

25. Hagel HP and McDonough RP (2003). Pharmaceutical care for

patients with specific diseases. In: Rovers JP, Currie JD, Hagel
HP, McDonough RP, Sobotka JL (eds). A practical guide to
pharmaceutical care (Second edition). APhA, Washington DC:
153-173.
 CHAPTER TWENTY TWO

PHARMACEUTICAL CARE IN HIV/AIDS

Patrick O Erah
Learning Objectives
At the end of this chapter, you should be able to:
I. Describe the history and basic pathophysiology of HIV/AIDS.
ii. Indicate when to initiate antiretroviral therapy in patients with
HIV infection.
iii. Describe the goals of therapy and how to set them.
iv. Recommend pharmacotherapy (especially appropriate first line
therapy for naïve patients) for all HIV patients.
v. Determine monitoring parameters for patients on ART.
vi. Recognize how to identify and resolve drug-related problems in
the care of HIV positive individuals.
vii. Provide effective counseling to patients on ART.
viii. Be able to set up an effective pharmaceutical care practice for
HIV/IADS patients in resource-limited setting.
List of Abbreviations

3TC ? lamivudine NVP ? nevirapine

ABC ? abacavir OHL ? oral hairy leukoplakia

AIDS ? acquired immunodeficiency syndrome OI ? opportunistic infection

ALT ? alanine aminotransferase PCP ? Pneumocystis pneumonia

ART ? antiretroviral therapy PGL ? persistent generalized lymphadenopathy

ARV ? antiretrov iral PI ? protease inhibitor

ATV ? atazanavir PLWHA ? People living with HIV/AIDS

AZT ? zidovudine (also known as ZDV) PML ? progressive multifocal leukoencephalopathy

BMI ? body mass index /r ? low -dose ritonavir

CD4 ? CD4+ T -cell (T-lymphocyte bearing CD4 RBV ? ribavirin

receptor)
RT ? reverse transcriptase
CMV ? cytomegalovirus
RTI ? reverse transcriptase inhibitor
CTX ? co -trimoxazole
RTV ? ritonavir
CXR ? chest X -ray
SQV ? saquinavir
d4T ? stavudine
TB ? tuberculosis
ddI ? didanosine
TDF ? tenofovir d isoproxil fumarate
DNA ? deoxyribonucleic acid
TLC ? total lymphocyte count
EFV ? efavirenz
VL ? viral load
FDA ? Food and Drug Administration (USA)
WHO ? World Health Organization
FPV ? fos -amprenavir

FTC ? emtricitabine

HBV ? hepatitis B virus

HCV ? hepatitis C virus

HIV ? human immunodeficiency virus

IDV ? indinavir

LPV ? lopinavir

NFV ? nelfinavir

NNRTI ? non -nucleoside reverse transcriptase

inhibitor

NRTI ? nucleoside reverse transcriptase inhibitor

1
Introduction
AIDS was first recognized in 1981 and the virus that causes it was
identified in 1983 at the Institut Pasteur in Paris, France. The virus was
initially named lymphadenopathy-associated virus (LAV). In 1984, the
virus was confirmed at the National Cancer Institute in Bethesda, USA, to
be the cause of AIDS and renamed T-lymphotropic virus type 3 (HTLV).
Human immunodeficiency virus (HIV), which was introduced in 1986 by
an international expert committee, belongs to a family of viruses called
retrovirus known for many years to cause a number of different diseases
in animals. Since the first description of AIDS in 1981, researchers have
identified 2 serotypes of HIV (HIV-1 and HIV-2), both of which are
transmitted through sexual contact, blood, and from mother to child.
Although HIV-1 is the predominant virus because of its high rate of
replication, and rapid mutation into subtypes, the two serotypes both
cause indistinguishable AIDS. HIV-2 is less easily transmittable and the
period between initial infection and illness is often longer than that of HIV-
1
1.
HIV/AIDS is now one of the leading causes of death in the world. In sub-
Saharan Africa alone, the epidemic has orphaned nearly 12 million
children aged under 18 years. As at 2007, 33 million [30 million36 million]
were estimated people living with HIV worldwide. Although the annual
number of new HIV infections declined from 3.0 million [2.6 million3.5
million] in 2001 to 2.7 million [2.2 million3.2 million] in 2007, the number
of children younger than 15 years living with HIV increased from 1.6
million [1.4 million2.1 million] to 2.0 million [1.9 million2.3 million] during
2
the same period with almost 90 % living in sub-Saharan Africa. However,
most national epidemics have stabilized or begun to decline in sub-
Saharan Africa. In Nigeria, for example, the adult prevalence rose
progressively from 1.8 % in 1991 to 5.8 % in 2001 and then declined.
Unfortunately, the epidemic is rising outside the sub-Saharan Africa in
countries such as China, Germany, Indonesia, Mozambique, Papua
New Guinea, the Russian Federation, Ukraine, the United Kingdom and
2
Viet Nam.
HIV infection is a tragic human condition aggravated by poverty, abuse,
violence, prejudice and ignorance. Vulnerability to the infection is often
engineered by poverty. Social and economic circumstances intensify its
impact. The virus depletes the human body of its natural defenses and
generates and amplifies the very conditions that enable the epidemic to
thrive. Different communities often face different epidemic dynamics
which they must respond to in a timely and efficient manner to mitigate
1
the impact of this disease.

HIV/AIDS is a devastating disease which has become a major social,

health and developmental challenge in many developing countries of
the world, particularly those of Africa. Like many other chronic illnesses,
HIV infection affects nearly every organ system of the body. Super-
infection by bacteria, other viruses, or fungi is common in the advanced
stages. Among those at high risk for HIV infection are intravenous drug
3
users and the severely mentally ill , whose conditions may discourage
testing for HIV infection or disclosure of HIV status and can also hinder
treatment. Discrimination against HIV-infected individuals in housing
and employment persists and may impede the delivery of health care by
disrupting the stability of home and work life. Understanding of the basic
pathophysiology and immunology of HIV infection continues to evolve
on an almost-daily basis, and drug development occurs at a rapid pace.
Unlike some other illnesses, HIV infection can be prevented by curbing
4
high-risk behaviors.
Since 1990, an average of one new antiretroviral (ARV) agent has been
approved each year by the United States Food and Drug Administration
5
(FDA); some years have seen the approval of two or three new ARVs.
With these rapidly changing and complex therapeutic options (see
Tables 1 and 2 for some available options), it is a challenge for many
primary care providers to keep abreast of state-of-the-art strategies for
managing HIV infection and provide comprehensive treatment
population of patients in need of these medicines. The advent of
effective antiretroviral therapies has increased the need for health
professionals with broad knowledge of and experience in managing HIV
infection's concomitant diseases. Important drugdrug interactions are
known to exist between some ARV agents and medicines used to treat
opportunistic infections, between antiretroviral agents and medicines
used to treat non-HIV-related co-morbidities, and among the
antiretroviral agents themselves. Failure to recognize these drug-
related problems may result in additional or exacerbated adverse
effects, non-adherence, therapeutic failure, or irreversible drug
resistance. Furthermore, HIV-infected patients need effective
counseling and education regarding their treatment to be able to
recognize and cope with long-term consequences of therapy.
Table 22.1: List of some available antiretroviral drugs

Single Formulations Fixed Dose Combinations

Abacavir 300mg tabs Nevirapine 200mg tabs

Abacavir oral sol. Nevirapine oral susp. Lamivudine 150mg + zidovudine 300mg +
100mg/5ml 50mg/5ml abacavir 300mg tabs

Didanosine 25mg tabs Ritonavir 100mg caps

Didanosine 50mg chewable Saquinavir 200mg h.g. Lamivudine 150mg + zidovudine 300mg
tabs caps

Didanosine 100mg tabs Stavudine 15mg caps

Didanosine 150mg Stavudine 20mg caps Lamivudine 150mg + stavudine 30mg

chewable tabs

Didanosine 200mg Ritonavir 100mg caps Lamivudine 150mg + stavudine 40mg

chewable tabs

Efavirenz 50mg caps Stavudine 30mg caps

Efavirenz 200mg caps Stavudine 40mg caps Lamivudine 150mg + stavudine 30mg +
nevirapine 200mg tabs

Efavirenz 600mg tabs Stavudine oral sol. Lamivudine 150mg + stavudine 40mg +
1mg/ml nevirapine 200mg tabs

Efavirenz oral sol. 30mg/ml Tenofovir 300mg tabs

Indinavir 200mg caps Zidovudine 100mg tabs Lopinavir + RTV oral sol. 400+100mg/5ml

Indinavir 400mg caps Zidovudine 250mg tabs Lopinavir + RTV 133.3+33.3mg caps

Lamivudine 150mg tabs Zidovudine 300mg tabs

Lamivudine oral sol. Zidovudine oral sol.

50mg/5ml 50mg/5ml

Nelfinavir 250mg tabs

Nelfinavir 50mg/g powder

 Table 22.2: Some FDA-approved antiretroviral agents

Generic Brand Manufacturer

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Abacavir Ziagen GlaxoSmithKline

Abacavir + Lamivudine +
Trizivir GlaxoSmithKline
Zidovudine

Didanosine Videx, Videx EC Bristol Myers-Squibb

Lamivudine Epivir GlaxoSmithKline

Lamivudine + Zidovudine Combivir GlaxoSmithKline

Stavudine Zerit Bristol Myers-Squibb

Tenofovir* Viread Gilead

Zalcitabine Hivid Roche

Zidovudine Retrovir GlaxoSmithKline

Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Generic Brand Manufacturer

Delavirdine Rescriptor Agouron

Efavirenz Sustiva Bristol Myers-Squibb

Nevirapine Viramune Boehringer-Ingelheim

Protease Inhibitors (PIs)

Generic Brand Manufacturer

Amprenavir Agenerase GlaxoSmithKline

Indinavir Crixivan Merck

Lopinavir + Ritonavir Kaletra Abbott

Nelfinavir Viracept Agouron

Ritonavir Norvir Abbott

Saquinavir-HGC (hard gel

Invirase Roche
capsule)

Saquinavir-SGC (soft gel

Fortovase Roche
capsule)

*Nucleotide reverse transcriptase inhibitor

Antiretroviral therapy (ART) can delay disease progression and increase

6
life expectancy of PLWHA. Once an individual is diagnosed to be
infected by HIV, pharmacotherapy is often one of the first considerations,
particularly when the symptoms of HIV/AIDS become apparent. For HIV-
positive patients, pharmacotherapy presents special challenges and
opportunities for pharmacists interested in developing a specialized
knowledge base about HIV treatment. Within an integrated health
system, pharmacists are likely to interact directly with patients infected
with HIV in outpatient pharmacies, ambulatory care clinics, inpatient
settings, dialysis units, hospices, and home infusion and home health
care companies. Pharmacists are often considered the most accessible
health professional as they are frequently at the frontline in helping HIV-
infected patients deal with medication related issues including barriers to
access, managing adverse effects and drug interactions, and adhering to
medication regimens.
There are indications that HIV/AIDS-related mortality and morbidity
depend largely on the availability, accessibility and rational use of
 7-8
antiretroviral therapy (ART). Appropriate use of ART has improved the
health of many HIV positive individuals who otherwise may have died.
9
Adherence to medication is a major predictor of the survival of PLWHA
and poor adherence to treatment remains a major obstacle in the fight
against HIV/AIDS. Adherence is defined as a patient's ability to follow a
treatment plan, take medications at prescribed times and frequencies,
10
and follow restrictions regarding food and other medications. Although
the exact degree of adherence needed to ensure successful outcomes
from drug therapy is not known, there are indications that patients must
take 95% of their doses to maintain drug levels that will achieve viral
11
suppression, prevent drug resistance, and avert treatment failure. . Lack
of adherence is often cited as the most common cause of the
development of drug resistance and reduced effectiveness or
therapeutic failure. Known causes of non-adherence are multi-factorial,
and generally fall into three categories namely, patient-related
(psychosocial and educational) factors, patient-provider factors
(interaction with physicians and other health workers and access to
medications) and clinical factors (pill burden, dosing frequency and
12
adverse effects of medications). The contribution of each factor to non-
adherence in a particular patient depends on several factors including
mental illness (particularly untreated depression), unstable housing,
active substance abuse, major life crises, medication adverse effects,
inconvenient frequency of drug administration, dietary restrictions, and
13
pill burden.
In developing countries such as Nigeria, the psychosocial and economic
challenges confronting PLWHA (including anxieties, uncertainties
regarding the side effects of medications, societal oppression, stigma
and discrimination) significantly affect their quality-of-life (QoL). As the
burden of HIV/AIDS continues to take its toll in many countries, many
challenges face the pharmacists. An opportunity exists to apply the
principles of pharmaceutical care to redesign the role of pharmacy.
Pharmaceutical care concept is a method of delivering services that
match individual patient needs with the services provided by
14
pharmacists. It is the direct, responsible provision of medication-
related care for the purpose of achieving definite outcomes that improve
15
a patient's quality-of-life. In general, the pharmacist establishes
relationship with patients to ensure the appropriateness of medication
therapy and patients' understanding of their therapy and to monitor the
effects of that therapy. In collaborative drug therapy management, the
pharmacist enters into agreements with physicians who may authorize
the pharmacist to select appropriate medication therapies for patients
who have a confirmed diagnosis and adjust them on the basis of
patients' responses. Due to the complex and progressive course of HIV
disease, patients will require varying types and intensities of medical
care. Throughout a patient's illness, ambulatory, community, and
hospital stay, pharmacists can play key roles in assisting patients with
their medication-related concerns.

Caring for HIV Positive Patients

Until relatively recently, the majority of HIV clinical care in resource-poor

countries was confined to managing the terminal stage of infection,
including extremely late diagnosis of opportunistic infections and
cancers, use of basic palliative symptom management, and short-term
hospitalization just before death. Not many people were aware of their
HIV status until the onset of severe HIV-associated illness, and most did
not seek help from medical experts until they were already terminally ill.
The introduction of primary prophylaxis (use of medications to prevent a
first episode of opportunistic infection) and treatment for opportunistic
infections, including tuberculosis, is leading to prolonged survival to a
limited extent but this has done nothing to restore immune function. The
restoration was not possible until the arrival of ART.

Once diagnosis of HIV/AIDS is made, the next issue is usually how to

manage the disease. Effective management of HIV/AIDS goes beyond
the use of medicines. The World Health Organization (WHO) clinical
staging system has been widely used in resource-limited countries,
particularly in the African Region, and has proved pragmatic and useful
in facilities at both the first level and the referral level in taking major
decisions about the management. Some of the objectives of the clinical
staging system include:
· Assisting with clinical decision-making, including decisions on
starting, substituting, switching and stopping ART, and with
routine follow up of patients on treatment;
· Permitting the inclusion of laboratory testing, especially CD4
count, where available, so as to guide prognosis and assist in
determining the need for ART and other therapies;
· Guiding clinicians in assessing the response to ART, particularly
where viral load and/or CD4 counts or percentages are not
widely or easily available (new or recurrent stage 4 events may
suggest failure of response to treatment; new or recurrent stage
2 or stage 3 events may suggest an inadequate response to
treatment, potentially because of poor adherence; however
further evidence is required in order to determine the
significance of staging events once ART has commenced; and
· Providing surveillance definitions for advanced stages of HIV
infection which reflect disease requiring ART either immediately
16
or in the near future.

Clinical events in HIV/AIDS are categorized as those where a

presumptive clinical diagnosis may be made (conditions that can be
diagnosed clinically or with basic laboratory tests) and those where a
definitive diagnosis may be made (for conditions requiring more
complex and sophisticated laboratory investigations). Clinical staging
(Table 3) needs to be performed at determination or confirmation of HIV
infection, and on entry to clinical care (pre-ART) to help guide ART and
care-related decisions. Assessment of clinical stage at each clinical visit
also provides useful information on current clinical status, and can guide
clinical decision-making.
Table 22.3: Revised WHO clinical staging of HIV/AIDS for adults and adolescents16

Primary HIV infection

Asymptomatic

Acute retroviral syndrome

Clinical stage 1

Asymptomatic

Persistent generalized lymphadenopathy (PGL)

Clinical stage 2

Moderate unexplained weight loss (<10% of presumed or measured body weight)

Recurrent respiratory tract infections (RTIs, sinusitis, bronchitis, otitis media,

pharyngitis)

Herpes zoster

Angular cheilitis

Recurrent oral ulcerations

Papular pruritic eruptions

Seborrhoeic dermatitis

Fungal nail infections of fingers

Clinical stage 3

Conditions where a presumptive diagnosis can be made on the basis of clinical

signs or simple investigations

Severe weight loss (>10% of presumed or measured body weight)

Unexplained chronic diarrhoea for longer than one month

Unexplained persistent fever (intermittent or constant for longer than one month)

Oral candidiasis

Oral hairy leukoplakia

Clinical Stage 4

Conditions where a presumptive diagnosis can be made on the basis of clinical

signs or simple investigations

HIV wasting syndrome

Pneumocystis pneumonia

Recurrent severe or radiological bacterial pneumonia

Chronic herpes simplex infection (orolabial, genital or anorectal of more than one
months duration)

Oesophageal candidiasis

Extrapulmonary TB

Kaposis sarcoma

Central nervous system (CNS) toxoplasmosis

HIV encephalopathy

Conditions where confirmatory diagnostic testing is necessary

Extrapulmonary cryptococcosis including meningitis

Disseminated non-tuberculous mycobacteria infection

Progressive multifocal leukoencephalopathy (PML)

Candida of trachea, bronchi or lungs

Cryptosporidiosis

Isosporiasis

Visceral herpes simplex infection

Cytomegalovirus (CMV) infection (retinitis or of an organ other than liver, spleen or

lymph nodes)
Any disseminated mycosis (e.g. histoplasmosis, coccidiomycosis, penicilliosis)
Recurrent non-typhoidal salmonella septicaemia
Lymphoma (cerebral or B cell non-Hodgkin)
Invasive cervical carcinoma
Visceral leishmaniasis
Although the data on CD4 levels are not always a prerequisite for starting
ART, CD4 testing, in conjunction with consideration of the clinical stage,
is useful for determining the degree of immuno-compromise. Where
CD4 facilities are available, they support and reinforce the clinical
decision-making. The relationship between the severity of immuno-
suppression and CD4 levels is presented in Table 4. It should be noted
that the immunological staging of disease reverses with successful
17
ART.

Table 22.4: CD4 levels in relation to the severity of immuno

suppression

Variable CD4 level

Not significant immuno- > 500/mm3

suppression

Mild immuno-suppression 350 499/mm3

3
Advanced immuno- 200 349/mm
suppression

Severe immuno-suppression <200/mm3

WHO recommends that in settings where CD4 testing is available,

antiretroviral therapy should be initiated when a patient's CD4 count falls
below 350 cells/ml but where CD4 testing is unavailable, therapy should
be started when clinical signs of advanced or severe immune
suppression are exhibited by patients.2,16,18 Tables 5 6 summarize the
immunological criteria for the initiation of ART in adults, adolescents
children and infants.
Table 22.5: Recommendations for initiating antiretroviral therapy
(ART) in HIV-infected adults and adolescents according to clinical
stage and availability of immunological markers16, 18

CD4 testing
WHO not
clinical CD4 testing available
staging Available

1 Do not treat Treat if CD4 count is below 350

cells/mm3 a
2 Do not treat b

Consider treatment if CD4 count is

3 Treat
below 350 cells/mm3 a

4 Treat Treat irrespective of CD4 cell count

a
CD4 cell count advisable to assist with determining need for immediate
therapy for situations such as pulmonary TB and severe bacterial
infections, which may occur at any CD4 level. This recommendation will
enable many more people in high-burden areas to live longer and
healthier lives.
b 3
A total lymphocyte count of 1200/mm or less can be substituted for the
CD4 count when the latter is unavailable and mild HIV disease exists. It
is not useful in asymptomatic patients. Thus, in the absence of CD4 cell
counts and TLCs, patients with WHO adult clinical stage 2 should not be
treated.
Table 22.6: Recommendations for initiating antiretroviral therapy (ART)
in HIV-infected infants and children according to clinical stage and
19
availability of immunological markers

Availability of Age specific treatment

WHO paediatric recommendation*
CD4 cell
stage
measurements e 11 months d 12 months
CD4
4a Treat all
No CD4

Treat all, CD4-guided

a b in those children with
3 CD4 Treat all
TB c, LIP, OHL,
thrombocytopenia
b d
CD4 CD4-guided
2
d
No CD4 TLC-guided
b d
CD4 CD4-guided
1
b e
No CD4 Do not treat

LIP, lymphocytic interstitial pneumonia; OHL, oral hairy leukoplakia; TB,

tuberculosis; TLC, total lymphocyte count
* Strength of recommendation/level of evidence.
a
Stabilize any opportunistic infection before initiation of ART.
b
Baseline CD4 is useful for monitoring ART even if it is not required to
initiate ART.
c
In children with pulmonary or lymph node tuberculosis the CD4 level and
clinical status should be used to determine the need for and timing of
initiation of ART in relation to tuberculosis treatment.
d
Refer to Table treat 5 for CD4 and table 6 for TLC values.
e
Many experts neat infants in the absence of symptoms.

However, the United States Department of Health and Human Services

recommends initiation of antiretroviral therapy in patients who have
experienced an AIDS-defining opportunistic illness or have a CD4 count
less than 350 cells/ml.2
Although different classes of ARVs are available for the management of
HIV/AIDS, the public health approach to ART scale-up in resource-
limited settings aims to support the development of treatment
programmes that can reach as many people as possible. Among the key
tenets of this approach are the standardization and simplification of ARV
regimens. Recognizing that individuals who cannot tolerate or fail the
first-line and second-line regimens may require input from more
experienced clinicians, it has been suggested that first-line regimen and
a limited number of second-line regimens should be selected.16 When
selecting appropriate ARV regimens, the following factors are often
considered:
· Suitability of the drug formulation, especially the availability of
fixed-dose combinations
· Licensing approval by national drug regulatory authorities for the
product and recommended dose
· Toxicity profile
· Laboratory monitoring requirements
· Potential for maintenance of future treatment options
(sequencing of ARVs)
· Promotion of adherence (ARVs with once-daily or twice-daily
dosing)
· Prevalent coexistent conditions (TB and hepatitis B)
· Special considerations for women of childbearing potential or
who are pregnant
· Availability from local and international manufacturers, including
procurement and supply chain logistics
· Price and cost-effectiveness
· Specific ARV requirements for HIV-2 infections that are naturally
resistant to NNRTIs
First-line Therapy
It is recommended that the first-line regimens for adults and adolescents
contain two NRTIs plus one NNRTI as they are efficacious, generally
less expensive than other regimens, have generic formulations, often
available as fixed-dose combinations and do not require a cold chain.
The thiacytadine analogues (3TC or FTC) are pivotal to first-line
regimens. 3TC or FTC should be used with a companion nucleoside or
nucleotide analogue, the choices here being AZT, TDF or ABC. The use
of d4T as first-line drug is no longer recommended because of its long-
18
term, irreversible side-effects . The preferred NRTI backbone is
composed of AZT or TDF combined with either 3TC or FTC. Didanosine
(ddI) is an adenosine analogue NRTI recommended to be reserved for
second line regimens. Finally an NNRTI, either EFV or NVP, is added. A
triple NRTI regimen is considered as an alternative for first-line ART
when the NNRTI options provide additional complications and to
preserve the PI class for second-line treatment (e.g. in women with CD4
counts of 250-350 cells/mm3; co-infection with viral hepatitis or
tuberculosis; severe adverse reactions to NVP or EFV, infection with
HIV-2). The recommended triple NRTI combinations are zidovudine +
lamivudine + abacavir and zidovudine + lamivudine + tenofovir.
Second-line Therapy
While ARVs will suppress the HIV virus, treatment failure can occur.
Therefore, during treatment with ARVs, CD4 cell count remains the
strongest predictor of HIV-related complications. A change from first-line
to second-line ARV regimen is recommended if treatment failure occurs.
Although viral load testing is not yet widely available, it is a sensitive and
informative way to identify treatment failure. In the absence of viral load
measurements in resource-limited settings, assessment of treatment
success, and time-based decision on changing from first-line to second-
line regimens should be based clinical or immunological monitoring or
both. Since antiretroviral drugs do not eradicate the virus but rather
maintain viral replication at low levels, treatment must be continued
without interruption.2 The new second-line regimen should involve drugs
that retain activity against the patient's virus strain and should ideally
include a minimum of three active drugs, one of them drawn from at least
one new class. This is to increase the likelihood of treatment success
and minimize the risk of cross resistance. The PI class is reserved for
second-line treatments and is preferably supported by two new NRTIs
and boosted with ritonavir.16 Detailed recommendations for switching to
second-line ARV regimens in adults and adolescents are provided in
Table 22.7.

Table 22.7: Detailed recommendations for switching to second-line ARV

regimens in adults and adolescents16,19
Second-line regimen
First-Line regimen
PI
RTI component a
component

ddI + ABC or
b
AZT + 3TC + TDF + ABC or
NVP or EFV TDF + 3TC (
AZT) c
Standard ddI + ABC or
b
strategy TDF + 3TC +
ddI + 3TC ( AZT)
NVP or EFV c
d
PI/r
ddI + 3TC ( AZT)
b c
ABC + 3TC + or

NVP or EFV TDF + 3TC (

AZT) c

AZT or d4T + 3TC

Alternative b
+ EFV or NVP ddI
strategy
TDF or ABC
a
NFV does not need refrigeration and can be used as a PI alternative in
places without a cold chain.
b
3TC and FTC are considered interchangeable because they are
structurally related and share pharmacological properties and
resistance profiles.
c
3TC can be considered to be maintained in second-line regimens to
potentially reduce viral fitness, confer residual antiviral activity and
maintain pressure on the M184V mutation to improve viral sensitivity to
AZT or TDF. AZT may prevent or delay the emergence of the K65R
mutation.
d
There are insufficient data to detect differences among currently
available RTV-boosted PIs (ATV/r, FPV/r, IDV/r, LPV/r and SQV/r) and
the choice should be based on individual programme priorities (see
text). In the absence of a cold chain, NFV can be employed as the PI
component but it is considered less potent than an RTV boosted PI.

HIV and Tuberculosis

Active tuberculosis (TB) can be present when ART needs to be initiated
or in patients receiving first-line or second-line therapy. Co-management
of HIV and TB is complicated by drug interactions between rifampicin
and both the NNRTI and PI classes, immune reconstitution inflammatory
syndrome (IRIS), pill burden, overlapping toxicities, and adherence
issues. Collaboration between TB and HIV programmes is therefore
essential for the delivery of an integrated package of HIV and TB
services. For patients with active TB in whom HIV infection is diagnosed
and ART is required, the first priority is to initiate standard anti-
tuberculosis treatment. It is recommended that, in persons with CD4 cell
counts below 200 cells/ml, ART should be started between two and eight
weeks after the start of TB therapy when the patient has stabilized on TB
treatment.16
Antiretroviral therapy may be delayed until after the initial intensive
phase of TB treatment has been completed in patients with CD4 cell
counts above 200 cells/ml in order to simplify the management of TB
treatment and to deal with the challenges mentioned above. In patients
with CD4 counts above 350 cells/ml, ART can be delayed until after the
completion of short-course TB therapy, following a reassessment of the
patient's eligibility for ART and evaluation of the response to TB therapy
and of CD4 cell counts, if available. It is recommended that HIV-positive
patients routinely receive co-trimoxazole to reduce mortality and all
people living with HIV be screened regularly for active tuberculosis; in
the absence of evidence of active disease, individuals should be
considered for treatment of latent tuberculosis infection with a 6-9-
month course of preventive therapy.2 Details of the guidelines for
choosing ARVs for adults, adolescents, children and infants are
provided in the WHO documents16,19.

Other Considerations
The prevention and treatment of opportunistic illnesses are vital for
effective HIV treatment and care. Decline of the nutritional status of
patients is frequently associated with HIV disease progression. In both
adults and children, HIV infection increases protein, micronutrient and
energy requirements. Therefore, timely nutritional support for people
living with HIV may help extend the asymptomatic period of relative
health or reduce the risk of death where severe immune deterioration
has already occurred.2 Paying attention to mental health, and social and
economic factors, such as access to transport, maximizes the success
of HIV treatment.
Goals of Therapy
Regardless of any patient's socio-demographic background,
treatment goals for HIV/AIDS patients fall into three categories
namely, clinical, immunological and virological and failure to achieve
every one of the therapeutic goals is referred to as a discordant
response. The primary goal of initial ART is to achieve maximum
sustained suppression of HIV replication as determined by the
patient's viral load and/or CD4 count. Other goals include
· maintenance of durable suppression of HIV replication
· delay of disease progression and extension of AIDS-free survival
time
· prevention of emergence of drug-resistant virus
· support of optimal immune system function
· maximization of adherence to ARV regimens through effective
counselling
· reduction of HIV transmission, and
20
· improvement of quality-of-life of affected patients.

As appropriate, it is recommended that highly active antiretroviral

therapy (HAART) should be initiated as early as possible. Challenge,
however, occurs in patients with co-existing TB. One of the foremost
concerns of ART programmes is the ability of PLWHA to maintain near
perfect adherence over the long term. In order to achieve the goal of
ART, undetectable levels of the virus in the blood, patients are required to
10
maintain more than 9095% adherence. Both patients and health care
providers face significant challenges with respect to adherence to ART.
Once initiated, ART is a life-long treatment that consists of multiple
medications to be taken daily with varying dietary instructions. These
medications also have side effects, some of which may be temporary
while others may be more permanent and requiring a change of
treatment. Inadequate adherence to treatment is associated with
detectable viral loads, declining CD4 counts, disease progression,
episodes of opportunistic infections and poorer health outcomes.
Responsibilities of a Pharmacist in HIV/AIDS Treatment
Caring for dying patients is part of the continuum of pharmaceutical care
that pharmacists should provide to patients. Pharmacists have a
professional obligation to work in a collaborative and compassionate
manner with patients, family members, caregivers, and other health care
professionals to help fulfill the pharmaceutical care needsespecially
nutrition support, the management of diarrhea, electrolyte imbalances,
pain, and depression; and other quality-of-life needsof dying patients. In
general, every pharmacist involved in the care of HIV/AIDS patients
should perform the following functions in collaboration with physicians
and other members of the health care team:21
1. Patient assessment for medication-related factors. The
pharmacist screens patients' medication profiles for potential and actual
drugdrug and drugfood interactions. A number of antiretroviral drugs
cannot be taken with certain foods. For example, garlic reduces the
effectiveness of saquinavir. Therefore, it is the responsibility of the
pharmacist to ensure that the patient and caregivers (dietitians, nurses,
family members, and friends) are aware of these dietary restrictions.

2. For any drug-related problems identified, the pharmacist makes

recommendations for dosage modification or alternative
therapies, if appropriate. The pharmacist can also initiate or
modify medication therapy or patient care plans on the basis of
patient responses.

3. Interpret data related to medication safety and effectiveness.

4. Order or recommend laboratory tests necessary for monitoring

outcomes of medication therapy and potential drug toxicities,
and cancel unnecessary laboratory tests.

5. Provide information, education, and counseling to patients about

medication-related care; communicates relevant issues to
physicians and other members of the health care team in strict
confidence.
6. Document the care provided in patients' records. The
professional actions of pharmacists that are intended to ensure
safe and effective use of drugs and that may affect patient
outcomes documented in the patients' medical records.
Pharmacists in every practice setting routinely document the
quantity and quality of services provided and the estimated effect
on patient outcomes. Confidentiality for the HIV-infected person
is a critical issue because of the stigma that is sometimes still
associated with the illness.

7. Assessing patients' readiness to adhere to drug therapy,

assisting in the design of therapeutic plans to increase the
likelihood of adherence, assisting the patient in successful
implementation of drug therapy, intervening when the patient
states or intimates that he or she cannot or will not adhere to
treatment, and providing ongoing monitoring of adherence. The
pharmacist identifies any barriers to patient adherence to
medication regimens and communicates with the prescribers
known instances of non-adherence to medication therapy and
proposes strategies to the prescribers and patients to improve
the likelihood of success of subsequent regimens. The
pharmacist can promote patient adherence by considering the
patient's history of adverse effects when recommending a
regimen; helping to develop a daily medication administration
schedule that accommodates the patient's sleep, work, and meal
schedules; providing memory aids for medication taking;
recruiting an adherence coach; and educating and motivating
21, 22
patients and caregivers.

8. Participate in multi-disciplinary reviews of patients' progress.

9. Communicate with payers to resolve issues that may impede

access to medication therapies.
 10. Participates in post-marketing surveillance of adverse drug
events.

In addition to the aforementioned functions, pharmacists practicing in

some settings and with some interdisciplinary relationships may engage
in the following activities:21
1. Monitoring efficacy of the therapeutic regimen by tracking CD4
counts and viral load and providing input about patients'
response to therapy to other members of the health care team.

2. Providing individualized health promotion recommendations and

disease prevention advice and activities.

3. Assessing patient knowledge about HIV infection and its

treatment and educating patients about the HIV infection,
progression to AIDS, prevention, testing and counseling,
community involvement in care and support, preventing spread;
the goals, mechanism of action, and duration of antiretroviral
drug therapy; potential adverse effects from and interactions with
ART and ways to manage adverse effects; the concept of drug
resistance and the importance of adherence to the therapeutic
regimen; laboratory monitoring of therapeutic response to
antiretroviral drug therapy; and therapeutic strategies for
overcoming therapeutic failure.

4. Recognizing when patients are at risk for opportunistic

infections, recommending initiation or discontinuation of
prophylaxis, and intervening to ensure evaluation and
management by a physician or other practitioner (e.g., physician
assistant, nurse practitioner, or clinical pharmacist).

5. Performing limited physical assessment and supervising

medication therapy with appropriate collaborative drug therapy
 management authority.

6. Assessing the indications for HIV drug-resistance testing, the

appropriateness of timing for sample collection, interpreting test
results, and designing a new antiretroviral regimen in
consultation with an expert in drug resistance.

7. Referring patients to other health care or social service

providers, such as psychologists, psychiatrists, social workers,
or support groups in conjunction with the patient's primary
physician.

8. Educating the community about modes of HIV transmission and

effective techniques for prevention of transmission.

9. Encouraging public policy decisions that reduce the risk of

transmission of HIV, hepatitis B, hepatitis C, and other sexually
transmitted diseases.

10. Performing research related to antiretroviral therapy (e.g.,

adherence, quality of life, pharmacokinetics).

Therapeutic Plan for HIV/AIDS Patients

Pharmaceutical care plan is a written, individualized, comprehensive
medication therapy plan based on clearly defined therapeutic goals. For
HIV positive patients, it should be developed by all pharmacists and
updated with each major change in each patient's status. As
appropriate, the physician is informed about the care plan to ensure
common goals. Patients should also be informed about the general
content of the care plan as means of gaining their agreement regarding
drug therapy. In general, the following plans will be included:
1. Assess patient's database
If the patient is seeing the pharmacist for the first time and records are
not available, the first step in the care planning process is the creation of
a comprehensive patient database, which should at least include
patients' demographic characteristics, diagnoses and past medical
history, present medications and medication history, medication
allergies/intolerances, smoking/alcohol/caffeine/drug use history,
abnormal laboratory and physical exam results, and renal and liver
function data. For refills, the pharmacist should assess the patient's
medical information including both prescription and nonprescription
medication histories and the reasons why the medications were
prescribed. Some information may be obtained from the physician, e.g.,
laboratory test results and history of hospitalizations.
2. Review relevant literature
It is important that relevant textbook(s), and appropriate guidelines are
consulted to be well informed on patient's disease condition and drug
treatment. It may also be necessary to check indications, dosage, side
effects and contraindications of drugs (other than ARVs) prescribed
from quick reference materials such as British National Formulary (BNF)
or Emdex (Index of Essential Medicines, Lindoz Products Ltd, Lagos,
Nigeria). WHO and other bodies publish guidelines for the management
of HIV/AIDS which are reviewed regularly.16,19 Also, many HIV/AIDS-
related websites have wide collections of information on
pharmacokinetics, indications, dosage, side effects, contraindications,
etc of both ARVs and other drugs that may be prescribed for the
HIV/AIDS patients.
3. Assess drug-related problems
The pharmacist should evaluate the patient's drug therapy. This will
include:
· Assessment of the patient for drug-related problems these
include untreated indications, improper drug selection, sub-
therapeutic dosage, overdosage, failure to receive prescribed
 drug, adverse drug events, drug-drug and drug-food
interactions, and treatment failure;
· Determination of whether drug-related problems are being
treated;

· Evaluation of whether current drug therapy is appropriate; and

· Estimation of whether additional drug therapy is needed.
It is important that both objective and subjective findings are assessed.
Subjective findings are those that the patient describes (e.g., 'I feel tired
all the time, “I feel bloated,” or "I woke up feeling dizzy"). Objective
findings are those that can be observed or measured by the pharmacist
(e.g., patient appears tired, blood pressure is 180/105 mmHg, pitting
edema in ankles). An understanding of the types of drug-related
problems that may occur facilitates the evaluation process.
It is recommended that pharmacists:
§ List the drug-related problems in order of importance;
§ Assess the severity of the clinical problem -- examining the
patient's daily signs and symptoms or determining if the patient
had been hospitalized previously could accomplish this;

§ Analyze and integrate the information gathered above and

attempt to determine if drugs caused or exacerbated the problem
in the patient;

§ Draw conclusions on the therapeutic problem in preparation for

developing a patient-specific plan; and
§ Discuss with patient's physician to be sure why the therapeutic
measure was being adopted if there is any problem identified
with patient's drug therapy (it might be a new evidence-based
approach being adopted).
The following may be followed in the evaluation of ARV regimen:
· Determine if the ARV regimen consisted of a strongly
 recommended or alternate regimen according to the latest
guidelines.

· Once a patient fails an ARV regimen, a new regimen is usually

constructed based on the use of a resistance test (i.e., HIV
genotype), and the regimen may differ from those recommended
for initial therapy. However, certain combinations of NRTIs
should be avoided due to potential antagonism (stavudine with
zidovudine or lamivudine with zalcitabine) or overlapping
toxicities (didanosine with zalcitabine or stavudine with
zalcitabine).

· Due to poor bioavailability, the hard gel capsule formulation of

the PI, saquinavir (Invirase), should not be used unless
combined with ritonavir.
· In order to clarify the ARV a patient should be taking, the
pharmacist should consult the patient's clinic notes and question
the patient about his or her medication regimen.

· Determine the appropriateness of dosing of the ARVs based on

the patient's weight, renal function, and concomitant
medications. The NRTIs, didanosine, lamivudine and stavudine,
require different dosing based on the patient's weight.

· Evaluate the appropriateness of dosing with respect to meals by

consulting the medication administration record and
interviewing the patient.
· Ensure that all formulations of didanosine are taken on an empty
stomach for optimal absorption.

· If the patient was receiving therapy that included the NRTI

abacavir, the patient is questioned about any lapses in therapy
and the presence of any signs and symptoms of a
 hypersensitivity reaction. The hypersensitivity reaction to
abacavir usually manifests in the first 4-6 weeks of therapy.
Signs and symptoms may include any combination of the
following: rash, fever, cough, dyspnea, nausea, diarrhea, and
pharyngitis. If the patient has had a hypersensitivity reaction, a
severe life-threatening reaction can occur upon re-initiation of
therapy.

· Check patient's last CD4 cell count and/or viral load or order as
appropriate.

For the evaluation of opportunistic infection primary/secondary

prophylaxis, the following steps may be followed:

· Check the patient's past medical history in the chart to determine

whether the patient had any OIs in the past;
· Check whether the patient's last CD4 count was obtained to
determine the need for continuation of primary or secondary
prophylaxis. Primary prophylaxis is the use of medications to
prevent a first episode of opportunistic infection. Secondary
prophylaxis is the use of medications to prevent recurrence of an
opportunistic infection following acute disease; and
· Refer to WHO guidelines for the Prevention of Opportunistic
Infections in HIV-infected patients. The opportunistic infections
for which primary prophylaxis is routinely recommended in
susceptible patients are Pneumocystis carinii pneumonia (PCP),
toxoplasmosis, and Mycobacterium avium complex (MAC)
infection. Secondary prophylaxis is recommended for certain
infections, such as PCP, toxoplasmosis, MAC, CMV retinitis, and
Cryptococcal meningitis (Table 8). The following table lists
criteria for discontinuing secondary prophylaxis based on CD4+
cell count and viral load response to antiretroviral therapy.
 Table 22.8: Primary and secondary prophylaxis of selected opportunistic infections

Indication for Secondary**

Drug(s) of
Infection Primary Alternatives Prophylaxis After
First Choice*
Prophylaxis Acute Disease
+
Pneumocystis CD4 cell Septra Dapsone or Continue until CD4+ cell
carinii count <200 atovaquone or count >200 cells/mm3
pneumonia cells/mm3, inhaled for >3 months
(PCP) percent pentamidine
<14%, or
oropharyngeal
candidiasis

Toxoplasmosis CD4+ cell Septra Dapsone plus Consider

count <100 pyrimethamine discontinuation in
cells/mm3 and plus patients who have
positive leucovorin, or responded to therapy
Toxoplasma atovaquone and have CD4+ cell
IgG antibody +/- count >200 cells/mm3
pyrimethamine for >6 months
plus
leucovorin

Mycobacterium CD4+ cell Azithromycin Rifabutin or Consider

avium complex count or azithromycin discontinuation in
(MAC, MAI) <50 cells/mm3 clarithromycin plus rifabutin patients who are
asymptomatic, have
completed at least a 12
month treatment course
for MAC, and have a
increase in CD4+ cell
count
Candidiasis Not generally N/A N/A Not generally
recommended recommended

Cryptococcosis Not generally N/A N/A Consider

recommended discontinuation in
patients who have
successfully completed
a treatment course for
cryptococcosis and who
have a viral load >100-
200 cells/mm3 for >6
months

Cytomegalovirus Not generally N/A N/A Consider

infection recommended discontinuation on a
patient by patient basis
in patients who have a

* Refer to USPHS Guidelines for dosing of agents

** Refer to USPHS Guidelines for agents used for secondary prophylaxis
Potential drug interactions can be evaluated as follows:

· The pharmacist should evaluate the patient's medication

profile for potential drug interactions may consult relevant
guidelines as well as online sources such as “Clinical
Pharmacology Online” to evaluate the presence of drug
interactions.
· If a potential interaction is identified, the pharmacist evaluates
the clinical significance of the interaction, available data on
dosage adjustments, or alternative agents that could be used
with less potential for an interaction.

· Determine how to manage the interaction. If an absolute

contraindication (e.g., the use of simvastatin with the PIs or the
NNRTI delavirdine) was identified, the pharmacist should
recommend an alternative agent to the prescriber (e.g.,
pravastatin. fluvastatin or low-dose atorvastatin). If data were
available on dosage adjustments (e.g., increase of dose of
Kaletra to 4 capsules twice daily when combined with the NNRTI
efavirenz) the pharmacist recommended the appropriate dosage
adjustments to the prescriber.

· Consulted the appropriate reference materials (e.g., Medical

Administration Record) to determine interactions involving food
or other agents that could be avoided by changing the timing of
administration of one or more agents.

4. Establish therapeutic goals

These goals must be established for each drug-related problem so that
the pharmaceutical care planning process can be effective. Therapeutic
goals should be definite, realistic and, if possible, measurable. Most of
the goals will relate to those earlier discussed above.
In order to ensure maximum adherence, the pharmacist should first
determine whether or not it is an appropriate time to discuss the
medications with the patients. He should determine the patient's current
knowledge of their medications. Information sheets for the patient's
antiretroviral agents and any other agents for which he or she may
request information may be used. Patients should be informed of the
purpose of each medication, administration requirements including food
restrictions, common and/or serious potential side effects, drug
interactions, and medication storage requirements. If necessary, the
pharmacist should provide the patient with a written medication
schedule and pillbox. A suggested adherence maximization approach is
provided in Figure 22.1.

· Assess readiness to start medications

· Teach HIV basics
– Viral load, CD4 count
– How medications work
– Concept of resistance
· Elicit information about patient's life style to determine best
schedule for taking regimen, and ability to adhere to regimen
· Elicit patient's perceptions about medications, side effects,
health beliefs, disclosure of status
· Reduce barriers to adherence
– refer to mental health or addiction counselor prior to initiating
ARV therapy
– recommend that ARV therapy be postponed if patient is
unwilling to take medications
– monitor OI prophylaxis medications use prior to initiating ARV
treatment (to assess adherence)
– set up medication schedules, provide calendars and pictures
of each medication
– teach patients how to fill weekly pill boxes
· Tracks medication pick up dates
· Refills medication one week before next pick up is due
· Synchronizes all medications (if possible) so that all
medications can be picked up on monthly basis
· Phones patients to remind them that medicines are due for pick
up
· Ensures laboratory investigations are done at time of pick up
· Ensures that patients meet with physician, pharmacist or other
staff as appropriate
· Contacts Nurse or physician if patient is more than 2 weeks late
for pick up before dispensing
· Monitor program “graduates”. Patients who have achieved Viral
Load <50 or best achievable goal viral load
· Continue to track medication pick up, refill prospectively, and
make reminder phone calls
· Notify physician when patient is >2 weeks late for pick-up or
adheres to protocols for late pick-up when physician is not
available
· Collect patient-specific data on 100 adherence graduates to
assess ongoing adherence, knowledge of their regimens, and
management of side effects
Interdisciplinary Team
· Interdisciplinary team should meet regularly (e.g., bi-weekly), to
discuss programme logistics and specific patient problems
· All physicians are strongly encouraged to refer patients to
adherence programmes
· Patients may refuse to participate in programme
Pill Boxes
· Pharmacy should prepare medication boxes for patients
· Filled weekly, bi-weekly or monthly by pharmacy for patients who
are unable to organize medications on their own
5. Specify monitoring parameters
The monitoring parameters must be defined so that the patient's
progress can be followed. Monitoring parameters must also include
potential adverse events. It is essential that the desired endpoints for
each parameter and the frequency of monitoring are determined. In
addition, the pharmacist should plan the duration of time necessary to
recognize the monitoring parameters, e.g., the time for a response to
first-line ARVs. A time schedule to follow up the symptoms with the
patient should be planned. Each goal should be stated in terms of
measurable outcomes that indicate the extent to which the particular
problem has been resolved.
6. Consultation and implementation
The plan should be discussed with the patient, colleagues, supervisor
and then the physician. It should then be implemented on the basis of the
physician's response. For discharged patients,
· Arrange for discharge medications and counseling.
§ Establish links between patient and his/her pharmaceutical
equivalent in the primary or secondary health care sector
(depending on the practice site) to enable the transfer of
information about the patient.

§ Provide the patient with a list of pharmaceutical contacts to help

him/her in times of need (for example, telephone numbers).

7. Document patient's progress

The pharmacist evaluates and documents the patient's progress in
achieving the desired therapeutic goals and avoidance of potential
adverse effects. The pharmaceutical care plan may be updated with
23
each major change in patient status.
Outcomes Assessment in HIV/AIDS Treatment
Any patient diagnosed to be having HIV infection undergoes a baseline
clinical and laboratory assessment in order to confirm the presence of
the disease, determine the stage of HIV infection and eligibility for ART,
and other interventions. The baseline assessments includes both
clinical and laboratory evaluation (see description of parameters below)
and serve as entry points into chronic care and means to provide
counselling and support in relation to secondary HIV prevention and the
disclosure of HIV diagnosis to others.

Once it is assessed that a HIV positive patient is not yet eligible for ART,
the patient should be monitored for clinical progression and by CD4
count measurement every six months. Clinical evaluation should
include weight changes and development of clinical signs and
symptoms of progressive HIV disease. These clinical parameters and
the CD4 cell count should be used to update the WHO disease stage at
each visit and to determine whether patients have become eligible for
co-trimoxazole prophylaxis or ART. Clinical evaluation and CD4 counts
may be obtained more frequently as the clinical or immunological
threshold for initiating ART approaches.
1. Clinical and laboratory monitoring of patients on ART
Once therapy has been initiated or changed, clinical and laboratory
evaluation should be determined at reasonable time intervals. Since
many programmes dispense ART on monthly basis, clinical monitoring
can be effectively done every 4 weeks even though the frequency of
clinical monitoring should usually depend on the response to ART.
The necessary clinical assessment includes:
· Clinical staging of HIV disease;
· Concomitant medical conditions (e.g. HBV, HCV, TB,
pregnancy, injecting drug use, major psychiatric illness) and
frequency of infections (bacterial infections, oral thrush,
 and/or other opportunistic infections);
· Concomitant medications (including traditional and herbal
medicines);
· Weight (body mass index evaluation);

· Patient readiness for continuing therapy as well as

understanding of ART;
· Adherence to treatment; and
· Symptoms of potential drug toxicities or treatment failure (i.e.
reassessment of clinical stage).

Laboratory assessment includes:

· Measurement of CD4, where possible - HIV viral load
measurement is currently not recommended for monitoring
patients on ART in resource-limited settings;

· Haemoglobin measurement if initiation of AZT is being

considered;
· Pregnancy test in women if initiation of EFV is being
considered;

· Hepatic enzymes measurements (if available) at weeks 2, 4,

8 and 12 after NVP is initiated in women with CD4 counts
3
between 250 and 350 cells/mm ;

· Renal function test in patients can be considered before the

initiation of TDF and every six months on the therapy; and
· Screening for TB and malaria (and diagnostic testing for other
co-infections and opportunistic diseases where clinically
indicated).
The CD4 counts, which should be determined at diagnosis and
rechecked every three to six months, are important not only because
they indicate the risk for development of opportunistic infections, but
they help to initiate therapy or evaluate the effectiveness of current
therapy. More frequent measurements are desirable if a patient has a
change in therapy, contracts opportunistic infection, or has an increase
in viral load.15 Other than CD4 count, plasma HIV RNA is another
surrogate marker for determining whether a person is infected with HIV
and the extent of infection. Though it is considered to be more useful
than CD4 count, it may not be available for patients in resource-poor
settings.

2. Measuring adherence to antiretroviral therapy

There is no gold standard for measuring adherence to ARVs and

therefore different methods (alone or in combination) have been
employed 24. Although impractical for most clinical settings, a number of
studies have shown that the objective measures used in research are
more sensitive than patient self-report for detecting medication non-
adherence. Some common methods used in measuring adherence
include the following:

(i) Self-Reporting

As earlier described, patients are interviewed about their adherence

over the previous day, previous week and previous month successively
in an attempt to minimize recall bias. Adherence is defined as taking
95% of prescribed doses over the previous month which correspond to
missing no more than one dose in a 10-day period (in a 2 times a day
dosing regimen), one dose per week (in a 3 times a day regimen) or one
dose per day (in a once daily dose regimen). Patients are classified as
non-adherent if they missed more than 5% of their doses in at least one
of the three categories or if they indicated missed doses in all three
25
categories.

(ii) Pill Counts

This can be conducted in clinic or at unannounced home visits. Pill count

adherence is usually calculated by counting the remaining doses of
medication and assuming that the remaining pills in excess of what is
expected represent missed doses. This method is more easily
performed if the patient uses a pill organizer. The sensitivity of this
method for detecting non-adherence is compromised when patients
remove pills from their containers without taking them (ie, "pill dumping"
or "decanting"). This practice leads to an overestimation of adherence.
Unannounced pill counts were developed to account for this practice but
are too intrusive and cumbersome for common clinical practice.24

(iii) MEMS Caps

This utilizes a computer chip embedded in a specially designed pill-bottle

cap to record the time and duration of each bottle opening. MEMS
adherence usually is calculated by dividing the number of time-
appropriate bottle openings by the number of expected doses over the
study period. Although this method appears to be the most sensitive
method for detecting non-adherence, a number of limitations to the
accuracy and practicality of the system restrict its use primarily to
research settings. For example, the use of commonly utilized pill
organizers or blister packs is impeded because the patient must retrieve
all doses of the studied medication from the MEMS bottle. MEMS usually
can assess only 1 prescribed medication and adherence to the other
components of a combination therapy is generally not measured. The
number of pills withdrawn at each bottle opening is not recorded and if the
patient withdraws an additional dose to be taken at a later time, the
system may underestimate adherence. Some adjustment in an attempt
to adjust the MEMS adherence calculation to account for extra "pocket
24
doses" removed from the bottle to be taken later has been reported.

(iv) Biological Markers

This refers primarily to plasma concentrations of ARVs. Biological

markers have been reported to be associated with virologic outcomes.
Also, plasma concentrations of PIs have been significantly associated
with adherence behavior in self-reporting, unannounced pill counts, and
MEMS caps. However, plasma concentrations are limited by their ability
to detect only recent adherence behavior. In addition, unexpected low
concentrations of ARVs may be caused by factors other than adherence,
such as malabsorption, drug interactions, and individual metabolic
differences. Other markers of adherence such as serum lactate have
been reported but are coarse measures of adherence and are of limited
use in clinical practice. Antiretroviral concentrations in hair samples are
also being evaluated as a marker for antiretroviral exposure and, less
directly, long-term adherence.24

(v) Pharmacy Refill Data

Records of refill available in the pharmacy can serve as an adherence

measure by providing the dates on which antiretroviral medications were
dispensed. In the event that refills are not obtained in a timely fashion, it is
assumed that the patient is not taking medication between refills or is
missing doses in a way that allows the medication to last longer than it
should. This provides a less effective and intrusive means of measuring
adherence than most other measures, particularly in resource-poor
settings. There is evidence that patients whose adherence is measured
in this way are more likely to be associated with resistance to drug
24
therapy, and progression to AIDS and death.

3. Antiretroviral toxicities assessment

ARVs are responsible for a broad range of toxicities (adverse events),
ranging from low-grade intolerances that may be self-limiting to life-
threatening side-effects (Table 9). Differentiating between complications
of HIV disease and ART toxicity can be difficult. Alternative explanations
for a patient's presenting symptoms should be considered before it is
concluded that toxicity is ART-related. Considerations include inter-
current illness (e.g. hepatitis A virus infection in patients with symptoms
of hepatitis, or malaria in patients with severe anaemia), or a reaction to
medications other than ARVs, e.g. isoniazid-induced hepatitis or
peripheral neuropathy, and rash induced by co-trimoxazole. Drug-
related adverse events can occur in the first few weeks or months of
treatment (early) and/or after six months or more of treatment (late).
Adverse events can vary in severity from mild to severe and life-
threatening and may be specific to a particular ARV or to the class of
ARVs in use. Regardless of their severity, they may affect adherence to
therapy and hence a proactive approach to managing toxicity is
recommended.
Table 22.9: Common antiretroviral toxicities

Type Events

Haematological toxicity Drug-induced bone marrow suppression, most commonly seen

with AZT (anaemia, neutropenia).

Mitochondrial Primarily seen with the NRTI drugs, including lactic acidosis,
dysfunction hepatic toxicity, pancreatitis, peripheral neuropathy, lipoatrophy,
myopathy.

Renal toxicity Nephrolithiasis, commonly seen with IDV. Renal tubular

dysfunction is associated with TDF

Other metabolic More common with PIs. Include hyperlipidaemia, fat

abnormalities accumulation, insulin resistance, diabetes and osteopenia.

Allergic reactions Skin rashes and hypersensitivity reactions, more common with
the NNRTI drugs but also seen with certain NRTI drugs, such as
ABC and some PIs.

The guiding principles in the management of ARV drug toxicity are as

follows:
1. Determine the seriousness of the toxicity.
2. Evaluate concurrent medications and establish whether the
toxicity is attributable to an ARV drug or drugs or to a non-ARV
medication taken at the same time.

3. Consider other disease processes (e.g. viral hepatitis in an

individual on ARV drugs who develops jaundice) because not all
problems that arise during treatment are caused by ARV drugs.
4. Manage the adverse event according to severity. In general:
· Grade 4 (severe life-threatening reactions): Immediately
 discontinue all ARV drugs, manage the medical event (i.e.
symptomatic and supportive therapy) and reintroduce ARV drugs
using a modified regimen (i.e. with an ARV substitution for the
offending drug) when the patient is stabilized.
· Grade 3 (severe reactions): Substitute the offending drug
without stopping ART.
· Grade 2 (moderate reactions): Consider continuation of ART
as long as feasible. If the patient does not improve on
symptomatic therapy, consider single-drug substitutions.
· Grade 1 (mild reactions): Though bothersome, changes in
therapy are often not required.

5. Stress the maintenance of adherence despite toxicity for mild

and moderate reactions.
6. If there is a need to discontinue ART because of life-threatening
toxicity, all ARV drugs should be stopped until the patient is
stabilized.16

4. HIV drug resistance testing

There is often a significant correlation between ARV-resistant HIV and
poor virological response. This accounts for the need for HIV drug
resistance testing. Although this may not be available in resource-poor
settings, both phenotype and genotype assays are available.
Phenotype assays are rapid and detect the inhibitory drug
concentrations (50% to 90% or IC50 to IC90) of HIV isolates. Unlike
phenotype assays, genotype assays detect mutations in the HIV virus
which may confer resistance to ARVs. However, the controversies
surrounding the usefulness of these assays necessitates their
recommendation as adjuncts to only clinical decision-making.26
Conclusion
Providing care to patients infected with HIV can be a challenge, due to
the complexity of the disease state and the increasing use of multiple
drug regimens. Many of the currently approved ARVs have complicated
dosing and administration requirements, as well as many potentially
serious or life-threatening adverse effects and drug interactions.
Additional agents are prescribed for prophylaxis and treatment of
opportunistic infections (OIs) associated with HIV as well as
complications of HIV infection, such as neoplasms or infections,
cytopenia, wasting, renal disease, hepatic disease, or concurrent
problems such as psychiatric illnesses. Due to the complexity of these
drug regimens, there is a potential for medication errors and adverse
outcomes when clinicians who are not familiar with these agents are
involved in their prescribing and dispensing.
The primary challenge for pharmacists in the care of HIV/AIDs patients is
focused on providing medication for HIV/AIDS patients and ensuring that
the medications are effective and properly used. To this end,
pharmacists work closely with colleagues from different disciplines to
develop innovative programmes that help patients achieve desired
outcomes. In this respect, the pharmacist ensures that all HIV/AIDS
patients receive all needed medications including ARV's, OIs
prophylaxis; selected antibiotics, anti-emetics, anti-diarrheals, blood
modifiers, anti-depressants, anti-psychotics, interferon, metformin, etc.
Experience shows that more than half of the prescriptions for HIV
positive patients are for medical problems other than ARV or OI
treatment or prophylaxis. The current nexus of political commitment, new
sources of funding, ARV availability and lower drug prices have created
opportunities for improved quality-of-life of HIV positive patients.
Pharmaceutical care has provided excellent opportunities for
pharmacists to contribute to the care of HIV infected people.
 Key Learning Points

· Once an individual is diagnosed to be infected by HIV, ART is

often one of the first considerations, particularly when the
symptoms of HIV/AIDS become apparent, in order to
prolonged survival of the HIV positive individual.

· WHO recommends that in settings where CD4 testing is

available, ART should be initiated when a patient's CD4 count
falls below 350 cells/ml but where CD4 testing is unavailable,
therapy should be started when patients exhibit clinical signs
of advanced or severe immune suppression.

· Preferred first-line regimens include two nucleoside reverse

transcriptase inhibitors (NRTIs) and one non-nucleoside
reverse transcriptase inhibitor (NNRTI).

· In the absence of viral load measurements in resource-

limited settings, clinical or immunological monitoring or both
should be used for the assessment of treatment success, and
time-based decision on changing from first-line to second-
line regimens.

· Prevention and treatment of opportunistic illnesses are vital

for effective HIV treatment and care. Timely nutritional
support may help people living with HIV/AIDS extend the
asymptomatic period of relative health or reduce the risk of
death where severe immune deterioration has already
occurred. Paying attention to mental health, and social and
economic factors can maximize the success of HIV
treatment.

· Failure to recognize drug-related problems often associated

 with the use of antiretroviral therapy may result in additional
or exacerbated adverse effects, non-adherence, therapeutic
failure, or irreversible drug resistance.

· Pharmaceutical care contributes to the care of people living

with HIV/AIDS through pharmacists involvement in clinical-
decision making in drug therapy, detection and resolution of
drug-related problems, monitoring and optimization of
patients responses to ART, reduction (and possible
elimination) of antiretroviral drug resistance, improvement of
patients' adherence to ART and overall treatment cost
reduction.

· Effective monitoring parameters include determination of

clinical staging of HIV disease, CD4 count and/or viral load,
concomitant medical conditions, concomitant medications,
patient's body mass index and readiness for continuing
therapy as well as understanding of ART, adherence to
treatment, symptoms of potential drug toxicities or treatment
failure, haemoglobin levels (if initiating AZT), pregnancy in
women (if initiating EFV), hepatic enzymes (if available) and
renal function (if on TDF), as well as screening for TB and
malaria.

References

1. Erah PO, Kubeyinje EP. HIV/AIDS: Information for the

Community. Pharmacotherapy Group, Benin City, Nigeria,
2005.
2. UNAIDS (Joint United Nations Programme on HIV/AIDS). 2008
Report on the global HIV/AIDS epidemic, 2008.
3. Rosenberg SD, Goodman LA, Osher FC, et al. Prevalence of HIV,
hepatitis B, and hepatitis C in people with severe mental illness. Am
J Public Health. 2001; 91:317.

4. Centers for Disease Control and Prevention (CDC). HIV/AIDS

surveillance report, 2001; 13(2):145.

5. Food and Drug Administration (FDA). Antiretroviral drugs

approved by FDA for HIV. www.fda.gov/oashi/aids/virals.html
(accessed 2003 Feb 24).
6. Erah PO, Osahon PT. Quality of life of HIV/AIDS patients receiving
treatment in a health facility in Nigeria. J Pharm Res 2008; 7(4):
233-238.
7. Deeks SG, Smith M, Holodniy M, Kahn JO. HIV-1 Protease
Inhibitors. A review for clinicians. JAMA, 1997; 277:145-153.

8. Saag MS, Schooley RT. Antiretroviral Chemotherapy. Current

Clinical Topics Infectious Diseases, 1998; 18:154-179.
9. Mills EJ, Nachega JB, Buchan I et al. 2006. Adherence to
Antiretroviral Therapy in Sub-Saharan Africa and North America: A
Meta-analysis. JAMA 296:679-90.
10. Horizons/Population Council, International Centre for
Reproductive Health and Coast Province General Hospital,
MombasaKenya. Adherence to Antiretroviral Therapy in Adults: A
Guide for Trainers. Population Council, Nairobi, 2004.

11. Peterson D, Swindells S, Mohr J, et al. Adherence to protease

inhibitor therapy and outcomes in patients with HIV infection. Ann
Intern Med. 2000; 133:2130.
12. Erah PO, Arute JE. Adherence of HIV/AIDS patients to
antiretroviral therapy in a tertiary health facility in Benin City. Afr J
Pharm Pharmacol 2008; 2(7):145-152.
13. Chesney MA. Factors affecting adherence to antiretroviral therapy.
Clin Infect Dis 2000; 30(suppl 2):S1716.
14. al-Shaqha WM, Zairi M. Re-engineering pharmaceutical care:
towards a patient-focused care approach. Int J Health Care Qual
Assur Inc Leadersh Health Serv 2000;13(4-5):208-17.

15. American Society of Hospital Pharmacists (ASHP). ASHP

statement on pharmaceutical care. Am J Hosp Pharm 1993;
50:17203.
16. World Health Organization (WHO). Antiretroviral Therapy for HIV
Infection in Adults and Adolescents: Recommendations for a Public
Health Approach. The Organization, Geneva, 2006.
17. World Health Organization (WHO). Interim WHO Clinical Staging of
HIV/AIDS and HIV/AIDS Case Definitions for Surveillance: African
Region. WHO/HIV/2005.02. The Organization, Geneva, 2005.

18. World Health Organization (WHO). New HIV recommendations to

Improve Health, Reduce Infections and Save Lives, 2010. Available
f r o m
http://www.who.int/mediacentre/news/releases/2009/world_aids_
20091130/en/index.html. Accessed February 4, 2010.
19. World Health Organization (WHO). Antiretroviral Therapy for HIV
Infection in Infants and Children: Recommendations for a Public
Health Approach. The Organization, Geneva, 2007.
20. Butcher RO, Hood RG, Jordan WC. Optimizing treatment for African
Americans and Latinos with HIV/AIDS. J Nat Med Assoc 2005;
97(8):1093-1100.

21. American Society of Health-System Pharmacists (ASHP). ASHP

statement on the pharmacist's role in the care of patients with HIV
infection Am J Health-Syst Pharm. 2003; 60:19982003.
22. Bartlett JA. Addressing the challenges of adherence. J Acquir
Immune Defic Syndr 2002; 29:S210.
23. Erah PO, Okhamafe AO, Oviasu E. Patient Care in Hospitals:
Guidelines for Pharmacists. Pharmacotherapy Group, Benin City,
2003; 68-74p.

24. Machtinger EL, Bangsberg DR. Adherence to HIV Antiretroviral

T h e r a p y, M a y 2 0 0 5 . Av a i l a b l e f r o m
http://hivinsite.ucsf.edu/InSite?page=kb-03-02-09#S1X. Accessed
February 4, 2010.

25. Erah PO, Arute JE. Adherence of HIV/AIDS patients to antiretroviral

therapy in a tertiary health facility in Benin City. Afr J Pharm
Pharmacol. 2008; 2(7):145-152.
Arcanglo VP, Peterson AM. Pharmacotherapeutics for Advanced
Practice: A Practical Approach.Lippincott Williams & Wilkins,
Philadelphia, 2001; 700p.
 CHAPTER TWENTY FOUR

PHARMACEUTICAL CARE RESEARCH

Azuka C Oparah
Learning Objectives
At the end of this chapter, you should be able to:
I. Define the scope of pharmaceutical care research
ii. Explain patient expectation and its assessment
iii. List the importance of patient satisfaction
iv. Name three models to assess patient satisfaction
v. Illustrate the impact of pharmaceutical care on selected patient
outcomes

Introduction

Pharmaceutical Care Research

Pharmaceutical care research (PCR) may be regarded as a relatively
new area of research within pharmaceutical practice since the impetus
in this area of research started after the philosophical paper of Hepler
1
and Strand.
In the classical idea, science has three important characteristics:
2
reductionism, repeatability, and refutation. The first important
characteristic of science is reductionism. Within this line of thought all
scientific problems are reduced to physics. The reductionist ideal would
be an explanation of PCR in terms of social pharmacy of social
3
pharmacy and social science. It is assumed that in PCR many
researchers will have a pharmaceutical background. They may be
regarded as researching pharmacists, so to speak. It is argued that
especially their experiences may be of great importance for the
performance of PCR. These would relate to deduction (general to
specific) and induction (specific to general), learning organisms in an
environment and away from laboratory to the field.
In general, PCR concentrates on facts and interventions. On one hand,
researchers try to catch relevant facts in pharmacy practice with
methodologies, methods and techniques, and by doing so refine these
tools and improve their knowledge about the current professional
practice. On the other hand, researchers also make interventions in
pharmacy practice, either with the study results or with the performance
of a pharmaceutical care study as such. The main tools applied to
visualize these events originate from qualitative and quantitative
methodologies.4
PCR provides evidence for professional advancement. The major
sources of evidence are written texts (documentation and archival
records), interviews, and observation: direct observation and participant
observation.4 It is advisable to use combination of sources of evidence.
The benefits from these sources of evidence can be maximized if three
principles are followed.5 The first principle is to use triangulation.
Triangulation comprises combined application of sources of evidence.6
This principle is a major strength of case study data collection. Four
types of triangulation can be distinguished:7 triangulation of data sources
(data triangulation), triangulation of different researchers (researcher
triangulation), triangulation of theoretical perspectives (theoretical
triangulation), and triangulation of methodologies, methods and
techniques (methodological triangulation). The second principle is to
create a case study database. This database should always separate
the collections of the data and evidence from the report. The third
principle is to maintain a chain of evidence. Such a principle should allow
an external observer, the reader of your scientific work, for example, to
follow the derivation of any evidence from initial research questions to
ultimate case study conclusions. Here a researcher has to juggle with
imitability, consistency, and relevancy at the same time in order to
enable others to agree or disagree with the conclusions, which may lead
4
to refutation of the assumptions and a new process of inquiry.
Pharmaceutical care research is mainly outcomes research that
documents the effectiveness of pharmacists' interventions and this is
essential to the future of pharmacy. In the era of healthcare reforms that
focus on quality, accessibility and cost, stakeholders should be
interested in evidence based positive clinical, humanistic and economic
outcomes. Some of such outcome investigations are highlighted below.

Patient Expectations
Pharmaceutical care is an outcome-oriented practice, and such
outcomes include patient satisfaction and expectation, which are
humanistic components. Several studies have shown the positive
8-10
impact of pharmaceutical care on these and other outcomes.
In a study that compared consumer expectations to the reported use of
pharmacy services in Northern Mississippi Counties, results obtained
through a survey indicated that the population expected comprehensive
pharmaceutical services. Patient profiles were the most desired service
and consumers were least interested in pharmacist counseling on
health matters unrelated to drugs. Most services however were sought
11
and or delivered less frequently than expected. Provision of
pharmacists contact in an appropriate ambulatory setting increased
consumers' awareness of services available and patient expectations
also improved. Patients of an officepractice pharmacy reported more
frequent consultation with a pharmacist regarding drugtherapy and
12-13
health issues more than patrons of the traditional pharmacy. An
investigation in Japan that assessed patients' perceptions and
expectations of pharmacy services identified seven dimensions of
expectations, namely availability of over- the- counter drugs, availability
of special delivery medicines such as acceptance of mail order, facilities,
convenient location, attitude of pharmacy/pharmacist, information
management, and convenient hours. The three most important to
patients and patrons were attitude of pharmacy/pharmacist, convenient
14
hours, and information management. Results of a consumer survey on
medication usage provided evidence that consumers desire different
types of services given the context in which they find themselves when
15
they visit the pharmacy.

An investigation of pharmaceutical care expectations of patients in a

Nigerian teaching hospital indicated a high expectation of activities
congruent with the rubric of pharmaceutical care. Over 80 percent of the
patients expected the hospital pharmacist to ask them how their
medications are working, discuss their health with them, and
communicate with their physicians on their behalf.

Assessment of patient expectations

Different approaches are used to evaluate patients' expectations of
pharmacy services.

Exposing patients to a series of video clips showing pre-tested patient

16
provider encounters has assessed patients' expectations. The study
exposed the need to examine client expectations and tailor services
accordingly since satisfaction measures can only diagnose a problem
while expectation assessment can identify needs and thus program
managers can better design health services delivery.

A questionnaire-based survey is commonly employed to assess

patients' expectations of pharmaceutical care. Expectation has been
defined as a reference point consumers use to assess their service
experience.17 Patients do utilize prior experience, market-based and ideal referent expectations
and hence impact of cognitive services should compare current service encounters with ideal
norms or with services other pharmacists provide.8 Pharmaceutical care expectations represent
professional aspiration or ideal, and where there is no formal pharmaceutical care, it is logical to
employ an ideal referent model in assessing patients' expectations that pharmacists would perform
activities congruent with pharmaceutical care.
Often times, professionals render services without considering the dynamics of consumer
expectations. Pharmaceutical care practice reflects a fulfilment of patient expectations from the
pharmacist. A study on patients' expectations of pharmaceutical care turns to patients themselves
whose expectations from the pharmacist affect their satisfaction with pharmacy services and the
image of pharmacy, as well as the image of the pharmacist.
A 12-item questionnaire has been employed to assess patient expectations of pharmaceutical care
in the USA practice setting9 and in the Nigerian study. The item stems of the instrument, which has
both “pro” and “con” items are presented in Table 24.1

Table 24.1: Item stems for assessing patient expectations9

I do not expect my pharmacist to be friendly [C]

I expect my pharmacist to dispense my
prescriptions accurately. [P]
I do not expect my pharmacist to make me wait
a long time to get my prescriptions filled . [P]
I expect my pharmacist to ask how my medications
are working. [P]
I expect my pharmacist to discuss my health with me. [P]
I expect my pharmacist to communicate with my
physician about my medications. [P]
I expect my pharmacist to help me identify desired
effects from my medications. [P]
I expect my pharmacist to understand my feelings
and/or situation. [P]
I do not expect my pharmacist to explain my
medications to me. [C]
I expect my pharmacist to come up with ways to
make it easier to take my medications. [P]
I expect my pharmacist to spend as much time
as necessary with me. [P]
I do not expect my pharmacist to ask me about the
side effects of my medications on the phone. [C]

P = “Pro” and C = “Con”

Patient Satisfaction
Most pharmacoeconomic studies have focused on the clinical and
economic outcomes of pharmaceutical care rather than on the
humanistic outcomes because of the subjective nature of the latter.
However, Coons and Johnson believe that humanistic outcomes are
often a better reflection of how profoundly pharmacy services impact on
18
patients' lives. One humanistic outcome they describe is patient
satisfaction with pharmacy services. Patient satisfaction has been
defined as a function of patient expectations and perceptions of the
19
service rendered. The author assumed that satisfaction consists of a
cognitive evaluation of and an emotional response to the structure,
process, and outcomes of a system.
In a survey of patient satisfaction of pharmaceutical services in a
Nigerian teaching hospital, respondents reported low satisfaction with
overall service provision indicating a need for pharmaceutical care. That
study identified two components of the expected pharmaceutical care to
be friendly explanation (communications) and managing therapy.
Importance of patient satisfaction
Pharmaceutical care is a dominant pattern of pharmacy practice
worldwide in the past decade and is aimed at improving patient outcomes.
Patient satisfaction is one of such subjective outcomes that can be
predetermined and assessed. Patient satisfaction with pharmacy services
is important in many respects.
· Patient satisfaction is becoming increasingly popular, as an
20-23
indicator of quality of health care services.
· There is evidence that satisfaction with health services is closely
24
related to mental health status of patients.
· Patient patronage of a pharmacy department depends on their
satisfaction with services obtained. Patient satisfaction is a
predictive measure of the probability that a patient will continue to
use the services of a particular provider. In a competitive health
care market, it is important pharmacists provide competent
services in a manner satisfactory to the consumer to ensure that
25
patients will continue to seek their services.
· Patient satisfaction affects adherence
· Satisfaction surveys can identify new service areas as well as
used to provide patient feedback after introduction of a novel
service such as pharmaceutical care
· Patient satisfaction no doubt affects the image of the pharmacist
and pharmacy profession and as such efforts should not only be
made to track patient satisfaction with pharmacy services but to
improve it.

Assessment of patient satisfaction

Satisfaction can be conceptualized as performance evaluation,
disconfirmation of expectations, an affect-based assessment, or an
26
equity-based assessment.
An interviewer administered Pharmacy Encounter Survey to patrons of
randomly selected chain and independent pharmacies in Philadelphia
County showed that the respondents were most satisfied with pharmacy
location and least satisfied with time spent waiting for prescription to be
27
filled. A mail questionnaire sent to randomly selected outpatients in a
large university hospital revealed that of the number that received their
prescriptions but did not fill them in the university, less than a third was
unaware of the existence of the pharmacy, over that number found the
pharmacy inconvenient for refills, while about a quarter thought that the
waiting time to fill prescriptions was too long. Of the respondents that
received prescriptions, nearly half filled at the university. Reasons given
for this consumer behaviour were mainly convenience, followed by
28
availability of medication, and low prices.
Based on responses to questionnaire survey of patient demand for
community pharmacies in Tokyo and Osaka, attitude of pharmacists
such as general attitude and specialized activities such as providing
information and explanations, and convenience of hours influenced
patient satisfaction. Furthermore, comfortable facilities and availability
of OTC drugs that the respondents rated low in terms of importance
29
influenced satisfaction while convenience of location did not. These
studies reveal that while there may be some general satisfaction
indicators in pharmacy services, there is need to undertake site specific
studies in order to meet the expectations of clientele served.
In another study that was undertaken to determine relevant components
of outpatient pharmacy service which impact the patient's perception of
satisfaction, results of the principal components analysis delineated two
dimensions of patient satisfaction which pharmacy managers can
emphasize to produce a more satisfied patient, repeat patronage, and
30
enhanced viability for the pharmacy. These components were defined
as professional communication and physical and emotional well being of
the patient. This finding is similar to two dimensions of friendly
31
explanation and managing therapy derived in another study. There are
several studies showing that patient satisfaction improved after
provision of pharmaceutical care, though not all the studies have found a
9, 32-34
positive association.
Higher directive guidance behaviours by pharmacists are associated
35
with greater patient satisfaction with pharmaceutical services.
Directive guidance behaviours are social support behaviours and
include such activities as supplying information about medications and
35
providing encouragement and feedback regarding drug therapy. Some
examples of Directive Guidance Behaviours by pharmacists are listed in
Table 24.2.
Several instruments are available in pharmaceutical literature for
evaluating patient satisfaction with pharmacy services; some of them
are patented. Since there are technical and interpersonal elements of
care that affect satisfaction, an assessment of patient satisfaction
should indeed reflect changes in professional practice or else the
31
instrument would lack content validity. Larson et al. have developed
and updated a validated instrument for assessing patient satisfaction
with pharmaceutical care. This instrument provides information on
patients' satisfaction with two dimensions of pharmacy services namely
friendly explanation, and managing therapy. Furthermore it has not been
widely tested. The constructs of this instrument are listed in Table 24.3
Kucukarslan and Schommer found out that patients' prior experiences,
ideal referents, or market-based expectations affect patients'
8
satisfaction with pharmacy services. The authors also concluded that
satisfaction surveys should be designed to specifically assess the type
of services provided by the pharmacy.
Table 24.2: Examples of Directive Guidance Behaviours by
35
Pharmacists

Provision of Instruction

Informing patients how to take their medication

Informing patients what to expect from their medications

Helping patients understand how to take their medications in special
circumstances (e.g., when a dose is missed)
Helping patients understand what is expected of them in regard to their
medications
Teaching patients specifics about what to avoid while taking their
medications
Helping patients understand their diseases better

Feedback and goal setting

Helping patients set goals for themselves with respect to taking their
medications correctly
Checking periodically with patients to determine whether they are
following advice
Providing feedback to patients about how they are doing with regard to
their medication regimens
Helping patients understand who to contact for assistance

Table 24.3: Items for assessing patient satisfaction31

The professional appearance of the pharmacy

The availability of the pharmacist to answer your questions
The pharmacist's professional relationship with you
The pharmacist's ability to advise you about problems
that you might have with your medications
The promptness of prescription drug service
The professionalism of the pharmacy staff.
How well the pharmacist explains what your medications do
The pharmacist's interest in your health
How well the pharmacist helps you to manage your medication
The pharmacist's efforts to solve problems that you have with your
medications
The responsibility that the pharmacist assumes for your drug therapy
How well the pharmacist instructs you about how to take your
medications
Your pharmacy services overall
How well the pharmacist answers your questions
The pharmacist's efforts to help you improve your health and stay
healthy
The courtesy and respect shown you by the pharmacy staff
The privacy of your conversations with the pharmacist
The pharmacist's efforts to assure that your medications
do what they are supposed to
How well the pharmacist explains possible side effects
The amount of time the pharmacist offers to spend with
you

Pharmaceutical care in disease states

There is disagreement amongst pharmacists on the relative merits of
disease management versus generalist approaches to pharmaceutical
36
care. Rovers et al. are of the view that disease management is
essentially a method to market pharmaceutical care, rather than a style
of pharmaceutical care practice. According to them, the only real
difference between the two approaches relates to how pharmacists
define the population to whom they are providing care; pharmacists
should begin with a generalized approach and progress to disease
management programmes.

Strand contends that the practice of pharmaceutical care is similar to

medicine where they have both generalists and specialists, both using
essentially the same care process.37 Accordingly, there could be
specialist pharmaceutical care pharmacists addressing a restricted
group of drug therapy problems in depth. When the generalist
pharmaceutical care pharmacist felt he could not cope with a particular
patient he could refer him on to the specialist. Once the problem had
been assessed, the patient would be referred back to the generalist.

The notion of pharmaceutical care primarily refers to involvement of

pharmacists in pharmacotherapy. Miller of the Iowa College of
Pharmacy has outlined some factors to be considered in the evolving
role of pharmacists in the area of pharmacotherapy as well as what
enables health professionals to provide pharmacotherapy. These are
listed in Table 24.4.

Table 24.4: Factors that can influence pharmacotherapeutic role of

pharmacists

Evolving role of pharmacists in

pharmacotherapy

Change in education programs: B.Pharm to Pharm.D

! Residency programs

! Prescriptive authority

! Collaborative practice agreements

! Disease management protocols

! Health and disease assessment

! Preventive health care

What enables professionals to provide pharmacotherapy?

! State practice acts

! Prescriptive authority acts for pharmacists: State statue or

regulations

! Collaborative practice agreements: Organized health care settings,

state statue or regulations

! Treatment protocols: Organized health care settings, state statue or

regulations

! Credentialing within organized health systems

! Delegated responsibility with physician review in office or organized

health care settings

!
Impact of pharmaceutical care interventions
Pharmacists perform numerous activities that benefit patients and
physicians, save money for third-party payers, and enhance the delivery
of health care services. By identifying, resolving, and preventing under
treatment, over treatment, or inappropriate treatment, pharmacists can
prevent or reverse many drug-therapy-related interactions/events.
However, the impact of pharmacists' interventions on drug therapy has
been largely unrecognized and un-reimbursed. For reimbursement
changes to occur for the correction of drug-related problems and for
greater involvement in disease management programs there must be a
philosophical and structural change in how third-party payers and others
38
view the pharmacist's role and scope of practice.

Studies have shown that pharmacists providing pharmaceutical care to

hypertensive patients at community and institutional settings improve
outcomes of therapy. Some of these studies are now presented to
illustrate the changing pattern of pharmacy practice towards
pharmaceutical care. Erickson et al.39 measured the impact of
pharmaceutical care on outcomes of antihypertensive therapy for
patients with elevated baseline blood pressures who were attending an
urban university-affiliated internal medicine clinic. The intervention
group received education about hypertension, drug and non-drug
management, and assistance to enhance compliance. The pharmacist
made recommendations to physicians regarding pharmacotherapy. The
control group received no such education, and interventions relating to
pharmacotherapy were only physician initiated. The results of that study,
after over a period of five months follow-up, showed significant
decreases in mean arterial blood pressures between the intervention
group and control group, from baseline to final assessment. Also, there
was no significant difference in SF-36 Health Survey scores between
groups. A significant difference in the SF- 36 physical functioning domain
was seen in the intervention group, but no other significant changes in
health-related quality of life scores.
In another exploratory cross-sectional study in Ohio that employed
matched pair survey instruments, the results of matching surveys of
pharmacists and patients indicated that nearly all pharmacists
counselled patients and monitored therapy in accordance with the
minimal OBRA (Omnibus Budget Reconciliation Act) 90 requirements.
When comparing patient and pharmacist perceived patient clinical as
well as humanistic outcomes, a high level of association was reported
between the two groups. This indicates that pharmacists are cognizant
of patient clinical and humanistic outcomes, and hence, they are in an
excellent position to improve patient outcomes by making appropriate
drug therapy changes.40
Gourley et al.33 evaluated the effects of pharmaceutical care on selected
outcomes in patients with hypertension or chronic obstructive pulmonary
disease (COPD). Clinic patients with these two conditions were
randomly assigned to a treatment group (pharmaceutical care) or a
control group (traditional pharmacy care) over a period of six months.
Clinical pharmacists and pharmacy residents conducted the protocols.
The results of the main outcome measures indicated statistically
significant differences in patient satisfaction, and patient disease
management knowledge, as well as improvement in the patient reported
quality of life.

Reeder noted that the traditional view of valuing pharmaceutical

products and services by examining efficacy and cost is shifting toward
41
examining effectiveness and efficiency in reaching desired outcomes.
In the past, many viewed the delivery of pharmacy services simply in
terms of the cost of drug therapy and efficiency of providing the drug to
the patient. Now, the focus includes examining the outcomes of care,
which may include clinical assessments; economic evaluations; and
humanistic outcomes such as patient satisfaction, adverse drug effects,
and quality of life.

Pharmacists have made some impact on preventing or reversing drug-

related problems at numerous practice sites, including long-term care
facilities, health-system-pharmacy sites, and community pharmacies.
Since 1974, consulting pharmacists in the USA have been compensated
by various sources, including Medicare and Medicaid, for long-term care
interventions for the correction of drug-therapy-related problems and for
suggesting better therapeutic alternatives. These interventions resulted
in the enhancement of clinical, economic, and humanistic outcomes of
42-45
care.

Pharmacists in hospitals and other institutional settings have also helped

to decrease the incidence of improper drug use.46-48 Departments of
pharmacy services have used the economic, clinical, and humanistic
outcome results from these intervention efforts to gain new pharmacist
lines and/or garner other financial rewards for departments, such as
additional staffing and increased budgets.

Likewise, community pharmacists have performed several interventions

and enhanced health outcomes for many patients through correcting
errors of omission and commission made by physicians and other
providers and saving vast expenditures by private, governmental, and
other third-party programs.

Cost savings that arise from pharmacists' drug-therapy interventions

have been increasingly documented in the literature. Studies indicate an
enhanced quality of life for patients and an improved profit potential for
the pharmacy.49 A large study conducted by Rupp and colleagues50
(1992) noted that roughly 2% of prescriptions examined contained one
or more prescribing errors. They found that pharmacist interventions
produced an added value of $2.32 to each prescription filled.50 The
value-added determination was based on the estimated direct cost of
medical-care expenditures due to the participating pharmacists'
interventions. Expert evaluators were asked to determine the medical
care that would necessarily be required to treat the patients. Each level
of medical care was assigned an economic value. The total potential
avoided expenses were then divided by the number of prescriptions to
obtain the value-added amount per prescription.

A Minnesota study also found that 2% of prescriptions needed dosage

corrections or other actions. Iverson concluded that the cost savings
amounted to $16.74 per prescription. Another study by Rupp found that
$123 in medical-care costs were avoided through pharmacist
51
interventions. Rupp and DeYoung found that prescribing errors on the
part of physicians represented the most common errors detected in the
prescribing process.52 Elsewhere, the influence of pharmacists has
produced lower drug expenditures and, in some cases, the
administration of fewer doses.53 In managed care settings, pharmacist
interventions have been calculated to save $24 per intervention.54 In
another study, Harrington and associates55 described cost savings
associated with educating physicians and influencing prescribing
patterns for NSAIDs, anti-ulcer medications, lipid- lowering agents, and
antibiotics. They found that pharmacists saved an average of $6200 per
intervention over several months through working in a nonthreatening
collaborative mode with primary care physicians.

Key learning points

• Pharmaceutical care research is outcomes research clinical,

humanistic and economic outcomes of therapy are investigated
• Pharmaceutical care research employs both qualitative and
quantitative methods
• Expectation has been defined as a reference point consumers use
to assess their service experience. Patients do utilize prior experience,
market-based, and ideal referent
• Satisfaction consists of a cognitive evaluation of and an emotional
response to the structure, process, and outcomes of a system.
• Patient satisfaction has been defined as a function of patient
expectations and perceptions of the service rendered.
• Disconfirmation of expectations therefore represents a model to
assess patient satisfaction i.e. if expectation is high satisfaction tends to
be low and vice versa.
• The importance of patient satisfaction include:
ü Indicator of quality of service
ü related to mental health status of patients
ü predictor of patronage and repeat patronage
ü indicator of adherence
ü affects the image of the pharmacist/pharmacy

• Literature provides evidence that pharmaceutical care

interventions improve clinical outcomes in disease state
management

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