(1) How pharmacokinetics and pharmacodynamics help doctors?

The goal of therapeutics is to achieve a desired beneficial effect with

minimal adverse effects. When a medicine has been selected for a
patient, the clinician must determine the dose that most closely
achieves this goal. A rational approach to this objective combines
the principles of pharmacokinetics with pharmacodynamics
to clarify the dose-effect relationship. Pharmacodynamics governs
the concentration-effect part of the interaction, whereas
pharmacokinetics deals with the dose-concentration part. The
pharmacokinetic processes of absorption, distribution, and
elimination determine how rapidly and for how long the drug
will appear at the target organ. The pharmacodynamic concepts
of maximum response and sensitivity determine the magnitude
of the effect at a particular concentration.

Pharmocokinetics Pharmocodynamics governs

Dose-----------------------------> Drug Concentration--------------------------------> Effects
ADME govern

Dose of drug
administered

Input

Drug concentration Distribution Drug in tissues Pharmacokinetics

in systemic circulation of distribution

Elimination
Drug metabolized or excreted
Drug concentration
at site of action

Pharmacologic effect
Pharmacodynamics
Clinical response

Toxicity Effectiveness

(2) Fundamental Hyothesis of Pharmocology

The fundamental hypothesis of pharmacology states that a
relationship exists between a beneficial or toxic effect of a drug and
the concentration of the drug.

(3)EFFECTIVE DRUG CONCENTRATION

The effective drug concentration is the concentration of a drug
at the receptor site, which is usually proportional to the drug’s
concentration in the plasma at equilibrium. The plasma
concentration is a function of the rate of input of the drug
(by absorption) into the plasma, the rate of distribution into
other tissues, and the rate of elimination. If the rate of input is
known, the remaining processes are well described by 2
primary parameters: apparent volume of distribution (Vd)
and clearance (CL). These parameters are unique for a
particular drug and a particular patient but have average
values in large populations that can be used to predict drug
concentrations.
(4) Drug Biodisposition

Drug
administration
(IM, PO, etc.)

Absorption into plasma

Plasma
Distribution to tissues Sites of
Tissue Bound drug action
storage
Receptors
Free drug

Drug excretion Note which arrows point in both directions.

Drug metabolism
(Liver, lung, blood, etc.) (Renal, biliary,
exhalation, etc.)

1 Drug Biodisposition
The biodisposition of a drug involves its permeation across cellular membrane barriers.

What is a bound drug?

Once a drug has been absorbed into the circulation it may become attached (we say bound) to plasma proteins. However this
binding is rapidly reversible and non-specific – that is many drugs may bind to the same protein.
What is the difference between free drug and bound drug?
Many drugs in circulation are bound to plasma proteins, and because bound drug is too large to pass through biologic
membranes, only free drug is available for delivery to the tissues and to produce the desired pharmacologic action.
Tissue Storage : Upon entering the systemic circulation, drugs can distribute into the interstitial and intracellular fluid of
various tissue cells. This distribution is facilitated by the binding of drugs to different cellular components within tissues, which
may lead to drug accumulation in specific areas. Drugs bound to tissue components serve as reservoirs that release free drugs
back into the system, prolonging the drug's overall action. However, this accumulation can also result in local toxicity.
(5)Routes of Drug Admnistration

Administration Absorption and distribution Elimination

Bile

Portal
Liver Kidney Urine

m
system Metabolites
Oral or rectal Gut Faeces

Percutaneous Skin
.

Milk,
Intravenous PLASMA Breast, sweat glands

k
sweat

Intramuscular Muscle
Brain

Placenta
Intrathecal CSF
t

Fetus
Expired
Inhalation Lung
air

Fig. 9.8 The main routes of drug administration and elimination. CSF, cerebrospinal fluid.
k

Note that bile (salt) is excreted in faces

 Ocular Otic

Nasal Parenteral:
IV, IM, SC
Inhalation

Oral
Sublingual
Buccal

Transdermal
patch Topical

Epidural

Rectal
or
vaginal

Figure 1.16
Commonly used routes of drug
administration. IM = intramuscular;
IV = intravenous; SC = subcutaneous.

A
Subcutaneous
Intravenous injection
injection
Intramuscular
Dermal injection
injection

Epidermis
Dermis

Muscle Subcutaneous
tissue

Fig. 1.1: Angles for inserting injections by different routes

 ROUTE OF ABSORPTION
ADVANTAGES DISADVANTAGES EXAMPLES
ADMINISTRATION PATTERN
Oral • Variable; affected by many • Safest and most common, • Limited absorption of some drugs • Acetaminophen
factors convenient, and economical • Food may affect absorption tablets
route of administration • Patient compliance is necessary • Amoxicillin
• Drugs may be metabolized before suspension
systemic absorption

Sublingual • Depends on the drug: • Bypasses first-pass effect • Limited to certain types of drugs • Nitroglycerin
Few drugs (for example, • Bypasses destruction by stomach • Limited to drugs that can be • Buprenorphine
nitroglycerin) have rapid, acid taken in small doses
direct systemic absorption • Drug stability maintained because • May lose part of the drug dose if
the pH of saliva relatively neutral swallowed
Most drugs erratically or • May cause immediate
incompletely absorbed pharmacological effects

Intravenous • Absorption not required • Can have immediate effects • Unsuitable for oily substances • Vancomycin
• Ideal if dosed in large volumes • Bolus injection may result in • Heparin
• Suitable for irritating substances adverse effects
and complex mixtures • Most substances must be slowly
• Valuable in emergency situations injected
• Dosage titration permissible • Strict aseptic techniques needed
• Ideal for high molecular weight
proteins and peptide drugs

Intramuscular • Depends on drug diluents: • Suitable if drug volume is moderate • Affects certain lab tests (creatine • Haloperidol
Aqueous solution: prompt • Suitable for oily vehicles and certain kinase) • Depot
irritating substances • Can be painful medroxy-
Depot preparations: • Preferable to intravenous if patient • Can cause intramuscular progesterone
slow and sustained must self-administer hemorrhage (precluded during
anticoagulation therapy)

Subcutaneous • Depends on drug diluents: • Suitable for slow-release drugs • Pain or necrosis if drug is irritating • Epinephrine
Aqueous solution: prompt • Ideal for some poorly soluble • Unsuitable for drugs administered • Insulin
suspensions in large volumes • Heparin
Depot preparations:
slow and sustained

Inhalation • Systemic absorption may • Absorption is rapid; can have • Most addictive route (drug can enter • Albuterol
occur; this is not always immediate effects the brain quickly) • Fluticasone
desirable • Ideal for gases • Patient may have difficulty
• Effective for patients with respiratory regulating dose
problems • Some patients may have
• Dose can be titrated difficulty using inhalers
• Localized effect to target lungs: lower
doses used compared to that with
oral or parenteral administration
• Fewer systemic side effects

Topical • Variable; affected by skin • Suitable when local effect of drug is • Some systemic absorption can occur • Clotrimazole
condition, area of skin, and desired • Unsuitable for drugs with high cream
other factors • May be used for skin, eye, intra- molecular weight or poor lipid • Hydrocortisone
vaginal, and intranasal products solubility cream
• Minimizes systemic absorption • Timolol eye
• Easy for patient drops

Transdermal • Slow and sustained • Bypasses the first-pass effect • Some patients are allergic to • Nitroglycerin
(patch) • Convenient and painless patches, which can cause irritation • Nicotine
• Ideal for drugs that are lipophilic • Drug must be highly lipophilic • Scopalamine
and have poor oral bioavailability • May cause delayed delivery of drug
• Ideal for drugs that are quickly to pharmacological site of action
eliminated from the body • Limited to drugs that can be
taken in small daily doses

Rectal • Erratic and variable • Partially bypasses first-pass effect • Drugs may irritate the rectal • Bisacodyl
• Bypasses destruction by stomach acid mucosa • Promethazine
• Ideal if drug causes vomiting • Not a well-accepted route
• Ideal in patients who are vomiting,
or comatose

Figure 1.19
The absorption pattern, advantages, and disadvantages of the most common routes of administration.
(Figure continues on next page)
FORMS ABSORPTION PATTERN ADVANTAGES DISADVANTAGES
Vaginal douche (for Washing or cleaning out the • Helps to remove unpleasant odors, • Vaginal infection as it upsets
example, Betadine inside of the vagina with water or wash away menstrual blood, avoid the natural balance of bacteria
douche) other mixtures of fluids getting sexually transmitted dis- in the vagina—that is, vaginal
eases, and prevent pregnancy after flora
intercourse • Pelvic inflammatory disease
Pharmaceutical pessary It is a device that is placed into • Easy to use • Difficulty in getting pregnant in
the vagina for local action (for • Local action women who douche more than
example, Clotrimazole vaginal once a week. May increase the
pessary) incidence of complications in
pregnancy—ectopic pregnancy
Support/therapeutic It is a device to provide support • Vaginal support pessary is a useful • Increased risk of vaginal
pessary (for example, to the uterus or bladder and nonsurgical treatment for the man- discharge, vaginal irritation,
Ring, Shaatz, Gellhorn, rectum agement of pelvic support defects ulceration, bleeding, and dys-
Ring with support) such as cystocele, rectocele, stress, pareunia
and urinary incontinence • A neglected pessary can be-
• Support pessaries fit by trial and come embedded in the vaginal
error of several sizes and/or styles. In mucosa and may be difficult to
patients who use a diaphragm, the remove
size of the diaphragm does not cor- • Improperly fitted ring pessary
relate with the size of the pessary can lead to strangulation and
necrosis of the cervix and uterus

Figure 1.19 (Continued)

The absorption pattern, advantages, and disadvantages of the most common routes of administration.

ROUTE OF VARIABLE (MIN-

ADMINISTRATION UTES TO HOURS)
Oral ingestion 30–90 minutes
Rectal 5–30 minutes
Subcutaneous 15–30 minutes
Intramuscular 10–20 minutes
Sublingual 3–5 minutes
Inhalation 2–3 minutes
Endotracheal 2–3 minutes
Intraosseous 30–60 seconds
Intravenous 30–60 seconds

Figure 1.20
Route of administration and time to
effect.
(6) Dosage forms

Figure 2 Dosage forms