PHARMACOLOGY

part 3
Autonomic Pharmacology
• INTRODUCTION

• anatomical organization of the nervous system

• comparison at the parasympathetic and

sympathetic decisions of the autonomic nervous
system

• drugs affecting nervous system stimulate or inhibit

its cholinergic or adrenergic component
http://philschatz.com/anatomy-book/contents/m46500.html
http://www.enchantedlearning.com/subjects/anatomy/brain/Neuron.shtml
https://www.slideshare.net/IsyafiqAhmadi/5-cns-1
• PERIPHERAL NERVOUS SYSTEM

• Cranial and spinal nerves

• somatic -supplies the muscles and the skin

• Autonomic nervous system (supplies the smooth

muscles, cardiac and the glands)

• Parasympathetic Nervous System

• Sympathetic Nervous System

http://slideplayer.com/slide/9054461/
Fight and flight Rest and Digest

in salivary glands, both secretes

salivation but this and
scan and mucoid in sympathetic and thin,
profuse and enzyme rich in parasympathetic

Ach NE/EPi

https://courses.lumenlearning.com/boundless-ap/chapter/structure-of-the-autonomic-nervous-system/
• The anterior ocular segment and pupillary reflexes
are examined in detail with a strong light and
under magnification in a darkened room.
MENACE TEST DAZZLE TEST
the movement of the eyeball is opposite the
movement of the head, try it!

positional nystagmus, indicated brain damage,

nutrition, etc.
PRIUPUS greek
fertility god
• 1-4. Factors affecting drug distribution

• 5.percent body weight of plasma

• 6. percent body weight of ECF

• 7. percent body weight of Interstitial

• 8.percent body weight of transcellular

• 9. substance used to measure the plasma

• 10.substance used to measure the ECF

• 11-12. Factors affecting the rate and extent of drug distribution

• 13-15. Factors affecting the Physiochemical properties of drugs in

drug distribution
 Parasympathetic Sympathetic

Length of Pre-
Long Short
Ganglionic Fiber

length of Post-
Short Long
Ganglionic Fiber

Ganglionic Synapse Discrete (1:1) Diffuse (1:20)

Massive discharge of
Function Conservation of energy
energy
• STATE OF TONUS

• a state where there is predominance of one

division into another.

• Note that most organs are innervated by the two

divisions and have antagonistic effects

• eg. HEART…tachychardia with sympathetic

stimulation and Bradychardia with
parasympathetic stimulation

• MUSCLES?
myoclonus vs twitch
 MAJOR NEUROCHEMICAL
TRANSMITTERS released at the
neuroeffector junctions
• NOREPINEPHRINE / EPINEPHRINE

• also known as adrenaline is the major neurotransmitter at the

terminals of the postganglionic fibers in the sympathetic
division, that is at the neuroeffector junction

• postganglionic fibers are called adrenergic fibers

• response mediated is called the adrenergic response

• The chromaffin cells. at the adrenal medulla are modified

adrenergic cells. Stimulation of the splanchnic nerves causes
the release of the epinephrine into blood circulation, adrenalin
rush
adenosine
• ACETYLCHOLINE

• acetylcholine is released at:

• Postganglionic parasympathetic fibers at the neuroeffector

junction

• Preganglionic parasympathetic fibers

• Preganglionic systemic fibers

• Splanchnic nerve at the adrenal medulla

• Somatic nerve terminals as in the neuromuscular junctions.

These are somatic nerves and not included in the ANS
 Types of Receptors in the
Autonomic Nervous System
• Cholinergic Receptors

• Muscarinic receptors

• specifically stimulated by muscarine, a poisonous substance from certain

species of mushroom

• Stimulation of this receptors produce muscarinic effects which are similar to

the effect of acetylcholine in the neuroeffector auction int he autonomous
nervous junction

• Nicotinic Adrenergic Receptors

• specifically stimulated by nicotine, a substance derived from tobacco

• produces nicotinic effects which are similar to the acetylcholine at the sites
other than the parasympathetic effector junctions. These other sites include
the somatic (motor) nerf fibers and sympathetic and parasympathetic ganglia
 Types of Receptors in the
Autonomic Nervous System
• Adrenergic Receptors

• they may mediate the effects of adrenergic transmitters

• Beta adrenergic Receptors

• Beta-1

• Beta-2

• Alpha Adrenergic Receptors

• Alpha-1

• Alpha-2

• Dopaminergic Receptors

• All these receptors can be stimulated by the different adrenergic transmitters but produce
varying degrees of response
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http://www.biologydiscussion.com/pharmacology-2/animals/neurohumoral-transmission-meaning-and-steps-animals/74245
General Categories of Drugs acting
on the autonomic Nervous System
• Stimulator of the Neurotransmitter synthesis

• Inhibitor of the Neurtransmitter synthesis

• Modifier of the Neurotransmitter storage

• Stimulator of the release of neurotransmitter

• Inhibitor of the release of the neurotransmitter

• Stimulator of the removal of neurotransmitter

• Inhibitor of the removal of neurotransmitter

CHOLINERGIC
DRUGS
lesson 2
Cholinergic Transmission
• Na+ and choline transport in the membrane through channels. The Choline
reacts with Acetyl CoA to for the ACETYLCHOLINE with the action of the
Acetylcholinetransferase

• Transportation of Ash to vesicles to prevent degradation

• Action potential causes the voltage sensitive calcium channel open causing
influx of Calcium ions inside thus causing the release of Ach from the vesicles

• Binding of Ach to post synaptic receptors leading to the cholinergic response

• Ach can also bind to presynaptic receptors that inhibits release and binding
of Ach to postsynaptic cleft (NEGATIVE FEEDBACK LOOP)

• Acetylcholinesterase breaks up Ach to Choline and acetate. Choli e is taken

up again and goes back to the presynapse
 Cholinergic Transmission

3
4
5

http://pharmacology-online.blogspot.com/2011/04/cholinergic-transmission.html
 REMINDERS:

*** Gq receptors are coupled with G proteins that increases the influx of calcium
ions causing increasing secretion, contraction and transmission of the nervous
system

***. Gi increases the influx of potassium ions which causes hyperpolarization and
reduction of heart rate

*** N receptors are influx of sodium ions.

short acting
Sjogren's
inhibition of acetylcholinesterase
 categories of Cholinergic
Drugs
• CHOLINE ESTERS

• Metacholine

• derivatives of Acetylcholine

• act directly on muscarinic receptors, no effect on muscarinic

receptors

• typical muscarinis effects such as increase glandular secretion,

bradycardia and hypotension

• Cattle: 50ml of 20% solution of iodide form, IV or SC

• Dog: 11 mcg/kg, IV of chloride form

 categories of Cholinergic
Drugs
• CHOLINE ESTERS

• Carbachol (Carbamylcholine)

• has an amine group instead of the methyl in the esoteric end of Act molecule which make sit resistant to
acetylcholinesterase

• marked effect on urinary bladder and the gut

• treatment of hypo motility and bladder paralysis, also for glaucoma

• ophthalmic solution dosage: IM or IV

• Cattle: 2-5mg

• Horse: 2-5mg

• Foal: 0.5-1mg

• Pig: 0.5-2mg

• Sheep: 0.25mg-0.5mg

• Dog: 0.5-1 ml of 1:1000 solution for emesis

• Dog: 0.5-1 ml of 1:10000 solution for purgative

 categories of Cholinergic
Drugs
• CHOLINE ESTERS

• Bethanecol

• resistant to cholinesterase with action lasting for several hours

• used in cases of neurogenic bladder paralysis and post surgical

treatment of esophageal achalasia

• Dosage:

• Dog: 50mcg/kg once SC; 0.5-1 mg/kg q6h oral

• Cat: 2.5-5 mg total dose oral

• Horse: 0.05 mg/kg SC

 categories of Cholinergic
Drugs
• NATURAL ALKALOIDS (plant origin)

• Muscarine

• belongs to the mushroom family of genus Amanita

• of toxicological importance only and not use in therapeutics

• signs of muscarine toxicities are salivation, lacrimation,

dyspnea, colic, diarrhea, and cardiovascular collapse

• ATROPINE is the antidote, not to be given in GI problems

and glaucomaoma
 categories of Cholinergic
Drugs
• Pilocarpine

• derived from the leaves of Pilocarpus jaborandi.

• has most marked effects on the murcarinis receptors

in the eye and exocrine glands

• causes pupillary constriction, open the canal

Schlemm, it used for the treatment of glaucoma

• also used in gut impaction in large animals but it is

very dangerous, not recommended
 categories of Cholinergic
Drugs
• NATURAL ALKALOIDS

• Arecholine

• derived from the fruit of Areca catechu (betel

nut)

• has both muscarinic and nicotinic effects

• maybe used to eradicate tapeworms by its

purgative effects but may cause toxicities in host
 categories of Cholinergic
Drugs
• CHOLINESTERASE INHIBITORS

• 2 types:

• a. Acetylcholinesterase (aChE)

• can hydrolyze acetylcholine only

• location: nerve terminals in the PNS, NMJ, CNS gray matter,

erythrocytes

• b. Pseudocholinesterase (pChE)

• can hydrolyze acetylcholine and other esters of choline and some

local anesthetics

• location: plasma, CNS white matter

• Generally, a cholinesterase maybe inhibited by:

• ACETYLATION: readily reversible (in seconds)

and does not cause clinical problems

• CARBAMYLATION: carbamylated enzymes takes

longer time (hours) to restore activity and may
cause signs of poisoning in patients

• PHOSPHORYLATION: generally irreversible

inhibition of cholinesterase
• 1-3. Give 3 process where cholinesterase can be
inhibited

• 4-5. Give 2 types of cholinesterase inhibitors

• 6-8. Give three directly acting cholinergic drugs

(CHOLINE ESTERS)

• 9-11. Give three directly acting cholinergic drugs

(NATURAL ALKALOIDS)

• 12-15. Give three directly acting cholinergic drugs

(SYNTHETIC AGONISTS)
 Indirectly acting cholinergic
drugs

• IRREVERSIBLE CHOLINESTERASE INHIBITORS

• includes organophosphates compounds (OP)

which are used commonly as insecticides/
acaricides, pesticides, anthelminthics and
agricultural pesticides to which domestic animals
maybe exposed.
 organophosphates
• highly soluble, well absorbed and widely distributed

• volatile that they can be absorbed through the lungs

and skin

• extensively metabolized in the liver

• dealkylation may lead to either activation (lethal

synthesis) or inactivation of the compounds

• mainly excreted in the urine as inactive metabolites

 organophosphates
• based on the ability to undergo lethal synthesis, OP can be:

• Directly-acting: inhibit cholinesterase without prior metabolism (eg.

phosphonates)

• Indirectly-acting: those that need to metabolized first before they

can inhibit cholinesterase (eg. phosphothionates)
• STAGES OF CHOLINESTERASE INHIBITION by OP:

• Stage I. Phosphorylation of the enzyme

• Stage II. Spontaneous phosphorylation or recovery of

the enzymes

• Stage III. Aging

• Stage IV. Biosynthesis of new cholinesterase

 organophosphates
• Pharmacological effects of OP:

• CNS effects: excitation and mainly progressing to convulsion and coma

• Respiratory failure: usually death: bronchoconstriction, dyspnea,

excessive salivation and mucus secretion, paralysis of the respiratory
muscles

• Treatment of OP:

• 1. Atropine: blocks the muscarinis effects but not the nicotinic effects.
Given IV to effect. overdosage may cause hyperthermia and CNS
stimulation. Dosage: 0.2-2 mg/kg (give 1/4 dose IV, the rest SC and IM)

• 2. Pralidoxime (2-PAM) is clinically useful only during the early stages of

poisoning. Dose: 10-50mg/kg IM, IV q12h.
ATROPINE CAN
CAUSE
HYPERTHERMIA,
WHY?

HYPERTHERMIA
VS. FEVER

X
 Indirectly acting
cholinesterase inhibitors
• REEVERSIBLE

• Neostigmine

• synthetic quaternary wine analogue of physostigmine and has a dual action

• inhibit cholinesterase

• directly stimulates the cholinergic receptors

• the dramatic clinical uses:

• gut hypo motility

• urinary bladder paralysis

• myasthenia gravis

• counteract the muscle paralysis caused by such drugs like curare or

aminoglycosides antibiotics
NEOSTIGMINE: directly
stimuliting reeptors and
prevention of
acetylcholineesterase
 Ach

esterase

cholinergic crisis myasthenia graves

increase muscle improved
weakness
 Indirectly acting
cholinesterase inhibitors
• REEVERSIBLE

• Edrophonium

• similar to neostigmine but shorter duration

• clinical uses:

• to differentiate muscles weakness and myasthenia gravis

• Ambemonium and pyridostigmine are moderately long acting

• Carbamate insecticides are used to control external parasites of both large

and small snimals. Carbamates cause carbamylation of the esteric site of the
cholinesterase and blocks its action of the cholinesterase

• example: Carabaryl (sevin) proposer, Moban adicarb

 CHOLINERGIC BLOCKING
AGENTS

• Anticholinergics or paraympathomimetic drugs are

more specifically antagonist of acetylcholine at the
muscarinic receptors

• have little or no action on the nicotinic sites

• ex. ATROPINE
 ATROPINE
• a racemic mixture of D and L-hyocyamine is the prototype of parasympathomimetic drugs

• important therapeutically rather than toxicologically

• active poisons in deadly nightshade (Atropa belladonna), jimsyn weed (Dature

stramonium) and henbane (Hyocyamus niger).

• well absorbed orally, parenterally and from the eye.

• distributes widely and crosses the blood brain barrier (BBB) and produces central
nervous effects

• Goats and rabbits are resistant to atropine due to the presence of ATROPINASE
(esterases that breaks down atropine).

• Horses and castles are also quite resistant to oral administration but responsive
parenteral.

• Pigs, dogs and cats are not resistant to either oral or parenteral
• pharmacological effects:
ATROPINE
• Heart: tachycardia, in some cases preceded by initial bradycardia

• Blood vessels: little effect because blood vessels tone is primarily under the control of the sympathetic
nervous system and rapid IV administration may cause fall in blood pressure, perhaps due to histamine
release

• Smooth muscles: relaxation resulting in antispasmodic effect

• Secretion: decreased exocrine secretions

• Eye: relaxation of the ciliary muscles causing cycloplegia (loss of ability to accommodate for near vision);
increase intra ocular pressure due to the closure of the canal of Schlemm (avoid in glaucoma)

• CNS: large doses lead to CNS stimulation and hyperthermia followed by secondary CNS depression

• clinical uses:

• preanesthetic agents

• produce mydriasis i eye

• treatment of OP poisoning

• Antispasmodic therapy and management of certain types of colic

• To couter the affect of cholinergic drug abuse

other atropine like drugs
• Scopolamine - natural congener of atropine, has more CNS effects on
atropine. used in women to produce twilight sleep during childbirth

• Homatropine - shorter duration of action than atropine and has only

10% of atropine’s potency

• Eucatropine - shorter duration of action than atropine produces

mydriasis with little cycloplegia

• Glycopyrrolate - preanesthetic anticholinergic agent, 5 times more

potent than atropine, lacks the initial decrease in heart rate usually
observe with atropine. less CNS effects than atropine

• Propantheline - synthetic atropine substitute. has high ganglionic

blocking to antimuscarinc activity. used as GI antispasmodic agent
 Ganglionic Blocking
agents
• block cholinergic receptors in the autonomic ganglia in
both parasympathetic and sympathetic divisions

• 1. Non depolarizing blockers: compete with Ach for

receptor sites in the ganglia and adrenal medulla.effects
include:

• fall in blood pressure (blockade of sympathetic tone)

• decreased gut motility and constipation

• examples: tetraethylammonium (TEA),

Hexamethonium, Pentolinium, Mecamylamine
Ganglionic Blocking agents

• 2. Depolarizing blockers - powerful and persistent

stimulation of cholinergic receptors leading to
receptor blockade and fatigue. the effect is bi-
phasic initial stimulation and then inhibition.

• example: Nicotine. absorb from all sort of

administration

• uses: wildlife capture drug and as insecticide

ADRENERGIC DRUGS
 PENAM PENICILLINS
• derivatives of 6-aminopenillanic acid

• developed in 1930s and 1940s

• became available in veterinary medicine in the late

1940s

• produced by the Penicillium molds and the first

antibiotic available for clinical use.

• at present, represents the large group of

compounds

• only the primary ones used in veterinary medicine.

 CHEMISTRY
• penicillin nucleus made of a thiazolidine ring (A) connected to a Beta
Lactam Ring (B) to which a side chain (R) is attached

• an intact Beta Lactam ring is essential against bacterial action

• the side chain alters the antimicrobial activity and the

pharmacokinetics of the molecule
 CHEMISTRY
• the penampenicillin are weak organic acids, and some
are not stable
PENICILLIN V AMOXICILLIN

• most are relatively unstable in solution and are therefore

formulated as powders which have relatively short half
life if reconstituted.
 • NEUROMUSCULAR
BLOCKADE

• curare-like paralysis
is dose related and
may occur only with
high doses.

• Aminoglycosides
inhibit pre-junctional
release of
acetylcholine, which
also reducing post-
synaptic sensitivity to
acetylcholine
NOTE: important when other neuromuscular inhibitors such as muscle relaxants and anaesthesia is concurrently
administered
NEOSTIGMINE AND CALCIUM antagonise the blockade produced by aminoglycosides, and are used in the treatment of this
form of toxicity.
 DRUG INTERACTIONS
• Aminoglycosides and penal
penicillins in the same container
inactive each other except
PENICILLIN G and
STREPTOMYCIN

• Penicillin-Streptomycin suspension,
however, must be used within 24
hours after reconstitution

• Interaction also occurs in the body

fluids when both types of
antibiotics are present in high
concentrations
• Gentamicin shows antagonism with
Chloramphenicol, Tetracyclines and Erythromycin

• Aminoglycosides will potentiate the toxicity of

nephrotoxic drugs and neuromuscular blocking
drugs

• Aminoglycosides bind to pus, calcium, and

magnesium, ; 32X more potent in the alkaline urine
 SPECTINOMYCIN
• produced by the Streptomyces spectabilis.

• a non-aminoglycoside aminocyclitol, and therefore structurally related

to aminoglycosides

• however does not contain amino sugars attached in glycosidic

linkages
non amino sugars - no amino sugars
-NH attached on the
cyclitol

glycosidic linkages
• it is a weak organic base with two pKa (6.4 and
8.7.

• low lipid solubility but it is highly water soluble

and relatively stable in solution
MECHANISM OF ACTION
• Spectinomycin binds with the 30s ribosomes but
does not cause misreading on the genetic code, it
just interrupts, thus just delaying the synthesis

• unlike the ahminoglycosides, it is bacteriostatic

 SPECTRUM OF ACTIVITY
AND CLINICAL USE
• Narrow spectrum including primarily Gram-
negative bacteria, but not as active as the
aminoglycosides

• Has some activity against Mycoplasma but none

against anaerobes

• Used in veterinary medicine in the treatment of

Mycoplasma infections, diseases caused by
eneterobacterioceae and respiratory diseases
caused by gram negative bacteria

• It is available in combination with lincomycin, a

lincosamide antibiotic, and used to treat
Mycoplasma infections in poultry
 RESISTANCE

• resistance to spectinomycin can develop rapidly

as a result of mutation or R-factor transfer

• Some resistance is the result of adenylation of

spectinomycin by bacterial enzymes
 PHARMACOKINETICS
WHY
• Poorly absorbed from the gut (<10% in dogs)

• HAs low volume of distribution; limited to extracellular fluids

because of poor lipid solubility

• Tissue concentration seldom exceed 25-50% of the serum

concentrations
Pharma term for this?
• There is little penetration into the brain, aquaus humour and bone
WHY
• Exceed rapidly unchanged in the urine by GFR; 75% doses is
cleared in 4 hours; the half life is only 60 minutes in most cases

• DOC: uncomplicated gonorrhoea

 CATECHOLAMINES
• all endogenous adrenergic neurotransmitters

• DOPA

• Norepinephrine - alpha agonist property

• Epinephrine - mixes (alpha and beta agonist)

• Dopamine - immediate precursor of NE

• isoporoteronol - selective beta agonist

 CATECHOLAMINES
• catecholamine structure contains catechol moiety
which is a benzene ring, with adjacenthydroxy
groups at position 3 and 4(3,4 Dihydroxybenzene)
and an amine group

http://www.sciencedirect.com/science/article/pii/S0223523415301720

https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines
Synthesis of Norepinephrine
inhibited by alpha-methyl-p-tyrosine

inhibited disulfiram

catalyzed by phenylethanolamine
 CATECHOLAMINES vesicle associated membrane
proteins vesicular monoamine transporter

exocytosis

mechanism of terminating
adrenergic response
COMT
1. Diffusion - diffusion in blood
2. Enzymatic destruction (MAO and
COMT) - 20% removal of NE
3. reuptake to nerve terminals - 65%
removal of NE
http://pharmacology-online.blogspot.com/2011/04/adrenergic-transmission.html
 MAKING LOVE, MEDICINE
AND PHARMACOLOGY
Rita Watson, MPH and Associate Fellow at Yale's Ezra Stiles College writes in
Psychology Today that "naturally occurring hormone oxytocin and love are
intimately related." Dr David Moore explains in New York Daily News that the
powerful release of dopamine and other hormones can keep us craving more
from that person person, which feels a lot like love. Plus, the adrenaline causes
your heart rate to rise, according to The Daily Mail. So sex is basically like
jaegerbomb and a hug all in one.
 Properties of Adrenergic
Receptors
• very important for direct application in clinical use of adrenergic antagonist and agonist

• History

• AlQUIST (1948) investigated the potency of the 3 catecholamines (NE, EP, and IS)

• observed 2 orders of potency:

• 1)EP>NE>IS and 2) IS>EP>NE

• in the second order, beta receptors are involve:

• a) Beta 1 - chiefly in the heart

• b) Beta 2 - blood vessels, liver, bronchi, etc.

• c) Beta 3 - Fat tissues

• in the first order, alpha receptors are involved

• a) alpha 1 -postsynaptic fibers, smooth muscles

• b) alpha 2 -pre and post synaptic fibers

make an outline of the receptors to know the effects

ADRENERGIC RECEPTORS

https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines
note: renin
https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines
BRONCHIOLES B2 - bronchodilation
decrease motility and decrease motility and
GUT
increase spincther tones increase spincther tones
https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines

treatment of hyperactivity
 Clinical Uses of
Sympathomimetic Agents
• adjunct to local anesthesia (vasoconstriction prolongs the effect of anesthesia)

• Mydriatic in eyes and used in examining the interior of the eye. versus atropine, does not cause
cycloplegia

• in anaphylactic reactions, EPINEPH is drug of choice due to hypotension and bronchospasm (what is the
difference between bronshospasms with bronchoconstriction?

• as Bronchodilator, best treatment for bronchial asthma (Beta 2 adrenergic agonists)

• ISOPROTERONOL affects bronchi and Beta 1 effect on heart

• EPHEDRINE causes CNS effects to increase bronchodilation

• treatment of local skin - alpha adrenergic

• Decongestant. alpha adrenergic agonists

• Diagnosis of heaves in horses (ISOPROTERONOL)

• treatment of cardiac arrest: intracardiac injection of Beta1 adrenergic stimulants

• treatment of hypertensive conditions: DOPAMINE

• treatment of local skin -

•
• treatment of hypertensive conditions: DOPAMINE
 DIRECTLY ACTING

Alpha Beta Mixed

Phenylephrine
Alpha 2 Methoxamine
Beta 1 Beta 2
Norepinpehrine Metaraminol Epinephrine
Isoproteronol
Methoxyphenamine

Albuterol
Clonidine Clenbuterol
Oxytetrazoline
adapted from EF Landicho’s notes Terbutaline
Dopamine
Xylazine Isoetharine
Dobutamine
Medetomidine Salbutamol
 INDIRECT ACTING
Ampethamine
Metamphetamine
Ephedrine
Pseudoephedrine
Hydroxyampethamine
Metaraminol (Boths direct and indirect)
adapted from EF Landicho’s notes
 ADRENERGIC BLOCKING
AGENTS
• ALPHA ADRENERGIC BLOCKERS

• Phenoxybenzamine, dibenamine, phentolamine (Regitime

HCL), Tolazoline (priscoline HCL), piperoxan, dibozane,
azapetine and prazosin.

• ergot alkaloid such as ergocristine and ergocryptine blocks

alpha receptors and directly stimulate smooth muscles

• phenothiazine and butyrophenone tranquilizers such as

chlorpromazine, acepromazine, and haloperidol blocks alpha
2 adrenergic receptors.

• YOHIMBINE reverses xylazine effects in animals

adapted from EF Landicho’s notes
 Pharmacological effects of
Alpha Adrenergic Blockers
• little effect on resting blood pressure

• postural hypertension dependent on alpha receptors

• hypotension maybe severe to cause cerebral and hypoxia and ataxia

• Postural hypotension is specifically prominent when there is massive

release of epeineph, or when epineph is concurrently administered

• remember, epinephrine when given in absence of alpha adrenergic

blocker causes an increase rather than a decrease in blood pressure

• little effect on GIT

• used in treatment of PHEOCHROMOCYTOMA catecholamine secreting

tumor of the adrenal medulla
adapted from EF Landicho’s notes
Beta adrenergic blockers
• dichloro-isoproteronol

• propranolol (Inderal)

• Timolol

• Alprenolol

• pindolol

• Nadalol

• Sotalol

• Metoprolol (selective B1 blockers)

• butoxamine ( selective B2 blockers)

adapted from EF Landicho’s notes
 EFFECTS OF BETA
BLOCKERS
• cardiac depression, aggravation of heart failure

• may cause bronchoconstriction due to Beta 2 adrenergic receptors

• Clinical Uses:

• drug of choice for treatment of essential hypertension in humans

• Used for reversing digitalis-induced cardiac arrhythmia

• For treatment of obstructive cardiomyopathy; rare disease of dogs

and cats

• Used to block the effect of excessive epinephrine in

pheochromocytoma
adapted from EF Landicho’s notes
 ASSIGNMENT

If the adrenergic drugs are blockers

of sympathomimetic drugs, can we
replace it with parasympathomimetic
drugs to revert its effect?
EPINEPHRINE EFFECTS

HEART

BLOOD
note: renin
EPINEPHRINE EFFECTS
EPINEPHRINE EFFECTS

insulin vs.
glucagon?
 EPINEPHRINE catechol-o-
methytransferase/
monoamine oxidase

if it is on
respiratory tract, is it
broncho constriction or
dilation?what specific
https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines
receptor?
 EPINEPHRINE

https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines decreases fluid in the eye

https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines
 EPINEPHRINE

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https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines
 NOREPINEPHRINE
what
receptor

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NOREPINEPHRINE

CI for decrease
in blood supply
in kidney?

https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines
 increase heart
rate

https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines bronchodilator
 ISOPROTERONOL

inotropic - contraction of
the heart

chronotropic - heart rate

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promo - conduction of
the heart
 ISOPROTERONOL

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 ISOPROTERONOL
increase in diastole
rather than the systole

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https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines
 DOPAMINE

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 DOPAMINE

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 what is cathecol again?
hehehehe

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https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines
ephedrine, phentermine and fenfluramine.

orlistat - xenical
https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines
https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines
https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines
 AMPETHAMINE

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https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines
https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines
https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines
https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines
https://www.slideshare.net/Sindhukuberappa/catecholamines-noncatecholamines
 NEUROMUSCULAR
DRUGS AND MUSCLE
RELAXANTS
NEUROMUSCULAR DRUGS
AND MUSCLE RELAXANTS

• agents that induce relaxation of the skeletal muscles

• many substance can cause muscle relaxation

(paralysis) but only a few are used for this purpose

• relaxation maybe induced to restrain animals and

relieve muscular spasms

adapted from EF Landicho’s notes

Site Of Action and examples
of muscle relaxants

• CENTRAL NERVOUS SYSTEM

• can relax skeletal muscle by depressing the flow

of impulse long the somatic nerves

adapted from EF Landicho’s notes

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
Site Of Action and examples
of muscle relaxants
• CNS

• centrally acting skeletal muscle relaxants do not depress CNS thus there is no loss of
consciousness and some sedation occurs

• meprobamate

• mephensin

• guafenesin (Gyceryl guaiolate)

• methocarbamol

• used clinically for relief of skeletal muscle spasms in vertebral disc protrusion

• Guaifenesin is used as 5% solution to cast horses and cattles

• In horses, under chloral hydrate necrosis, 3-4mg/kg guaifenesin causes abdominal muscle
relaxation lasting for 10-15 minutes without significant respiratory depression

• laryngeal paralysis to facilitate endotracheal intubation

adapted from EF Landicho’s notes
Site Of Action and examples
of muscle relaxants

• Motor Nerve Fibers

• local anesthetics applied or around the nerve

fibers as in induction of the epidural anesthesia.
They are commonly used for muscle relaxant
effect but are used more for the reason of sensory
blockade.

adapted from EF Landicho’s notes

Site Of Action and examples
of muscle relaxants
• Motor Nerve Terminal

• no clinically used for this group.

• occurs in poisoning with botulinum toxins and

aminoglycosides antibiotics

• substances prevent the release of acetylcholine from

nerve endings

• Calcium is needed for the release of Acetylcholine and

maybe the reason for skeletal muscle paralysis in milk
fever.
adapted from EF Landicho’s notes
Site Of Action and examples
of muscle relaxants
• Acetylcholine receptors in motor end plate

• non depolarizing neuromuscular blocking drugs compete with acetylcholine for cholinergic receptors in the end
plate

• D-Tubocurarine (Curare) from Chondendron spp. also known as South American Arrow Poison

• charged quaternary ammonium

• poorly absorbed from the gut and not metabolized but excreted in urine and bile

• given IV, onset of action is 5 minutes lasting for 20-30 minutes to 24 hours

• sequence of muscle blockade: eye muscle>neck muscles>extremities>abdominal muscles>intercostal

msucles>diaphragm

• clinically given at a dose to relax the muscle and then put the patient on a positive pressure ventilation that
release histamine causing hypotension.

• in surgery, used to obtain an adequate skeletal muscles relaxation; in orthopedic, relieves muscle spasms for
setting bone fractures

• useful in stopping convulsions due to strychnine poisoning, tetanus, and status epileptics.

• Dose: Dog (0.4mg/kg) Pig (0.3mg.kg) Horse (0.22-0.25mg/kg)

adapted from EF Landicho’s notes

Site Of Action and examples
of muscle relaxants
• SPECIFIC AGENTS

• Amino esters agents

• 1. PROCAINE (low potency, short duration of action, allergy due to PABA metabolite)

• 2. CHLOROPROCAINE (rapis onset, low systemic toxicity)

• 3. TETRACAINE (high potency, long duration of action, undergoes slow hydrolysis in plasma,
greater systemic toxicity)

• 4. COCAINE (used as surface anesthetics and an abused drug)

• Amino amid Agents

• Lidocaine (most versatile anesthetics, high potency, ;rapid onset and moderate duration of
action)

• Mepivacaine (similar to lidocaine, not used in obstetrics due to prolonged metabolism in fetus)

• Bupivacaine (slow onset, long duration of action, separation of sensory analgesia and motor
blockade and exhibit more serious cardiovascular toxicity
adapted from EF Landicho’s notes
Site Of Action and examples
of muscle relaxants
• Amino amide Agents

• Etidocaine - cause profound muscular relaxation, similar to bupivacaine in

duration of acton but has more rapid onset)

• Prilocaine (similar to lidocaine but with lower potential for systemic reactions)

• Dibucaine (very potent and long duration of action)

• agents restricted to ophthalmological use

• Benoxamine

• Proparacaine

• Agents used to anesthetize less delicate mucous membranes and skin:

• Cyclomethycaine, Dimethisoquin, Diclonin, Hexyclaine, Pramoxine, Butamben

adapted from EF Landicho’s notes
 How your body reacts when
you fall in love By Lindsay Tigar, Health.com

Updated 1647 GMT (0047 HKT) February 12, 2016

Like drugs, the more time you spend with this person, the more addicted you become. dopamine, oxyto
adrenaline, and vasopressin)
Your cheeks flush, palms sweat, and heart races
Your pupils dilate
Being in love might give you superpowers
You won't be able to keep your eyes off your partner
The desire to literally look at your partner's face comes from the brain's release of dopamine, says Dr.
Kirk. "This is the same effect on the brain as taking cocaine because it stimulates the desire/reward
response related to intense pleasure,"

Your voice might actually get higher

According to a study published in 2011 in the Journal of Evolutionary Psychology, researchers found
that when women spoke to men they were more attracted to physically, their voice tended to get
higher and more feminine.
 If you get married, you may live a longer, healthier life
Another study from NYU Langone Medical Center in New York found that both married men and women may
have stronger hearts than those who've never walked down the aisle. Men especially have stronger hearts
thanks to their wives, with 5% lower odds of any vascular disease, according to the research.

You might have trouble sleeping

Staying awake dreaming of that Tinder match date that went surprisingly well? Those feel-good crush-like
symptoms may disrupt your sleep. According to a study of adolescents, when you're in those initial stages of
euphoria, you feel more energized and positive in the early morning and evenings, causing you to not sleep as
well, or have restless sleep

It'll make you more sexually adventurous

Penn State sociologists who interviewed women in Pennsylvania, New Jersey, and New York found that
when they're in a committed relationship, women are more keen to try something new—including in the
bedroom.
It can ease chronic pain
A passionate, all-consuming relationship may work just as well as medication at easing chronic pain, according
to a 2010 Stanford University School of Medicine study. Intense feelings of love activate the same areas of the
brain as painkillers, say researchers.

You will worry when they're not around

When we're separated from our partner for brief or extended periods of time, we respond like a drug addict who is
coming off of their addiction, says Serena Goldstein, a naturopathic doctor in New York City. "Corticotrophin
releasing factor is increased as part of a stress response when we are away from our partner, contributing to
anxiety and depression,"