ANS

PHARMACOLOGY
DR RONO
 General Considerations
• Nervous system is very complex and highly integrated, divided into central
nervous system & peripheral nervous system.
• The peripheral nervous system is further divided into:
• somatic nervous system(voluntary)- 12 pairs of cranial nerves and 31 pairs of spinal nerves
all distributed throughout the body. Controls activities(functions) of the skeletal muscles.
• autonomic nervous system(involuntary). It controls activities(functions) of the heart,
blood vessels, smooth muscles of viscera and exocrine glands.
• ANS is divided into parasympathetic NS and sympathetic NS whose differences are
shown in the table in the next slide.
• The two systems are state of dynamic equilibrium in the body to maintain
homeostasis(internal environment). Dominance of the PNS occurs in the placid
state whereas the dominance of sympathetic system occurs in stressful and
emergency situation.
• ANS is under higher control of hypothalamus and reticular activating
systems(RAS). Limbic system coordinates emotions with autonomic reactions.
Final coordination between somatic and autonomic functions occur in cerebral
cortex.
 Differences between PNS & SNS
Parasympathetic NS Sympathetic NS
Cranial sacral outflow (C Thoracolumbar outflow (T1-12,
Origin
3,7.9 and S2-4) L1-3)
Limited (1 or 2 Wide( 5-50 postganglionic
Distribution
postganglionic fibres fibres))
Ganglia On or close to organ. Away from the organ

Long, myelinated. Short, myelinated

Preganglionic fibres
Postganglionic
Short myelinated. Long myelinated.
fibres
Noradrenaline( major),
Neurotransmitter Acetylcholine
Acetylcholine (minor)
Conservation of body
Utilization of body energy,
energy, regulation of
tackling of stress and
Important functions tissue building process
emergency and preparing
(digestion and assimilation
individual for fight or flight .
of food)
Important of the Vital for life as functions Not so vital for life, organism
system of organs stop without it. can survive without it.
 General Considerations
• Neuronal transmission.
• Occurs by axonal conduction(passage of a nerve impulse along an axon/muscle
fibre) and junctional transmission.
• Nerve impulses elicits a response in smooth, cardiac, and skeletal muscles, exocrine
glands and post synaptic neurons(effector tissues) through liberation of specific
chemical transmitters like acetylcholine and noradrenaline.
• Junctional regions in ANS include;
• Synaptic junctions- is junction between two neurons, where information from one neuron
is relayed to the other neuron but there is no protoplasmic continuity between the
neurons. Are present in autonomic ganglia & enteric nervous system ganglia.
• Neuroeffector junction- is the junctional region between a post ganglionic autonomic
nerve fiber with the effector tissue( smooth, cardiac muscle or exocrine gland).
• Myoneuronal junction- is junctional region between a somatic nerve fibre and skeletal
muscle.
• In all these junctional sites, neurotransmission occurs by chemical transmission
with the help of neurotransmitter.
 General Considerations
• Neurotransmitter (neurohumor).
• Is a chemical substance which is synthesized and stored in the nerve endings and
released from there by nerve stimulus. It stimulates or inhibits postsynaptic
neurone. It has a short latency(onset of action) and short duration of action.
• Acetylcholine is the neurotransmitter in PNS and noradrenaline is the major
neurotransmitter & acetylcholine is minor neurotransmitter in SNS.
• Properties of neurotransmitter include;
• It should be present in the presynaptic nerve fibre and its distribution should be discrete
rather than uniform.
• It should be synthesized in the presynaptic nerve fibre by specific enzymes and stored in
synaptic vesicles/storage granules.
• It should be released from the nerve ending by nerve impulse.
• It should interact with specific receptors on effector cells/tissues.
• Its effects should be terminated by enzymatic destruction, diffusion from the site of
receptors or reuptake by the nerve endings.
• It should have agonists and antagonists to produce desired effects.
• It should produce identical responses when used extrinsically to the tissue as produced by
stimulation of nerve wherefrom it is released.
 General Considerations
• Steps in neurohumoral transmission;
• Synthesis of neurotransmitter in the nerve fibre by specific enzyme.
• Storage of the neurotransmitter in the synaptic vesicles or storage granules of nerve endings.
• Release of the neurotransmitter into the synaptic cleft or other medium by nerve
impulse(NAP).
• Interaction of the neurotransmitter with the receptor on the effector cell membrane
producing response(effect).
• Rapid removal of the neurotransmitter from the site of receptor by enzymatic destruction,
diffusion from the site or reuptake mechanism.
• Recovery of the effector cell to the state that preceded transmitter action.
• Cholinergic transmission is where acetylcholine is the neurotransmitter. It occurs in
the following sites;
• All preganglionic Para and Sympathetic nerve fibres.
• All postganglionic parasympathetic nerve fibres;
• Postganglionic sympathetic nerve fibres supplying sweat glands, hair follicles, few blood
vessels(arterioles) of skin of face and neck(vasodilator fibres)
• Nerve fibres supplying adrenal medulla
• Somatic nerve fibres supplying skeletal msucles.
• Certain synapses in the CNS(brain and spinal cord).
 General Considerations
• Cholinergic system(parasympathetic nervous system).
• Synthesis, storage, release and degradation of acetylcholine.
• Acetyl choline is synthesized from choline(transported from into neurone via
active transporters) & glucose(converted to pyruvate then finally acetyl coA).
Both combine to form acetyl choline catalyzed by choline acetyl transferase.
• Acetyl choline is then transported to synaptic vesicles for storage. It is
released from synaptic vesicles by excocytosis due to arrival of nerve
impulse(producing a nerve action potential (NAP)).
• It then crosses the synaptic cleft by diffusion and interacts with specific
receptors(muscarinic & nicotinic) on the effector cells to produce
responses(effect).
• The released acetylcholine is rapidly hydrolyzed to choline and acetate by
acetylcholinesterase. About 50% of choline is taken by the neurone via active
transport(reuptake mechanism), and utilized in the synthesis of acetylcholine
while the rest is carried away in circulation.
 General Considerations
• The drugs that modify cholinergic transmission are group;
• Drugs inhibiting synthesis of acetylcholine in cholinergic nerve endings( by blocking active
uptake of choline) e.g. hemicholinium, vesamicol and triethylcholine.
• Drugs inhibiting release of acetylcholine from cholinergic nerve endings(by blocking
exocytosis), e.g. procaine, streptomycin, verapamil, magnesium sulphate, and botulinium
toxin(Type I).
• Drugs potentiating(increasing) the action of acetylcholine ( by causing accumulation of
acetylcholine at cholinergic receptor sites) e.g. anticholinesterases (physostigmine,
neostigmine, and diisophyflourophosphate).
• Drugs antagonizing(decreasing) the action of acetylcholine (by blocking cholinergic
receptors) e.g. anticholinergic drugs (atropine, scopolamine, etic. at muscarinic receptors),
neuromuscular blockers (d-tubocurarine, gallamine etic.) and ganglion blockers
( hexamethonium trimthaphan etic. at nicotinic receptors).
• Cholinergic receptors are present on the cell membrane of the effector cells with
which acetylcholine(endogenous or exogenous) interacts to produce
responses(effects). They are of two types;
• Muscarinic receptors- stimulated by muscarine
• Nicotinic receptors – stimulated by nicotine.
• See table in next slide.
 Cholinergic receptors
Muscarinic receptors Nicotinic receptors
Selective Selective Selective
Receptor Site Functions Selective agonists
antagonists Receptor Site Function
Neurones agonists antagonist
(CNS &
Phenyltrime
PNS),
Oxotremonrine Unknown Skeletal contraction of D-tubocurarine,
ganglia, Stimulation of Nm receptor thyl
gastric neuronal and muscle skeletal muscle gallamine
M1 glands. ganglion cells ammonium
Stimulation of Pirenzipine
Unknown Stimulation of
gastric secretion. Telenzepine
Neurons,
M2 Heart (myocardium)
Depression of Heart Methacholine
Methoetramin neuronal and
e Tripitramine ganglia, Hexamethonium
Vascular Nn receptor ganglion cells, DMPP
smooth Relaxation, adrenal , Trimethaphan
release of
M3 muscle, contraction, Bethanechol Derifenacin
medulla
endocrin secretion catecholamines
e glands
 General Considerations
• Adrenergic system (noradrenaline is the major neurotransmitter while
acetylcholine is the minor neurotransmitter).
• Synthesis, storage, release and degradation of noradrenaline.
• Noradrenaline is synthesized from amino acid tyrosine which is either got
from diet or synthesized by the liver from phenylalanine. It is actively
transported into adrenergic neuronal cells & chromaffin cells of adrenal
medulla.
• Most of the noradrenaline stored in the storage vesicles of adrenergic
neurons and release via exocytosis after being stimulated by arrival of nerve
impulse.
• The released noradrenaline then acts on post synaptic adrenergic
receptors(α and β) on the effector cells to produce responses.
• Most of the adrenaline is then rapidly reabsorbed(reuptake mechanism)
and stored in storage granules and vesicles. The rest is removed by
metabolizing enzymes (COMT and MAOs).
 General Considerations
• Drugs modifying adrenergic transmission includes;
• Drugs inhibiting synthesis of noradrenaline in adrenergic nerve
endings e.g. αmethyl dopa.
• Drugs inhibiting storage of noradrenaline e.g. reserpine.
• Drugs inhibiting release of noradrenaline e.g. imipramine
• Drugs promoting release of noradrenaline from storage vesicles e.g.
amphetamine.
• Drugs inhibiting metabolism of noradrenaline e.g. selegiline.
• Adrenergic receptors are present on the cell membranes of
effector cells with which noradrenaline and other adrenergic
drugs interact to produce responses. These are two types α
and β receptors which are subdivided in to α1, α2, β1 and β2
respectively. See the table in the next slide.
 General Considerations
Beta receptors
Receptor Location Functions Agonists Antagonists
Stimulation( increase
Dobutamine Atenolol,
Myocardium rate & force of
, prenalterol metoprolol
β1 contraction)
Increase release of
JG cells of the kidney renin
Vascular & non
vascular smooth Salbutamol,
Relaxation propranolol
muscle (bronchi, GIT, terbutaline
urinary bladder etc)
Adrenergic nerve Inhibition of NA
β2
ending release
Glycogenolysis,
Liver gluconeogenesis
glycogenolysis,
Skeletal muscle uptake of K+
Lipolysis in
β3 Adipose tissue adipocytes
 General Considerations
Alpha receptors
Receptor Location Functions Agonist Antagonists
Vascular smooth
α1 Contraction Phenylephrine Prasozin
muscle
Non vascular smooth
muscle ( in sphincters,
Contraction
radial muscle of iris,
piloerector muscle etc
inrease in rate
Heart and force of
contraction
Glycogenolysis,
Liver
gluconeogenesis
Adrenergic nerve Inhibition of NA clonidine, α
α2
endings release methyldopa
Inhibiton of
Pancreatic β cells
insulin release
Aggregation of
Platelets
platelets
 General considerations
• In summary autonomic drugs which act on autonomic
receptors include;
• Cholinergic/parasympathetic drugs e.g. acetylcholine
• Anticholinergic drugs/parasympatholytic drugs e.g.
atropine, scopolamine etic.
• Neuromuscular blocking agents e.g. D-tubocurarine,
gallamine etic
• Ganglion stimulating/blocking agents e.g. hexamethonium
• Adrenergic drugs/sympathomimetic drugs e.g. adrenaline
• Antiadrenergic drugs/symphatolytic drugs namely alpha
receptor blockers (e.g. prazosin) and beta blockers (e.g.
propranolol).
 Cholinergic/parasympathetic
drugs.
• Are drugs that produce effects similar to those of acetylcholine
acting directly on cholinergic receptors or indirectly by inhibiting
the enzyme cholinesterase and causing accumulation of
acetylcholine at cholinergic receptor sites.
• Are of two groups;
• Directly acting (at cholinergic receptors)
• Choline esters- acetylcholine(natural drug), methacholine, carbachol,
methanecol (all synthetic drugs).
• Cholinomimetic alkaloids- pilocarpine, muscarine, arecholine.
• Miscellanous drugs- oxotremorine, metoclopramide
• Indirectly acting( at cholinergic receptors)
• Reversible anticholinesterases –physostigmine(natural drug),
carbamates, pyridostigmine, rivastigmine, edrophonium, demecarium,
acridine, tetrahyroaminoacrine (all synthetic drugs).
 Cholinergic/parasympathetic
drugs.
• Irreversible anticholinesterases(all are synthetic drugs). Are in two groups;
• Organophosphorus compounds e.g. diisopropylflourophosphate, and echothiophate (used as
miotics glaucoma), parathion, malathion, diazinon(used as insecticides and pesticides).
• Carbamate esters e.g. carbaryl and propoxur(used as insecticides and pesticides).
• Choline esters.
• Acetyl choline is described as a prototype of cholinergic agonists.
• Pharmacologic actions.
• Cholinergic agonists have two types of actions;
• Muscarinic actions exerted on heart muscle, smooth muscles, exocrine glands and CNS by
interacting with muscarinic receptors.
• Nicotinic actions exerted on autonomic ganglia, adrenal medulla, skeletal muscles and CNS by
interacting with nicotinic receptors.
• They produce the following effects;
• Cardiovascular effects.
• It depresses the heart by acting on M2 receptors on myocardium which are inhibitory
in nature. It slows the heart rate(negative chronotropic action) and decreases the
force of cardiac contraction(negative ionotropic contraction) leading to decrease in
cardiac output.
 Cholinergic/parasympathetic
drugs.
• On blood vessels, it relaxes smooth muscle and cause vasodilation.
• Nonvascular smooth muscle effects.
• In the eye it produces miosis(constriction of pupil) and spasm of
accommodation(cyclospasm) by interacting with M3 receptors in circular muscle of iris
and ciliary muscle of the eye respectively.
• In the airy way, it causes contraction of bronchial smooth muscle leading to
bronchospasm and dyspnea.
• In the GIT, it contracts the smooth muscles, increasing tone and peristalsis but it relaxes
gut sphincters.
• In the urinary tract it contracts the smooth muscle of ureters increasing tone and
peristalsis. It also causes contraction of detrusor muscle but relaxes trigonal sphincter
which causes urgency and voiding of urine.
• Exocrine glands (M3 receptors).
• Increases secretion of all exocrine glands which have cholinergic innervation producing
salivation, sweating, lacrimation and tracheobronchial secretion. It increases gastric
secretion via M receptors and can aggravate peptic ulcer. It does not affect pancreatic,
intestinal, milk and bile secretion.
 Cholinergic/parasympathetic
drugs.
• Cholinomimetic alkaloids
• Pilocarpine
• It has prominent muscarinic actions producing profuse salivation,
lacrimation, sweating etc. (see above effects of acetylcholine.).
• It is too toxic for systemic use, mainly use as eye drops in the treatment
of both narrow angle(acute congestive) glaucoma and wide
angle(chronic simple) glaucoma to reduce intraocular pressure.
• It is also used to reverse mydriatic effect atropine.
• Atropine is used as an antidote in acute pilocarpine poisoning.
• Muscarine
• Is an alkaloid obtained from the mushroom Amanita muscaria but it
has no clinical use. It has toxicological importance because mushroom
poisoning is common.
 Cholinergic/parasympathetic
drugs.
• Anticholinesterases.
• These drugs are indirectly cholinergic acting by inhibiting acetylcholinesterases
hence causing accumulation of acetylcholine at cholinergic sites.
• There adverse effect are similar to acetylcholine but it also initially produces CNS
stimulation (manifested as anxiety, restlessness, headache, giddiness, delirium and
convulsions) followed by CNS depression ( manifested by sedation, sleep and coma).
• Antidote is atropine.
• Irreversible anticholinesterase
• These are organic esters of phosphoric acid and produce powerful and irreversible
inhibition of acetylcholinesterases.
• Their pharmacological actions is due to acetylcholine.
• They differ from reversible inhibitors of acetylcholinesterase (quarternary
ammonium compounds) because;
• They have a high lipid solubility,
• They can be absorbed by all routes including intact skin, mucous membrane, and lungs.
• They can easily cross the BBB and produce CNS effects.
• They are inactivated mainly in the liver by oxidation and hydrolysis and breakdown products
are excreted in urine.
 Cholinergic/parasympathetic
drugs.
• The have limited clinical uses due to their prolonged action and high
toxicity. DFP and echothiopate are used as miotic drops in the treatment of
glaucoma. It’s adverse reactions include local eye irritation and headache.
• Other compounds are used as insecticides and pesticides.
• Organophosphorus compound poisoning.
• Acute poisoning may be occupational, accidental or suicidal due to
ingestion or inhalation or through contact.
• It is manifested as;
• Muscarinic effects-
• Localized exposure of eyes to the compound causes irritation of producing miosis,
spasm of accommodation and headache.
• Inhalation of the compound produces bronchospasm, increased tracheobronchial
secretion, cough, pulmonary edema and sense of chest tightness.
• Ingestion of the compound produces anorexia, nausea, vomiting, intestinal
cramps, diarrhea, excessive salivation, lacrimation, tracheobronchial secretions,
sweating, constricted pupils, involuntary defecation, and micturition, hypotension,
bradycardia, or reflex tachycardia, cardiac arrhythmias, cardiovascular collapse
and respiratory failure.
 Cholinergic/parasympathetic
drugs.
• Nicotinic effects. These are twitchings and fasciculations of muscles, generalized muscular
weakness and a spastic type of paralysis of muscles including respiratory muscles.
• CNS effects- excitement, restlessness, anxiety, confusions, giddiness, insomnia, ataxia, loss of
reflexes, respiratory depression, convulsions and coma.
• Treatment
• Decontamination measures to stop further exposures to the poison, the patient is
removed from the site of exposure of the poison and placed in fresh air. Soiled
clothes are removed and soiled skin, mouth and eyes are washed with clean water.
Gastric lavage is done to remove poison from the stomach.
• Supportive measures. To maintain respiration, oxygen inhalation, and in severe cases
artificial respiration.
• To maintain BP and to prevent circulatory failure (shock), intravenous fluids and
vasoconstrictors like noradrenaline or dopamine, are administered.
• Diazepam for convulsions prevention.
• Specific measures.
• This is to counteract/reverse adverse effects with specific antidotes which include;
• Anticholinergic drugs like atropine is used to counteract muscarinic and CNS effects
of these compounds.
 Cholinergic/parasympathetic
drugs.
• Cholinesterase reactivators (Oximes) like pralidoxime is used to conteract
nicotinic effects especially at neuromuscular junctions where atropine is
ineffective.
• Organophosphorus inactivate cholinesterase by phosphorylation of the
esteretic site of the enzyme. Oximes combine with the phosphoryl group of
the phosphorylated cholinesterase by a site directed nucleophilic attack and
dephosphorylate the enzyme.
• This results in setting free of the phosphoryl group from the esteretic site
and a reactivation of the enzyme. With the reactivation of cholinesterase,
the intensified effects of acetylcholine begins to disappear.
• The treatment with oximes must be done within a short time(6 hrs.) after
poisoning, because the phosphorylated cholinesterase undergoes aging
process i.e. changes to a stable complex form (by covalent form) which
cannot be reversed. So late administration is useless.
• Oximes can produce local irritation, drowsiness, giddiness, blurring of vision,
diplopia, tachycardia, hypotension. In high doses, they can themselves cause
neuromuscular blockade and skeletal muscle paralysis.
 Anticholinergic/
parasympatholytic drugs.
• These drugs antagonize(block) the actions acetylcholine on muscarinic
receptors at different sites. They are also called antimuscarinic drugs.
• They are competitive and equilibrium or reversible antagonists of
acetylcholine at muscarinic receptor sites.
• Classification- are of three groups;
• Natural drugs e.g. belladonna alkaloids like atropine and
scopolamine(hyoscine).
• Semisynthetic atropine/scopolamine derivatives e.g. atropine methonitrae,
homatropine hydrobromide(produces mydriasis and cycloplegia).
• Synthetic atropine substitutes;
• Used as mydriatics and cycloplegics in eye e.g. cyclopentolate, tropicamide and
dibutloine (produce mydriasis and cycloplegia)
• Used as antispasmodics and antisecretory drugs e.g. ipratropium,
• Besides these drugs, some other drugs also possess atropine like
anticholinergic activity;
 Anticholinergic/
parasympatholytic drugs.
• Phenothiazine's like chlorpromazine and thioridazine.
• Tricyclic antidepressants like imipramine and amitriptyline.
• Antiarrhythmic line quinidine and disopyramide.
• Narcotic analgesics like pethidine and fentanyl.
• Antihistaminic like promethazine and diphenylhydramine.
• Belladona alkaloids( atropine & scopolamine).
• They are readily absorbed from GIT following oral administration and also absorbed
from mucous membranes like conjunctiva. They are widely distributed in the body
after absorption. They can cause the BBB and placental barrier. They are secreted in
milk and saliva.
• Although they are esters they are not hydrolyzed by cholinesterase. 50% plasma
protein bound. They are metabolized in the liver (50%) & excreted as glucuronides
while the rest is excreted unchanged in urine.
• They have a plasma half life of 4-12 hrs. but their effects in eye persists for 3-7 days.
• Pharmacological actions.
• The effects of both atropine and scopolamine are qualitatively similar except;
 Anticholinergic/
parasympatholytic drugs.
• Atropine is a CNS stimulant while scopolamine is CNS depressant producing sedation.
• Atropine has more prominent on the heart, GIT and bronchial smooth muscle while
scopolamine has more prominent effects on the iris, ciliary body, and salivary, bronchial and
sweat secretions.
• These the following effects;
• Exocrine secretions.
• They reduce secretions of all exocrine glands except milk secretion by mammary glands
producing dryness of the mouth(xerostomia), dryness of the conjunctiva, dryness of the
respiratory tract and dry & hot skin. They inhibit gastric secretion( gastric HCI, pepsin
and mucus secretion and volume of gastric juice) which is more marked if induced by
cholinergic drugs. They do not inhibit gastric secretion induced by histamine, caffeine,
nicotine or alcohol.
• They have insignificant effects on intestinal, pancreatic and biliary secretions, which are
controlled non cholinergic neurons & local hormones(secretin, pancreozymin and
cholecystokinin).
• Non vascular smooth muscle.
• They produce mydriasis(dilatation of pupil) and cycloplegia (paralysis of visual
accommodation), both through blocking muscarinic receptors M3. Midriasis is due to
paralysis of circular muscle of the iris(sphincter pupillae) causing its relaxation and thus
leading to unopposed sympathetic activity of the radial muscle of the iris(dilator
pupillae) causing its contraction. Cycloplegia is due to paralysis of cillary muscle leading
to flattening of the lens and the eye is accommodated for distant vision.
 Anticholinergic/
parasympatholytic drugs.
• In the GIT, they decrease both tone and motility of all parts of GIT resulting in
prolongation of gastric emptying time, closure of sphincters, and reduced intestinal
movements. They can cause constipation and completely abolish the excessive
motility produced by cholinergic drugs.
• Biliary tract- They have a mild antispasmodic act on the biliary tract and the
gallbladder.
• Respiratory tract- cause bronchodilatation by relaxing smooth muscle of bronchi
and bronchioles. Are particularly effective in relieving bronchoconstriction produced
by cholinergic drugs. They reduce airway resistance in asthmatics but are not useful
in bronchial asthma, where other spasmogens like histamine, leukotrienes,
bradykinins, prostaglandins are involved besides acetylcholine. Moreover they
cause drying of bronchial secretions leading to accumulation of thick viscid and
tenacious sputum in bronchial tree which is difficult to expectorate.
• Urinary tract-Have antispasmodic action on urinary tract reducing ureteral
peristalsis. They relax detrusor muscles of the urinary but contract trigonal
sphincter and may cause urinary retention especially in elderly patients with benign
prostatic hypertrophy.
 Anticholinergic/
parasympatholytic drugs.
• Cardiovascular effects.
• They cause transient bradycardia(decrease in heart rate) due to their partial
agonist action at acetylcholine receptors or stimulation of the medullary vagal
centers.
• This effect is followed by tachycardia(increase in heart rate) due to blocking of
inhibitory effects of vagus nerve on the heart by blocking muscarinic M2
receptors.
• They antagonize the effects of cholinergic drugs on the heart but have
insignificant effects on peripheral blood vessels and BP. Even at high doses, BP
and cardiac output are not altered because compensatory hemodynamic
mechanism.
• They also completely antagonize(reverse) peripheral vasodilation and fall of BP
produced by cholinergic drugs.
• CNS effects.
• They interfere with muscarinic cholinergic transmission in the brain resulting in
mild sedation, dysphoria or severe toxic psychoses depending on the dose.
 Anticholinergic/
parasympatholytic drugs.
• In therapeutic doses, atropine causes mild CNS stimulation while scopolamine
produces CNS depression leading to sedation.
• Atropine in moderate doses controls tremors and rigidity in parkinsonism and high
doses produces restlessness, excitement, disorientation, irritability hallucinations and
delirium.
• Scopolamine in therapeutic doses produces depression of reticular activating system
causing sedation, euphoria, drowsiness, amnesia and dreamless sleep with a reduction
in REM sleep.
• It relieves motion sickness by blocking muscarinic receptors (M1) in the motor cortex
and vesicular apparatus of internal ear.
• Clinical uses.
• Ocular uses
• Locally as eye drops/ointment to produce mydriasis and cycloplegia for funduscopic
examination of the eye and to measure refractive error of eye lens for fitting of glasses.
• In the treatment of acute iritis, iridocyclitis and keratitis to relieve pain in this
conditions by relaxing the inflamed muscles of iris and ciliary body.
 Anticholinergic/
parasympatholytic drugs.
• For prevention of anterior or posterior synechia alternating with miotic
drops/ointment to break adhesions between the iris and the lens or the cornea(due
to inflammation and exudation of iris in iritis.
• Gastrointestinal uses.
• Used as spasmolytics to control hypermobility and colicky pain associated with
diarrhea, and dysenteries.
• They may relieve constipation due to spastic state of the bowel induced by
morphine and lead.
• Previously used in the treatment of peptic ulcer disease for their antisecretory and
antispasmodic effects but nowadays H2 blockers and PPIs are preferred due to less
side effects and better acceptance by patients.
• Cardiac uses.
• Useful in abolishing A-V block due to excessive vagal activity e.g. Brady arrhythmias
following myocardial infarction, cerebral strokes or head injuries, or induced by
cholinergic agonists like succinylcholine and general anesthetics like ether.
• Used in digitalis toxicity to control bradyarrhytmias.
 Anticholinergic/
parasympatholytic drugs.
• Also used to counteract syncope and bradycardia in partial heart block (Stokes-Adams
syndrome) due to hypersensitive carotid sinus.
• Atropine is more active in accelerating heart rate (thereby preventing bradycardia) whereas
scopolamine (which may slow the heart rate) is preferred when tachycardia must be avoided as
in pts with mitral stenosis.
• Anesthetic uses.
• Used as preanesthetic medications to reduce stimulation of salivary and tracheobronchial
secretions caused by inhalation of anesthetics like ether and by neuromuscular blocker
succinylcholine.
• In addition, they prevent bradycardia, hypotension and even cardiac arrest that may result from
anesthesia or surgical procedures.
• Other uses
• In mushroom poisoning due to muscarine, it is also used in poisoning due to cholinergic
agonists, organophosphate poisoning and other anticholinesterases.
• Contraindications.
• Narrow angle glaucoma (can precipitate acute attack of congestive glaucoma).
• Enlarged prostate (can precipitate acute urine retention due to closure of trigonal sphincter.)
• Bronchial asthma & COPD (they aggravate these conditions by drying and reducing