ANTICHOLINERGIC

DRUGS

Dr. Muhammad Adil Rasheed

Associate Professor

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• They can be defined as drugs which block action of
neurotransmitter acetylcholine at all effector sites
innervated by cholinergic nerves in central and/or
peripheral nervous systems.

ANTI-MUSCARINIC AGENTS

• The anti-muscarinic agents are highly selective for

muscarinic receptors over nicotinic receptors and block
action of acetylcholine on muscarinic receptors.

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 CLASSIFICATION
Depending on the sources, chemical structures and therapeutic
uses, the anti-muscarinic drugs have been divided into:
I.NON-SELECTIVE MUSCARINIC RECEPTOR ANTAGONISTS /NON-
SELECTIVE ANTIMUSCARINIC DRUGS
1. Natural alkaloids e.g. atropine, hyoscine.
2. Semi-synthetic and synthetic anti-muscarinic drugs
A. Mydriatic-cycloplegic antimuscarinic agents e.g. tropicamide,
cyclopendolate.
B. Antisecretory-antispasmodic anti-muscarinic
a.Quaternary ammonium compounds e.g. propantheline,
isopropamide.
b.Tertiary amines e.g. oxybutynin, dicycloverine.
C. Antiparkonsonian antimuscarinic agents e.g. trihexyphenidyl,
benzatropine.

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II. SELECTIVE MUSCARINIC RECEPTOR ANTAGONISTS/
SELECTIVE ANTIMUSCARINIC DRUGS

1. Selective M1-muscarinic receptor antagonists e.g.

pirenzepine and telenzepine.
2. Selective M2-muscarnic receptor antagonists e.g.
tripitramine and methoctramine.
3. Selective M3-muscarinic receptor antagonists e.g.
darifenacin and solifenacin.

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 I. NON-SELECTIVE MUSCARINIC RECEPTOR
ANTAGONISTS
1. Natural Alkaloids / Natural Antimuscarinics
• Two natural anti-muscarinic alkaloids in clinical use
are atropine and hyoscine (scopolamine).

• Atropine is a prototype of muscarinic receptor

antagonists because actions and effects of most
clinically available muscarinic receptor antagonists
differ only quantitatively from those of atropine.

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 ATROPINE
• Atropine is a tropane
alkaloid obtained
naturally from Atropa
belladonna (deadly night
shade) and other plants.

• Atropine is obtained from

the plants along with
other active alkaloids such
as hyoscyamine and
hyoscine.
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 MECHANISM OF ACTION
• Atropine and related anti-muscarinic compounds
are competitive antagonists of acetylcholine.

• High doses of atropine may also block nicotinic

receptors at the autonomic ganglia and at the
neuromuscular junction.
• The binding action of atropine at the muscarinic
receptor is reversible as its action can be overcomed
by increasing the concentration of acetylcholine.

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 PHARMACOLOGICAL EFFECTS
• Non-selective antagonist of all muscarinic
receptor sites causing inhibition of all muscarinic
functions.
• The pharmacological effects are generally dose-
related i.e.
• Salivary and sweat glands are quite susceptible to
small dose of atropine
• Pupil and heart are stimulated at modest systemic
dose
• GI and urinary tract require high doses and inhibition
of GI secretions need very high doses.
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 PHARMACOLOGICAL EFFECTS
• HEART: Dose dependent effects. At low doses it produces
bradycardia and at high doses causes tachycardia.
• SMOOTH MUSCLES: All non-vascular smooth muscles
become relaxed by atropine mainly due to blockade of
M3 receptor subtype.
• GIT: Causes relaxation of GI smooth muscles by inhibiting
contractile responses to endogenous ACh.
• It reduces tone and motility of gut resulting in
prolongation of gastric emptying time, closure of
sphincters, and decrease in tone, amplitude and
frequency of peristaltic movements.
• Enhanced motility due to exogenous cholinergic drugs is
more completely antagonized by atropine.

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• RESPIRATORY SYSTEM: Relaxation of bronchiolar
smooth muscles. Single dose of atropine induces
bronchodilation within 15 min.
• URINARY TRACT: Cause relaxation of ureter and
urinary bladder. The tone of ureter is reduced, which
is useful in the treatment of ureteric colic.
• EYE: Cause mydriasis in mammals by blocking
contraction of the circular pupillary sphincter muscle.
• EXOCRINE GLANDS: Atropine markedly decreases
sweat, salivary, tracheobronchial and lachrymal
secretions.
• Eyes become dry.
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• CENTRAL NERVOUS SYSTEM: In larger doses,
atropine stimulates CNS. Very high doses may
produce excitement in domestic animals, followed by
depression and coma.

• OTHER EFFECTS: Atropine in high doses may cause

rise in body temperature in some species (e.g.
humans) due to both inhibition of sweating as well as
stimulation of temperature regulating center in the
hypothalamus.
• It has mild local anesthetic action on the sensory
nerves.

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 SIDE EFFECTS
• May cause dry mouth, dysphagia, constipation,
increased thrust, mydriasis, tachycardia, restlessness
and urine retention.
• Because of the dry mouth, atropine may cause some
animals to drink excess water.
• CNS effects may include stimulation, seizures,
respiratory depression, coma and death.
• Ophthalmic effects include blurred vision, pupil
dilation, and photophobia.

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 2. SEMI-SYNTHETIC AND SYNTHETIC
ANTIMUSCARINIC
• The natural alkaloids have been used for a wide
range of clinical conditions as anti-muscarinic agents,
but they suffer from several shortcomings like lack of
selectivity, long duration of action, and potential
adverse effects and toxicity.

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A. Mydriatic-Cycloplegic Antimuscarinic Agents
• This group of semi-synthetic or synthetic anti-
muscarinic drugs are used topically by instillation
into conjunctival sack to produce mydriasis and/or
cycloplegia.
• Unlike, belladonna alkaloids (atropine and hyoscine),
they have short duration of action and are devoid of
systemic effects when administered topically.
• These drugs, particularly synthetic mydriatics, can
also be used in cases of intolerance to atropine.

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 TROPICAMIDE
• Synthetic anti-muscarinic agent primarily used in eye.

• Similar to atropine, produces mydriasis and cycloplegia.

• It has rapid onset (20-40 minutes) and brief duration (6-

12 hours) of action in most animals. Therefore it is more
commonly used for eye examination.

• Tropicamide is often preferred to atropine as a mydriatic

because of its shorter half-life.

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 CYCLOPENTOLATE

• Synthetic anti-muscarinic agent with actions similar

to those of atropine.

• It is a potent and rapidly acting (30-60 minutes)

cycloplegic and mydriatic agent.

• It is used as 0.5% or 1 % ophthalmic solution.

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