Cholinergic antagonists

Cholinergic antagonists are divided in two

subgroups on the basis of their specific
receptor affinities:
● Muscarinic antagonists (i.e. antimuscarinic
drugs).
The most useful of these agents selectively
block the muscarinic synapses of the parasympathetic
nerves. The effects of parasympathetic innervations
are thus interrupted, and the actions of sympathetic
stimulation are left unopposed.

● Nicotinic antagonists (i.e. ganglion-blocker

and neuromuscular junction blocker).
Antimuscarinic
agents
Antimuscarinic agents (atropine, scopolamine,
ipratropium) block muscarinic receptors
causing inhibition of all muscarinic functions.
In addition, these drugs block the few
exceptional sympathetic neurons that are
cholinergic, such as those innervating sweat
glands.

Atropine
a. Atropine
Atropine, a belladonna alkaloid, has a high
affinity for muscarinic receptors, where it
binds competitively, preventing acetylcholine
from binding to that site.
Atropine is both a central and peripheral
muscarinic blocker.
Its general actions last about 4 hours except
when placed topically in the eye, where the
action may last for days.
Mechanism of action
Atropine causes reversible blockade of
cholinomimetic actions at muscarinic
receptors- i.e., blockade by a small dose of
atropine can be overcome by a larger
concentration of acetylcholine or equivalent
muscarinic agonist.
Atropine is highly selective for muscarinic
receptors. Its potency at nicotinic receptors is
much lower, and actions at non-muscarinic
receptors are generally undetectable
clinically.
Ocular effects
Atropine blocks all cholinergic activity on the
eye, resulting:
Mydriasis: Dilation of the pupil
Photophobia: Intolerance of light
Cycloplegia: Inability to focus for near vision

In patients with glaucoma, intraocular pressure may

rise dangerously which is not significant in normal
individuals.
Therapeutic uses: In the eye, topical
atropine exerts both mydriatic & cycloplegic
effects and permits the measurement of
Atropine is isolated from the plant Atropa
belladonna. ‘Bella donna’ means ‘beautiful
woman’. In the old days, in Italy atropine was
used by young women to augment their looks
before attending festivities. It widens the
pupils of the eyes, and it prevents sweating,
therefore leading to accumulation of heat and
to red cheeks.
At higher dosages, it also causes
hallucinations, which may or may not be
helpful with falling in love.
Smooth muscle
Relaxation of all smooth muscle:
GIT: reduction of tone and peristalsis.
Therefore, gastric emptying time is prolonged,
and intestinal transit time is lengthened.
(produce constipation)
Lungs: relaxation of bronchial smooth muscle
but not as β-adrenoreceptor agonist.
Bladder: reduce hypermotility states of the
Therapeutic
urinary bladderuses: Atropine is used as an
antispasmodic agent to relax the
gastrointestinal tract and bladder.
Exocrine glands
Salivary: Decrease salivation significantly (dry
mouth).
Gastric: Gastric secretion is blocked less
effectively: the volume and amount of acid,
pepsin, and mucin are all reduced, but large
doses of atropine may be required.
Pirenzepine and a more potent analog,
telenzepine, reduce gastric acid secretion with
fewer adverse effects than atropine and other
less selective agents.
Sweat: Decrease sweating. In adults, body
temperature is elevated by this effect only if
large doses are administered, but in infants
and children even ordinary doses may cause
“atropine fever”.
Bronchial: Decrease bronchial secretion.
Antimuscarinic drugs are frequently used prior
to administration of inhalant anesthetics to
reduce the accumulation of secretions in the
trachea and the possibility of laryngospasm.
Therapeutic uses: Antisecretory agent: The
drug is sometimes used as an antisecretory
agent to block secretions in the upper and
lower respiratory tracts prior to surgery.
Cardiovascular
effect
Atropine produces divergent effects on the
cardiovascular system, depending on the
dose.
At low doses the predominant effect is a
decreased cardiac rate (bradycardia).
Originally thought to be due to central
activation of vagal efferent outflow.
[Parasympathetic innervation of the heart is mediated
by the vagus nerve]

With higher doses of atropine, the cardiac

receptors on the SA node are blocked, and the
Antidote for cholinergic
agonists
Atropine blocks the effects of excess
acetylcholine that results from inhibition of
acetylcholinesterase by drugs such as
physostigmine.
Massive doses of antagonists may be required
over a long period of time to counteract the
excess acetylcholine.
Adverse effects:
Depending on the dose, atropine may cause
dry mouth, blurred vision, "sandy eyes",
tachycardia, and constipation.
Effects on the CNS include restlessness,
confusion, hallucinations, and delirium, which
may progress to depression, collapse of the
circulatory and respiratory systems and death.
In older individuals, the use of atropine to
induce mydriasis and cycloplegia is
considered too risky since it may exacerbate
an attack of glaucoma in someone with a
b.
Scopolamine
Scopolamine is another belladonna alkaloid,
produces peripheral effects similar to those of
atropine. However, scopolamine has greater
action on the CNS and a longer duration of
action in comparison to those of atropine.
Scopolamine also has the unusual effect of
blocking short-term memory.
Actions: Scopolamine is one of the most
effective anti-motion sickness drugs available.
In contrast to atropine, scopolamine produces
sedation, but at higher doses can instead
Therapeutic action: Though similar to
atropine, its therapeutic use is limited to
prevention of motion sickness and blocking of
short-term memory.
c. Ipratropium
Inhaled ipratropium, a quaternary derivative
of atropine, is useful in treating asthma and
chronic obstructive pulmonary disease in
patients unable to take adrenergic agonists.
Ipratropium is also used in the management
of chronic obstructive pulmonary disease.

Atropin Ipratropiu
The hallucinations are, obviously, caused by
atropine entering the central nervous system.
The central effects are lessened by
derivatization of the tertiary amine found in
atropine to a quaternary amine, as in
ipratropium. Because of its permanent charge,
ipratropium does not easily cross the blood
brain barrier by ‘non-ionic diffusion’, and it is
therefore often preferred over atropine in
clinical medicine.