Cholinergic Antagonists

CHOLINERGIC ANTAGONISTS
• Drugs that block the activation of muscarinic/ nicotinic receptors.
• Divided into 3 groups:
1. Antimuscarinic drugs
2. Ganglionic blocker
3. Neuromuscular blocker

1. ANTI- • used predominantly to inhibit effects of parasympathetic activity in the

MUSCARINIC respiratory tract, urinary tract, GI tract, eye, and heart, lacrimal & salivary
DRUGS glands.
• Main drugs that you have to remember: Atropine, scopolamine &
ipratropium.
• Remember that the effect of these antagonists should antagonise the
muscarinic activation!
Relaxation of ciliary muscle

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Naturally, an ANTAGONIST will have a ‘reversal’ effects (the physiological

effects will be the opposite) OPPOSITE to the Mnemonics for muscarinic
receptors: SLUDGE-M (salivation, lacrimation, urination, defecation, GI
motility, emesis, and miosis) or Cholinergic (muscarinic activation)

Atropine • Isolated from Belladonna sp.

(alkaloid compound)
• Competitively compete with
ACh for the ACh site on the
muscarinic receptor, abolishing
the parasympathetic effect.
• Does not distinguish the
subtype of muscarinic receptor
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 Cholinergic Antagonists
(non-selective).

Pharmacological effects of atropine 1. Increase heart rate, results in

tachycardia by blocking the M2
receptor, thereby antagonizing
parasympathetic tone to the heart.
Clinically indicated in
bradycardia & MI patients.
2. Inhibit the
bronchoconstriction caused by
histamine, bradykinin, and the
eicosanoids. Administration is
useful in the treatment of asthma.
3. Inhibits the secretions of the
airways. Decrease rhinorrhea
(“runny nose”) associated with
the common cold or with allergic
and nonallergic rhinitis.
4. Inhibits the gut motility and
partially inhibits the gastric acid
secretory responses.
5. Inhibits the activity of sweat
glands innervated by sympathetic
cholinergic fibers, and the skin
becomes hot and dry. Sweating
may be depressed enough to raise
the body temperature, but only
notably so after large doses or at
high environmental temperatures.
6. Reduces excessive salivation,
such as drug-induced salivation
and that associated with heavy-
metal poisoning and Parkinson
disease.
7. Antidote for
anticholinesterase poisoning
(organophosphates,
pyridostigmine or other
anticholinesterases
administered in the treatment of
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myasthenia gravis - most useful
early in therapy, before tolerance
to muscarinic side effects of
anticholinesterases has
developed.
Ipratropium • used for COPD treatment &
asthma.
• block all subtypes of
muscarinic receptors and
antagonizes the inhibition of
ACh release by presynaptic M2
receptors on parasympathetic
postganglionic nerve terminals in
the lung.
• approved by the FDA for use in
nasal inhalers for the treatment of
the rhinorrhoea (common cold or
with allergic/nonallergic
perennial rhinitis).
Only for symptomatic relief (does
not affect the natural course of
the
condition).
• Other drugs: tiotropium,
aclidinium, and umeclidinium
Other muscarinic antagonists and their • Overactive bladder- e.g
uses oxybutynin, tolterodine,
trospium chloride, darifenacin.
• GI tract, as treatment and
prevention of gastric ulcers
• Pirenzepine displays a limited
degree of selectivity for M1
receptors. Central effects are not
seen because of the drug’s limited
penetration into the CNS.
• Telenzepine, an analogue of
pirenzepine, has higher potency
and similar selectivity for M1
receptors. Most studies indicate
that pirenzepine is as effective as
the H2 receptor antagonists
(cimetidine or ranitidine ) in
treating and preventing
recurrence of gastric ulcers.
• Glycopyrrolate is used to
reduce GI tone and motility,
which is less likely to cause
adverse CNS effects than
atropine, scopolamine, and other
tertiary amines.
• Diarrhea associated with
irritation of the lower bowel, such
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as mild dysenteries and
diverticulitis, may respond to
atropine-like drugs, an effect that
likely involves actions on ion
transport as well as motility.
However, muscarinic antagonist
is ineffective in more severe
conditions such as Salmonella
dysentery, ulcerative colitis, and
Crohn disease
• Reduce drooling(e.g., in
patients with Parkinson disease)
• Glycopyrrolate is indicated and
is less likely to penetrate the
CNS.
• Produce mydriasis
• Homatropine hydrobromide,
a semisynthetic derivative of
atropine, cyclopentolate
hydrochloride, and tropicamide
are agents used
ophthalmologically. These agents
are preferred to topical atropine
or scopolamine because of their
shorter duration of action.
• Early stages of Parkinson
disease if tremor is predominant,
particularly in young patients-
Benztropine mesylate,
trihexyphenidyl hydrochloride,
and biperiden
• Relief of symptoms of allergic
rhinitis, sinusitis, and the
common cold. Methscopolamine
bromide –scopolamine
derivative, but lacks the central
action of scopolamine.
Scopolamine • Belladonna alkaloid-derived
compound, structurally similar to
atropine.
• Competitively inhibits
muscarinic receptors for
acetylcholine non-selectively,
producing both peripheral
antimuscarinic properties and
central sedative, antiemetic,
and amnestic effects.
• The vomiting center of the brain
is located in the medulla
oblongata and contains a high
amount of M1 muscarinic
acetylcholine, which is targeted
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by scopolamine.
• A transdermal preparation is
highly effective for the
prevention of motion sickness
(as a
prophylaxis)
• Meant for short (4- to 6-h)
exposures to severe motion and
probably for exposures of up to
several days.

2. GANGLIONIC • Chemical compounds that block synaptic transmission through the autonomic
BLOCKERS ganglia selectively.
• Reduced sympathetic outflow leads to decreased vascular tone, vasodilation,
reduced vascular resistance, thereby reduces arterial pressure.
• Nicotinic (NN) antagonist
• The inhibition of cholinergic activity at the level of autonomic ganglia can
block both sympathetic and parasympathetic activities.
• Example of drugs are mecamylamine (first antihypertensive agent),
trimethaphan (lower blood pressure during surgery), hexamethonium.

3. NMJ • Neuromuscular blockade inhibits NM receptors, causing skeletal muscles

BLOCKERS paralysis.
• Neuromuscular blockade is frequently used in anesthesia to facilitate
endotracheal intubation, optimize surgical conditions, and assist with
mechanical ventilation in patients who have reduced lung compliance.
• Neuromuscular blocking agents (NMBAs) come in two forms:
• depolarizing neuromuscular blocking agents (e.g., succinylcholine) act by
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persistent depolarization makes the muscle fiber resistant to further stimulation by
ACh.
• nondepolarizing neuromuscular blocking agents (e.g., tubocurarine,
rocuronium,
vecuronium, atracurium, cisatracurium, mivacurium)- competitive ACh
antagonists that bind directly to nicotinic receptors on the postsynaptic membrane,
blocking the binding of ACh so the motor endplate cannot depolarize, leading to
muscle paralysis.
Contraindications Anorexia
and Adverse Effects Blurry vision
Constipation/ Confusion/cognitive impairment
Dry Mouth/dyspepsia
Sedation/ Stasis of urine

• Contraindications: urinary tract obstruction, GI obstruction, and uncontrolled

(or susceptibility to attacks of) angle-closure glaucoma, benign prostatic
hyperplasia.
• These adverse effects and contraindications generally are of more limited
concern with muscarinic antagonists that are administered by inhalation or used
topically in ophthalmology.

KEY CONCEPTS
• Muscarinic activation & what is the opposite effects (that will points you to pharmacological effects/
adverse effects of the drug)
• Type of anti-muscarinics & clinical indications
• Ganglionic blocker- basic MOA, example of drugs, main clinical indication.
• NMJ blocker- basic MOA, example of drugs, main clinical indication.

~End😊

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