Cholinergic antagonists
“Anticholinergic drugs,
Parasympatholytics”
Lecture 3
Dr. Hiwa K. Saaed
College of Pharmacy/University of Sulaimani
2017-2018
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Cholinergic antagonists
Drugs that block cholinergic receptors (M or N), and prevent
the effects of Ach and other cholinergic agonists.
The actions of sympathetic stimulation are left unopposed.
They are classified to two subclasses:
1. Muscarinic (M1-M5) receptor antagonists: the most useful clinically.
atropine, cyclopentolate, Ipratropium, scopolamine, tropicamide.
2. Nicotinic receptor antagonists: further subdivided into 2 groups:
i. NMJ Blocking agents: inhibit the efferent impulses to skeletal
muscle via the (NM) receptor:
Atracurium, Cisatracurium, Doxacurium, Metocurine, mivacurium,
Pancuronium, Rocuronium, Scuccinylcholine, Tubocurarine, Vecuronium.
ii. Ganglionic Blocking agents: inhibit the nicotinic neuronal
receptor (NN) of both parasympathetic and sympathetic
ganglia: Mecamylamine, Nicotine.

Sites of action of cholinergic antagonists
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Muscarinic antagonists:
Atropine (prototype): is a tertiary amine belladonna alkaloid with
a high affinity for muscarinic receptors. acts both centrally and
peripherally. The greatest inhibitory effects are on bronchial tissue
and the secretion of sweat and saliva.
Scopolamine (hyoscine): Like atropine, this drug is a belladonna
alkaloid. But it has a longer duration of action and more potent
CNS effect Nonselective competitive blockade of muscarinic
receptors
Therapeutic uses: Prevention of motion sickness
Propantheline, Dicyclomine: Rx of peptic disease, hypermotility
Clidinium (Librax), isopropamide (stelabid), Mebeverine
(Duspataline)
Homatropine:Cyclopentolate, Tropicamide: mydriasis and
cycloplegia
Pirenzepine & telenzipine: Selective M1 blocker. Rx of Gastric
ulcer
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Muscarinic antagonists:
Darifenacin, fesoterodine, oxybutynin, solifenacin,
tolterodine, and trospium chloride: selective M3 blocker
Rx of urinary incontinence
Flavoxate: also indicated for overactive bladder
Benztropine and trihexyphenidyl: Rx of Parkinsonism
Ipratropium, Tiotropium: Rx of Asthma
*Imipramine a TCA with strong antimuscarinic actions,
has long been used to reduce incontinence in elderly
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Atropine (hyoscyamine) Mechanism of action:
Reversible, nonselective blockade of muscarinic receptors.
Pharmacokinetics
• Atropine as a tertiary amine, it is well absorbed from the
GIT and conjunctival membrane.
• It is excreted through both hepatic metabolism and renal
function.
• Atropine’s duration of action is ~ 4 hrs, except when it is
placed in the eye, where it usually lasts about 14 days
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Pharmacologic actions of atropine
CNS: at toxic doses can cause restlessness, hallucinations, and
delusions.
CVS: At low doses, atropine reduces heart rate through central
stimulation of the vagus nucleus.At high doses, atropine blocks
muscarinic receptors of the heart and thus induces tachycardia.
GIT: reduces salivary gland secretion and GI motility.
Pulmonary system: reduces bronchial secretions and stimulates
bronchodilation.
Urinary system: blocks muscarinic receptors in the bladder wall,
which results in bladder wall relaxation.
Eye: causes paralysis of the sphincter muscle of the iris and ciliary
muscle of the lens, resulting in mydriasis and cycloplegia
Sweat glands: Suppresses sweating, especially in children.
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Atropine effects in order of increasing dose
• Decreased secretions (Salivary,
bronchiolar, sweat)
• Mydriasis and cycloplegia
• Hyperthermia (vasodilation)
• Tachycardia
• Sedation
• Urinary retention and constipation
• Behavioral excitation
• and hallucinations
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Therapeutic uses of Muscarinic Blockers
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• Bradycardia
• Mydriasis and cycloplegia- beneficial when
a thorough fundus examination or an
accurate refraction is required.
NB: atropine contraindicated in a patients
who has narrow-angle glaucoma, because
this may result in acute crisis due to closure
of the canal of Schlemm
• GIT and bladder spasms:
• Organophosphate poisoning.

Adverse effects of atropine
• Dry mouth (dry as bone)
• Inhibition of sweating especially in young children (hot as a hare)
• Tachycardia and cuetaneous vasodilation (red as beet)
• Blurring of vision (blind as a bat)
• Hallucinations and delirium (mad as a hatter)
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Neuromuscular blocking agents
I. Nondepolarizing blocking agents (antagonists)
Tubocurarine (prototype), Pancuronium: longer duration of action,
Atracurium and Vecuronium
II. Depolarizing blocking agents (agonists):
Succinylcholine: 3-6 minutes if given as a single dose, Metabolized
by plasma cholinesterase
Mechanism of action:
At low dose: these drugs competitively block cholinergic transmission at
the nicotinic (Nm) receptors by preventing the binding of Ach to its
receptor.
Their action can be reversed with edrophonium or neostigmine ????
At high dose: block the ion channels of the end plate. This action can not be
reversed by CE inhibitors.
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I. Nondepolarizing NM blockers
• All NM junction blockers must be given I.V because oral
absorption is poor.
• Therapeutic use:
They are used as adjuvant drugs for anesthesia, they promote
muscle relaxation; the muscle of the eye and face are affected
first, whereas the respiratory muscles are affected last.
Sequence of Paralysis
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Fingers, orbit (small muscles) limbs Trunk
neck Intercostals Diaphragm
Recovery in Reverse

II. Depolarizing NM junction blockers Succinylcholine:
Mech. of action:
Phase I- opens the Na channels-membrane depolarization-
transient fasciculations. Flaccid paralysis will follow in a few
minutes
Phase II: the membrane partially repolarize. However, these
receptors are now desensitized to Ach, Thus preventing the
formation of further action potentials. In other words, is
now acting in a manner similar to tubocurarine.
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Therapeutic Use
As an adjuvant to GA to facilitate rapid intubation.
Orthopedic procedures for alignment of fractures.
In electroshock treatment of psychiatric disorders.

Drug Interaction
Cholinesterase inhibitors: can overcome the action of
nondepolarizing NM blockers
Halogenated hydrocarbon anesthetics: Drugs such as
halothane sensitize the NM junction to the effects of NM
blockers.
Aminoglycoside antibiotics: inhibit Ach release from
cholinergic nerves by competing with calcium ions.
(Synergistic)
Calcium-channel blockers: These agents may increase the Nm
block of tubocurarine and other competitive blockers as well
as depolarizing blockers.
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Adverse effects of NM blockers:
• Bronchoconstriction caused by histamine release
• Decreased tone and motility in GI tract
• Depolarizing agent can cause increased K+ efflux in patients
with burns, trauma, or denervation and lead to
hyperkalemia
• Hypotension
• Arrhythmias
• Apnea due to respiratory paralysis (check for
psudocholinesterase genetic polymorphism)
• Malignant hyperthermia (succinylcholine+halothane
especially);
Rx by dantroline. It blocks the release of Ca+2 from the sarcoplasmic
reticulum which subsequently reduces skeletal muscle contraction.
Q. Do NM junction blocking agents block autonomic ganglia as
well???
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Ganglionic blockers
Nicotine, Hexamethonium, Mecamylamine, Trimethaphan
Ganglionic blockers compete with Ach to bind with nicotine
receptors of both Parasympathetic and Sympathetic ganglia
Ganglionic blockers divided into two groups:
1. Drugs such as nicotine, which initially stimulate the
ganglia and then block them because of a persistent
depolarization
2. Drugs such as hexamethonium, mecamylamine, and
trimethaphan, which block ganglia without any prior
stimulation.
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Ganglionic blockers
The physiologic effects of ganglionic blockers can be predicted depending
on which division of the ANS exercises dominant control of the organ in
question:
• Heart: tachycardia results because the parasympathetic system is
normally dominant on the heart.
• Arterioles and veins: vasodilation, increased peripheral blood
(sympathetic normally dominant)
• Eye: cycloplegia, mydriasis (parasympathetic normally dominant)
• GIT: reduced motility; diminished gastric and pancreatic secretions
(parasympathetic normally dominant)
• Urinary system: urinary retention (parasympathetic normally
dominant)
• Sweat glands: reduced sweating (sympathetic normally dominant)
Therapeutic use: Because they lack the selectivity, the ganglionic blockers
very rarely used clinically. In the past, these drugs were used in
hypertensive emergencies.
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