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Drugs that block cholinergic
receptors (M and/or N).
The actions of sympathetic
stimulation are left
unopposed.
Cholinergic antagonists

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They are classified to two subclasses:
1. Muscarinic (M1-M5) receptor
antagonists: the most useful clinically.
2. Nicotinic receptor antagonists:
further subdivided to:
 NMJ Blocking agents: inhibit the efferent
impulses to skeletal muscle via the (NM)
receptor
 Ganglionic Blocking agents: inhibit the
nicotinic neuronal receptor (NN) of both
parasympathetic and sympathetic ganglia
Cholinergic antagonists

Sites of action of cholinergic antagonists
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Muscarinic antagonists:
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 Atropine (prototype): comes from the plant Atropa
belladonna and is known as a belladonna
alkaloid. Belladonna in Latin means pretty lady.
Inhibit all M functions.
 Scopolamine (hyoscine): Rx of motion sickness ;
natural occurring alkaloid
 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
 Oxybutinin: somewhat selective for M3 receptors

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 Trospium: nonselective comparable in efficacy
and SE with oxybutinin
 Darifenacin and Solifenacin: selective M3 blocker
 Tolterodine: selective M3 blocker Rx of urinary
incontinence
 Flavoxate: also indicated for overactive bladder
 Benztropine: Rx of Parkinsonism
 Ipratropium, Tiotropium: Rx of Asthma
 *Imipramine a TCA with strong antimuscarinic
actions, has long been used to reduce
incontinence in elderly
Muscarinic antagonists:

Atropine (hyoscyamine) Mechanism of
action:
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It causes reversible, nonselective blockade of
muscarinic receptors.
Therefore, High concentration of Ach or an equivalent
muscarinic agonists can be used to counteract the
effects of atropine

Pharmacologic actions of atropine
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 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

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 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.
Pharmacologic actions of atropine

Atropine effects in order of increasing dose
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 Decreased secretions (Salivary,
bronchiolar, sweat)
 Mydriasis and cycloplegia
 Hyperthermia (vasodilation)
 Tachycardia
 Sedation
 Urinary retention and constipation
 Behavioral excitation and
hallucinations

Therapeutic uses of atropine
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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.

Pharmacokinetics
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 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

Adverse effects
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 Dry mouth (dry as bone)
 Inhibition of sweating especially in young
children (hot as a hare)
 Tachycardia and coetaneous vasodilation
(red as beet)
 Blurring of vision (blind as a bat)
 Hallucinations and delirium (mad as a
hatter)
Urine retention

Scopolamine
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 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
 Adverse effects: similar to those
of atropine
Others:
Homatropine,
cyclopentolate &
Tropicamide: In
ophthalmology, they are
given topically for
mydriasis and
cycloplegia.
Pirenzepine:
a selective M1
muscarinic inhibitor, used
for treating gastric ulcers

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15

2. Neuromuscular blocking agents
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NM blockers
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I. Nondepolarizing blocking agents (antagonists)
1. Tubocurarine (prototype)
2. Pancuronium: longer duration of action
3. Atracurium
4. Vecuronium
II. Depolarizing blocking agents (agonists):
1. 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
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

I. Nondepolarizing NM blockers
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 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
IntercostalsDiaphragm
Recovery in Reverse

II. Depolarizing NM junction blockers
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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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1. As an adjuvant to GA to facilitate rapid
intubation.
2. Orthopedic procedures for alignment of
fractures.
3. In electroshock treatment of psychiatric
disorders.
Therapeutic Use

Drug Interaction
 Cholinesterase inhibitors: can overcome the action of
nondepolarizing neuromuscular blockers
 Halogenated hydrocarbon anesthetics: Drugs such as
halothane sensitize the neuromusclular junction to the
effects of neuromuscular blockers.
 Aminoglycoside antibiotics: inhibit Ach release from
cholinergic nerves by competing with calcium ions.
(Synergistic)
 Calcium-channel blockers: These agents may increase
the neuromuscular block of tubocurarine and other
competitive blockers as well as depolarizing blockers.
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Adverse effects of NM blockers:
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1. Bronchoconstriction caused by histamine release
2. Decreased tone and motility in GI tract
3. Depolarizing agents can cause increased K+ efflux in
patients with burns, trauma, or denervation and lead
to hyperkalemia
4. Hypotension
5. Arrhythmias
6. Apnea due to respiratory paralysis (check for
psudocholinesterase genetic polymorphism)
7. 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???

Classification of Blockers
Agent Pharmacological
Properties
Onset time
(min)
Duration
(min)
Elimination
Succinylcholine Ultra-short acting;
Depolarizing 1-1.5 6-8
Plasma
cholinesterase
D-tubocurarine Long duration;
Competitive 4-6 80-120
Renal and liver
Atracurium Intermediate duration;
Competitive 2-4 30-40
Plasma
cholinesterase
Mivacurium Short duration;
Competitive 2-4 12-18
Plasma
cholinesterase
Pancuronium Long duration;
Competitive 4-6 4-6
Renal and liver
Rocuronium Intermediate duration;
competitive 1-2 1-2
Renal and liver
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3. Ganglionic blockers
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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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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)
3. Ganglionic blockers

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 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)
3. Ganglionic blockers

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Therapeutic use
Because they lack the selectivity, the ganglionic
blockers very rarely used clinically.
In the past, these drugs were used in hypertensive
emergencies.
3. Ganglionic blockers