DRUGS THAT ACT ON ACETYLCHOLINE RECEPTORS

Muscarinic agonists
(parasympathomimetic)
Direct-acting
Muscarinic antagonists
Muscarinic (parasympatholytic)

Indirect-acting Anticholinesterases

Nicotinic (nicotine)
agonists
Ganglion-acting

Nicotinic Ganglion blockers

Neuromuscular
blockers
 MUSCARINIC AGONISTS
Agonist Structure Selectivity Hydrolysis
CH3
O
Ach +
N CH3 Muscarinic, Very rapid
H3 C O nicotinic
CH3
CH3
O
Carbachol + Muscarinic, No
N CH3 nicotinic
H2 N O
CH3

CH3
O CH3
Methacholine + Muscarinic rapid
N CH3
H3 C O
CH3
 MUSCARINIC AGONISTS (cont’d)

Agonist Structure Selectivity Hydrolysis

CH3
Bethanechol O CH3 Muscarinic No
+
N CH3
H2 N O
CH3

Pilocarpine CH3 Muscarinic No

H3 C N
O O N
 CLINICAL USES OF MUSCARINIC
AGONISTS
 Paralytic ileus (Bethanechol)
 Urinary retention (Bethanechol)
 Miotic in cataract surgery (Ach)
 Testing for bronchial hyperreactivity
(Methacholine)
 Glaucoma (Pilocarpine, carbachol)
THE EYE
 The eye

Canal of Iris
Schlem

Lens

Trabecular Ciliary Muscle

meshwork
 Side Effects of Muscarinic Agonists

a. Hypotension (vasodilation, via NO) and

reflex tachycardia (overrides bradycardia)

b. Bronchospasm (no significance in normals

but may precipitate asthma in asthmatics).

c. Others (nausea & vomiting, GIT cramps and

diarrhoea).
 Contra-Indications of Muscarinic Agonists

a. Coronary insufficiency (worsened by

hypotension).

b. Hyperthyroidism (may precipitate atrial

arrhythmias).
c. Peptic ulcer
d. Asthma
MUSCARINIC ANTAGONISTS
 SOME IMPORTANT MUSCARINIC
ANTAGONISTS
 Atropine, an alkaloid found in
Deadly Nightshade (Atropa belladonna)

 Hyoscine (scopolamine) -another plant product

 Homatropine - a synthetic analogue of
atropine with briefer action
 Pirenzepine - a member with selectivity for
M1 subclass
 Ipratropium - quarternary nitrogen compound
PHARMACOLOGICAL ACTIONS OF
MUSCARINIC ANTAGONISTS

Peripheral
 Blocks secretions (saliva, bronchial, GIT, etc.)
 Dilates pupil (mydriasis)

 Tachycardia (block of vagal influence)

 Blocks GIT motility (constipation)

 Relaxes bronchial smooth muscles

CNS
 Atropine has no effect at low dose
(excitation at high dose)

 Hyoscine depressant at therapeutic dose

(sedation, drowsiness, amnesia)

 Antiemetic (Hyoscine)
 CLINICAL USES OF MUSCARINIC
ANTAGONISTS

1. In surgery: as pre-anaesthetic to inhibit

salivary and bronchial secretions (atropine,
hyoscine)

2. As mydriatic to dilate pupil and paralyse

lens for eye examination and treatment,
(short lasting homatropine; long-lasting
atropine).
3. In the treatment of anticholinesterase
poisoning (atropine)

4. Treatment of Motion sickness (hyoscine)

5. Treatment of peptic ulcer (pirenzepine)

6. Treatment of GIT cramps (atropine, hyoscine)

7. Treatment of asthma and chronic bronchitis
(ipratropium)

8. Treatment of Parkinson's disease

(atropine, benzatropine)

9. Treatment of sinus bradycardia after MI

(atropine)
 SIDE EFFECTS OF MUSCARINIC
ANTAGONISTS
 Dry mouth and skin

 Blurring of vision
 Tachycardia
 Skin blush and increased body temperature
(poisoning)
 Behavioural disturbances (poisoning)
 Glaucoma in pre-disposed
 DRUGS ACTING ON
AUTONOMIC GANGLIA
 GANGLION STIMULANTS

NICOTINE

 Major Constituent of tobacco

 In low doses stimulates all ganglia

 In high doses blocks all ganglia

STIMULANT EFFECTS OF LOW DOSE
NICOTINE ON AUTONOMIC GANGLIA

• Rise in blood pressure

• Tachycardia
(bradycardia overridden by release of Adrenaline)

• Increase in GIT motility

• Release of antidiuretic hormone

 GANGLION BLOCKING DRUGS

 Hexamethonium (now of historical interest)

 Trimetaphan (only clinically used member)

 ACTIONS OF GANGLION BLOCKERS

 Cardiovascular system
Fall in blood pressure & loss of cardiovascular reflex (sy(mpath

 Gastrointestinal tract:
Inhibition of motility and secretions (constipation)((parasymp

Genitourinary system:
Impairment of micturition, failure of erection (parasymp)
Failure of ejaculation (sympath)
Eye:
Loss of accommodation/blurred vision, loss of pupillar
reflex/photophobia (parasymp)
 Uses of Ganglion Blockers

Originally used to treat hypertension-

but no longer in use
OnlyTrimethaphan is occassionally used-
for controlled hypotension during surgery
 LEARNING OBJECTIVES

Describe the clinical uses of muscarinic agonists and antagonists .1

pointing out any pharmacodynamic and the pharmacokinetic factors
.that govern the choice of drugs

.List the adverse effects and contra-indications of muscarinic agonists .2

Explain the mechanism of hypotensive action of intravenous .3

.muscarinic agonists

Understand glaucoma and how muscarinic agonists work in .4

.its treatment

Compare and contrast the actions and clinical uses of atropine and .5
.hyoscine

.Know why muscarinic antagonists are contra-indicated in glaucoma .5

.List the consequences of ganglionic blockade .6

PHARMACOLOGICAL ACTIONS OF
MUSCARINIC ANTAGONISTS

 Dilation of pupil (mydriasis)

 Inhibition of secretions
 Increase in heart rate
 Inhibition of GIT motility
 Bronchodilation
MUSCARINIC ANTAGONISTS
(PROTOTYPE DRUGS)