Drugs Affecting Acetylcholine

Question 1

How is acetylcholine produced in the nerve terminal?

Answer 1

Choline is taken up into the nerve terminal by a transporter –> the enzyme choline acetyltransferase transfers the acetyl group from acetyl coenzyme A to the choline –> acetylcholine is formed.

Question 2

What type of receptor is the nicotinic acetylcholine receptor?

Answer 2

Ligand-gated ion channel

Question 3

What type of receptor is the muscarinic receptor?

Answer 3

G protein-coupled receptor

Question 4

What are the different subtypes of the muscarinic receptor?

Answer 4

M1 = ‘neural’ - found mainly on neurons
M2 = ‘cardiac’ - found mainly in the heart
M3 = ‘glandular/smooth muscle’ - stimulates glandular secretions and contraction of smooth muscle
M4 and M5 - are found mainly in the CNS but their function is poorly understood

Question 5

What are the effects of muscarinic agonists?

Answer 5

Muscarinic agonists affect:

(1) cardiovascular: decrease heart rate and decrease force of contraction of atria –> leads to decreased cardiac output; also cause vasodilation, which in combination with the decreased CO –> decreased blood pressure
(2) smooth muscle: increased GIT motility, bronchoconstriction, and contraction of the bladder
(3) eyes: cause contraction of the ciliary muscle and the constrictor pupillae –> contraction of the constrictor pupillae aids drainage of aqueous humour into the canal of Schlemm and decreased intraocular pressure

Question 6

What are the clinical uses of muscarinic agonists?

Answer 6

Pilocarpine eye drops –> treatment of glaucoma
Pilocarpine and cevimeline –> used to increase salivation and lacrimation to treat dry eyes and mouth in Sjogren’s syndrome
Bethanecol –> can be used to stimulate bladder emptying

Question 7

What are the effects of muscarinic antagonists?

Answer 7

CVS: tachycardia
Smooth muscle: inhibition of GIT motility, bronchodilation, relaxation of smooth muscle of biliary and urinary tracts
Secretion: inhibit salivation, lacrimation, bronchial secretions and sweating

Question 8

What is the action of varenicline?

Answer 8

Varenicline is an autonomic ganglia stimulant used to treat nicotine addiction.

Question 9

What are the two main MOA of NMJ blockers?

Answer 9

(1) competitive antagonist at the nicotinic acetylcholine receptor or
(2) activate the nicotinic receptor to cause persistent depolarisation

Question 10

What is the action of suxamethonium?

Answer 10

NMJ blocker - causes persistent depolarisation of the motor endplate