Peripheral neural transmission: cholinergic (muscarinic) transmission

Question 1

Acetylcholine

Answer 1

Non-selective muscarinic agonist

Only muscarinic agonist readily broken down by cholinesterases.

Question 2

Carbachol

Answer 2

Non-selective muscarinic agonist

Question 3

Muscarine

Answer 3

Non-selective muscarinic agonist

First isolated from fly agaric mushroom in 1869, no current use in UK.

Question 4

Methacholine

Answer 4

Non-selective muscarinic agonist

2 isomers. Neither hydrolysed by BuChE
(+) methacholine is a substrate for AChE, and also ~200x more potent than the (-) isomer at muscarinic receptors

Question 5

Bethanechol

Answer 5

Non-selective muscarinic agonist
Poorly absorbed from GI tract
Used systemically in bladder dysfunction.

Question 6

Pilocarpine

Answer 6

Non-selective muscarinic agonist
Poorly absorbed from GI tract.

Treatment of glaucoma:
Administered by instillation as eye drops, readily absorbed across conjunctival membrane.
Contracts ciliary muscle -> produces traction on the trabecular meshwork, opens Canal of Schlemm-> facilitates aqueous humour drainage, lowering intraocular pressure.

Question 7

Cevimeline

Answer 7

M3 selective agonist

Used to increase salivation & lacrimation in e.g dry mouth, Sjogren’s syndrome (AI disease of glands that secrete fluid)

Question 8

Atropine

Answer 8

Non-selective muscarinic antagonist
Produces dilatation of the pupils (mydriasis) for opthalmic examination/ cosmetic purposes.
Duration of action is v long, adrenoceptor agonists more suitable.

Question 9

Benzilylcholine mustard

Answer 9

Non-selective muscarinic irreversible antagonist.

Question 10

Pirenzepine

Answer 10

M1 selective antagonist

Had a wider use as an antisecretory agent in the treatment of gastroduodenal ulcers (was thought to act on intramural nerves serving the oxyntic cells)

Question 11

Darifenacin

Answer 11

Selective M3 antagonist
(M3 receptors mediate bladder constriction)
Treatment of urinary incontinence.

Question 12

Uses of muscarinic antagonists

Answer 12

Treatment of peptic ulcers until H2 histamine receptor blockers developed
Treatment of diarrhoea until opiate receptor agonist developed (effective in the enteric nervous system without significantly crossing BBB & acting centrally)

Used for premedication prior to anaesthesia.