Lecture 25 : Pharmacology of Neuromuscular Junction

Question 1

How is ACh synthesised

Answer 1

Cholinacetyltransferase (CAT) catalyses reaction between acetyl-CoA and choline.

Question 2

What drug prevents ACh from entering vesicles

Answer 2

Vesamicol

Causes less ACh present everywhere coz its not in vesicles, so reduced cholnergic neurotransmission

Question 3

What drug blocks the choline transporter

Answer 3

Hemicholinium

Prevents reuptake of choline so there is a reduced concentration of substrate for ACh synthesis

Question 4

What blocks proteins involved in exocytosis of vesicles containing ACh? How to treat it pharmacologically? Immunologically?

Answer 4

Botulinum Toxin

Causes muscle paralysis -> Death

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Treated with 4-aminopyridine PHARMACOLOGICALLY
- Blocks voltage gated K+
- K+ efflux decreases during repolarisation phase of action potential, so prolonged depolarisation, Ca2+ influx increases
- Pre-synaptic mechanism leads to increased ACh release

Immunologically…
- Antibody against toxin binds to it and prevents entry into nerve terminal

Question 5

What is curare (D-tubocurarine)

Answer 5

• Blow dart poison
• Now, pancuronium, vecuronium
• COMPETITVE ANTAGONIST at ACh receptors
• Decrease endplate potential
• General anaesthetic

Question 6

Example of a depolarisation blocker

Answer 6

Suxamethonium
- Agonist at ACh receptors
- Causes endplate depolarisation
- Causes uncoordinated fine contractions (fasciculations)
- Not broken down by acetylcholinesterase in synaptic cleft
- Prolonged depolarisation
- Paraylysis due to inactivation of Na+ channels

Question 7

What are cholinesterase inhibitors

Answer 7

• Interact with acetylcholinesterase and plasma cholinesterase
• Prevent breakdown of ACh
• Enhance synaptic function

Question 8

Non-depolarising NMJ blockers

Answer 8

Question 9

Uses of anticholinesterases

Answer 9