Cholinergic - Nicotinic

Question 1

Which drug competitively blocks nAChRs at the NMJ?

Answer 1

Tubocurarine

Question 2

Which drug blocks nAChRs at the autonomic ganglia?

Answer 2

Hexamethonium

Question 3

Which drug prevents choline uptake?

Answer 3

Hemicholinium

Question 4

Which drug prevents ACh packaging into vesicles?

Answer 4

Vesamicol

Question 5

Which drug prevents ACh release?

Answer 5

Botulinum

Question 6

Which type of drug prevents ACh breakdown?

Answer 6

ChE inhibitors

Question 7

Name a depolarising NMJ blocker

Answer 7

Suxamethonium

Question 8

What is the equation for ACh breakdown?

Answer 8

ACh + ChE AChE + choline

Question 9

What are the 2 sites of ChE and what are their roles?

Answer 9

Catalytic (esteratic) site - has reactive serine OH group

Anionic site - binds quaternary ammonium of ACh

Question 10

Describe the stages of ACh hydrolysis

Answer 10

ACh binds to both ChE sites
Acetyl group of ACh transferred to serine OH of esteratic site
Dissociation of choline from anionic site
Spontaneous hydrolysis of acetylated serine OH - acetate released

Question 11

Name a short-acting anticholinesterase drug

Answer 11

Edrophonium

Question 12

Name a medium-acting anticholinesterase drug

Answer 12

Neostigmine

Question 13

Name a long-acting irreversible anticholinesterase drug

Answer 13

Organophosphates (e.g. sarin, VX)

Question 14

What is the mechanism of short-acting anticholinesterases?

Answer 14

Quarternary ammonium group - forms ionic bond with anionic site
No group complementary to esteratic site
Reversible and competitive

Question 15

What is the mechanism of medium-acting anticholinesterases?

Answer 15

Binds to anionic site

Forms ester bond with serine OH of esteratic site - drug hydrolysed - slower than ACh

Question 16

What is the mechanism of long-acting anticholinesterases?

Answer 16

No quarternary group - do not bind to anionic site

Phosphorylate serine OH of esteratic site - very slow hydrolysis