acetylcholinesterase inhibitors

Question 1

are nicotinic agonists used in MG

Answer 1

no - no activity

Question 2

how do acetylcholinesterase inhibitors work

Answer 2

Increase the concentration of circulating acetylcholine at the neuromuscular junction by altering the natural control mechanism to break down acetylcholine

Question 3

what are irreversible inhibitors

Answer 3

poisons such as novichok

Question 4

what should reversible acetylcholinesterase inhibitors do

Answer 4

• contain a leaving group that dissociates like acetyl in acetylcholine - leave a residual group bound to serine hard to hydrolyse - positively charged to bind

Question 5

why have a carbamate in aacetylcholinesterase inhibitor

Answer 5

charged nitrogen mimics acetylcholine for good binding, carbamylates enzyme - less hydrolysis susceptibility

Question 6

what is the catalytic triad

Answer 6

asp, his, ser

Question 7

MOA of acetylcholinesterase inhibitors

Answer 7

serine protease

Question 8

serine protease MOA

Answer 8

1. Ser nucleophilic attack of carbonyl 2. histidine facilitates movement of protons from ser to ACh 3. easter bond breakage and acylation of enzyme

Question 9

reformation of enzyme after ACh

Answer 9

1. water acts as nucleophile and attacks carbonyl 2. His provides proton for hydrolysis 3. breaking ester - reforming enzyme

Question 10

what are irreversibleacetylcholinesterase inhibitors

Answer 10

organophosphates - forms a covalent bond, poisonous

Question 11

irreversible inhibitors MOA

Answer 11

forms phosphate ester - harder to hydrolyse, can cause ageing

Question 12

what is ageing

Answer 12

instead of releasing phosphate group, there is hydrolysis of the other phosphate ester bond - almost impossible to regenerate enzyme

Question 13

what are the antidotes for irreversible acetylcholinesterase inhibitors

Answer 13

oximes, highly reactive nucleophile that attacks phosphorus and cleaves bond