parasympathetic nervous system

Question 1

examples of reversible anticholinesterases

Answer 1

physostigmine, neostigmine, donepezil (Aricept - Alzheimer’s disease)

Question 2

examples of irreversible anticholinesterases

Answer 2

ecothiopate (organophosphate), (dyflos, sarin - used as nerve gases)

Question 3

what do cholinesterase enzymes do

Answer 3

metabolise ACh to choline and acetate

Question 4

2 types of cholinesterase enzyme (differ in distribution, substrate specificity and function)

Answer 4

acetylcholinesterase (true/specific cholinesterase), butyrylcholinesterase (pseudocholinesterase)

Question 5

where is acetylcholinesterase found

Answer 5

all cholinergic synapses (peripheral and central)

Question 6

time frame of acetylcholinesterase hydrolysis

Answer 6

very rapid (>10000 reactions per second)

Question 7

how are acetylcholinesterase highly selective for ACh

Answer 7

in active site of acetylcholinesterase, exposed OH on serine allows hydrolysis of acetate group on ACh

Question 8

where is butyrylcholinesterase found

Answer 8

in plasma and most tissues but not cholinergic synapses

Question 9

how does butyrylcholinesterase show broad substrate specificity, and its impact on plasma ACh

Answer 9

hydrolyses other esters e.g. suxamethonium, and causes low plasma ACh; shows genetic variation (so people respond differently to drugs like suxamethonium)

Question 10

effect of low dose cholinesterase inhibitors

Answer 10

enhanced muscrinic activity

Question 11

2 effects of moderate dose cholinesterase inhibitors

Answer 11

further enhancement of muscarinic activity, increased transmission at all ANS ganglia (nAChRs)

Question 12

effect of high dose (toxic) cholineserase inhibitors

Answer 12

depolarising block at all ANS ganglia and NMJ (inactivating receptors and causing respiratory depression)

Question 13

how do reversible anticholesterase drugs function

Answer 13

compete with ACh for active site on cholinesterase enzyme

Question 14

how do reversible anticholesterase drugs (e.g. physostigmine) prevent ACh from binding

Answer 14

donate a carbamyl group to AChE enzyme, binding to serine and blocking active site

Question 15

reversible anticholesterase drugs e.g. physostigmine: how is the donated carbamyl group removed, and impact

Answer 15

slow hydrolysis (mins rather than msecs), increases duration of ACh activity in synapse

Question 16

where does physostigmine primarily act

Answer 16

at postganglionic PSNS synapse (half life of 30 mins)

Question 17

what is physostigmine used to treat

Answer 17

glaucoma by aiding intraocular fluid drainage, treat atropine (competitive ACh antagonist) poisoning (esp. in children) by effectively raising ACh level

Question 18

examples of irreversible anticholesterase drugs

Answer 18

organophosphate compounds such as ecothiopate, dyflos, parathion and sarin

Question 19

how do irreversible anticholesterase drugs work

Answer 19

rapidly react with enzyme active site, leaving large blocking group which is stable and resistant to hydrolysis

Question 20

how does the body overcome irreversible anticholesterase drugs

Answer 20

may require production of new enzymes, taking days or weeks

Question 21

what irreversible anticholesterase drug is in clinical use

Answer 21

ecothiopate (potent inhibitor of AChE); others used as insecticides or nerve gases

Question 22

what is ecothiopate used to treat

Answer 22

eye drops for glaucoma, acting to increase intraocular drainage with prolonged duration of action as slow reactivation of enzyme by hydrolysis takes several days

Question 23

systemic side effects of ecothiopate

Answer 23

over stimulating muscarinic receptors so sweating, blurred vision, GI pain, bradycardia, hypotension, respiratory difficulty

Question 24

what can non-polar anticholinesterases like physostigmine do

Answer 24

cross the BBB so cause CNS effects

Question 25

effects of low doses of non-polar anticholinesterases

Answer 25

excitation with possibility of convulsions

Question 26

effects of high doses of non-polar anticholinesterases

Answer 26

unconsciousness, respiratory depression, death