parasympathetic nervous system

Question 1

synthesis, release and metabolism of acetylcholine

Answer 1

acetyl CoA (from mitochondria) + choline -> ACh + CoA (via choline acetyltransferase; CAT) in post-ganglionic nerve terminal (PSNS); ACh packaged into vesicles on protein carriers, and upon Ca2+ influx, after action potential, and binding after action potential undergoes exocytosis; binds to ACh receptor on postsynaptic cell; broken down by acetylcholinesterase (bound by basement membrane so breaks it down rapidly in synaptic cleft) to choline and acetate; choline pumped back into presynaptic cell via specific transporter

Question 2

what do directly acting cholinomimetic drugs do, and 2 typical agonists at muscarinic receptors with examples

Answer 2

mimick ACh as agonists: choline esters e.g. bethanechol; alkaloids e.g. pilocarpine

Question 3

is pilocarpine selective or non-selective

Answer 3

non-selective (selects for muscarinic over nicotinic, but doesn’t select for muscrinic subtypes)

Question 4

properties of pilocarpine as a non-selective muscarinic agonist

Answer 4

similar to ACh, efficacy for muscarinic (more selective) vs nicotinic receptors, good lipid solubility (given as local eye drops), plasma half life of 3-4 hours (medium), useful in opthalmology as local treatment for glaucoma (flatten iris)

Question 5

side effects of pilocarpine

Answer 5

low levels of drug in circulation as applied locally, so low incidence of side effects; blurred vision (bulging of lens), sweating, GI disturbance and pain, hypotension, respiratory distress

Question 6

is bethanechol selective or non-selective

Answer 6

selective, as only minor modification of ACh (very similar structure to ACh, just extra methyl group)

Question 7

what type of agonist is bethanechol

Answer 7

M3 AChR selective (some degree for stimulation of M3); cevimeline is a more selective M3 agonist

Question 8

properties of bethanecol as a selective muscarinic agonist

Answer 8

resistant to degradation, orally active, limited access to brain (limits CNS side effects), half life of 3-4 hours (medium), useful in assisting bladder emptying (M3) and enhancing gastric motility (M3) e.g. after surgery

Question 9

side effects of bethanecol

Answer 9

higher incidence as using bethanecol systemically; sweating, impaired vision, bradycardia, hypotension, respiratory difficulty

Question 10

what do indirectly acting cholinomimetic drugs do

Answer 10

increase effect of normal PSNS stimulation by inhibiting cholinesterase enzymes and therefore increasing endogenous ACh concentration, not mimicking ACh