Cholinergic Activators

Question 1

How do direct-acting agents work?

Answer 1

directly bind to and activate muscarinic or nicotinic receptors

Question 2

How do indirect-acting agents work?

Answer 2

inhibit acetylcholinesterase, thereby increasing concentration of endogenous Ach in synaptic cleft

Question 3

What are the two groups of direct-acting drugs?

Answer 3

esters of choline and non-esters

Question 4

Name one direct-acting ester. Is it selective?

Answer 4

bethanechol; poorly absorbed by CNS; it’s muscarinic selective and stable

Question 5

Name four non-ester cholinomemetics.

Answer 5

muscarine, pilocarpine, cevimeline, nicotine

Question 6

Effects of direct-acting cholinomemetics in the eye.

Answer 6

contraction of sphincter muscle of iris; contraction of ciliary muscle

Question 7

Effects of direct-acting cholinomemetics in the heart.

Answer 7

decrease rate of SA node; decrease in contractile strength of atria; decrease in refractory period of atria; decrease in conduction velocity of AV node; increase in refractory period of AV node; small decrease in contractile strength of ventricles

Question 8

Effects of direct-acting cholinomemetics in the blood vessels.

Answer 8

dilation of arterioles and veins (via NO; constriction at very high dose!!)

Question 9

Effects of direct-acting cholinomemetics in the lungs

Answer 9

bronchoconstriction; stimulation of bronchial glands

Question 10

Effects of direct-acting cholinomemetics in GI tract.

Answer 10

increase motility; relaxation of sphincters; stimulation of secretion

Question 11

Effects of direct-acting cholinomemetics in urinary bladder

Answer 11

contraction of detrusor; relaxation of trigone and sphincter

Question 12

Effects of direct-acting cholinomemetics in glands

Answer 12

stimulate secretion in sweat, salivary, lacrimal, nasopharyngeal

Question 13

Name the cholinesterase inhibitors. Are they therapeutically useful or used as poisons?

Answer 13

therapeutically useful - neostigmine, donepezil, physostigmine, edrophonium
poisons (organophosphates) - echothiophate, soman, sarin

Question 14

MOA of cholinesterase inhibitors.

Answer 14

neostigmine, physostigmine - covalent bond to enzyme for 0.5-6hrs
edrophonium, donepezil - binding, but not covalent
organophosphates - phosphorylate enzyme, with time becomes irreversible

Question 15

What can be used to reactivate acetylcholinesterase before it’s irreversibly inhibited by organophosphates?

Answer 15

pralidoxime (PAM)

Question 16

TU of D&I cholinomemetics in the eye

Answer 16

glaucoma - ciliary muscle contraction and reduced intraocular pressure
pilocarpine, physostigmine, echothiophate

Question 17

TU of D&I cholinomemetics in the GI tract

Answer 17

postop atony, adynamic ileus - GI smooth muscle contraction and increased motility
bethanechol, neostigmine

Question 18

TU of D&I cholinomemetics in the urinary tract

Answer 18

urinary (post-op) retention - bladder smooth muscle contraction and emptying
bethanechol, neostigmine

Question 19

TU of D&I cholinomemetics in the salivary glands

Answer 19

xerostomia due to radiation or Sjogrens syndrome - increased salivation
cevimeline

Question 20

TU of indirect cholinomemetics in the NMJ

Answer 20

myasthenia gravis - increased Ach and muscle strength; reversal of paralysis induced by non-depolarizing NMJ blocker
neostigmine, edrophonium

Question 21

TU of indirect cholinomemetics in the CNS

Answer 21

Alzheimers - increased Ach and possible cognitive enhancement
donepezil