Cholinomimetics

Question 1

Name the 5 direct-acting cholinergic agonists.

Answer 1

Nicotine, muscarine, bethanechol, pilocarpine, cevimeline

Question 1

Name the 6 indirect-acting, AChE inhibiting cholinomimetics

Answer 1

Neostigmine, physostigmine, donepezil, edrophonium, echothiophate, and soman

Question 1

What is the one indirect-acting cholinomimetic that is not an AChE inhibitor? How does it work?

Answer 1

Pralidoxime; regenerates phosphorylated AChE

Question 1

Name the 2 indirect-acting carbamic acids.

Answer 1

Neostigmine and physostigmine

Question 1

Name the 2 indirect-acting non-ester alkaloids.

Answer 1

Donepezil and edrophonium

Question 2

Name the 2 indirect-acting organophosphates.

Answer 2

Echothiophate and soman

Question 3

Besides muscarine, what are the other 3 direct-acting cholinomimetics that act on muscarinic receptors?

Answer 3

Pilocarpine, cevimeline, and bethanechol

Question 4

Which direct-acting cholinomimetic is a choline ester / carbamic acid?

Answer 4

Bethanechol

Question 5

Which receptors do indirect cholinomimetics affect: nicotinic or muscarinic receptors?

Answer 5

Both, because the indirect cholinergic agonists inhibit AChE, leading to a global increase in ACh at all cholinergic receptors

Question 7

What condition is pilocarpine used to treat, and how does it work?

Answer 7

Glaucoma - activate papillary sphincter and ciliary muscles to decrease intraocular pressure

Question 7

What condition is cevimeline used to treat, and how does it work?

Answer 7

Dry mouth (ex. from Sjogren’s or radiation therapy) - increase salivation

Question 8

Do most direct-acting cholinomimetics target nicotinic or muscarinic receptors, and what kind of effects occur as a result?

Answer 8

Activate muscarinic receptors, which increases parasympathetic responses such as bradycardia, vasodilation, pupillary constriction, salivation, etc.

Question 9

What conditions is bethanechol used to treat, and how does it work?

Answer 9

Ileus and urinary retention - activate bowel and bladder smooth muscle

Question 10

Do the indirect-acting cholinomimetics affect nicotine or muscarinic receptors? Do they cause sympathetic or parasympathetic effects?

Answer 10

Activate both muscarinic and nicotinic receptors, broadly increase ACh for both parasympathetic and sympathetic effects.

Question 11

Rank the following AChE inhibitors from shortest to longest half life: neostigmine, physostigmine, edrophonium, echothiophate

Answer 11

Edrophonium (~10 min) - neostigmine and physostigmine (~1 hour) - echothiophate (>100 hours)

Question 12

What is the major use for nicotine?

Answer 12

Reduce cravings in smoking cessation

Question 13

What 3 cholinomimetics are used to treat glaucoma?

Answer 13

Pilocarpine, physostigmine, and echothiophate

Question 14

Pralidoxime is a strong nucleophile that acts indirectly on Ach synapses. How is it used therapeutically?

Answer 14

Used to counter nerve gas or insecticide poisoning

Question 15

Soman and Sarin are indirect acting organophosphate nerve gases that can lead to paralysis and death. How do they cause toxicity?

Answer 15

They inhibit AChE, leading to increased ACh signalling

Question 16

What 2 cholinomimetics can be used to treat post-operative and neurogenic ileus as well as urinary retention? What third cholinomimetic can also treat ileus?

Answer 16

Bethanechol and neostigmine; edrophonium

Question 17

What 2 cholinergic agonists are used to treat myasthenia gravis? Which one can be used to diagnose the disease?

Answer 17

Neostigmine and edrophonium; edrophonium can diagnose

Question 18

What condition is donepezil used to treat? What feature of its molecular structure makes it well suited for this function?

Answer 18

Alzheimer’s; it is hydrophobic so can cross BBB

Question 23

What 2 drugs are used to counter poisoning by soman and other organophosphates, and how does each one work?

Answer 23

Pralidoxime regenerates phosphorylated AChE, and atrophine inhibits the ACh-receptor

Question 24

All cholinergic agonists except pralidoxime can cause SLUDGE as side effects. What does SLUDGE stand for, and what drug can counter these effects?

Answer 24

Salivation, Lacrimation, Urination, Defecation, GI distress, and Emesis; atropine

Question 25

What cholinomimetic drug can be used to reverse a neuromuscular blockade, as well as treat ileus, urinary retention, and myasthenia gravis?

Answer 25

Neostigmine

Question 26

Which cholinomimetics are more selective: nicotinic or muscarinic agonists?

Answer 26

Nicotinic are slightly more selective (can distinguish NN vs NM); muscarinic cholinomimetics tend to activate all muscarinic receptors.

Question 27

In addition to SLUDGE and general increase in cholinergic neurotransmission, what is a possible side effect of any indirect cholinomimetic drug?

Answer 27

paralysis