Section 4: anticholinesterase agents

Question 1

Name four anticholinesterase agents (anti-AChE). One of them is irreversible for which there are two antidotes.

Answer 1

Neostigmine, physostigmine, donepezil, and malathion (irreversible treated by pralidoxime or atropine).

Question 2

Neostigmine (the prototype drug) main mechanism of action

Answer 2

competitive inhibition of AChE allows ACh to remain in the synaptic cleft.

Question 3

Which anticholinesterase is the only one which also acts as an agonist at NMJ nicotinic receptors?

Answer 3

neostigmine

Question 4

Very lipid soluble, common source of agricultural poisoning and agent used in sarin, VX gases

Answer 4

Malathion. Absorbed through all routes including skin. Head lice drug.

Question 5

More selective for AChE in the CNS

Answer 5

Donepezil

Question 6

Uncharged anticholinesterase which crosses BBB

Answer 6

Physostigmine. Treats poisoning by atropine and related drugs that cause peripheral and central Muscarinic blockade.

Question 7

Used to treat myasthenia gravis

Answer 7

neostigmine increases strength of muscle contractions by + ACh levels at NMJ.

Question 8

low dose anti-AchE effects are seen at what receptors?

Answer 8

Muscarinic and Nicotinic muscular receptors

Question 9

High dose anti-AchE effects are seen at what receptors?

Answer 9

All levels of ACH neurotransmission: muscarinic, ganglionic, NMJ and CNS

Question 10

Ptosis and difficulty swallowing involve which receptors? What disease manifests these symptoms and what drug can be used to treat it?

Answer 10

M3. Myasthenia gravis. Neostigmine.

Question 11

Used to treat cognitive decline (alzheimers)

Answer 11

Donepezil

Question 12

Excess anti-AChE will likely cause what adverse effects? What can be used to counteract the muscarinic stimulation?

Answer 12

Muscarinic overstimulation: most commonly see nausea/vomitting, GI cramping, bradycardia. Atropine can be used to block M receptors.

Question 13

What happens to the force of contraction with low doses versus toxic doses of anti-AChE?

Answer 13

Low dose=increased contraction. Toxic/high dose=decreased contraction which can lead to respiratory depression.

Question 14

Patient comes in with pinpoint pupils, frothing at the mouth, sweating, and confused. What receptors have been overstimulated? What are two possible drug treatments/antidotes?

Answer 14

Large doses of atropine at short intervals or PRALIDOXIME.

Question 15

Pralidoxime mechanism of and location of action

Answer 15

reactivates AChE only at NMJ as long as it is administered prior to conformational “aging”.