Anticholinesterases

Question 1

MOA of anticholinesterases

Answer 1

Blocks hydrolytic inactivation of ACh in synapse to enhance and prolong stimulation of cholinergic receptors

Question 2

Anticholinesterase sites of action

Answer 2

ANS- muscarinic, nicotinic, and NMJ nicotinic receptors
CNS- cholinergic neurons (especially for cognition)

Question 3

Anticholinesterases cause _____ paralysis

Answer 3

Flaccid

Question 4

Reversible (non-covalent) anticholinesterase

Answer 4

Donepezil

Question 5

Donepezil can/can’t cross BBB

Answer 5

Can

Question 6

Donepezil clinical use

Answer 6

Treatment of Alzheimer’s

Question 7

Donepezil Alzheimer’s MOA

Answer 7

Deficiency of cerebral ACh counteracted by central inhibition of ACh degradation
Doesn’t affect disease progression

Question 8

Donepezil adverse effects

Answer 8

Diarrhea
N/V
Bradycardia

Question 9

Prototype reversible covalent anticholinesterase

Answer 9

Neostigmine

Question 10

Low (therapeutic) doses of neostigmine increase/decrease contractile force

Answer 10

Increase

Question 11

High (toxic) doses of neostigmine increase/decrease contractile force

Answer 11

Decrease (N receptor desensitization)

Question 12

Neostigmine MOA

Answer 12

Direct agonist at Nm receptors; induce muscle contraction without ACh release

Question 13

Duration of neostigmine action

Answer 13

2 hours

Question 14

Circulating neostigmine is cleared by ____

Answer 14

Butylcholinesterase

Question 15

Neostigmine does/doesn’t cross the BBB

Answer 15

Doesn’t

Question 16

Clinical uses of neostigmine

Answer 16

Reverses effect of competitive neuromuscular blockers (paralyzing drugs) after surgery
Myasthenia gravis

Question 17

How does neostigmine help with myasthenia gravis?

Answer 17

Increases response of myasthenic muscle to repetitive somatic nerve impulses (auto-antibodies destroy Nm receptors)

Question 18

Adverse effects of neostigmine

Answer 18

Excess muscarinic stimulation
Paralysis of diaphragm at toxic doses

Question 19

What drug fixes excessive muscarinic stimulation?

Answer 19

Atropine

Question 20

Physostigmine is the antidote for _____ poisoning

Answer 20

Atropine

Question 21

Difference between physostigmine and neostigmine

Answer 21

Physostigmine can cross the BBB

Question 22

Malathion is commonly used as an _____

Answer 22

Insecticide

Question 23

Malathion has a very long/short duration of action

Answer 23

Long (>50 hours)

Question 24

Malathion is a _____ that is converted to its highly toxic metabolite

Answer 24

Prodrug

Question 25

Clinical use of malathion

Answer 25

Topical lotion for head lice

Question 26

Diagnostic test for anticholinesterase poisoning

Answer 26

Decreased plasma cholinesterase (butylcholinesterase) activity

Question 27

Symptoms of anticholinesterase poisoning (cholinergic crisis)

Answer 27

Muscarinic: sweating, salivation, mitosis, bronchospasm, involuntary urination and defecation Nicotinic: muscle weakness CNS: confusion, ataxia, coma, respiratory depression

Question 28

Antidotes of anticholinesterase poisoning

Answer 28

Atropine Pralidoxime

Question 29

Proalidoxime reactivates AChE only at the ___

Answer 29

NMJ