Ch 15: Cholinesterase Inhibitors and Their Use in Myasthenia Gravis

Question 1

Cholinesterase inhibitors are also known as…

Answer 1

…anticholinesterase drugs.

p. 127

Question 2

Because cholinesterase inhibitors do not bind directly with cholinergic receptors, they are viewed as…

Answer 2

…indirect-acting cholinergic agonists.

p. 127

Question 3

What is the primary problem with cholinesterase inhibitors in terms of their therapeutic applications?

Answer 3

They lack selectivity. Use of these drugs results in transmission at all cholinergic junctions (muscarinic, ganglionic, and neuromuscular).

(p. 127)

Question 4

What are the 2 basic categories of cholinesterase inhibitors?

Answer 4

1. reversible inhibitors
2. irreversible inhibitors

(p. 127)

Question 5

What are the two brand names of neostigmine? What are they used for?

Answer 5

Bloxiverz (used to reverse the actions of nondepolarizing neuromuscular blockade following surgery) and Prostigmin (used for management of myasthenia gravis)

(p. 127)

Question 6

Describe the mechanism of action of neostigmine.

Answer 6

Neostigmine and other reversible cholinesterase inhibitors act as substrates for cholinesterase. Neostigmine reacts with cholinesterase similarly to the way that acetylcholine and cholinesterase react, however, the difference is that cholinesterase splits neostigmine more slowly than it splits acetylcholine.
Because they remain bound until the neostigmine is degraded, less cholinesterase is available to degrade acetylcholine, resulting in a greater availability of acetylcholine to activate cholinergic receptors.

(p. 127)

Question 7

When used therapeutically, cholinesterase inhibitors usually affect only…

Answer 7

…muscarinic receptors on organs and nicotinic receptors of the neuromuscular junction. Ganglionic and CNS transmission are usually unaltered.

(p. 127)

Question 8

Cholinesterase inhibitors can reverse the effects of competitive NMBA’s (e.g. pancuronium), but CANNOT be used to counteract…
In fact, because cholinesterase inhibitors will…

Answer 8

…succinylcholine, a depolarizing NMBA.
(p. 128)

…decrease the breakdown of succinylcholine by cholinesterase, they will actually intensify neuromuscular blockade caused by succinylcholine.
(p. 129)

Question 9

Cholinesterase inhibitors can be used to overcome…

And conversely…

Answer 9

…excessive muscarinic blockade by atropine.

…atropine can be used to reduce excessive muscarinic stimulation caused by cholinesterase inhibitors.

Question 10

What are the symptoms of a cholinergic crisis? (use mnemonic.)

Answer 10

SLUDGE and the killer B’s:
Salivation, Lacrimation, Urination, Diaphoresis/Diarrhea, Gastrointestinal cramping, Emesis, Bradycardia, Bronchospasm, Bronchorrhea
(also, miosis)

(p. 129)

Question 11

What is one major difference between physostigmine and neostigmine?

Answer 11

Neostigmine is a quaternary ammonium compound.
Physostigmine is not; rather, it is uncharged, and the drug crosses membranes with ease, including the blood-brain barrier.

Question 12

Physostigmine is the drug of choice for treating poisoning by…

Answer 12

…atropine and other drugs that cause muscarinic blockade.

(p. 129)

Question 13

All irreversible cholinesterase inhibitors contain an atom of phosphorus, therefore, these drugs are known as…

Answer 13

…organophosphate cholinesterase inhibitors.

p. 130

Question 14

Almost all irreversible cholinesterase inhibitors are…

Answer 14

…highly lipid soluble. They are readily absorbed from all routes of transmission.

(p. 130)

Question 15

Easy __________, coupled with high ________ is what makes these drugs good…

Answer 15

absorption, toxicity
…insecticides and chemical warfare agents.

(p. 130)

Question 16

What is the one indication for irreversible cholinesterase inhibitors?
What drug is available for this?
And how is this drug different from other irreversible cholinesterase inhibitors?

Answer 16

glaucoma
echothiophate
It is not highly lipid soluble.

(p. 130)

Question 17

What is the treatment for poisoning by organophosphate cholinesterase inhibitors?

Answer 17

1. mechanical ventilation
2. giving atropine to reduce muscarinic stimulation
3. giving pralidoxime to reverse inhibition of cholinesterase
4. giving a benzodiazepine to suppress convulsions

(p. 131)

Question 18

Once the process called aging occurs, pralidoxime is…

Answer 18

…unable to cause the inhibitor to dissociate from the enzyme.

(p. 131)

Question 19

The time required for aging depends on the agent involved. For example…

Answer 19

…with soman, aging occurs in just two minutes, but with tabun, aging requires 13 hours.

(p. 131)

Question 20

What should you know about administering IV pralidoxime?

Answer 20

It must be infused slowly over 20-30 minutes to avoid hypertension.

(p. 131)

Question 21

What is myasthenia gravis and what causes it?

Answer 21

It’s a neuromuscular disorder characterized by fluctuating muscle weakness and a predisposition to rapid fatigue. It is caused by an autoimmune process in which the patient’s immune system produces antibodies that attack nicotinic M receptors on skeletal muscle. As a result, the number of functional receptors at the NMJ is reduced by 70% - 90% causing profound muscle weakness.

(p. 131)

Question 22

If muscarinic responses (to MG drugs) are excessive, ________ may be given to suppress them. However, it should not be employed routinely because the drug can…

Answer 22

atropine
…mask the early signs of overdose with anticholinesterase agents.

(p. 131)

Question 23

What are symptoms that a patient with MG is undermedicated? Overmedicated?

Answer 23

ptosis, difficulty in swallowing
excessive salivation and other muscarinic responses

(p. 131)

Question 24

Left untreated, myasthenic crisis can result in…

Answer 24

…death from paralysis of the muscles of respiration.

p. 131

Question 25

How can you distinguish myasthenic crisis from cholinergic crisis when they both present with muscle weakness and paralysis?

Answer 25

A history of medication use or signs of excessive muscarinic stimulation are usually sufficient to permit a differential diagnosis. If these clues are inadequate, a challenge dose of edrophonium may be given. If it alleviates symptoms, the crisis is myasthenic.

(p. 132)