NMJ Agents

Question 1

What is the onset, duration, and biotransformation of Cisatracurium?

Answer 1

Intermediate in onset and duration of action. Able to be given to those with renal and hepatic impairment.

Question 2

What is the onset, duration, and biotransformation of Tubocurarine?

Answer 2

Not used clinically due to significant histamine release

Question 3

What is the onset, duration, and biotransformation of Pancuronium?

Answer 3

Intermediate onset with a long duration. Hepatic transformation to 3-, 17-, and 3,17-hydroxy steroids.

Question 4

What is the onset, duration, and biotransformation of Rocuronium?

Answer 4

Rapid onset with intermediate duration. Steroid biotransofrmation.

Question 5

What is the onset, duration, and biotransformation of Vecuronium?

Answer 5

Intermediate onset and duration. Steroid biotransformation.

Question 6

What is the mechanism of action for Non-depolarizing agents?

Answer 6

They are antagonists to the N-AchR

Question 7

How is reversal of neuromuscular blockade performed?

Answer 7

Administration of an AchEI such as neostigmine, physostigmine, or edrophonium

Also, an antimuscarinic such as atropine or glycopyrrolate is given to black PANS activity.

Question 8

Describe the mechanism of Phase I and II neuromuscular blockade of succinylcholine.

Answer 8

Phase I - binding cause irreviersible depolarization
Phase II - prolonged block leads to repolarization without the possibility of depolarization

Reversed by AchEIs

Question 9

Describe the Onset, Duration, Biotransformation, and MOA of succinlycholine.

Answer 9

Onset and duration are both rapid. Biotransformation occurs in the plasma due to choliesterases.

Question 10

What are the DDIs of non-depolarizing NMJ blockers?

Answer 10

Inhaled anesthetics and aminoglycosides both enhance the neuromuscular blockade.

Carbemazepine and phenytoin cause a requirement for high doses

Question 11

What are the disease considerations for the administration of non-depolarizing NMJ blockers?

Answer 11

There is prolonged action in impaired renal and hepatic funciton, reduce dose if > 70 y/o.

Burn patients and upper motor neuron disease are resistant, while myasthenia gravis is sensitive.

Question 12

Describe butyryl and acetyl cholinesterase.

Answer 12

Butyrylcholinesterase - produced by the liver and found in the plasma; metabolizes succinylcholine and cocaine.

Acetylcholinesterase - produced at the synaptic end plate of the NMJ; major target of AchEIs

Question 13

What are the quaternary AchEIs? Describe their absorption, distribution, and metabolism.

Answer 13

Drugs - Edrophonium, echothiophate (organophosphate), pyridostygmine, and neostygmine.

Absorption is parenteral with no CNS distribution. Duration depends on the stability of the the enzyme-inhibitor complex.

Question 14

What are the tertiary AchEIs? Describe their absorption, distribution, and metabolism.

Answer 14

Physostigmine

Well absorbed and distributed.

Question 15

What are the organophosphates AchEIs? Describe their absorption, distribution, and metabolism.

Answer 15

Extremely well absorbed and widely distributed. Irreversible binding.

Question 16

Describe the metabolism of alcohols, carbamates, and organophosphates.

Answer 16

Alcohols - short duration, up to 30 minutes
Carbamates - two-step hydrolysis, which involves a covalent bond (30 min - 6 hours)
Organophosphates - stable covalent bond which can be strengthened by aging.

Question 17

What are the clinical uses of AchEIs?

Answer 17

Reversal of pharmacologic paralysis, dementia, anti-muscarnici toxicity, myasthenia gravis, myasthenic crisis

Question 18

What are the DDIs of AchEIs?

Answer 18

Combination with non-depolarizing drugs will be antagonistic.

Beta-blockers - enhance bradycardia

Question 19

How can AchEI toxicity be managed?

Answer 19

Antagonize muscarinic effects with atropine, but peripheral neurommuscular block, must be relieved by AchE regenerators. Benzodiazepines are given to prevent seizures.

Question 20

What is a AchE regenerator and when must it be given?

Answer 20

Pralidoxime cleaves the phosphorous bong between organophosphates and the AchE. This must be given before aging. Has no effect on the central activity of organophosphates.