Muscle relaxants actin on the nMF

Question 1

Long acting direct NMJ inhibitors

Duration of inhibition

Answer 1

Doxacurium
Pancuronium
Pipecuronium

Duration 1-3 hours

-curonium suffix means they are steroid compounds

Question 2

Medium acting NMJ inhibitors

Answer 2

Vecuronium, Rocuronium, Atracurium and Cisatracurium

Question 3

Short acting NMJ inhibitors

Answer 3

Mivacurium

Question 4

What are all of the direct muscle nicotinic receptor inhibitors derived from?

Answer 4

Tubocurare, the frog poison.

Question 5

General/common kinetics of the NMJ inhibitors

Answer 5

Highly polar,

Administered parenterally

Rapid onset within 2-6 minutes.

Question 6

Progression of the paralysis

Answer 6

centrally to peripherally, starting at the eyes, then the head, then extremeties, trunk, diaphragm last.

Question 7

Which NMJ inhibitors are metabolized by liver

Answer 7

Vecuronium and Rocuronium

Question 8

How are atracurium and cisatracurium metabolized

Answer 8

Spontaneous degradation in the plasma by ‘hofmann elimination’

Forms a Laudanosine intermediate which can cross the BBB and cause seizures.

Atracurium also has some liver metabolism and creates more laudanosine.

Cisatracurium is the ONLY NMJ antagonist that does not need to be dose adjusted in patients with renal deficiency or with multiorgan failure.

Question 9

How is Mivacurium metabolized?

Answer 9

By plasma pseudocholinesterase, causing its very short duration, 10-15 minutes.

Question 10

General side effects of NMJ antagonists

Answer 10

Hypotension - from some ANS inhibition at the ganglia.
Reflex tach

Weak M2 inhibition also, also generating tachycardia

Respiratory depression and possible asphyxia

Question 11

Side effect of Tubocurarine and Atracurium

Answer 11

Histamine release

Bronchospasm
Pruritus
Hypotension

Question 12

Side effect of Pancuronium

Answer 12

NE release, NE reuptake inhibition,

Tachycardia

Question 13

How do you reverse the effects of any of the tubocurare derivatives?

Answer 13

AChE inhibitors, specifically Neostigmine, quaternary amine to stay peripheral.

plus Atropine to compensate for the excessive muscarinic stimulation caused by the AChE.

Question 14

How to reverse the effects of the steroid NMJ inhibitors?

Answer 14

Sugammadex

hydrophobic pocket that binds the steroid structures directly.

Question 15

What drugs potentiate the actions of the NMJ inhibitors?

Answer 15

The anesthetics

Elderly patients
Myasthenia gravis patients

Question 16

Succinylcholine other name

Answer 16

Suxamethonium

Question 17

Succinylcholine clinical uses

Answer 17

Short surgeries and procedures

Intubation, Bronchoscopy

Question 18

Succinylcholine adverse effects

Answer 18

Respiratory paralysis

Malignant hyperthermia in genetically susceptible patients

Bradycardia from muscarinic activaiton

Hyperkalemia, from K+ outflow of nicotinic receptors and from repolarization

Myalgia from muscle twitching and fasciculations
Vomiting from muscle spasms and increased GI pressure

Question 19

Order of paralysis in succinylcholine

Answer 19

Begins peripherally, with the arms, legs, diaphragm, and the head last.

Question 20

Onset, duration, and phases of succinylcholine

Answer 20

onset 30-60s
Duration only 5-10 minutes. Rapidly degraded by pseudocholinesterase. Very slowly degraded by AChE

Phase 1: Depolarization.
Persistent depolarization leads to fasciculations followed by flaccid paralysis despite depolarization. No amount of AChE overcomes the paralysis, and in fact potentiates it.

Phase 2: Desensitization.
The muscle slowly repolarizes, but the receptors are inactivated and can only be stimulated by very high concentrations of ACh.

Question 21

Reversal of succinylcholine effects

Answer 21

Can only be done during phase 2, when AChE inhibitors and increased ACh concentration begin to activate receptros in the desensitized state.

If administered during phase 1 this actually potentiates the blockade.