Katzung 12th ed - Chapter 27 - General Anaesthetics - Muscle Relaxants (1)

Question 1

Review the mechanism of neuromuscular transmission at the motor end plate.

Answer 1

Acetylcholine is released from the motor nerve terminal, diffuses across the synaptic cleft, and binds to nicotinic receptors on the motor end plate. The nicotinic receptor (an ion channel) then opens, and there is sodium influx, causing depolarization.

Question 2

Structurally, all skeletal muscle relaxants are similar to _________.

Answer 2

Acetylcholine.

Question 3

What is the basic mechanism of action of non-depolarizing muscle relaxants?

Answer 3

They inhibit the opening of the nicotinic ACh receptor ion channel, preventing sodium influx, and thus preventing depolarization.

Question 4

What is the basic mechanism of action of depolarizing muscle relaxants?

Answer 4

They function just as ACh, causing motor end plate depolarization by opening sodium channels. However, they are not metabolized effectively at the synapse (not like ACh, which is rapidly broken down by AChE), and so the membrane does not repolarize, and so no further action potentials can be propagated.

Question 5

Name one commonly used depolarizing muscle relaxant.

Answer 5

Suxamethonium.

Question 6

Name one commonly used non-depolarizing muscle relaxant that is NOT a steroid.

Answer 6

Atracurium (it is an isoquinolone).

Question 7

Name three commonly used non-depolarizing muscle relaxants that are steroids.

Answer 7

Pancuronium.
Rocuronium.
Vecuronium.

Question 8

What is the dose of suxamethonium given for use in intubating?

Answer 8

1-1.5mg/kg IV.

Question 9

What is the dose of vecuronium given for use in intubating?

Answer 9

0.1mg/kg IV.

Question 10

Describe some of the adverse effects of depolarizing muscle relaxants.

Answer 10

Muscle pain (the most common AE)
Bradycardia (can be prevented by premedicating with atropine).
Hyperkalaemia (particularly in burns and renal failure)
Raised IOP, raised ICP, raised intragastric pressure.
Malignant hyperthermia (rare)

Question 11

Describe the metabolism, and thus the duration of action, of suxamethonium.

Answer 11

Onset of action: 30 seconds.

Duration of action 5-10 minutes, due to rapid breakdown by pseudo-cholinesterase.

Question 12

What are the onsets of action of the non-depolarizing muscle relaxants?

Answer 12

Rocuronium - very fast
Vecuronium - 2-3 minutes
Pancuronium - 2-3 minutes

Question 13

What is the (most significant) route of elimination for pancuronium, vecuronium and rocuronium?

Answer 13

Pancuronium - kidney
Vecuronium - liver
Rocuronium - liver

Question 14

What is the difference in duration of action of pancuronium, vecuronium and rocuronium? Explain a mechanism behind this difference.

Answer 14

Pancuronium has a longer duration of action than the others, because it is eliminated by the kidney (occurs more slowly), whilst the others are eliminated more quickly by the liver.
Pancuronium - 35-60 minutes
Vecuronium - 20-35 minutes
Rocuronium - 20-35 minutes

Question 15

What is dantrolene used for?

Answer 15

To treat malignant hyperthermia.

Question 16

Describe an adverse effect of suxamethonium encountered by less than 1% of the population.

Answer 16

Prolonged apnoea, up to several hours, due to their extreme deficiency of pseudo-cholinesterase.

Question 17

Which muscle relaxant is associated with histamine release?

Answer 17

Atracurium.

Question 18

How is atracurium eliminated?

Answer 18

Hofmann elimination (non-liver, non-renal)

Question 19

How does dantrolene work? Describe the basic pharmacodynamics.

Answer 19

Dantrolene reduces skeletal muscle strength, it is a spasmolytic. It reduces calcium release from the sarcoplasmic reticulum.