B - 10. Skeletal muscle relaxants acting on the neuromuscular junction

Question 1

Curare-like drugs: action

Answer 1

Competative antagonist on NMJ muscular-type nicotinic ACh receptors (Nm)

Non-depolarizing

Question 2

Short acting curare-like drugs

Answer 2

mivacurium

Question 3

Medium acting curare-like drugs

Answer 3

atracurium
cisatracurium
rocuronium

Question 4

Long acting curare-like drugs

Answer 4

pipecuronium

Question 5

Metabolism of curare like drugs

Answer 5

o rocuronium are metabolized by the liver

o Atracurium and cisatracurium are spontaneously degraded (via the
Hofmann elimination)

o Mivacurium is degraded by pseudocholinesterases (this is why it’s
short-acting)

Question 6

Side effects of curare-like drugs (general)

Answer 6

o Weakness after coming off the drugs
o Hypotension (maybe with some reflex tachycardia)
o M2 blockade also → tachycardia

Question 7

atracurium specific SE

Answer 7

→ Histamine release (itching,

bronchospasm, hypotension)

Question 8

Hofmann elimination of atracurium and cisatracurium

Answer 8

laudanosine intermediate, which crosses BBB (lipophilic) and may
cause seizures or otherwise interfere with anesthesia

Question 9

How to pharmacologically reverse the effects of curare:

Answer 9

o AChE-inhibitiors: particularly neostigmine is used to provide more Ach in the NMJ.

o Sugammadex: can reverse the effects of steroids (only useful in the steroid curare drugs (-onium drugs))

Question 10

Succinylcholine: function

Answer 10

Agonist of Nm receptor, DEPOLARIZING blocker

Question 11

Depolarizing phase (phase 1)

Answer 11

Drug binds to nicotinic receptor -> opening of Na+ and Ca++ channels -> excitation -> depolarization

This will create an initial muscle twitching followed by prolonged inactivation -> paralysis

Question 12

Desensitizing phase (phase 2)

Answer 12

Continous exposure to succinylcholine -> desensitisation -> paralysis of muscle

Can be overcome by giving acetylcholinesterase inhibitors, but only in phase II. If given in phase I, the additional ACh will increase the desensitisation

Question 13

Side effects of succinylcholine

Answer 13

Myalgia (due to twitching)
Arrythmia (mostly bradycardia)
Hyperkalemia
Vomiting (muscle spasm increase gastric pressure)
MALIGNANT HYPERTHERMIA due to genetic RyR disorder - countered with dantrolene

Question 14

Indications for skeletal muscle relaxants

Answer 14

1. Intubation
2. Artificial ventilation
3. Intraoperative muscle relaxant