Neuromuscular blocking drugs

Question 1

Give 3 examples of NMJ blockers

Answer 1

Tubocurarine
Atracurium
Suxamethonium

Question 2

What is the method of action of tubocurarine?

Answer 2

Competitively antagonises nicotinic ACh receptors

Question 3

What % block of nAChRs is required for total muscle relaxation?

Answer 3

70-80%

Question 4

What sort of paralysis is produced by total nAChR block?

Answer 4

Flaccid

Question 5

Recall the distinctive relax-and-return pattern seen in nAChR-antagonist-induced muscle relaxation

Answer 5

Relax in this order, reverse in opposite order:
Extrinsic eye muscles
Small muscles of face/limbs/pharynx
Respiratory muscles

Question 6

What drug class is used to reverse the action of NMJ-blocking drugs? What is the caveat to this?

Answer 6

anti-cholinesterases - but only for POLARISING NMJ blockers

Question 7

Give an example of an anti-cholineesterase

Answer 7

Neostigmine

Question 8

Why is neostigmine always given with atropine?

Answer 8

Neostigmine increases [ACh] in all other cholinergic synapses so you give some atropine with it so that it blocks the muscarinic receptor over stimulation

Question 9

Give 2 clinical uses of spasmolytics

Answer 9

Cerebral palsy

Spasticity following stroke

Question 10

Give 2 clinical uses for suxamethonium

Answer 10

Endotracheal intubation

Muscle relaxant for electroconvulsive therapy

Question 11

Recall the mechanism of action of spasmolytics

Answer 11

Potentiate effects of GABA

Question 12

Give 2 examples of spasmolytics

Answer 12

Diazepam

Baclofen

Question 13

Recall the mechanism of action of diazepam

Answer 13

Facilitates GABA transmission

Question 14

Recall the mechanism of action of baclofen

Answer 14

GABA receptor agonist

Question 15

What sort of drug is atracurium?

Answer 15

Non-depolarising NMJ drug (= ANTagonist)

Question 16

Give an example of a depolarising NMJ drug?

Answer 16

Suxamethonium

Question 17

What is a depolarising NMJ drug?

Answer 17

Depolarising = agonist

Question 18

Recall the mechanism of action of suxamethonium

Answer 18

Causes Phase 1 Block by extending end-plate depolarisation

Question 19

What is a fasciculation?

Answer 19

Individual muscle fibre twitches

Question 20

What is a possible side effect of suxamethonium?

Answer 20

Fasciculations

Question 21

Recall the structure of suxamethonium

Answer 21

2 ACh molecules stuck together

Question 22

What is the normal method of administration and duration of action of suxamethonium?

Answer 22

IV - 5-10 minutes

Question 23

Describe the metabolism of suxamethonium

Answer 23

Metabolised by pseudocholinesterase in the liver and plasma

Question 24

Describe the structure of non-depolarising NMJ drugs

Answer 24

big and bulky with limited rotation around bonds

Question 25

What must always be done when suxamethonium is administered?

Answer 25

Assist respiration

Question 26

Recall 4 side effects of suxamethonium and the reasons for each

Answer 26

1. Post-operative muscle pain (initial fasciculations)
2. Bradycardia (direct muscarinic activation at heart)
3. Hyperkalaemia (only in de-innervation supersensitivity)
4. Raised IOP

Question 27

What are the 2 main causes of unwanted side effects of tubocurarine?

Answer 27

1. Overlap onto ganglionic nAChRs (despite preferential muscle action)
2. Histamine leakage out of mast cells

Question 28

Recall 5 unwanted side effects of tubocurarine

Answer 28

1. Hypotension
2. Tachycardia
3. Bronchospasm (from histamine release)
4. Excessive secretions
5. Apnoea