Neuromuscular blocking drugs

Question 1

Describe the somatic nervous system pathway

Answer 1

One motor neurone to the skeletal muscle, releasing ACh

Question 2

Explain the process of neuromuscular transmission

Answer 2

1. Acetylcholine is loaded into vesicles
2. AP depolarises the membrane
3. Calcium intake
4. ACh released from the pre-synaptic vesicles
5. ACh diffuses across the synapse
6. ACh binds to nicotinic ACh receptors on the end-plate region

Question 3

Describe the action of nicotinic acetylcholine receptor

Answer 3

1. Ach binds to the alpha subunit of the receptor
2. Channel opens
3. Sodium ions influx

Question 4

Which NM drugs target conduction of nerve AP in motor neurones

Answer 4

Local anaesthetics

Question 5

Which NM drugs target ACh release

Answer 5

Hemicholinium
Calcium entry blockers
neurotoxins

Question 6

Which NM drugs target Depolarisation of motor end-plate -> AP initiation

Answer 6

Tubocurarine

Suxamethonium

Question 7

Which NM drugs target propagation of AP along muscle fibres + muscle contraction

Answer 7

Spasmolytics e.g. dantrolene

Question 8

Describe neuromuscular blocking drugs with postsynaptic action

Answer 8

Non-depolarising (competitive antagonist) or depolarising (agonist)
They do not affect consciousness or pain sensation
Always assist respiration

Question 9

Give examples of non-depolarising and depolarising NM drugs

Answer 9

Non-D = tubocurarine, atracurium

D = suxamethonium

Question 10

What is the mode of action for suxamethonium

Answer 10

Extends end-plate depolarisation to cause a depolarisation block
Fasciculations -> flaccid paralysis

Question 11

Describe the pharmacokinetics of suxamethonium

Answer 11

IV (highly charged)
Duration of paralysis = 5 mins
Metabolised in pseudo-cholinesterase in liver and plasma

Question 12

What are the uses of suxamethonium

Answer 12

Endotracheal intubation

Muscle relaxant for electroconvulsive therapy

Question 13

What are the unwanted effects of suxamethonium

Answer 13

Post-operative muscle pains

Bradycardia (direct muscarinic action on the heart)

Hyperkalaemia (soft tissue injury or burns -> ventricular arrhythmias/cardiac arrest)

Increased intra-ocular pressure (avoid for eye injuries, glaucoma)

Question 14

Describe tubocurarine and its mode of action

Answer 14

Non-depolarising NM blocker
Naturally occurring quaternary ammonium compound (alkaloid) found in plants
Range of synthetic drugs are available

Competitive nAChR antagonist
70-80% block necessary

Question 15

What are the effects of tubocurarine

Answer 15

Flaccid paralysis
Extrinsic eye muscles (double vision)
Small muscles of face, limbs, pharynx
Respiratory muscles

Question 16

Describe the effect of tubocurarine on NM transmission (voltage-wise)

Answer 16

Recording from endplate - very small AP peak of -60

Away from endplate - no AP seen

Question 17

What are the uses of tubocurarine

Answer 17

Relaxation of skeletal muscles during surgical operations (less anaesthetic needed)
Permits artificial ventilation

Question 18

How may the actions of non-depolarising blockers be reversed

Answer 18

Anticholinesterases

e.g. neostigmine (+atropine)

Question 19

Describe the pharmacokinetics of tubocurarine

Answer 19

IV (highly charged)
Does not cross BBB or placenta 
Paralysis duration - 1-2 hrs 
Not metabolised 
Excretion: 70% urine, 30% bile (important if patient is in renal rare)
e.g. atracurium (15mins - unstable)

Question 20

What are the unwanted effects of tubocurarine

Answer 20

Ganglion block and histamine release

Hypotension (ganglion blockade, histamine released from mast cells)

Bronchospasm and excessive bronchial and salivary secretion

Tachycardia (arrhythmias, reflex, blockade of vagal ganglia)

Apnoea (always assist respiration)

Question 21

Which drugs target the central processes of NMJ action

Answer 21

Spasmolytics e.g. diazepam, baclofen