Neuromuscular Blocking drugs

Question 1

Describe neuromuscular transmission and name the 3 main neuromuscular blocking drug

Answer 1

ACh synthesised and their targets in post synaptic terminal is the nicotinic receptors. Acetycholinesterase bound to basement membrane

1. Tubocurarine
2. Attracium
3. Suxamethonium

Question 2

Describe the different sites of drug action at a NMJ

Answer 2

1. Central processes (diazepam and baclofen) are GABA receptor agonist and dissolve spasmicity and work to reduce AP in spinal cord
2. Conduction of nerve AP in motor neurone (LA): blocks sodium channel = less AP conducted to somatosensory centre in brain
3. ACh release (hemicholinium) : Ca2+ entry blockers, used when neurotoxins reduce ACh causing muscle paralysis
4. Depolarisation of motor end plate AP inhibition (tubocurarine and suxamethonium)
5. Propagation of AP along muscle fibre and muscle contraction (spasmolutics eg dentrohene)

Question 3

Summarise the effects of two types of NMJ drugs

Answer 3

1. Non depolarising competitive antagonist eg tubocurarine and antracurium
2. Depolarising nicotinic antagonist Eg suxamethonium

These drugs do not effect consciousness or pain and must always assist respiration until drug is inactive or antagonised because relaxes skeletal muscle

Question 4

Describe the structure of the drugs

Answer 4

Non depolarising - big, bulky, relatively restricted movement around the bonds

suxamethonium is made up of 2 acetylcholine molecules that are linked together which is much more flexible and allows movement and rotation. One sexamethonium can bind to two alpha subunits and stimulate receptor

Question 5

Describe the MOA of suxamethonium and its pharmacokinetics and unwanted effects

Answer 5

MOA- extended end plate polarisation, depolarisation block at NMJ called a phase 1 block, suxamethonium over stimulates receptor causing them to shut down. It also causes fasiculations (individual fibre twitches) leading to flaccid paralysis

Pharmacokinetics - IV highly charged, duration of paralysis - 5 mins, metabolised by pseudocholinesterase In the liver and plasma. It’s used for endotracheal intubation and muscle relaxant for electroconvulsive therapy.

Unwanted effects: post-operative muscle pain, bradycardia, hyperkalaemia, high intraocular pressure

Question 6

Describe the MOA, pharmacokinetics and unwanted effects of tubocurarine

Answer 6

Tubocurarine is a naturally occurring quaternary ammonium compound, MOA: competitive nAChR antagonist, same effect as suxamthethonium - flaccid paralysis and muscle relaxe of eye, face and limbs and pharynx

Used in muscle relaxation in surgery, permit artificial ventilation.

Pharmacokinetics: IV and doesn’t cross BBB or placenta duration of paralysis is 1-2 hours. And excreted in urine and bile.

Unwanted effects : ganglionic block, histamine release, hypotension, tachycardia, brinchospasm