neuromuscular blocking drugs

Question 1

2 classes of NM blocking drugs, and where they both act with regard to synapse

Answer 1

competitive (non-depolarising), depolarising; both act post-synaptically

Question 2

sites of drug action which cause relaxation of skeletal muscles in order

Answer 2

central processes, conduction of nerve action potential in motor neurone, ACh release, depolarisation of motor end-plate action potential initiation, propagation of action potential along muscle fibre and muscle contraction

Question 3

class of drugs affecting central processes and how they work

Answer 3

spasmolytics (GABAergic drugs: diazepam, baclofen; used to treat spasticity in MS etc.); work in spinal cords to reduce action potentials around cell body

Question 4

class of drugs affecting conduction of nerve action potential in motor neurone

Answer 4

local anaesthetics (block voltage-sensitive Na+ channels; if too close to motor fibre, not beneficial as skeletal muscle fibre weakness, so inject around terminals of sensory fibres)

Question 5

3 classes of drugs affecting ACh release

Answer 5

hemicholinium (blocks reuptake of choline), Ca2+ entry blockers, neurotoxins (e.g. botulinum: interacts with and inhibits proteins which mediate ACh release, potentially causing respiratory arrest)

Question 6

drugs affecting depolarisation of motor end-plate action potential initiation

Answer 6

NMJ blockers: tubocurarine, suxamethonium

Question 7

class of drugs affecting propagation of action potential along muscle fibre and muscle contraction

Answer 7

spasmolytics (dantrolene) by reducing release of Ca2+ ions in SR in skeletal muscle, causing relaxation of skeletal muscle to improve functionality

Question 8

non-depolarising NM blocking drugs

Answer 8

competitive nAChR antagonists, e.g. tubocurarine, atracurium

Question 9

depolarising NM blocking drugs

Answer 9

nAChR agonists, e.g. suxamethonium (same as succinylcholine - 2 molecules of ACh attached together)

Question 10

NM blocking drugs effects and susbequent assisting actions

Answer 10

don’t affect consciousness or pain sensation - purely relax muscle, so must always assist respiration as these cause muscle relaxation (until drug inactive or antagonised)

Question 11

structure-activity relationship between ACh and NM blocking drugs

Answer 11

very similar, with antagonists being more bulky and rigid with less rotation (e.g. tubocurarine), and agonists having more free rotation (good efficacy; e.g. suxamethonium)

Question 12

suxamethonium: mechanism of action

Answer 12

produces extended end-plate depolarisation, over-stimulating nAChR so it shuts down (depolarisation/phase 1 block); when diffuses into muscles, fasciculations (twitching) as stimulates individual fibres, before generating flaccid (relaxing) paralysis as not rapidly broken down, so receptor system shuts down

Question 13

suxamethonium: pharmacokinetics (administration, duration and metabolisation)

Answer 13

given IV (as highly charged), short acting NM blocker so short duration of paralysis (5 minutes), metabolised by pseudo-cholinesterase in liver and plasma

Question 14

suxamethonium: 2 uses

Answer 14

endotracheal intubation (for administering drugs or tube), muscle relaxant for electro-convulsive therapy (for severe depression)

Question 15

suxamethonium: 4 unwanted effects

Answer 15

post-operative muscle pains (due to fasciculations), bradycardia, hyperkalaemia, increased intra-ocular pressure

Question 16

suxamethonium: why is bradycardia caused, and what is administered to prevent it

Answer 16

directly stimulates muscarinic action of heart (atropine given to block this effect)

Question 17

suxamethonium: why is hyperkalaemia caused and how is it prevented

Answer 17

if reduced innervation to afferent input (e.g. soft tissue injury or burns), more nicotinic receptors onto end-plate region or along entire length to compensate for lower signal (denervation supersensitivity); when suxamethonium administered, big Na+ influx and big K+ efflux, leading to ventricular arrhythmias and cardiac arrest; avoid by giving non-depolarising NM blocker

Question 18

suxamethonium: patients to avoid due to raising intra-ocular pressure

Answer 18

eye injuries, glaucoma