Neuromuscular blocking drugs Flashcards
what neurotransmitters are used in the somatic nervous system?
Ach
-goes onto skeletal muscles
how does nACHR differ in NMJ?
The NMJ nAChR is different in structure to the ganglionic (ANS) nAChR and so we can produce selective drugs just for the somatic nervous syste
describe NM transmission
NM transmission – production of ACh using CAT AP propagation Ca2+ influx ACh exocytosis ACh binds to receptors and Na+ influx ACh esterase breaks down ACh à recycling by uptake.
what are 3 most important NM-blocking drugs?
o Competitive – tubocurarine, atracurium.
o Depolarising – suxamethonium.
what are the subunits in the nicotinic acetylcholine receptor?
There are 5 subunits in the receptor; a1, a2, b, d, g.
which subunit receptor does ACh bind to?
ACh only binds to the alpha receptors.
describe the density of these receptors on the motor-end plate
The density of these receptors on the motor-end plate is VERY high.
what is the difference between the extracellular and intracellular domains?
There is a large extracellular domain and a slightly smaller intracellular domain.
give examples of spasmolytics \+ where do spasmolytics act \+ what do they do?
e.g. Diazepam, Baclofen.
o Target central processes within the nerve cell.
o Spasmolytics relieve spasm of the muscles
local anaesthetics
where do they act?
Inhibit the influx of sodium and so reduce the propagation of the AP along the nerve.
Hemicolinium,
where do they act +
what do they do?
Hemicolinium, Ca2+-entry blockers, neurotoxins.
o Inhibit re-uptake of choline.
Tubocurarine, suxamethonium.
where do they act
o These react on the post-synaptic membrane.
Spasmolytics – e.g. Dantrolene.
where do they act/hat do they do?
PROPAGATION OF AP ALONG MUSCLE FIBRE + MUSCLE CONTRACTION
what are the two types of postsynaptic NM blocking drugs?
non-depolarising
depolarising
give examples of non-depolarising postsynaptic NM blocking drugs
competitive antagonists
o Tubocurarine.
o Atracurium.
give examples of depolarising
agonists - cause depolarising block
Suxamethonium/Succinylcholine.
-this is so good at stimulating due to its very similiar structure to Ach
what are the key points to remember about post-synaptic neuromuscular blocking drugs?
§ These drugs do NOT affect consciousness or pain sensation.
§ Respiration must ALWAYS be assisted when taking these drugs (until the drug is inactive or is antagonised).
what is the method of action of suxamethonium?
o Causes a long (takes a long time to break down in the synaptic cleft) depolarising block.
o Also causes fasciculations (brief twitches of muscle fibres) à flaccid (loss of tone) paralysis.
what are the pharmokinetics of suxamethonium?
o Administration – IV (it is highly charged and so IV is best ROA).
o Duration of paralysis is short (~5 minutes).
o Metabolised by a pseudo-cholinesterase in the liver and plasma.
what are the uses of suxamethonium?
o Intubation – relaxes vocal chords.
o Muscle relaxant for ECT (ElectroConvulsive Therapy
what are the unwanted effects of suxamethonium?
o Post-op muscle pains.
o Bradycardia – direct muscarinic action of the heart.
o Hyperkalaemia – soft tissue injuries or burns à ventricular arrhythmias/MI.
o Increase in IOP – thus avoid for glaucoma patients.
what are the methods of actions of tubocuraine?
(non-depolarising NM blocker)
o A competitive nAChR antagonist.
o A block of 70-80% is necessary to cause effect of skeletal muscle relaxation.
what are the effects of tubocuraine?
o Tubocurarine à flaccid paralysis.
o The flaccid paralysis then affects the muscles in a particular order:
§ Extrinsic eye muscles (double vision).
§ Small muscles of the face, limbs and pharynx.
§ Respiratory muscles.
o The recovery of this effect then works backwards and rewinds the effects.
§ I.E. eye muscles are blocked first and recover last!
what are the uses for tubocurarine?
o Relaxation of skeletal muscles during surgical operations (so less anaesthetic needed).
o Permits artificial ventilation – as it relaxes the respiratory muscles.
