Neuromuscular blocking drugs Flashcards
Describe the somatic nervous system pathway
One motor neurone to the skeletal muscle, releasing ACh
Explain the process of neuromuscular transmission
- Acetylcholine is loaded into vesicles
- AP depolarises the membrane
- Calcium intake
- ACh released from the pre-synaptic vesicles
- ACh diffuses across the synapse
- ACh binds to nicotinic ACh receptors on the end-plate region
Describe the action of nicotinic acetylcholine receptor
- Ach binds to the alpha subunit of the receptor
- Channel opens
- Sodium ions influx
Which NM drugs target conduction of nerve AP in motor neurones
Local anaesthetics
Which NM drugs target ACh release
Hemicholinium
Calcium entry blockers
neurotoxins
Which NM drugs target Depolarisation of motor end-plate -> AP initiation
Tubocurarine
Suxamethonium
Which NM drugs target propagation of AP along muscle fibres + muscle contraction
Spasmolytics e.g. dantrolene
Describe neuromuscular blocking drugs with postsynaptic action
Non-depolarising (competitive antagonist) or depolarising (agonist)
They do not affect consciousness or pain sensation
Always assist respiration
Give examples of non-depolarising and depolarising NM drugs
Non-D = tubocurarine, atracurium
D = suxamethonium
What is the mode of action for suxamethonium
Extends end-plate depolarisation to cause a depolarisation block
Fasciculations -> flaccid paralysis
Describe the pharmacokinetics of suxamethonium
IV (highly charged)
Duration of paralysis = 5 mins
Metabolised in pseudo-cholinesterase in liver and plasma
What are the uses of suxamethonium
Endotracheal intubation
Muscle relaxant for electroconvulsive therapy
What are the unwanted effects of suxamethonium
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)
Describe tubocurarine and its mode of action
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
What are the effects of tubocurarine
Flaccid paralysis
Extrinsic eye muscles (double vision)
Small muscles of face, limbs, pharynx
Respiratory muscles
Describe the effect of tubocurarine on NM transmission (voltage-wise)
Recording from endplate - very small AP peak of -60
Away from endplate - no AP seen
What are the uses of tubocurarine
Relaxation of skeletal muscles during surgical operations (less anaesthetic needed)
Permits artificial ventilation
How may the actions of non-depolarising blockers be reversed
Anticholinesterases
e.g. neostigmine (+atropine)
Describe the pharmacokinetics of tubocurarine
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)
What are the unwanted effects of tubocurarine
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)
Which drugs target the central processes of NMJ action
Spasmolytics e.g. diazepam, baclofen
