Neuromuscular blocking drugs Flashcards
How is acetylcholine synthesised?
From acetyl CoA and Choline by choline acetyltransferase (CAT)
Where is CAT only found?
Cholinergic nerve terminals
What is the end plate potential?
The depolarisation of the membrane that occurs due to a receptor being stimulated and influx of sodium ions
The end plate potential is graded, what does that mean?
The size of the potential depends on how much acetylcholine is released and how many receptors are stimulated- once it reaches a threshold it will generate an action potential
Where is acetylcholinesterase found?
In the synaptic cleft bound to the basement membrane
What does acetylcholinesterase break acetylcholine down into?
Acetate and choline
What are the three main neuromuscular blockers?
Tubocurarine
Atracurium
Suxamethonium
What are the two main subtypes of nicotinic receptors?
Ganglionic (or neuronal)
Muscle
What do spasmolytics do?
Potentiate the actions of GABA
Name two spasmolytics and what they do?
Diazepam- facilitates GABA transmission
Baclofen- GABA receptor agonist
What conditions are spasmolytics useful for?
Some forms of cerebral palsy and spasticity following stroke
What do local anaesthetics act on?
Conduction of action potentials down motor neurones (use leads to muscle weakness)
What toxins interfere with acetylcholine release and how?
Neurotoxins- Toxic and lethal because they inhibit release of acetylcholine and block contraction of respiratory skeletal muscle causing death
Botulinum is the same
Which two types of drugs act on depolarisation of the motor end plate?
Depolarising- Suxamethonium
Non-depolarising- Tubocurarine
How does dantrolene work?
It is a spasmolytic that works in the muscle fibres themselves- this inhibits calcium release in the muscle fibre
Where do neuromuscular blocking drugs act?
Post-synaptically on nicotinic receptors on the motor end plate
If they are non depolarising, what sort of neuromuscular blocking drug are they?
Competitive nicotinic receptor antagonists e.g. tubocurarine and atracurium
If they are depolarising, what sort of neuromuscular blocking drug are they?
Nicotinic receptor agonists e.g. suxamethonium
What effect do these drugs have on consciousness and pain sensation?
None
What do you always have to do when giving these drugs?
Assist respiration due to effect on respiratory muscles
What is the structure of non-depolarising drugs like?
Big, bulky molecules with relatively restricted movement around the bonds
What is the structure of suxamethonium like?
Made up of two acetylcholine molecules that are linked together
What does the difference in structure between suxamethonium and non-depolarising drugs mean?
Suxamethonium is such more flexible and allows rotation
As it is made up of two acetylcholine units, one suxamethonium can bind to two alpha subunits and stimulate the receptor
How does suxamethonium work?
It causes a phase 1 block- extended endplate depolarisation (overstimulation) which leads to a depolarisation block of the NMJ
Suxamethonium causes fasciculations, what are these?
Individual fibre twitches as the suxamethonium begins to stimulate muscle fibres- this leads to flaccid paralysis- no muscle tone
How is suxamethonium administered?
IV
How long does the paralysis due to suxamethonium last?
5 minutes
What is suxamethonium metabolised by?
Pseudocholinesterase in liver and plasma
What is suxamethonium used for?
Endotracheal intubation- relaxes skeletal muscle of airways
Muscle relaxant for electroconvulsive therapy- treatment for severe clinical depression
What are the unwanted effects of suxamethonium?
Post-op muscle pains due to fasciculations
Bradycardia- direct muscarinic effect on heart
Hyperkalaemia
Raised intraocular pressure- avoid for glaucoma
What is tubocurarine?
Non-depolarising neuromuscular blocker
What is the mechanism of action of tubocurarine?
Competitive nicotinic acetylcholine receptor antagonist
What percentage block do you need to reach to achieve full relaxation of the muscles?
70-80%- at this point end plate potential won’t reach the threshold
What are the effects of tubocurarine?
Same as suxamethonium including flaccid paralysis
What is the certain sequence that skeletal muscles relax in?
Extrinsic eye muscles
Small muscles of the face, limbs and pharynx
Respiratory muscles
What is the sequence of the skeletal muscle returning back to normal?
The opposite to the relaxing schedule:
Respiratory muscles
Small muscles of the face, limbs and pharynx
Extrinsic eye muscles
What is tubocurarine used for?
Relaxation of skeletal muscles during surgical operations (less anaesthetic needed)
Permit artificial ventilation
How can you reverse the actions of these non-depolarising neuromuscular blockers?
With anti-cholinesterase - They increase the concentration of acetylcholine so it can outcompete the antagonist
What is an example of a reversible anti-cholinesterase?
Neostigmine
Why do you give atropine when giving neostigmine?
With neostigmine, you increase acetylcholine concentration in all other cholinergic synapse so atropine will block muscarinic receptor over stimulation
How are all NM blockers given?
IV
How long does tubocurarine cause paralysis for?
40-60mins
How does your body get rid of tubocurarine?
It isn’t metabolised at all, it is excreted in urine (70%) and bile (30%)
What increases the duration of action of tubocurarine?
Impairment in hepatic or renal function
What would you use if the patient did have hepatic or renal impairment?
Atracurium (15 min duration of action and isn’t affected by hepatic or renal function)
What are the unwanted effects of tubocurarine?
Ganglion block
Histamine release from mast cells
Hypotension- due to ganglion blockade and histamine causes vasodilation
Tachycardia- reflex to hypotension
Bronchospasm- due to histamines
Excessive secretions- caused by histamine release
Apnoea- this is why you assist respiration
