Flashcards in Neuromuscular Blocking Drugs Deck (25)
Describe how impulses are transmitted across synapses.
Action potential propagates along the presynaptic neurone -> depolarisation of presynaptic membrane -> opening of voltage gated calcium channels -> calcium influx -> vesicle exocytosis
What type of receptor is found at the neuromuscular junction?
Nicotinic acetylcholine receptors
Where are these receptors found on the muscle fibre?
Motor end plate (usually in the middle of the muscle fibres)
Where is acetylcholinesterase found?
It is bound to the basement membrane in the synaptic cleft
State the three main neuromuscule blockers.
State the two main types of nicotinic acetylcholine receptor.
How many molecules of acetylcholine are required to activate one nicotinic acetylcholine receptor?
What are the two types of neuromuscular blocker?
Describe the difference in mechanism of action between depolarising and non-depolarising NM blockers. Which NM blockers fall into each category?
Depolarising = suxamethonium = nicotinic acetylcholine receptor AGONIST
Non-depolarising = tubocurarine + atracurium = nicotinic acetylcholine receptor antagonist
How do NM blockers affect consciousness and pain sensation?
They do NOT
What must you always do when giving NM blockers?
Assist respiration because of their effect on respiratory muscle action
Describe the difference in structure between non-depolarising and depolarising NM blockers?
Non-depolarising = big, bulky molecules with limited movement around their bonds
Suxamethonium = made up of two acetylcholine molecules that are linked together. This is more flexible and allows rotation. As it is madeup of two acetylcholine molecules it can binds to the two alpha subunits and activate the receptor.
Describe the mechanism of action suxamethonium.
Suxamethonium is a nicotinic receptor agonist.
It causes an extended end plate depolarisation leading to a depolarising block of the NMJ
This is a phase 1 block
NOTE: it is not metabolised as rapidly as acetylcholine so it will remain bound to the nicotinic receptors making them switch off due to overstimulation
What does suxamethonium normally cause before causing the flaccid paralysis?
Fasciculations – individual fibre twitches as the suxamethonium begins to stimulate the nicotinic receptor (remember it is an agonist)
What is the duration of paralysis of suxamethonium?
How is suxamethonium metabolised?
It is metabolised by pseudocholinesterase (butyrylcholinesterase) in the liver and plasma
What are some uses of suxamethonium?
Endotracheal intubation – relaxes the muscles of the airways
Muscle relaxant for electroconvulsive therapy – treatment for severe clinical depression
State and explain four unwanted effects of suxamethonium.
Post-operative muscle pains
Due to initial fasciculations
If there is soft tissue injury or burns you will lose some neurones innervating the tissuea
Then you will get upregulation of receptors in the skeletal muscle – deinnervation supersensitivity
So if you give suxamethonium you get an exaggerated response with a bigger influx of sodium and bigger efflux of potassium
This is due to the direct muscarinic action on the heart
This effects tends to be prevented because suxamethonium is usually given after GA and hence following administration of atropine (muscarinic antagonist) in the pre-med
Raised intraocular pressure
AVOID for eye injuries and glaucoma
Describe the mechanism of action of tubocurarine.
Tubocurarine is a competitive nicotinic acetylcholine receptor antagonist.
You only need 70-80% block to achieve full relaxation of the muscles
If you block this proportion of the receptors then the end-plate potential generated will NOT reach the threshold
State two uses of tubocurarine.
Relaxation of muscles during surgical operations (this means that less general anaesthetic is needed)
Permit artificial ventilation
How can the actions of NM blockers be reversed?
Give an anti-cholinesterase (e.g. physostigmine)
What else must you give with this drug when trying to reverse theactions of NM blockers?
Giving physostigmine will raise the synaptic concentration of acetylcholine at ALL cholinergic synapses (not just the neuromuscular junctions) so you need some atropine to block these unwanted effects
How are all NM blockers administered?
What is the duration of paralysis of tubocurarine?