Neuromuscular Blocking Drugs Flashcards
Describe how impulses are transmitted across synapses.
AP propagates along presynaptic neurone Depolarisation of presynaptic membrane Opening of VGCC Ca2+ influx Vesicle exocytosis
What type of receptor is found at the neuromuscular junction?
Nicotinic acetylcholine receptors
Where are nicotinic receptors found on the muscle fibre?
Motor end plate (usually in the middle of muscle fibres)
What does depolarisation of the membrane on muscle fibres cause? Describe the character of this depolarisation.
Change in end plate potential
This is a graded potential, thus is dependent on the amount of ACh released + the number of receptors stimulated
Once the EPP reaches a threshold, it generates an AP that propagates in both directions along the muscle fibre
Where is acetylcholinesterase found?
Bound to the BM in the synaptic cleft
State the 3 main neuromuscular blockers.
Tubocurarine
Atracurium
Suxamethonium
State the 2 main types of nicotinic acetylcholine receptor.
Ganglionic
Muscle
Describe the structure of nicotinic acetylcholine receptors.
Consist of 5 subunits (alpha, beta, gamma, delta, epsilon)
Always 2 alpha subunits, which bind to ACh + activate the receptor
How many molecules of acetylcholine are required to activate one nicotinic acetylcholine receptor?
2
Name two drugs that are used as spasmolytics and describe their action.
Diazepam
Baclofen
Both facilitate GABA transmission
Work in spinal cord to reduce generation of APs
Give 2 examples of conditions in which spasmolytics may be used.
Certain forms of cerebral palsy
Spasticity following strokes
What do local anaesthetics have their effect on?
Conduction of AP’s in motor neurones (injecting LA’s to a motor neurone causes muscle relaxation + weakness)
Describe the action of neurotoxins.
Inhibit the release of ACh + hence block contraction of respiratory skeletal muscle causing death
What are the two types of neuromuscular blocker?
Depolarising
Non-depolarising
Name a spasmolytic that has a different action to diazepam + baclofen
Dantrolene
Acts in muscle fibres themselves by inhibiting Ca2+ release from SR in the muscle fibre
Describe the difference in mechanism of action between depolarising and non-depolarising NM blockers. Which NM blockers fall into each category?
Depolarising = suxamethonium = nicotinic ACh receptor AGONIST Non-depolarising = tubocurarine + atracurium = nicotinic ACh 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 2 ACh molecules linked together: more flexible + allows rotation. As it is made up of 2 ACh molecules it binds to the 2 alpha subunits + activates the receptor.
Describe the mechanism of action suxamethonium.
=nicotinic receptor agonist.
Causes an extended end plate depolarisation leading to a depolarising block of the NMJ = a “phase 1 block”
Not metabolised as rapidly as ACh so will remain bound to receptors making them switch off due to overstimulation
Results in FLACCID PARALYSIS
What does suxamethonium normally cause before causing the flaccid paralysis?
Fasciculations: individual fibre twitches as the suxamethonium begins to stimulate the nicotinic receptor
What is the duration of paralysis of suxamethonium?
5 mins (short)
How is suxamethonium metabolised?
By pseudocholinesterase in the liver + plasma
What are some uses of suxamethonium?
Endotracheal intubation: relaxes muscles of the airways
Muscle relaxant for electroconvulsive therapy: treatment for severe clinical depression
