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
State and explain 4 unwanted effects of suxamethonium.
Post-operative muscle pains (Due to initial fasciculations)
Hyperkalaemia: soft tissue injury/ burns results in loss of some neurones innervating the tissue, + upregulation of receptors in skeletal muscle= deinnervation supersensitivity, causes exaggerated response with a bigger influx of Na+ + bigger efflux of K+
Bradycardia: due to direct muscarinic action on the heart (usually prevented by atropine (muscarinic antagonist) in the pre-med)
Raised intraocular pressure: AVOID for eye injuries + glaucoma
Describe the mechanism of action of tubocurarine.
Competitive nicotinic ACh receptor antagonist.
70-80% block to achieve full relaxation of the muscles
Describe the order of relaxation of skeletal muscles and the order in which they return back to normal when given tubocurarine.
Causes flaccid paralysis.
Order:
Extrinsic eye muscles (1st to relax, last to go back to normal)
Small muscles of the face, limbs + pharynx
Respiratory muscles
State 2 uses of tubocurarine.
Relaxation of muscles during surgical operations (so less GA 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 the actions of NM blockers?
Atropine
Giving physostigmine will raise the synaptic concentration of ACh at ALL cholinergic synapses (not just NMJ’s) so need atropine to block these unwanted effects
How are all NM blockers administered?
Intravenously
What is the duration of paralysis of tubocurarine?
1-2 hours (long)
Describe the metabolism and excretion of tubocurarine?
NOT metabolised at all
Excreted in the urine (70%) + bile (30%)
Under which conditions would you get an increased duration of action of tubocurarine? What would you change under these conditions?
Impairment of hepatic or renal function increases duration of action
Under these conditions use ATRACURIUM (15 min duration) + is NOT affected by liver or kidney function
State 5 unwanted effects of tubocurarine.
Ganglion block + histamine release from mast cells cause most of the unwanted effects
HYPOTENSION: histamine acts on H1 receptors, causes vasodilation + ganglion blockade
TACHYCARDIA: reflex tachycardia in response to hypotension + blockade of vagal ganglion
BRONCHOSPASM: caused by histamine release
EXCESSIVE SECRETIONS (bronchial + salivary): histamine release
APNOEA: so need to assist respiration
