neuromuscular junction - pharmacology Flashcards
describe the events that take place in a synapse
- Action potential propagated in motor neuron -
- voltage gated calcium channels open
- acetylcholine released into cleft
- acetyl choline binds receptor
- receptor’s ion channel opens
- acetylcholine destroyed by acetylcholinesterase
describe how an aciton potential activates a muscle fiber contraction
acetyl choline binds to sodium channels, they open and allow depolarizaiton of cell and the action potential continues in both directions
what sort of drug blocks the neuromuscular junction ?
neurotoxins
- including agonists and antagonists of the nAChR
inhibitors of the AChE - acetyl choline esterase breaks down ACh so if you block this enzyme you’ll build up on ACh
what are the sites of pharmacologic effects in neurotransmission at the skeletal neuromuscular junction?
post synaptic (mainly used clinically)
- nicotinic acetylcholine receptor -agonists/antagonists
- acetylcholinesterase-block enzyme from breaking down ACh
pre-synaptic
- machinery of exocytosis - block vesicle releases ACh
- presynaptic Ca2+ channel
what drugs activate the ACh receptor?
Acetylcholine
Nicotine
Carbachol
Suxamethonium (succinylcholine)
what drugs block the ACh receptor?
D- Tubocurare
Pancuronium
What is the use of D-Tubocurarine?
it is a non-depolarizing agent so it blocks the ACh at the receptor region - by inhibiting binding
used during surgical anaesthesia to paralyse skeletal muscle
What is Pancuronium used for?
more potent than tubocurarine - synthetic substance also used for relaxing muscles during surgery -
What is alpha-bungarotoxin used for?
synthesized from cobra toxin - bind essentially irreversibly to nAChR and block neuromuscular junction function
What does succinylcholine do?
it is an AChR agonist - that depolarizes the NM blocker - causes initial muscle twitches then relaxation/paralysis
explain how acetylcholine receptor agonists work
voltage gated ion channels have an inactivation gate - so shortly after a depolarization, an internal portion swings in and blocks the sodium channel
the agonists of the receptor inhibit the ACh esterase - so more of the nuerotransmitter remains in the junction maintaining the signal for longer - so the inactivation gate stays disengaged for longer -
how do antagonists of the neuromuscular junction work?
they are blockers of the pre-synaptic Ca2+ channel -
Mg2+ ions - compete with Ca2+ entry to reduce ACh release - magnesium salts once used as anaesthetics
how do anaesthetists decide which anesthesia to use?
they chose the right drug with a half-life closest to the time of the surgery
*different muscles repond differently to the blockers
what do m-conotoxins do?
they block the particular voltage gated Na+ channel on skeletal muscles - cause paralysis but ACh still released in response to nerve stimulation
what does w-conotoxin do (omega) ?
blocks the Ca2+ channel at the presynaptic junction inhibiting ACh release