TOXINS Flashcards
tetanus
-directly targets GABAergic neurons
-normally- GABAergic neurons make it harder for PMC to get AMN to threshold by hyperpolarizing the AMN with chloride (PMC uses glutamate which depolarizes)
-when tetanus gets into body, it knocks out synaptobrevin in GABAergic neuron so it can’t dock to AMN -> AMN becomes hyperactive + reaches tetanus/max contraction
-synaptobrevin = snare protein
botulinum
-directly targets AMN
-all botulinum variants knock out a type of snare protein so that AMN can’t release ACh
-B, D, F, G: knocks out synaptobrevin of AMN so that it can’t release ACh
-A, E, C1: knocks out SNAP-25 of AMN so that it can’t release ACh
-SNAP-25 = snare protein
-AMN won’t pass APs to skeletal muscle + paralysis will occur
succinylcholine
-paralytic drug used in emergency/tracheal intubation
-normally- immediately after ACh disassociates from nicotinic cholinergic receptors in NMJ, ACh esterase degrades ACh into choline + acetate -> acetate diffuses away + choline is reuptaken
-succinylcholine mimics ACh to bind to nicotinic cholinergic receptors + open them -> keeps receptors chronically open so that NMJ is chronically depolarized -> it is impossible to repolarize so voltage-gated sodium channels can’t reset -> APs can’t be fired to skeletal muscle, paralytic effect
-succinylcholine is an AGONIST + is very resistant to ACh esterase
-voltage-gated sodium inactivation gates can’t reopen until reaches -75mV
-succinylcholine can be degraded by esterase’s but if used for too long/high degree phase 2 block will occur -> nicotinic cholinergic receptors are desensitized to ACh + fibers can’t contract
pancuronium
-binds to nicotinic cholinergic receptors to block them from ACh -> skeletal muscle can’t generate APs so muscle can’t contract
-there are drugs to reverse pancuronium -> inhibit ACh esterase to increase ACh concentration -> ACh + pancuronium compete + ultimately nicotinic cholinergic receptor will depolarize enough to send AP
