Neuromuscular Blockers Flashcards
Somatic nervous system
NMJ
Nicotinic Cholinergic receptor at skeletal muscle
Single neuron pathway
Membrane depolarization + AP generation
Threshold has to be reached to fire AP
Degree of depolarization proportional to number of synaptic vesicles released
1-3 vesicles —> miniature endplate potential
100s of vesicles required to generate AP
Therapeutic uses of neuromuscular blocking drugs
1 - facilitate endotracheal tube intubation
2 - facilitate surgery with less anesthesia
3 - alignment of fractures in ortho procedures
4 - electroshock treatment of psychiatric disorders
Important usage considerations for neuromuscular blocks
NOT therapeutic used alone
DO NOT provide tranquilization, anesthesia, analgesia
Need mechanical ventilation due to respiratory muscle paralysis
Classes of neuromuscular blockers
- Non-depolarizing competitive blockers
- Depolarizing blockers
Non-depolarizing competitive blockers
D-tubocurarine, pancuronium, atracurium
Bind with high affinity to Nm but do not activate (no depolarization > no contraction)
Need to block 70-80% Nm to block contraction
Can be overcome by increasing [ACh] —> causes rightward shift in agonist curve in presence of fixed conc of competitive antagonist
Mechanisms to increase ACh at synapse
Increase nerve stimulation
Inhibit acetylcholinesterase activity
D-tubocurarine
Used in poison arrow
Not orally bioavailable (prey edible)
Not cross BBB
Concentrates at NMJ
IV administration / widely distributed
Short onset time, long duration
Not significantly metabolized in animals
Progressive paralysis: fingers, orbit > limbs > trunk > neck > intercostals > diaphragm
Histamine-mediated vasodilation > hypotension
Pancuronium
Synthetic steroid derivative; used in place of d-tubocurarine
Long duration, metabolized by liver, eliminated by kidney
Does not cause histamine release > decrease circulatory complications
Atracurium
Fast onset, intermediate duration
Hydrolyzed by plasma esterases, spontaneous degradation
Elimination does NOT involve liver (ok in liver disease)
Small liability for histamine release > hypotension
Depolarizing blockers - succinylcholine
Insurmountable antagonist producing effect by desensitizing receptor at NMJ
Hydrolyzed by plasma pseudocholinesterase, only iV administration
Ultra short onset time, very short duration (humans)
Effects not reversed by AChE inhibitors
Biphasic action of succinylcholine
Phase I - activate Nm receptors, muscle stimulation; compound slow off-rate; membrane repolarization prevented
Phase II - sodium channel eventually closes + membrane repolarizes; succinylcholine doesn’t leave binding site, so ACh cannot activate
