Lecture 12: Muscle Relaxants and Local Anesthetics Flashcards
botulinium toxin
prevents release of ACh (no synaptic vesicle fusion)
- adverse effects may include some anti-cholinergic FX
alpha-latrotoxin
from black widow
- promotes Ach release and leads to depletion of ACh stores
bungarotoxins
alpha - irreversibly binds to and blocks the nAChRs at the NMJ (paralysis)
beta - prevents release of ACh from motor nerve endings
curare
D-tubocurarine is active ingredient in curare which causes non-depolarizing block of nAChRs
- not available orally, so on the tip of poison arrows it’ll paralyze you but if you eat the animal you kill with the poison arrows it won’t affect you.
histrionicotoxin
binds and blocks nAChR (open channel blocker)
pharmacology of D-Tubocurarine
- given parenterally (no bioavailability)
- poor membrane penetration (which is why you can’t give orally)
- excreted in the urine unchanged
- blockage lasts 20 min - 2 hours
- onset of 2-3 minutes (too slow for intubation)
- causes BP drop and histamine release
pancuronium
similar MOA to D-tubocurarine (will cause non-depolarizing block of nAChR)
- also blocks M2 AchRs which leads to increases in HR (agonism of M2 leads to decreased HR meaning antagonism causes increased HR)
- also blocks NE uptake - further increases in HR and vasocontriction
used for general anesthesia and to facilitate mechanical ventilation
adverse FX: CV actions, slow onset (3 min) and duration (86 min)
basically it’s the same as curare except it doesn’t cause an allergic reaction
vercuronium
nondepolarizing NMJ blocker
- less potent at M2 ACh R
Rocuronium
nondepolarizing NMJ blocker
- less cardiac effects, doesn’t antagonize M2 Rs in the heart
- rapid onset with moderate duration
What kind of block does sugamadex reverse?
Non-depolarizing blocks of the NMJ by rocuronium (also vercuronium a bit)
- within 8 min, sugamadex will mop up all the rocuronium and reverse the block
Neostigmine, physostigmine, and edrophonium are all…
what are they used for?
AChE inhibitors
- they will reverse a non-depolarizing block by allowing more ACh to accumulate in the synapse and out-compete the blocker
used after surgery to reverse the block
can also be used symptomatic treatment of myasthenia gravis
interaction of nondepolarizing NMJ blockers with calcium channel blockers and amino glycoside antibiotics like streptomycin
calcium channel blockers - increase the block of nondepolarizing (competitive) and depolarizing blockers
amino glycosides decrease ACh release from cholinergic fibres (synergy with competitive blockers)
Depolarizing NMJ blockers (2)
decamethonium
succinylcholine
(actually bind the nAChR and allow cation influx)
Difference in metabolism between ACh and Succinylcholine
ACh is metabolized by AChE while sucicnylcholine is only metabolized by plasma cholinesterase, which isn’t in the NMJ at high conc.
How do you treat rare malignant hyperthermia associated with succinylcholine
dantrolene - stops calcium release from SR
Myasthenia gravis
what is it and what are diff ways to treat it
low concentrations of nAChR (no change in ACh or AChE at NMJ)
treat with
- AChE inhibitors like pyridostigmine with adjunct atropine to block increased incidence of muscarinic effects
- corticosteroids like prednisone to suppress immune system
- thymus removal
How does amide or ester linkage affect metabolism of local anesthetics?
amide link - longer half life, hepatic metabolism
ester link - shorter half life, AChE will break it down (think of the esteratic site of AChE)
Local anesthetics with either ester or amide linkage (2 from each)
ester - procaine, tetracaine
amide - lidocaine, bupivacaine
how does addition of epinephrine affect admin of local anesthetic
local epi will constrict small blood vessels in the skin and thus localize the drug to a specific area - reduce blood flow away from the site
methemoglobinemia
oxidation of hemoglobin to methemoglobin by “caine” oxidizing agents
- can be reversed by methylene blue (electron donor to reduce the hemoglobin back)
How does ionization affect local anesthetics
if it’s charged it can’t diffuse away
