Intro to NMJ Pharmacology Flashcards
cisatracurium
nondepolarizing isoquinoline derivative
tubocurarine
nondepolarizing isoquinoline derivative
pancuronium
steroid derivative nondepolarizing agent
rocuronium
steroid derivative nondepolarizing agent
vecuronium
steroid derivative nondepolarizing agent
succinylcholine
depolarizing neuromuscular blocking agent
dantrolene
spasmolytic - muscle relaxant
echothiophate
acetylcholinesterase inhibitor
edrophonium
acetylcholinesterase inhibitor
neostigmine
acetylcholinesterase inhibitor
physostigmine
acetylcholinesterase inhibitor
pyridostigmine
acetylcholinesterase inhibitor
atropine
antimuscarinic
pralidoxime
cholinesterase reactivator
spasmolytics
centrally acting
nondepolarizing neuromuscular blocking agent
agonist at nAChR
depolarizing neuromuscular blocking agent
excess of depolarizing agonist
ex. succinylcholine
all neuromuscular blocking agents
highly polar and inactive orally
must be given parenterally**
quaternary nitrogen
make poorly lipid soluble - limit CNS entry
kidney excretion
longer half life
liver excretion
shorter half life
rocuronium
fast onset and short duration of action
diaphragm
last muscle to be paralyzed and quickest to recover
reversal of neuromuscular blockade
reversed with ACh or succinylcholine
also - may give cholinesterase inhibitor
edrophonium
pure cholinesterase inhibitor
neostigmine and pyridostigmine
cholinesterase inhibitor AND increase release of ACh at motor nerve terminal
large dose of neuromuscular blockade
enter pore of nAChR - more intense blockade - diminish ability of acetylcholinesterase inhibitor to antagonize effect
adverse of nondepolarizing agents
histamine release
-wheals, bronchospasm, hypotension
tubocuraine
declined use
- because of histamine release
- and very long duration of action
inhaled anesthetic
potentiate neuromuscular blockade
aging and neuromuscular response
longer duration of action with nondepolarizing agents in older patient - bc of reduced hepatic and renal function
so need to decrease dose**
usually age >70yo
myasthenia gravis
enhanced effect of neuromuscular blockade
severe burn and upper motor neuron disease
resistant to nondepolarizing agents
need higher dose
laudanosine
breadown product of atracurium and cisatracurium
high concentration in brain - seizures
long acting steroid relaxant
pancuronium
high potency
intermediate acting steroid relaxant
vecuronium and rocuronium
steroid nondepolarizing agent for several days in ICU
3 hydroxy metabolite can cause prolonged paralysis
least tendency for histamine release
steroid neuromuscular blocking agents
paralysis for >1 hour
pancuronium
rapid time of onset, intermediate duration, low potency
rocuronium
rapid onset anesthesia
rocuronium
2-4 minute onset (slower), intermediate duration, high potency
vecuronium
succinycholine pharmacokinetics
ultra short duration of action
phase 1 succinylcholine block
depolarizing
depolarized membrane remains depolarized
-flaccid paralysis occurs
augmented by cholinesterase inhibitors
phase 2 succinylcholine block
desensitizing
initial end plate depolarization decreases and membrane repolarized
membrane unable to depolarize again - bc desensitized
reversed by AChE inhibitors
rapid sequence induction
succinylcholine
adverse effects of succinylcholine
cardiac arrhythmia
negative inotropic and chronotropic effect
larger dose - positive effects above
intraocular pressure
intragastric pressure
muscle pain
histamine release
CI for succinylcholine
fam hx of malignant hyperthermia
myopathies
major burn, multi trauma, denervation
black box warning succinylcholine
cardiac arrest risk
-health children with undiagnosed skeletal m myopathy
acute rhabdomyolysis, hyperK, ventricular dysrhythmia, cardiac arrest, and even death
tx of malignant hyperthermia
caused by abnormal release of Ca from stores in skeletal m
tx - dantrolene
first choice for rapid sequence intubation
succinylcholine
MOA dantrolene
inhibit RyR calcium channel
blocks release of Ca from SR
CI for dantrolene
no oral if hepatitis
MOA botulinum
cleave SNARE complex and block release of ACh
cholinesterase inhibitors
indirect acting
causes increase in ACh at synapse
butyrylcholinesterase
pseudocholinesterase
plasma and liver
acetylcholinesterase
in NMJ
edrophonium
alcohol AChE inhibitor
binding noncovalent and reversible
neostigmine
carbamic acid ester AChE inhibitor
noncovalent and reversible binding to AChE
pyridostigmine
carbamic acid ester AChE inhibitor
noncovalent and reversible binding to AChE
physostigmine
carbamic acid ester AChE inhibitor
noncovalent and reversible binding to AChE
echothiophate
organophosphate AChE inhibitor
tertiary and uncharged AChE inhibitors
CNS distribution
physostigmine
quaternary and charged AChE inhibitors
no CNS distribution
neostigmine, pyridostigmine, echothiophate
alcohol AChE inhibitors
short duration of action 2 - 10 mins
carbamic acid ester AChE inhibitors
30min to 6 hour action
organophosphate AChE inhibitors
hundreds of hours of action
aging
breaking of one O-P bonds of inhibitor
-further strengthens interaction
difficulty to break
organophosphate and tertiary AChE inhibitors
central and peripheral activity
tx of myasthenia gravis
pyridostigmine
neostigmine
ambenonium
do not cross BBB
dosing based on titrations
diagnosis of myasthenia gravis
edrophonium test
has been phased out
now - ice pack test - to fix ptosis temoprarily
myasthenic vs. cholinergic crisis
myasthenic - severe enough for intubation
cholinergic - side effect of excessive AChE inhibitors
differentiate two - edrophonium test
- myasthenic - symptoms improve
- cholinergic - symptoms unchanged or worsen
paralytic ileus tx
AChE inhibitors
tx of dementia
alzheimer type and parkinson association benefit from AChE inhibitor
physostigmine
crosses BBB
used as antimuscarinic antidote for intoxication
sx - vasodilation, anhidrosis, mydriasis, delirium, hallucinations
homicide and suicide
organophosphate and carbamate AChE inhibitors
sx - miosis, salivation, sweating, bronchial constriction, vomiting, diarrhea
route of admin - determines the sx
antidote - atropine - mAChR agonist
miosis
contraction of pupil
cholinesterase regenerator
pralidoxime
regenerate active enzyme from organophosphorous cholinesterase complex
give before aging
don’t reverse central effects - doesn’t enter CNS
prophylactic pyridostigmine
reduce incapacitation and mortality of nerve agent poisoning
for combat use military personnel
