Kruse - skeletal muscle relaxants - agents that act on NMJ Flashcards
admin of all nondepolarizing agents
paternal
shortest acting drug with most histamine release in nondepolarizing class.
What is notable about combination with AChE inhibitor?
mivacurium
prolong the NM blockade if combined with AChE inhibitor
long acting drug in nondepolarizing class that is CI in renal failure
doxacurium
MOA of NM blocking drugs
act at NMJ in skeletal muscle at post junctional folds of motor end plates
hypotension and tachycardia are AE of which drug in the nondepolarizing class
metocurine
AChR blockade at autonomic glanglia and adrenal medulla, causing hypotension and tachycardia
nondepolarizing class + ___antibiotic____ = enhance NM blockade?
aminoglycosides
Botulinum toxin, local anesthetics, tetrodotoxin - all do what to nondepolarizing agent?
enhance action
Use of nondepolarizing agents in myasthenia gravis does what?
enhances the muscle relaxation
Which steroid derivative has ultrashort DOA.
- elimination
- use
Rocuronium - bilary/hepatic elimination and used for jaw/laryngeal mm relaxation before intubation.
What drug has this MOA: nAChR agonist with longer effects at NMJ than ACh
succinylcholine
Phases and results of succinycholine action. What phase do AChE inhibitors affect?
- Phase 1 - depol MEP making it unresponsive to further impulses –> flaccid paralysis
- Phase 2 - membrane desensitized bc it cannot depol again after repolarizing (**AChE inhibitors work here!)
tansient mm fasciculations are caused by
succinylcholine
AChE inhibitors
what reverses actions of succinylcholine?
plasma cholinesterases
CI of succinylcholine
- malignant hyperthermia
- BLACK BOX: cardiac arrest
tx for malignant hyperthermia
dantrolene - a mm relaxant that inhibits RyR calcium channels, impairing muscle contraction
MOA of__: cleaves SNAR complex, blocking ACh release from vesicle
botulinum toxin
Overall MOA of acetylcholinesterase inhibitors
decrease AChE levels, thus increasing ACh levels throughout hte body
tertiary/uncharged AChE inhibitors (5)
Do they cross BBB?
which agent has high heaptotoxic agents?
donepezil* galantamine* physostigmine rivastigmine* tacrine*
Yes, do cross BBB = toxic.
*dementia
quaternary/charged AChE inhibitors (5)
Do they cross BBB?
ambenonium echothiophanate edrophonium neostigmine pyridostigmine
No, do not cross BBB = safer
Which AChE inhibitors are reversible?
the carbamic acid esters - noncovalent
ambenoium, neostigmine, physostigmine, pyridostigmine
Antidote for overexposure to organophosphate
pralidoxime and benzodiazepine - give pralidoxime BEFORE aging has occurred.
AChE inhibitors used for MG
ambenoium, neostigmine, pyridostigmine
prophylaxis for organophosphate poisoning
pyridostigmine
acute AChE inhibitor intoxication - sx
mAChR stimulation sx: miosis, salivation, sweating, bronchial constriction, V/D
-Earliest sx: GI, then sweating and muscle fasciculations
tx of acute AChE inhibitor intoxication/cholinergic poisoning. Need to coadminister with___.
atropine (mAChR antagonist)
coadminister with pralidoxime
use what class to tx dementia?
AChE inhibitor
use what class to treat glaucoma?
AChE inhibitor - reducing intraocular pressure via mAChR stimulation that facilitates aqueous outflow
drug used to reverse anticholinergic overdose (sx: cutaneous vasodilation, anhidrosis, delirium, hallucinations, reduced urination, anhidrotic hyperthermia –> SNS like effects)
Physostigmine
reverses nondepolarizing NM blocking drugs by increasing ACh
do not coadminister AChE inhibitors with ____ in pts with MG
systemic corticosteroids
Atropine is ineffective at what receptors?
nAChR
MOA of ____ : antagonist of the (NMDA) type of glutamate receptors. Why useful in Alzheimer’s Disease?
memantine
Pathologic or excessive receptor activation (AD), prevents
Mg from reentering and blocking the channel pore resulting in a chronically open state and excessive calcium influx
Memantine binds to the intra-pore Mg site, but with longer dwell time, and thus functions as an effective receptor blocker only under conditions of excessive stimulation. Does not affect normal neurotransmission.
