Pharm NMJ part II Flashcards
what are the clinical uses of NMJ blocking drugs
surgical relaxation
endotracheal intubation
control of ventilation
how do NMJ blockers help control ventilation
reduce chest wall R and improve thoracic compliance
permit adequate gas exchange and prevents atelectasis in patients who have ventilatory failure
pancuronium and vecuronium most common if >24 hours
MOA dantrolene
inhibition of RYR Ca Ch blocking release of Ca from SR and so no muscle contraction
side effects dantrolene
generalized muscle weakness, sedation, and occasionally hepatitis
what is dantrolene used for
Tx for spascitiy associated with UMN disorders and management of malignant hyperthermia
what patients are at risk for malignant hyperthermia
hereditary mutations in RyR gene
permits excessive Ca release from SR under certain triggering agents
increase Ca, increase lactic acid, increase temperature
what do we use to reduce Ca in malignant hyperthermia
IV dantrolene
MOA botulinum toxin
cleaves SNARE and blcoks release of ACh by preventing vesicle exocytosis
what is botulinum used for
generalized spastic disorders, cervical dystonia and blepharospasm
what are direct acting cholinomimetics
bind and activate mAChR and nAChR
what are indirect acting cholinesterase inhibitors
inhibit AChE increasing ACh in the celft
where is butyrylcholinesterase made
liver and found inliver and plasma
AChE is found where
highly [ ] postsynaptic end plate and prevents lateral diffusion from adjacent nAChRs
primary target for cholinesterase inhibiting drugs
AChE but also block BuChE
3 chemical groups of cholinesterase inhibitors
Alcohols
Carbamic acid esters
Organophosphates
how does alcohol work as AChE inhibitor
+ charged quaternary ammonium that binds to AChE noncovalently
how do carbamic acid esters work like AChEI
quaternary and tertiary ammonium groups that bind to AChE noncovalently
which AChEI are carbacmic acid esters
neostigmine, pyridostigmine, physostigmine, carbaryl
what AChEI are alcohols
edrophonium
what AChEI are organophosphates
echothiophate, parathion and malathion, sarin, soman, tabun
what is a precaution with organophosphates
CNS toxicity since neutrally charged and lipid soluble
bond between organophosphates and AChE
covalent and irreversible
what is preferred administration for the AChE I with quaternary ammoniums
parenteral
no CNS distribution
What are the tertiary uncharged AChE I and distribution?
physostigmine, donepezil, tacrin, rivastigmine, glantamine
CNS distrivution
what organophosphate is safe for use as insetidiced
malation
what is “aging” or organophosphates
phosphorylated enzyme will break one of the O-PO4 bonds of inhibitor and strenghten the bond
high [ ] effects of AChEI on CNS
generalized convulsions d/t neuronal hyperstimulation
effects of AChE I on eyes
contraction of iris
contraction of ciliary muscle
AChE I effects on hearat
Sympathetic and Parasympathetic
parasympathetic dominates and CO decreases
bradycardia
Tx myasthenia gravis
pyridostigmine, neostigmine and ambenonium
do not cross bbb
repeated dose every 2-8 hours
what is favored test for myasthenia gravis
ice pack test
Myasthenic crisis
life threatening condision defined as weakness from acquired myasthenia gravis that is severe enough to necessitate intubation
excessive AChE I use can lead to what
cholinergic crisis
Sx cholinergic crisis
muscle weakness
how to differentiate cholinergic crisis from myasthenic crisis
edrophonium test
myasthenic crisis Sx will get better
cholinergic crisis will remain unchanged
what AChE I are pregerred to reverse paralysis induced by NMJ blockers
neostigmine and edrophonium
Tx paralytic ileus, atony urinary bladder and congenital megacolon
AChE I
What is glaucoma
increased intraocular P
how do AChE I help with glaucoma
reduce intraocular P by stimulating mACHRs of ciliary body and cause contraction which facilitates outflow of aqueous humor
what is preferred Tx for glaucoma
topical beta blockers and PG derivatives
What is used to Tx dementia
donepezil, rivastigmine, glantamine and physostigmine
intoxication from anticholinergic Sx
cutaneous vasodilation, anhidrosis, anhydrotic hyperthermia, nonreactive mydirasis, delerium, hallucinations, reduction or elimination of desire to urinate
reversal of antimuscarinc toxicity
physostigmine because crosses bbb
what occurs if combine succinylcholine with AChE I
enhance phase I block and antagonize phase 2 block
effects of beta blocker with AChE I
bradycardia
Sx AChE intoxication
miosis, salivation, sweating, bronchial constriction, vomiting, diarrhea
what are the CNS involvements of AChE intoxication
confusion, ataxia, generalized convulsions, coma and respiratory paralysis
what causes death in AChE intoxication
respiratory failure
Dx AChE intoxication
measure AChE activity in RBCs and plasma
antidote for AChE intoxication
atropine
except is ineffective in peripheral NMJ, need cholinesterase regenerators
pralidoxime
cholinesterase regenerator
what is window frame for effective use of pralidoxime against organophosphate toxicity
before aging has occured
does pralidoxime cross bbb
no
pyridostigmine is used in military for what
prophylaxis AChE inhibitor posioning
nerve gas
side effects of pyridostigmine
stomach cramps, diarrhea,nausea, urination, HA, dizziness, SOB, worsening peptic ulcer, blurred vision, watery eyes
