Smooth m relaxants part 2 Flashcards
Cholinesterases
- Butyrylcholinesterase- found in plasma and liver
- ACE
AChE inhibitors
- Alcohols
- Carbamic acid esters
- organophosphates
AChE inhibitors- alcohols
-edrophonium
AChE inhibitors- carbamic acid esters
-neostigmine, pyridostigmine, physostigmine, carbaryl
AChE inhibitors- organophosphates
- echothophate, parathion, malathion (insecticides), sarin, soman, and tuban (n gases)
- irreversible
AChE inhibitors- moa
- inhibit AChE
- ACh accum throut body- act of nAChRs and mAChRs
AChE inhibitors- duration of action
- alcohols short (2-10 min)
- carbamic acid esters- 2-step hydrolysis (30 m- 6 hrs)
- organophosphates- very long
AChE inhibitors- CNS
- CNS- low conc- diffuse act on EEG
- high conc- generalized convulsions
AChE inhibitors- eye, resp tract, GI tract, urinary tract
-innervated by mAChRs (parasymp)
AChE inhibitors- CV
- inc activity of symp and parasymp ganglia (n and mACHRs) supplying the heart and at mAChRs on cardiac cells
- parasymp tone dominates- CO dec
- modest bradycardia, dec in CO, modest dec in BP
- toxic doses- marked bradycarida, hypotension
AChE inhibitors- NMJ
- prolong and intensify actions of ACh- inc strength of contraction
- fibrillation of m fibers and fasciculations- high conc
- continued inhibition of ACHE- progression of depolarizing neuromuscular blockade to nondepolarizing blockade
AChE inhibitors- therapeutic uses
- glaucoma, accommodative esotropia
- postop atony, neurogenic bladder)
- MG, curare-induced neuromuscular paralysis
- central atrial arrhythmias
- Alzheimer dz
MG- tx
-pyridostigmine, neostigmine, ambenonium (AChE inhibitors)- dont cross BBB!!
dx agent for MG
Edrophonium test
- admin of edrophonium (short-acting)- relieves ptosis, diff speaking and swallowing, extremity weakness
- not used anymore- dangerous!!!- use ice pack test (2-3 min)- inhibits cholinesterase activity
Myasthenic vs cholinergic crisis
- Myasthenic crisis- weakness from acquired MG that is severe enough to necessitate intubation
- cholinergic crisis- SE of excessive ACHE inhibitors
- to distinguish b/w the 2- edrophonium test!- if in myasthenic crisis, sx’s will improve!
- should be assumed that pts w MG in crisis are in myasthenic crisis unless it is known t hat the doses of ACHE inhibitors exceed the daily allowable limits
ACHE inhibitors- reversal of pharmacologic crisis
- reverse the paralysis induced by neuromuscular blocking drugs
- can treat paralytic ileus, atony of urinary bladder, and congential megacolon
ACHE inhibitors- glaucoma
(inc intraocular P)
-reduce intraocular P by stim mACHRs of ciliary body- causes contraction- outflow of aqueous humor
ACHE inhibitors- dementia
-Alzheimers- def of intact cholinergic neurons
ACHE inhibitors- antidote
- intoxication of anticholinergic agents- cutaneous vasodilation, anhidrosis, nonreactive mydriasis, delirium, hallucinations, reduction to urinate
- physostigmine!!- crosses BBBB
ACHE inhibitors- drug-drug interactions
- nondepolarizing NM blocking agents- combo- dimishes NM blockade; exception is mivacurium
- succinylcholine- enhance phase 1 block, and antagonise phase 2 block
- cholinergic agonists- enhance effects
- B-blockers- enhance bradycardic effects
- systemic corticosteroids- enhance m weakness seen in pts w MG
ACHE inhibitors- acute intoxication
- mACHR stim- miosis, salivation, sweating, bronchial constriction, vomiting, diarrhea
- after ingestion- GI sx’s 1st
- percutaneous abs- sx’s of sweating and m fasciculations nearby
ACHE inhibitor poisoning- tx
- atropine!!!! (mACHR antagonist)
- pralidoxime- cholinesterase regenerator
prophylaxis in ACHE inhibitor poisoning
-pyridostigmine
