cholinoceptor-activating and cholinesterase inhibiting drugs Flashcards
(21 cards)
acetylcholine
rapidly hydrolyzed by cholinesterase (ChE)
duration 5-30 sec
poor lipid solubility
bethanechol (and carbachol)
M receptors: increases DAG, IP3 -bladder and bowel atony resistant to ChE orally active poor lipid solubility duration 30 mins-2 hours
pilocarpine
M receptors: increases DAG, IP3
-Sjogrens syndrome (increases salivation), glaucoma (causes myosis, cyclospasm)
good lipid solubility
-30-2 hours
nicotine
N receptors: opens Na-K ion channels in ganglia and skeletal NME plates
like pilocarpine
-duration of 1-6 hours
high lipid solubility
varenicline
N receptors partial agonist at N receptors -smoking cessation high lipid solubility duration 12-24 hours
indirect acting drugs
edrophonium neostigmine physostigmine pyridostigmine echothiophate parathion
edrophonium
inhibitor of cholinesterase, amplifier of acetylcholine
-reversal of Nm blocker, diagnosis of MA gravis
alcohol
quaternary amine
poor lipid solubility, used IV
NOT ORALLY ACTIVE
dur. 5-15 mins
neostigmine
like edrophonium, reversal of Nm blocker, carbamate quaternary amine poor lipid solubility (LS) ORALLY ACTIVE dur. 30mins-2 hours
physostigmine
like edrophonium -reversal of severe atropine poisoning carbamate tertiary amine good LS orally active dur. 30min-2 hours
pyridostigmine
like edrophonium carbamate -treat MA gravis like neo dur 4-8 hours
echothiophate
organophosphate
moderate LS
2-7 days
parathion
organophosphate
high LS
7-30 days
muscarinic MOA: M1 and M3
Gq coupled receptors to phospholipase C-> second messangers DAG and IP3
DAG-> protein kinase C
IP3-> release of Ca
muscarinic MOA: M2
coupled to adenylyl cyclase through Gi
carbamates and organophosphates inhibitors
bind to cholinesterase and undergo prompt hydrolysis
-prevents binding and hydrolysis of acetylcholine
AMPLIFY ACETYLHCHOLINE EFFECTS
how is edrophonium used to distinguish myasthenic crisis versus a cholinergic crisis?
if edrophonium administered, if having a MA crisis, will improve muscle strength
if having a cholinergic crisis: weaken muscle strength
cholinergic crisis
clinical condition of excessive activation of cholinoceptors, may include skeletal muscle weakness, maybe parasym signs
MA crisis
acute worsening of symptoms relieved by increasing cholinomimetric treatment
indirect acting cholinomimetic drugs
amplify effects of endogenous acetylcholine by inhibiting acetylcholinesterase
direct acting cholinomimetic drugs
directly bind and activate cholinceptors, effects mimic acetylcholine
succinylcholine
N receptor agonist
-muscle relaxation
highly polar
duration 5-10 mins
