1.3 Cholinergic Pharmacology Flashcards
_______ cholinomimetic agents directly bind and activate muscarinic or nicotinic receptors
direct acting
________ agents inhibit acetylcholinesterase, reduce hydrolysis of acetylcholine, increase endogenous Ach concentration in synpatic clefts, stimulates cholinoceptors to evoke increased responses
indirect acting
cholinoceptors are either ________ linked (muscarinic) or ________ (nicotinic)
G protein linked
ion channels
G protein linked cholinoceptors, located in CNS/tissues targeted by PNS, and vascular endothelium
muscarinic receptors
ion channels with receptors located on all ANS postganglionic cells, and muscles, result in electrical changes, prolonged agonist abolishes effector b/c we can diminish the electrochemical gradient (depolarizing blockade)
nicotinic receptors
- esters of choline or alkaloids
- choline esters: quaternary, insoluble in lipids, poorly distributed to CNS
direct acting cholinoceptor agonists
choline ester with exclusively muscarinic action?
methacholine chloride
choline esters with duration of action much longer than Ach, negligible susceptibility to cholinesterase?
carbachol chloride and bethanechol chloride
pilocarpine, nicotine, and lobeline are _______ cholinomimetic alkaloids with CNS activity, more lipophilic than choline esterss
tertiary
- all _______ receptors are G protein coupled
- agonist binding activates IP3, DAG cascade, increases potassium flux
- in some tissues inhibits adenylyl cyclase activity and opens K+ channels
muscarinic
- _______ receptor activation results in electrical and ionic hcanges
- depolarization of nerve cell or neuromuscular end plate membrane
- prolonged agonist occupany abolishes effector response, depolarizing blockage, and can produce muscle paralysis
nicotinic
-______ agonists in the eye produce contraction of iris (miosis), contraction of ciliary muscle (accommodation), and facilitiates aqueous humor outflow
muscarinic
muscarinic agonists in CV system ______ peripheral vasculature resistance, and direct effect is to ____ heart rate
reduce
slow
IV infusions of acetylcholine caused vasodilation and reduce ______, by releasing _______ that relaxes smooth muscle
blood pressure
nitric oxide
muscarinic ________ evokes SNS reflex, increase in heart rate
-larger Ach doses mask this reflex
vasodilation
cholinergic effects on respiratory system:
- ____ smooth muscle of bronchial tree
- glands of mucosa stimulated to secrete
- _______ symptoms of asthma
contracts
exacerbates
cholinergic effects on GI tract:
- increases secretions and _____ activity
- contracts _______ muscle and relaxes sphincters
peristaltic
longitudinal
cholinergic effects on GU tract:
- ______ detrusor muscle
- ______ trigone and sphincter muscles
- promotes voiding
contracts
relaxes
cholinergic effects on secretory glands:
-_______ of secretion by thermoregulatory sweat glands
stimulation
major site of action of nicotinic agonists with simulatenous SNS and PNS discharge?
autonomic ganglia
- only activates vascular muscarinic receptors (endothelium)
- NO, vasodilation, reflex tachycardia
- effects blocked by atropine (muscarinic antagonist)
low dose acetylcholine
- activates M receptors on vascular endothelial cells (NO, vasodilation)
- activates cardiac M receptors (profound bradycardia, slows AV conduction, reduces force of myocardial contractions)
high dose acetylcholine
a simple alcohol bearing a quaternary ammonium group,indirect cholinmimetic (inhibits acetylcholinesterase)
edrophonium
- carbamic acid esters of alcohols, carbamates
- indirect cholinomimetic, 30 min-6hrs inhibition
neostigmine, physostigmine, carbaryl (rapid CNS effects)
echothiphate, soman, sarin, malathion, parathion are _______, which are organic derivatives of phosphoric acid, indirect cholinomimetics
insecticides
organophosphates bind and are hydrolyzed, resulting in a phosphorylated AchE active site, bond extremely stable
-before aging, _______ can restore function
2-pralidoxime (2-PAM)
cholinesterase inhibitors for closed angle glaucoma reduce intraocular pressure by _________ of the ciliary body, facilitating outflow of aqueous humor
contraction
cholinesterase ________ used for postop ileus, congenital megacolon, urinary retention, reflux esophagitis, insufficient salivary secretion
inhibitors
drug used for reversal of competitive blockade by cholinomimetics, a muscarinic antagonist
atropine
- fatal dose 40mg, emetic
- CNS stimulation - convulsions, coma, respiratory arrest
- respiratory paralysis
- HTN, cardiac arrhythmias
- treatment: M and adrenergic antagonists
nicotinic toxicity
- acetylcholine
- bethanechol
- carbachol
- cevimeline
direct muscarinic agonists, choline esters
muscarine
pilocarpine
direct muscarinic agonist, alkaloids
nicotine
varenicline
direct nicotinic agonist
neostigmine physostigmine pyridostigmine reivastigmine ambenonium demecarium carbaryl
carbamates, cholinesterase inhibitors
echothiphate soman sarin parathion malathion isoflurophate DFP
organophosphates, cholinesterase inhibitors
