7- Cholinomimetric Drugs Flashcards
bind directly to and activate muscarinic or nicotinic cholinoceptos
direct-acting cholinomimetics
produce their effects by inhibiting the action of acetylcholinesterase, thus preventing the destruction of endogenous Ach
indirect-acting cholinomimetics
direct acting muscarinic agonists (6)
Acetylcholine Methacholine Carbachol Bethanechol Muscarine Pilocarpine
direct acting muscarinic agoinst that are choline esters (4)
acetylcholine
methacholine
carbachol
bethanechol
direct acting muscarinic agonist that are alkaloids (2)
muscarine
pilocarpine
direct acting alkaloid cholinoceptors (4)
muscarine
pilocarpine
nicotine
succinylcholine
indirect acting reversible cholinesterase inhbitors (5)
edrophonium neostigmine physostigmine denepezil tacrine
indirect acting irreversible organophosphate cholinesterase inhibitors (4)
echothiphate
malathion
parathion
sarin
why do choline esters have poor GI absorption and poor CNS distribution?
cationic quaternary ammonium compounds that make them insoluble in lipid
which of the choline esters have methyl groups giving them a longer half life?
methacholine and bethanechol
which of the choline esters are insusceptible to cholinesterase?
carbachol and bethanechol
effects of choline esters on the cardiovascular system
- hypotension from direct vasodilation
- bradycardia at high doses
- slowed conduction and prolonged refractory period of AV node
effects of choline esters on GI system
- increased tone and increased contractile activity of gut
- increased acid secretion
- nausea, vomiting, cramps, and diarrhea
effects of choline esters on genitourinary tract
involuntary urination from increased bladder motility and relaxation of sphincter
effects of choline esters on eye
miosis: contraction of sphincter muscle, resulting in reduced intraocular pressure
contraction of ciliary muscle; accomodated for near vision
effects of choline esters on respiratory system
bronchoconstriction
effects of choline esters on glands
increased secretory activity, resulting in increased salivation, lacrimation and sweating
Ach: _______ destruction by AchE
rapid
–> limited clinical use
muscarinic effects of Ach
cardio - low doses = vasodilation –> tachycardia
high doses = bradycardia; decreased AV conduction and negative inotropy
bronchial constricition and increased secretion
salivary excretion, tears, sweat
urinary bladder contraction
short lasting miosis in eye
nicotinic effects of Ach
not commonly seen since Ach does not penetrate the fat surrounding skeletal muscle and autonomic ganglia
clinical use of Ach
eye surgery (short-lasting miosis)
provocation test in coronary angiography (dx coronary vasospasm)
how does methacholine compare to Ach
similar in action
longer half life
diagnosis of bronchiolar hypersensitivity:
methacholine challenge
excessive bronchoconstriction via M3 receptors in bronchial muscle in asthmatic pts.
therapeutic doses of carbachol
both nicotinic and muscarinc effects
high doses of carbachol
may induce cardiac arrest
topical application for glaucoma
carbachol
contracts ciliary muscle which enlarges canal of schlemm and increases drainage of aqueous humor and decreases intraocular pressure
what are the indications for bethanechol?
-gastric atony (after vagotomy to reduce reflux; increases lower esophageal tone)
- gastric emptying abnormalitie
- urinary retention (in absence of obstruction)
where does bethanechol predominately act?
M3
effects on bethanechol on genitourinary and gastrointestinal tract?
increase detrusor tone, decrease outlet resistance of internal sphincter
increase motility and secretion
does muscarine have nicotinic acitivity?
no
signs of muscarine poisoning
salivation, sweat, tear flow
abdominal pain, nausea, diarrhea, blurred vision, dyspnea
symptoms subside w/i 2 hrs
severe may lead to death
which is more potent muscarine or Ach?
muscarine (100x)
also longer duration of action than Ach because not broken down by AchE
Pilocarpine predominate effects
opthalmic via M3
contracts iris sphincter muscles –> miosis
frees entrance to canal of Schlemm (therapy ofr narrow-angle glaucoma)
enhances tone of trabecular network (therapy for wide-angle glacuoma)
contract ciliary muscle for accommmodation and loss of far vision
drug of choice for glaucoma
pilocarpine
what does a pilocarpine hypersensitivity indicate?
PANS dysfunction
test on autonomic state
why is pilocarpine given for xerostomia?
given orally to stimualte saliva secretion
contraindications for direct acting cholinoceptor agonists
peptic ulcers
GI tract disorders
asthma
drug interactions with anti-muscarinc properties (do not use with direct acting cholinoceptor agonists)
quinidine (antiarrhythmics)
procainamide (antiarrhythmics)
tricyclic antidepressants
prototypical agonist for nAch receptors
nicotine
action of nicotine on Nm receptors
- skeletal muscle contraction
- fasiculations, spasm
- depolarizing blockade
action of nicotine on Nn receptors
increased HR
both symp and para effects depending on system
peripheral vasoconstriciton
increased gut motility and secretion
increased RR
nausea and vomiting via emetic chemoreceptors
clinical indication for nicotine
aid smoking cessation
used to differentiate myasthenia from cholinergic crisis
edrophonium
- will show imporvement
- short acting
do neostigmine and pyridostigmine go into the CNS?
no (quartenary amines)
what are the clinical uses for neostigmine and pyridostigmine
ileus, urinary retention, myasthenia, reversal of non-depolarizing NM blockers
does physostigmine enter the CNS?
yes (tertiary amine)
clinical use for physostigmine
glaucoma
antidote in atropine overdose
physostigmine
do donepezil and tacrine enter CNS?
yes - lipid soluble
clincal use donepezil and tacrine
alzheimer disease
nerve gas
sarin
malathion and parathion are…
insecticides
which of the organophosphates has clinical use?
echothiophosphate for glaucoma
this group has limited clinical use because they are irreversible inhibtors of AchE
DUMBBELSS
symptoms of intoxication of cholinesterase inhibitors
diarrhea urination miosis bronchiolar constriction bradycardia excitement lacrimation sweating salivation
antidote for cholinesterase inhbitor intoxication
atropine (muscarinc receptor agonist)
what drug could be used to regenerate AchE?
pralidoxim aka 2PAM
