Lecture 11: Cholinergics Flashcards
Muscarine and Pilocarpine
natural muscarinic receptor agonist
mimic ACh via binding
Carbachol
Synthetic agonist
mimic ACh via binding
(muscarinic > nicotinic)
function of Cholinesterase inhibitor and the adverse effect
inhibit acetylcholinesterase and plasma cholinesterase
increase ACh activity ONLY when ACh is actively released
can lead to cholinergic crisis (desensitization of nicotinic receptor, diaphragm paralysis -> respiratory depression)
Physostigmine, Neostigmine, Edrophonium
Reversible cholinesterase inhibitors
competitive
physostigmine: cross BBB, use for glaucoma
neostigmine: do not cross BBB, direct nAChR activity, treat myasthenia gravis, causes GI contractions and secretions
edrophonium: given IV, short acting, challenge to diagnose myasthenia gravis
Nerve gases, insecticides
Irreversible cholinesterase inhibitor
highly lipid soluble
cause toxicity
high dose kill quickly
MOA of irreversible cholinesterase inhibitors
Aged phosphorylation of serine esteratic site (slow process)
R2 removed via hydrolysis
irreversible
can be reactivated by 2-PAM prior to aging phosphorylation, a strong nucleophile which competes for the site
Pralidoxime
2-PAM, can reactivate acetylcholinesterase via phosphoryl group prior to aging phosphorylation
some AChase activity
Echothiopate
irreversible AChase inhibitor
treat glaucoma
risk of cataracts development
Atropine
muscarinic receptor antagonist
decrease secretions
decrease GI excessive tone, spasms
urine retention
Dose dependent
low dose: cause bradycardia
high dose: cause tachycardia due to vagal block (bind to M2 receptor, leads to more sympathetic response
NO DIRECT CHANGE IN BLOOD PRESSURE
Scopolamine (Hyoscine)
muscarinic antagonist
enter CNS similar to atropine
can cause sedation
transdermal patch use to prevent motion sickness
Darifenacin
synthetic m3 muscarine antagonist
decrease smc contraction in urinary tract
decrease urgency to urinate
Tolterodine
m2 m3 muscarine antagonist
decrease smc contraction in urinary tract
treat urinary retention
Ipratropium
non-selective muscarinic antagonist
treat asthma/COPD
Adverse effect of muscarinic antagonist
anticholinergic effects tachycardia (vagal reflex) dry mouth blurry eyesight CNS confusion Decrease GI motility, leads to constipation urinary retention
Nicotine
Nicotinic receptor agonist
active and addictive
potent and rapid insecticide
lipophilic
metabolized rapidly in liver and lung
DOSE DEPENDENT
low dose: sympathetic effects
high dose: sympathetic, desensitization of parasympathetic ganglia -> ganglionic blockade
