Cholinomimetic Drugs Flashcards
Acetylcholine
Direct-acting cholinoceptor agonist-choline esters
Rapid destruction by AChE
Muscarinic effect: low dose=vasodilation–>reflex tachycardia; high dose=bradycardia, decrease A-V conduction, (-) ionotropy; bronchial constriction; increased bronchial secretion; salivary excretion; tears; sweat; urinary bladder contraction; short-lasting miosis
Nicotinic effect: rare b/c Ach does not penetrate fat surrounding skeletal muscle and autonomic ganglia
Clinical use: eye surgery (miosis)’ provocation test in coronary angiography (Dx coronary vasospasm)
Methacholine (Provocholine*)
Direct-acting cholinoceptor agonist-choline esters
Similar to ACh (longer T1/2 b/c methyl group)
Diagnosis of bronchiolar hypersensitivity and belladonna alkaloid poisoning
Carbachol
Direct-acting cholinoceptor agonist-choline esters
Therapeutic dose: activate both nicotinic and muscarinic cholinoceptors (autonomic ganglia, adrenal medulla, skeletal muscle)
High dose: cardiac arrest
Clinical use: glaucoma= contracts ciliary muscle–>enlarges canal of Schlemm–>increases drainage of aqueous humor–>decreases intraocular pressure
Bethanechol (Urecholine*)
Direct-acting cholinoceptor agonist-choline ester
Not susceptible to AChE and does not have nicotinic action
Predominantly acts on M3: genitourinary= increase detrusor tone, decrease outlet resistance of internal sphincter; gastrointestinal= increase motility and secretion
Weak effects on M2: minimal cardiac effects
Clinical use: gastric agony after vagotomy to reduce reflux (increases lower esophageal sphincter tone); gastric emptying abnormalities; urinary retention (in absence of obstruction)
Muscarine
Direct-acting cholinoceptor agonist-muscarinic alkaloids
Found in mushrooms, not destroyed by AChE, no nicotinic activity
Poisoning symptoms: salivation, sweat, tears, abdominal pain, nausea, diarrhea, blurred vision, dyspnea; subside within 2 hrs; severe cases= cardiac & respiratory failure leading to death
Pilocarpine (Isopto Carpine, Salagen)
Direct-acting cholinoceptor agonists-muscarinic alkaloids
opthalmic (M3) effects: topical application, poor systemic absorption; contracts iris sphincter muscles–>miosis; free entrance to canal of Schlemm (therapy for narrow-angle glaucoma); enhances tone of trabecular network (therapy for wide-angle glaucoma); contracts ciliary muscle (accommodation an loss of far vision)
clinical use: glaucoma= Rx of choice; xerostomia= stimulate saliva secretion; test on autonomic state= PNS dysfunction
Direct-Acting cholinoceptor agonists: contraindications & Interactions
contraindications: peptic ulcers, GI tract disorders, asthma
drug interactions: antimuscarinic drugs can block effects of muscarinic agonists (Quinidine, procainamide, tricyclic antidepressants)
Nicotine
Direct-acting cholinoceptor agonist-nicotinic alkaloid
Action on Nm (at neuromuscular endplate): skeletal muscle contraction, fasciculations, spasm, depolarizing blockade
Action on Nn (stimulate both SNS and PNS post-ganglionic neurons): cardiac= increased heart rate (SNS); vascular= peripheral vasoconstriction (SNS); GI= increased gut motility and secretion; carotid bodies= increased respiratory rate; medullary emetic chemoreceptors= nausea and vomiting
clinical use: aid smoking cessation
Edrophonium
Indirect-acting cholinoceptor agonist-cholinesterase inhibitors
short-acting
Dx: differentiate myasthenia from cholinergic crisis (improve symptoms of MG)
Neostigmine, pyridostigmine
Indirect-acting cholinoceptor agonist-cholinesterase inhibitors
No CNS entry, immediate-acting
Treatment of MG
Paralytic ileus and urinary retention: abdominal distension and atony of detrusor muscle of urinary bladder (NOT used with urinary bladder obstruction)
Reversal of non-depolarizing NM blockers
Physostigmine
Indirect-acting cholinoceptor agonist-cholinesterase inhibitors
Enters CNS, intermediate-acting
antidote in atropine overdose
Glaucoma: open canal of Schlemm, relieve intraocular pressure, block accommodation and cause myopia, 2nd line treatment choice
Donepezil
Tacrine
Indirect-acting cholinoceptor agonist-cholinesterase inhibitors
Lipid-soluble (CNS entry)
Rx- Alzheimer disease= increase concentration of cholinergic neurotransmitters in CNS (beneficial b/c deficiency of intact cholinergic neurons)
Organophosphates
Indirect-acting cholinoceptor agonist-cholinesterase inhibitors
lipid-soluble, long lasting, irreversible inhibitors of AChE, often toxic
Rx: glaucoma (echothiophosphate)
Insecticides: malathion, parathion
Nerve gas: sarin
Indirect-acting cholinoceptor agonists- cholinesterase inhibitors: symptoms of intoxication
DUMBBELSS
Diarrhea, urination, miosis, bronchiolar constriction, bradycardia, excitement of CNS, lacrimation, sweating, salvation
Treatment: symptomatic, airway control, CV support, antidote=atropine (muscarinic receptro antagonist), regeneration of AChE=Pralidoxim (2-PAM) must be used early
