Cholinergic Pharmacology

CHOLINERGIC PHARMACOLOGY

Class Specific Agents Activity Therapeutic Uses Notes Direct Cholinergic Esters: Acetylcholine, Bind to ACh receptors to ↓ intraocular Activity of esters at nic. vs. Agonists Methacholine, Bethanecol, initiate response pressure musc. Carbamachol (40 Amine) ↑ GI motility post- Musc - All Alkaloids: Muscarine, op Nic – A+, C+, B-, M- Pilocarpine, Lobeline ↑ bladder tone Hydrolysis by ChE - A+, C-, B-, M+ Indirect Cholinergic Edrophonium (40 Amine) Carbamylate AChE, block Mysathenia gravis Effects seen at nicotinic & Agonists Stigmines (30 or 40 Amine) activity for hours ↓ intraocular muscarinic receptors. (Reversible) pressure Locations vary by ↑ GI motility post- circulation of agent. op ↑ bladder tone Indirect Cholinergic Organophosphates: DFP Phosphorylate AChE, block Mysathenia gravis Effects seen at nicotinic & Agonists (Lipophilic), Parathion activity for 100s of hours ↓ intraocular muscarinic receptors. (Irreversible) (Lipophilic), Echothiophate pressure Locations vary by (Polar) ↑ GI motility post- circulation of agent. op ↑ bladder tone Muscarinic Antagonists Alkaloid esters: Atropine, Bind to muscarinic receptors OrgPhos OD Contraindicated for Scopolamine, Pirenzepine antidote glaucoma, ulcers, benign (30 Amines) and Ipratropium, Dilate pupil for prostatic hypertrophy, Porantheline, and exam myasthenia gravis Glycopyrrolate ↑ HR for nodal (40 Amines) block ↓ Motion sickness ↓ Diarrhea, IBS ↓ Urinary Urgency Nicotinic Antagonists Competitive: Sympathoplegia, Trimethaphan: Very non-selective. (Ganglionic Blockers) Hexamethonium, Parasympathoplegia Induce stable Locations vary by Trimethaphan (Polar amines) Effect at sites determined by hypotension in circulation of agent. Non-competitive: normal predominating tone. emergencies & Mecamylamine surgeries Ganglionic Agonists: Nicotine Nicotinic Antagonists Depolarizing: Succinyl-CoA Initially ↑ transmission, Induce paralysis Depolarizing are fast- (NMJ Blockers) Receptors de-sensitize, for surgery. acting, but short-lived. Non-depolarizing: Curare Paralysis. derivatives