# Cholinometics ## Cholinomimetics ![](https://f001.backblazeb2.com/file/wikiFiles/DFOECoI.jpg) * mimic Ach of sympathetic nervous * Acetyl-Cola: acetylcholine receptor agonists * Mime drinking cola: cholinomimetics ![](https://f001.backblazeb2.com/file/wikiFiles/DFOECoI.jpg) Smoker: **nicotinic** acetylcholine receptor: * Ganglia-like transformers (wire to wire) near smoker: nicotinic acetylcholine receptors are found on autonomic ganglia * Outlet near smoker: nicotinic acetylcholine receptors are found on skeletal muscle motor end plates * Adrenal beanie on smoker: nicotinic acetylcholine receptors are found in the adrenal gland Motorcycle parking spots: **muscarinic** acetylcholine receptors (M1, M2, M3) (smooth muscles): * Brain helmet: M1 receptors are found in nerves and the CNS * Top of heart with atria visible and with jewels: M2 receptors are found in the atria, the SA and AV node. Ventricle is innervated by sympathetic not para sympathetic * Glandular sponge: M3 receptors are found on glands * Smooth muscle stripes: smooth muscle contains M3 receptors ![](https://f001.backblazeb2.com/file/wikiFiles/c5Ci9k2.jpg) ![](https://f001.backblazeb2.com/file/wikiFiles/FYfEEXp.jpg) ![](https://f001.backblazeb2.com/file/wikiFiles/DFOECoI.jpg) * Ion Channel news behind smoker: nicotinic receptors act as ion channels ![](https://f001.backblazeb2.com/file/wikiFiles/FYfEEXp.jpg) ![](https://f001.backblazeb2.com/file/wikiFiles/DFOECoI.jpg) * QIQ store: M1, M2, and M3 are coupled to Gq, Gi, and Gq, respectively * 3 "dags": M1 and M3 are coupled to Gq proteins which activate the IP3-DAG cascade, increase in Ca * Packed up camp tent: M2 is coupled to a Gi protein which decreases cAMP * Dilated nitric oxide exhaust: M3 receptor activation -> nitric oxide release in vascular smooth muscle cells-> increased cGMP and vasodilation * Constricted clogged pipe: atherosclerosis-> vascular epithelial damage-> direct muscarinic receptor activation-> vasoconstriction ![](https://f001.backblazeb2.com/file/wikiFiles/FYfEEXp.jpg) ![](https://f001.backblazeb2.com/file/wikiFiles/DFOECoI.jpg) * Beth with cola: bethanechol (a cholinomimetic) * Cement pouring from colon spout: muscarinic agonists (e.g. bethanechol) increase secretion and motor activity of the gut * "Do Not Obstruct": bethanechol is used to treat non-obstructive gastrointestinal dysmotility (e.g post-op ileus, neurogenic ileus) * Beth using bladder hose: bethanechol treats urinary retention ![](https://f001.backblazeb2.com/file/wikiFiles/DFOECoI.jpg) * Pile o' carp: pilocarpine (a cholinomimetic) * Dripping carp mouths: pilocarpine increases salivation * Round glass: muscarinic agonists (e.g. pilocarpine) cause accommodation of the lens * Smooth muscle crane with net zonules: pilocarpine contracts the ciliary muscle, zonular fibers relax, lens become spherical shaped, reduce intraocular pressure, increasing aqueous humor outflow (useful to treat glaucoma). * Constricted hood: pilocarpine activates the sphincter pupillae muscle to cause pupillary constriction (useful in acute angle-closure glaucoma) ![](https://i.imgur.com/8xFOg0Q.jpg) ![](https://f001.backblazeb2.com/file/wikiFiles/DFOECoI.jpg) * Carbon fumes from smoker: carbachol is both a muscarinic and nicotinic agonist * Constricted hood blocking carbon fumes: carbachol causes pupillary constriction (useful in acute angle-closure glaucoma) ![](https://i.imgur.com/8xFOg0Q.jpg) ![](https://f001.backblazeb2.com/file/wikiFiles/DFOECoI.jpg) * Marathon: methacholine (a cholinomimetic) * Challenge: methacholine challenge instigates asthma for pulmonary testing * Wheezing man: cholinomimetics (e.g. methacholine) contract bronchial smooth muscle which may exacerbate asthma or COPD ![](https://f001.backblazeb2.com/file/wikiFiles/DFOECoI.jpg) * 1-800-VERY-CLEAN: varenicline (a nicotinic receptor partial agonist) is used for smoking cessation ## Acetylcholinesterase Inhibitors ![](https://f001.backblazeb2.com/file/wikiFiles/2bEMl7O.jpg) * Indirect view of Acetyl-cola mime: indirect cholinomimetics (inhibit acetylcholinesterase) * Dumpster of acetyl-cola bottles: acetylcholinesterase degrades acetylcholine (ACh) * Knocked over dumpster with acetyl-cola spilling out: acetylcholinesterase inhibitors increase synaptic concentrations of ACh * ANTI-ESTablishment: anti-cholinesterase, a.k.a. acetylcholinesterase inhibitor * STIGMA: "c-stigmine"d drug suffix of acetylcholinesterase inhibitors ![](https://f001.backblazeb2.com/file/wikiFiles/2bEMl7O.jpg) * Skeletal muscle brick wall: acetylcholinesterase inhibitors enhance effects of ACh at the NMJ (increase activity of NICOTINIC ACh receptors) * Electrical end plate: motor endplate (at the NMJ), increase contraction ![](https://f001.backblazeb2.com/file/wikiFiles/2bEMl7O.jpg) * GRAVIS graffiti: myasthenia gravis (MG)-> antibodies against nicotinic ACh receptors at motor endplate (skeletal muscle NMJ) * Graffiti covering electrical end plates: MG causes progressive proximal weakness, ptosis, diplopia (inactivated nicotinic ACh receptors at motor endplate) ![](https://f001.backblazeb2.com/file/wikiFiles/2bEMl7O.jpg) * Community PRIDE: PYRIDOstigmine (acetylcholinesterase inhibitor used as long-term treatment for MG) * Removing graffiti on end plates: acetylcholinesterase inhibitors increase ACh at NMJ endplate to outcompete MG antibodies * Neon sign STIGMA: neostigmine (acetylcholinesterase inhibitor used as treatment for MG) * Phone booth: edrophonium (acetylcholinesterase inhibitor that transiently reverses symptoms of MG) * Quarters only: pyridostigmine, neostigmine and edrophonium are quaternary amines and **do not penetrate the CNS** ![](https://f001.backblazeb2.com/file/wikiFiles/2bEMl7O.jpg) * Phone wire tension: tensilon test -> edrophonium reverses (positive) or fails to reverse (negative) muscle weakness * Phone in working order: edrophonium REVERSES muscle weakness in undertreated MG patients (POSITIVE tensilon test) * Phone out of order, with anti-esterase graffiti: edrophonium FAILS to reverse muscle weakness during cholinergic crisis (NEGATIVE tensilon test) ![](https://f001.backblazeb2.com/file/wikiFiles/2bEMl7O.jpg) * CURARE crayons stuck in end plate: **nondepolarizing** neuromuscular blocking agents (e.g. tubocurarine, pancuronium, cisatracurium) inhibit nicotinic ACh receptors at NMJ endplate (for inducing paralysis in surgery) * Neon sign store owner kicking out CURARE crayon kid: acetylcholinesterase inhibitors (e.g neostigmine) reverse nondepolarizing neuromuscular blockade ![](https://f001.backblazeb2.com/file/wikiFiles/2bEMl7O.jpg) * SUCKS: succinylcholine is a depolarizing neuromuscular blocking agent (nicotinic ACh receptor AGONIST) * PHASE-1 cleanup crew getting shocked: initial PHASE-1 of depolarizing blockade is IRREVERSIBLE (acetylcholinesterase inhibitors potentiate blockade). Continuous depolarize: unresponsive muscles ![](https://f001.backblazeb2.com/file/wikiFiles/2bEMl7O.jpg) * Bladder hose: acetylcholinesterase inhibitors can be used to treat urinary retention (muscarinic activation of detrusor) ![](https://f001.backblazeb2.com/file/wikiFiles/2bEMl7O.jpg) * PHYS ED center: PHYSostigmine (acetylcholinesterase inhibitor with **CENTRAL** effects) **Cross BBB** * Atropine in Wonderland: atropine overdose -> "mad as a hatter, hot as a hare, blind as a bat" (reversed by physostigmine) * Deadly nightshade: belladonna flower is a naturally occurring form of atropine (overdose reversed by physostigmine) (work in a garden then present with symptoms) * GYM weeds: Jimson weed is a naturally occurring form of atropine (overdose reversed by physostigmine) * PHYS ED teacher reprimanding atropine "cartist"d: physostigmine reverses atropine overdose (peripheral and CENTRAL effects) ![](https://f001.backblazeb2.com/file/wikiFiles/2bEMl7O.jpg) * "Your brain on drugs": physostigmine (and organophosphates) enters CNS to reverse atropine and cause central cholinergic effects ![](https://f001.backblazeb2.com/file/wikiFiles/2bEMl7O.jpg) * DUMBBELS: acetylcholinesterase inhibitor toxicity (Diarrhea, Urination, Miosis, Bronchospasm Bradycardia, Lacrimation, Salivation) * Weak nicotine kid: acetylcholinesterase inhibitor toxicity includes flaccid paralysis (NMJ nicotinic ACh receptor over-activation) ![](https://f001.backblazeb2.com/file/wikiFiles/2bEMl7O.jpg) * THIOL spray: thiosulfate insecticides (parathion, malathion, echothiophate) are organophosphates, a type of acetylcholinesterase inhibitor (also includes nerve agents and herbicides) * Green fumes: organophosphates are a major cause of acute cholinergic toxicity (DUMBBELS) ![](https://f001.backblazeb2.com/file/wikiFiles/2bEMl7O.jpg) * Closing LID on TOXIC spray: praLIDoxime reverses organophosphate toxicity (DUMBBELS) * New toxic waste dumpsters: pralidoxime regenerates acetylcholinesterase at muscarinic and NICOTINIC receptors (reverses cholinergic toxicity INCLUDING FLACCID PARALYSIS) * Atropine Alice is in your head: atropine reverses both peripheral and CENTRAL muscarinic toxicity from organophosphate poisoning (pralidoxime is peripheral only) (atropine only M, but not reverse paralysis; pralidoxime reverses ) ![](https://f001.backblazeb2.com/file/wikiFiles/2bEMl7O.jpg) * Old pest-control man: "caging" of the organophosphate-cholinesterase complex leads to irreversible binding * Corroded dumpster: pralidoxime is ineffective once aging of organophosphate- cholinesterase complex has occurred ![](https://f001.backblazeb2.com/file/wikiFiles/2bEMl7O.jpg) * Alzheimer's GALA: galantamine (acetylcholinesterase inhibitor used to treat Alzheimer's disease) * REVERSE the STIGMA: rivastigmine (acetylcholinesterase inhibitor used to treat Alzheimer's disease) * Done with brain puzzle: donepezil (acetylcholinesterase inhibitor used to treat Alzheimer's disease) * Brain puzzle: galantamine, rivastigmine, and donepezil penetrate the CNS ## Antimuscarinics ![](https://f001.backblazeb2.com/file/wikiFiles/16e56oc.jpg) * Motorcycle parking spots: muscarinic acetylcholine receptors (M1, M2, M3) * Reversing into motorcycle parking spot: muscarinic antagonists reversibly block muscarinic receptors * Blocked tweedleDUMBBELS: antimuscarinics block the muscarinic effects of diarrhea, urination, miosis, bronchospasm, bradycardia, lacrimation, salivation * Blocked acetyl-cola bottle: antimuscarinics block the action of acetylcholine at M receptors ![](https://f001.backblazeb2.com/file/wikiFiles/16e56oc.jpg) * Alice: atropine (antimuscarinic) * Belladonna flower - a natural antimuscarinic alkaloid * Jimson weed - a natural antimuscarinic alkaloid ![](https://f001.backblazeb2.com/file/wikiFiles/16e56oc.jpg) * TeleSCOPE: scopolamine (antimuscarinic) * Seasick sailor outfit: scopolamine is used to treat motion sickness (vestibular nausea) * Eyepatch: scopolamine transdermal patch is used to treat motion sickness * CNS hat: antimuscarinics (e.g. scopolamine) cross the blood-brain barrier and inhibits central M1 receptors ![](https://f001.backblazeb2.com/file/wikiFiles/16e56oc.jpg) * Heart with jewel nodes: antimuscarinics block parasympathetic activation of M2 receptors on the SA and AV nodes (increased heart rate, increased AV conduction). Parasympa slows HR/AV conduction. Inhibition results in opposite * Elevated heart watch: antimuscarinics (e.g. atropine) increase heart rate (useful in the treatment of bradycardia) * Heart shield: heart block (atrioventricular block) * Falling heart shields: antimuscarinics (e.g. atropine) increase AV conduction (useful in the treatment of heart block) ![](https://f001.backblazeb2.com/file/wikiFiles/16e56oc.jpg) * Cat-ipra-tio-tropillar: ipratropium and tiotropium (M3 muscarinic antagonists) * Puffing: ipratropium and tiotropium are inhaled antimuscarinic bronchodilators * Blue bloater with pink puffer: ipratropium and tiotropium are useful in the management of COPD (antagonize M3 receptors -> bronchodilation, decreased secretions) * Long lasting TIO smoke rings: tiotropium dissociates more slowly from the M3 receptor (longer bronchodilator action) ![](https://f001.backblazeb2.com/file/wikiFiles/16e56oc.jpg) * Ox butler: oxybutynin (M3 muscarinic antagonist) * Turtle butler: tolterodine (M3 muscarinic antagonist) * Turning off bladder: oxybutynin and tolterodine treat incontinence (antagonize M3 receptors -> relax smooth muscle in ureters and bladder wall) ![](https://f001.backblazeb2.com/file/wikiFiles/16e56oc.jpg) * CENTER over M1: M1 muscarinic receptors are found in the CNS * PARKING over M1: M1 receptor antagonists can reduce tremors and rigidity in Parkinson's disease * Benz parked in M1: benztropine (centrally acting M1 muscarinic antagonist) * Tri-hex car parked in M1: trihexyphenidyl (centrally acting M1 muscarinic antagonist) * Shaking antenna: centrally acting antimuscarinics (e.g. benztropine, trihexyphenidyl) treat tremor and rigidity in Parkinson's (block excess cholinergic activity) * Cogwheel: excessive M1 activation is associated with cogwheel rigidity in Parkinson's disease * Falling "cextra parking" cone: antimuscarinics treat extrapyramidal side effects caused by antipsychotics: e.g. dystonia, akathisia, parkinsonism (re-establish dopaminergic- cholinergic balance) ![](https://f001.backblazeb2.com/file/wikiFiles/16e56oc.jpg) * Hot as a hare: antimuscarinics inhibit M3 receptors on sweat glands -> decreased sweating -> hyperthermia * Dry as a cracker: antimuscarinics decrease salivation and lacrimation -> dry mouth and eyes * Blind as a bat: antimuscarinics cause mydriasis and cycloplegia-> blurred vision * High-pressure as a kettle: antimuscarinics cause mydriasis -> decreased outflow of aqueous humor -> acute angle closure glaucoma * Mad as a hatter: antimuscarinics cross the BBB and antagonize central M1 receptors -> sedation, agitation, hallucination, coma (especially in elderly patients) **Cycloplegia** is paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation Large pupil gazing into the distance: antimuscarinics cause pupillary dilation (mydriasis) and cycloplegia (inability to accommodate the lens for near vision) ![](https://i.imgur.com/8xFOg0Q.jpg) --- # Agent Instructions: Querying This Documentation If you need additional information that is not directly available in this page, you can query the documentation dynamically by asking a question. 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