Cholinometics

Cholinomimetics

• mimic Ach of sympathetic nervous

• Acetyl-Cola: acetylcholine receptor agonists

• Mime drinking cola: cholinomimetics

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

• Ion Channel news behind smoker: nicotinic receptors act as ion channels

• 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

• 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

• 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)

• 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)

• 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

• 1-800-VERY-CLEAN: varenicline (a nicotinic receptor partial agonist) is used for smoking cessation

Acetylcholinesterase Inhibitors

• 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

• 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

• 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)

• 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

• 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)

• 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

• 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

• Bladder hose: acetylcholinesterase inhibitors can be used to treat urinary retention (muscarinic activation of detrusor)

• 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)

• "Your brain on drugs": physostigmine (and organophosphates) enters CNS to reverse atropine and cause central cholinergic effects

• 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)

• 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)

• 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 )

• 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

• 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

• 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

• Alice: atropine (antimuscarinic)

• Belladonna flower - a natural antimuscarinic alkaloid

• Jimson weed - a natural antimuscarinic alkaloid

• 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

• 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)

• 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)

• 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)

• 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)

• 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)