Atropine in Wonderland Muscarinic Antagonists

2.1 – “Atropine in Wonderlan Wonderland”: d”: Muscarinic Antagoni Antagonists sts (atropine, ipratrop ipratropium, ium, tiotropium, oxybutynin, toltero tolterodine, dine, scopolam scopolamine, ine, benztropine, trihexyphenidy trihexyphenidyl) l) • Muscarinic antagonists reversibly inhibit muscarinic receptors (mouse’s car reversing into muscarinic parking place). Block effects of cholinomimetic agents, including toxicity (Tweedledum with dumbbells & Tweedledee with Acetyl-cola are blocked from parking) • Note that any of these will have desired effects in one system but undesirable effects in another. Elevated heart rate is a particularly common side effect. • Atropine (Alice) o Jimson weed & Belladonna flowers are naturally occurring alkaloids. May be of clinical relevance in gardeners and children (Alice’s flowers, Jim's tea) ▪ Side note: The name Belladonna derived from Italian for beautiful woman. During the Renaissance, large pupils were perceived as beautiful & so women used a tincture of Belladonna flowers to dilate their eyes o Non-selective antagonist of M1, M2, & M3 receptors, causing effects in many systems ▪ Mydriasis & cycloplegia (walrus with telescope & very large pupil) ▪ CV effects: • PNS activation of M2 receptors in SA & AV nodes →↓HR (queen of hearts with stars for SA & AV nodes on her staff) • Reverses depressed SA & AV node action in MI or shock →↑HR, ↑AV conduction. (rabbit rushing toward antimuscarinic table with elevated heart watch) • Used in heart block to ↑conduction through AV node (rabbit pushing over heart shield) ▪ Block M1 receptors in CNS • Scopolamine o M1 specificity o used to treat motion sickness (walrus in a sailor costume) • Ipratropium & tiotropium (Uncle Caterpillar) o inhaled M3 antagonists used as bronchodilators in management of COPD (caterpillar inhaling off hookah; is a blue bloater on a pink puffer) ▪ Inhibit vagal nerve stimulation of M3 receptor, which causes bronchial airway constriction. o ↓mucosal secretions. o Tiotropium dissociates more slowly from M3 receptor, so has longer-lasting bronchodilator action. (Tioooooo smoke) • Oxybutynin & tolterodine (Fox & turtle butlers) o M3 antagonists. Relax smooth muscle of bladder & ureters, o Relieve urinary incontinence d/t spasm (turning off bladder shape spigots) • Trihexyphenidyl & benztropine (mouse car with 3 hexagons, and Benz) o Central acting M1 antagonists (in parking space M1; parking center sign over space M1) o Used in Parkinson’s to reduce tremor and rigidity (tremor: shaking antennae; cogwheel rigidity: cogwheels on old car) ▪ Tremors may be d/t excess acetylcholine activity in absence of dopaminergic activity. o Used to treat extrapyramidal adverse effects of antipsychotic medications by re-establishing dopaminergic/cholinergic balance (extra parking pyramid cone) ▪ Side effects d/t increased transmission of dopamine at nigra striatal tract ▪ Include dystonia, akathisia, drug-induced parkinsonism Anticholinerg Anticholinergic ic Toxicity • “Hot as a hare, red as a beet, blind as a bat, dry as a bone, mad as a Hatter, full as a flask, fast as a fiddle” (many of these are represented by the guests at the table) o Hyperthermia results from antimuscarinic inhibition of sweat gland M3 receptors →↓ sweating. o Flushing results from ↓sweating & hyperthermia o Blurred vision d/t mydriasis & cycloplegia o Dry mouth & eyes d/t decreased salivation & lacrimation d/t M3 receptors o CNS effects: sedation, agitation, amnesia, up to hallucination & coma, especially in elderly patients. o ↓ smooth muscle contraction in the balder & intestine → urinary retention and constipation o Tachycardia d/t ↓vagal tone at the sinoatrial node o Acute closed angle glaucoma d/t mydriasis & consequent decreased outflow of aqueous humor (high-pressure tea kettle with a lid shaped like a dilated pupil).