The Phantom of the Alpha α-adrenergic Drugs

2.3 – “The Phantom of the Alpha”: α-adre -adrenergic nergic dru drugs gs (α2 ag agonists: onists: clonid clonidine, ine, αmethyldopa ti tizanidine; zanidine; α antagonists: phent phentolamine, olamine, phenoxybenza phenoxybenzamine, mine, prazosin, mirtazapine) • Most of these bind to α1 & α2 receptors in periphery, preventing catecholamine & other agonists • α2 agonists • When given systemically reduce SNS outflow directly at the level of the brainstem → systemic BP (brain-shaped platform for CNS action) o Clonidine (Raoul with 2 claw weapons) ▪ Centrally acting α2 agonist – i.e. sympatholytic (2 lit candles; “sympathy” crossed out by claw marks) ▪ Indications • Used to treat HTN, including HTN crisis (High pressure pipes under stage, marked “urgent”) • Extended release effective in refractory ADHD (Raoul is distracted by HD mirror screen) • Tourette’s – α2 agonists preferred over neuroleptic agents d/t decreased risks of extrapyramidal adverse effects (Tourette’s marionette) o α-methyldopa (α-shaped noose) ▪ L-dopa analog (rope noose). Converted to α-methyldopamine & α-methyl-NE, which can act on central α2 receptors, similar to clonidine (2 lit α candles held near brain rug) ▪ Historically, used for HTN (high pressure pipes). Now, used mainly in gestational HTN (Christine is pregnant) ▪ Side effects: • Lupus-like syndrome (rare) (lupus wolf) • Autoimmune hemolytic anemia; may be d/t production of autoantibodies o Tizanidine (Letter to X-tine) ▪ Centrally acting α2 receptor. Muscle relaxant (recliner chair) • α antagonists (on stage, α-candles have been extinguished) o Phentolamine ▪ Reversible α1 & α2 receptor blocker (single & paired candles extinguished) ▪ Causes vasodilation (dilated sleeves). Can prevent pressor effects of sympathomimetics ▪ Can be used to treat cocaine induced HTN crisis, avoiding β-blocker effects (spilling mug of hot cocoa) ▪ Can be used intraoperatively in case of HTN crisis o Phenoxybenzamine (phoenix tattoo) ▪ Irreversible α1 & α2 receptor blocker (tattoos are permanent; single & paired candles extinguished) ▪ May take several days for new receptors to be synthesized. ▪ Normalize BP prior to pheochromocytoma removal (kidney-and-adrenal shaped ice cream) – causes intermittent headache, HTN, palpitation, sweating (scared looking manager holding head). o α agonists may be used to reverse widespread catecholamine-induced vasoconstriction, as in the case of cocaine toxicity (spilling mug of hot cocoa); tyramine-induced HTN crisis in patients on MAO-Is (tyramine found in aged wine & cheese) (wine & cheese table). o Side effects: ▪ Orthostatic HTN d/t ↓α1 effects (tilt table) accompanied by Reflex tachycardia (heart shaped reflex hammer). First dose is especially high risk • α1 selective antagonists o include prazosin, terazosin, doxazosin, tamsulosin (opera singer for -osin suffix holding 1 extinguished α candle) o Relax smooth muscle in urethra & prostrate (sitting on banner). Used for symptomatic control of BPH o Cause vasodilation (dilated sleeves) o Prazosin has CNS effects, including helping with sleep regulation. Used in PTSD (dog tags held by praying opera singer • Mirtazapine (misery & mirth masks) o Atypical antidepressant with antagonistic effects at α2 & other receptors (2 extinguished α candles) 2.4 – “Brahms’ “Brahms’ss LOL Lullaby”: β blocker blockerss • β-receptor antagonists (blocked β1 bugle & β2 tubas). Mostly end in -lol suffix (Brahms’ lullaby). o Decrease cardiac contractility d/t antagonism of β1 receptor (heart-shaped music stand weak arms) o β1: Inhibit SA node activity → bradycardia (low handing heart watch; SA & AV nodal notes) • • • • • o β1: Slowed AV conduction. Contraindicated in AV block (“Door to remain unblocked” on shield shaped sign – recurring symbol for AV) Indications o Used in management of chronic stable angina(xylophone on anvil). ↓Cardiac contractility & HR → ↓oxygen demand (oxygen cannula flying off) o β1 → ↓renin levels & JGA (blocked bugle in hand of rain jacket wearing player) o All have antihypertensive properties with mild to moderate HTN, but rarely used as initial monotherapy d/t risk for adverse CV outcomes (high pressure steam pipes on pipe organ). Especially helpful in CHF & MI. o Useful in management of hypertrophic obstructive cardiomyopathy, especially when acute hemodynamic collapse d/t obstruction (bagpiper with filled heart-shaped bags is blowing against an obstruction). o Metoprolol, propranolol, timolol can be used as episodic Migraine prophylaxis (pounding unilaterally on head-shaped bell). o Treatment of thyroid storm: catecholamine surge → agitation, delirium, fever, tachyarrhythmia, death (thyroid shaped bowtie with lightning bolts); treatment: propranolol, propylthiouracil, & prednisolone (3 Ps). β-blockers are used for symptomatic relief of thyroid overactivity as e.g. in Graves’ disease, thyroid toxicity o Essential tremor (conductor tremor while holding baton) o Type 1 antiarrhythmics. Effective in Ventricular and supraventricular arrhythmias (rhythmic record player in background) o Glaucoma. Topical administration of β blockers (timolol) inhibits β2 receptors at ciliary epithelium →↓aqueous humor production (Tim the tuba player with the eye-shaped block) Common adverse effects o Exacerbates asthma & COPD by non-selective β blockers (huffing blue bloated tuba player) o Impotence in men (floppy trombone) o Toxicity: glucagon administration (glucagon packets in conductor’s podium) β1 selective antagonists o include atenolol, betaxolol, esmolol, acebutolol, metoprolol (A-BEAM spotlight on β1 bugler). o Cardioselectivity (second A-BeaM spotlight). o Indications: ▪ β blocker reduces MI mortality if given within short order (MI = broken harp string; strings broken acutely for acute treatment). ▪ Used on CHF (sad heart balloon). Reduce structural remodeling and the effect of chronic exposure to catecholamines in CHF resulting in ↓mortality & morbidity (harpist in angle get-up, for ↓mortality; building is remodeling). May worsen acute HF, as catecholamines acutely help with cardiac contractility & maintaining sufficient function. o Carvedilol is nonselective β-antagonist with some α1 effects (carved candleholder with single snuffed α-candle). Used in conjunction with other β-blockers Laβlol o α1 & nonselective β activity (organ stops with snuffed α candle). o Vasodilation → ↓SVR (dilated sleeves). o Safe for pregnancy; may preserve utero-placental blood flow better than other blockers (pregnant organist). o Rapid onset makes useful in HTN crisis (“emergency stop” with ivy =IV). o Used in aortic dissection, where want to rapidly bring down BP (unlike other HTN crises where want to decrease, but more gradually) (dissecting pipe on organ) Partial agonists o Should not be used in HF & MI, as lack the protective effect of complete blockers (holes in failing heart balloon in audience) o Acebutolol – β1-selective with partial antagonist activity (plastic bugle). o Pindolol – Nonselective β blocker with partial agonist activity (agonizing sound of tiny bugle pin in audience).