selective beta blocker

**Mechanism:** Competitive antagonism of β1 receptors (Gs-coupled, ↑cAMP/PKA) in the heart and juxtaglomerular cells. Effects: ↓HR (negative chronotropy), ↓contractility (negative inotropy), ↓AV node conduction (prolonged PR interval), ↓renin release (↓angiotensin II/aldosterone), ↓myocardial O2 demand. Class II antiarrhythmics (slow phase 4 depolarization in SA node, ↓AV conduction).

**Selective agents (β1 > β2):** Acebutolol (also has partial agonist/ISA activity), Betaxolol (also used for glaucoma), Bisoprolol, Esmolol (ultra-short-acting IV, t½ ~10 min; used in acute aortic dissection, perioperative/intraoperative tachycardia, SVT), Atenolol (hydrophilic, renally cleared), Metoprolol (lipophilic, hepatic CYP2D6). Nebivolol is β1-selective plus stimulates endothelial NO release → vasodilation.

**Nonselective comparison:** Propranolol, nadolol, timolol, pindolol (ISA), and sotalol (also class III) block both β1 and β2. Carvedilol and labetalol block β plus α1 (vasodilation); not selective.

**Clinical uses:** - Hypertension (not first-line in uncomplicated HTN currently) - Angina (chronic stable): ↓O2 demand - Post-MI: ↓mortality - Heart failure with reduced EF: metoprolol succinate, bisoprolol, carvedilol reduce mortality (start only when euvolemic/stable, not in acute decompensation) - Rate control in atrial fibrillation/flutter, SVT - Acute aortic dissection (esmolol first, reduce dP/dt before vasodilators) - Performance anxiety, hyperthyroidism symptoms (propranolol preferred)

**Why selectivity matters:** - Fewer β2-related adverse effects: less bronchoconstriction (safer in asthma/COPD, though still used cautiously), less peripheral vasoconstriction (Raynaud, claudication), less impairment of glycogenolysis/gluconeogenesis (less masking of hypoglycemia in diabetics, though tachycardia may still be blunted; sweating is preserved), and less lipid disturbance. - Selectivity is dose-dependent and lost at higher doses.

**Adverse effects (class-wide):** Bradycardia, AV block, hypotension, fatigue, sexual dysfunction, depression/sleep disturbance (more with lipophilic agents crossing the BBB), masking of hypoglycemia symptoms, acute decompensation of HF if started in acute setting.

**Contraindications/cautions:** Severe bradycardia, 2nd/3rd-degree AV block, decompensated HF, cardiogenic shock, severe asthma (relative for selective agents), sick sinus syndrome. Do not abruptly discontinue (rebound tachycardia/hypertension, angina, MI from upregulated β receptors).

**Special points:** - Pheochromocytoma/cocaine toxicity: avoid unopposed α stimulation (give α-blocker first; for cocaine, benzodiazepines, and phentolamine/CCBs preferred; labetalol/carvedilol sometimes considered). - Beta-blocker overdose: bradycardia/hypotension → glucagon (↑cAMP bypassing β receptor), atropine, high-dose insulin euglycemic therapy, calcium, pressors. - Acute bronchospasm with β-blocker is a classic side effect of nonselective agents (e.g., timolol eye drops). - Esmolol is metabolized by RBC esterases, so it's not dependent on renal/hepatic function. - Beta-blockers that have ISA (acebutolol, pindolol) cause less resting bradycardia, and are used in patients prone to bradycardia; no mortality benefit post-MI.

**High-yield test pearls:** β1 = heart (“1 heart”), β2 = lungs/vasculature/uterus (“2 lungs”). Selective β-blockers are preferred in patients with asthma/COPD, diabetes, or peripheral vascular disease who require β-blockade.