====== Beta-Blockers ====== Beta-blockers antagonize beta-adrenergic receptors and reduce sympathetic stimulation of the cardiovascular system. Primary Physiologic Effects: • ↓ Heart rate • ↓ Contractility • ↓ Renin release • ↓ Cardiac output • ↓ Blood pressure Used in: • [[cardio:hypertension:start|Hypertension]] • [[cardio:heart_failure:start|Heart Failure (HFrEF)]] • [[cardio:arrhythmias:start|Arrhythmias]] • [[cardio:angina:start|Angina]] • Post-myocardial infarction ★ = Most commonly used / high-yield agents -------------------------------------------------------------------- ===== Mechanism of Action ===== β1 receptors: • Heart (↑ HR, ↑ contractility) • Kidney (↑ renin) β2 receptors: • Bronchi (bronchodilation) • Vascular smooth muscle Beta-blockers: • Block β1 (cardiac effects) • Some also block β2 • Some provide additional vasodilation (α1 or NO-mediated) Reference: [[autonomics:start|Autonomic Receptors]] -------------------------------------------------------------------- ===== Generations of Beta-Blockers ===== ==== 1st Generation – Nonselective (β1 + β2 Blockade) ==== Block both β1 and β2 receptors. • ★ [[cardio:beta_blockers:propranolol|Propranolol]] • [[cardio:beta_blockers:nadolol|Nadolol]] • [[cardio:beta_blockers:timolol|Timolol]] • [[cardio:beta_blockers:sotalol|Sotalol]] • [[cardio:beta_blockers:penbutolol|Penbutolol]] • [[cardio:beta_blockers:carteolol|Carteolol]] Clinical Notes: • Avoid in asthma / severe COPD • Sotalol also has Class III antiarrhythmic activity -------------------------------------------------------------------- ==== 2nd Generation – Cardioselective (β1 Selective) ==== Primarily block β1 receptors. • ★ [[cardio:beta_blockers:metoprolol|Metoprolol]] • ★ [[cardio:beta_blockers:bisoprolol|Bisoprolol]] • ★ [[cardio:beta_blockers:atenolol|Atenolol]] • ★ [[cardio:beta_blockers:esmolol|Esmolol]] (IV, ultra short-acting) • [[cardio:beta_blockers:nebivolol|Nebivolol]] • [[cardio:beta_blockers:acebutolol|Acebutolol]] • [[cardio:beta_blockers:betaxolol|Betaxolol]] • [[cardio:beta_blockers:celiprolol|Celiprolol]] Clinical Notes: • Preferred in reactive airway disease • Selectivity is dose-dependent • Esmolol used in ICU / acute arrhythmias -------------------------------------------------------------------- ==== 3rd Generation – Vasodilating Beta-Blockers ==== Provide additional vasodilation via α1 blockade or nitric oxide release. Alpha/Beta Blockade: • ★ [[cardio:beta_blockers:carvedilol|Carvedilol]] • ★ [[cardio:beta_blockers:labetalol|Labetalol]] Nitric Oxide–Mediated: • ★ [[cardio:beta_blockers:nebivolol|Nebivolol]] Less Common: • [[cardio:beta_blockers:bucindolol|Bucindolol]] Clinical Notes: • Lower SVR in addition to HR reduction • Carvedilol reduces mortality in HFrEF • Labetalol commonly used in hypertensive emergencies -------------------------------------------------------------------- ===== Beta-Blocker Comparison Table ===== ^ Drug ^ Generation ^ Beta-1 Selective ^ Alpha-1 / Vasodilation ^ Lipophilic vs Hydrophilic ^ HFrEF Mortality Benefit ^ Common Uses ^ |[[cardio:beta_blockers:propranolol|Propranolol]] | 1st | No | No | Lipophilic | No | Migraine, tremor, portal HTN | | [[cardio:beta_blockers:sotalol|Sotalol]] | 1st | No | No | Hydrophilic | No | AF, ventricular arrhythmias | |[[cardio:beta_blockers:metoprolol|Metoprolol]] | 2nd | Yes | No | Lipophilic | Only Succinate | HTN, CAD, AF | |[[cardio:beta_blockers:bisoprolol|Bisoprolol]] | 2nd | Yes | No | Moderate | Yes | HFrEF, HTN | |[[cardio:beta_blockers:atenolol|Atenolol]] | 2nd | Yes | No | Hydrophilic | No | HTN (historical) | |[[cardio:beta_blockers:esmolol|Esmolol]] | 2nd | Yes | No | Hydrophilic | No | ICU rate control | |[[cardio:beta_blockers:carvedilol|Carvedilol]] | 3rd | No | Yes (alpha-1) | Lipophilic | Yes | HFrEF, HTN | |[[cardio:beta_blockers:labetalol|Labetalol]] | 3rd | No | Yes (alpha-1) | Moderate | No | HTN emergency, pregnancy | |[[cardio:beta_blockers:nebivolol|Nebivolol]] | 3rd | Yes | Nitric Oxide-Mediated | Lipophilic | No | HTN | ===== Intrinsic Sympathomimetic Activity (ISA) ===== Partial agonist activity: • [[cardio:beta_blockers:pindolol|Pindolol]] • [[cardio:beta_blockers:acebutolol|Acebutolol]] • [[cardio:beta_blockers:penbutolol|Penbutolol]] Less commonly used in modern practice. -------------------------------------------------------------------- ===== Evidence-Based Heart Failure Agents (Mortality Benefit) ===== • ★ [[cardio:beta_blockers:carvedilol|Carvedilol]] • ★ [[cardio:beta_blockers:metoprolol|Metoprolol Succinate]] • ★ [[cardio:beta_blockers:bisoprolol|Bisoprolol]] → [[cardio:heart_failure:start|Heart Failure Module]] Not all beta-blockers reduce mortality in HFrEF. -------------------------------------------------------------------- ===== Indications by Clinical Context ===== Hypertension: • Not first-line for uncomplicated HTN • Preferred when CAD, arrhythmia, or HFrEF present → [[cardio:hypertension:start|Hypertension Module]] Arrhythmias: • Rate control in atrial fibrillation • SVT suppression → [[cardio:arrhythmias:start|Dysrhythmias Module]] Angina: • Reduce myocardial oxygen demand → [[cardio:angina:start|Anti-Anginal Module]] Hypertensive Emergency: • ★ [[cardio:beta_blockers:labetalol|Labetalol]] • ★ [[cardio:beta_blockers:esmolol|Esmolol]] -------------------------------------------------------------------- ===== Adverse Effects ===== • Bradycardia • AV block • Hypotension • Fatigue • Depression • Erectile dysfunction • Masked hypoglycemia • Bronchospasm (nonselective agents) -------------------------------------------------------------------- ===== Contraindications ===== • Severe bradycardia • High-grade AV block (without pacemaker) • Cardiogenic shock • Acute decompensated heart failure Use caution in: • Asthma • Severe peripheral vascular disease -------------------------------------------------------------------- ===== Clinical Pearls ===== ✔ Only certain agents reduce mortality in HFrEF ✔ 1st gen = nonselective ✔ 2nd gen = β1 selective ✔ 3rd gen = vasodilating ✔ Avoid abrupt discontinuation (rebound tachycardia) ✔ Not first-line for uncomplicated hypertension -------------------------------------------------------------------- Related: → [[cardio:hypertension:start|Hypertension Module]] → [[cardio:heart_failure:start|Heart Failure Module]] → [[cardio:arrhythmias:start|Dysrhythmias Module]] → [[cardio:intro:start|Return to Cardiovascular Modules]]