metoprolol
Summary
Metoprolol is a cardioselective beta-1 adrenergic receptor antagonist (beta-blocker) used to treat hypertension, angina, heart failure, and arrhythmias. It reduces heart rate, myocardial contractility, and cardiac output by blocking sympathetic stimulation of beta-1 receptors in the heart. Available in immediate-release (tartrate) and extended-release (succinate) formulations with different clinical indications.
Detail
Metoprolol selectively blocks beta-1 adrenergic receptors, predominantly located in cardiac tissue, at therapeutic doses (relative cardioselectivity, though selectivity is lost at higher doses). Mechanism: decreases cAMP production, reducing calcium influx, leading to negative chronotropic (decreased heart rate), negative inotropic (decreased contractility), and negative dromotropic (decreased AV node conduction) effects. This decreases myocardial oxygen demand, making it useful in angina, and decreases renin release from juxtaglomerular cells, contributing to blood pressure control.
Clinical uses: Hypertension, chronic stable angina, post-MI mortality reduction, chronic systolic heart failure (metoprolol succinate specifically, per COMET and MERIT-HF trials), atrial fibrillation/flutter rate control, and supraventricular tachycardia.
Formulations: Metoprolol tartrate (immediate-release, shorter half-life, used for acute rate control and BID dosing) vs metoprolol succinate (extended-release, once-daily, evidence-based for heart failure).
Adverse effects: Bradycardia, AV block, fatigue, bronchospasm (less than non-selective beta-blockers but caution in asthma/COPD), masking of hypoglycemia symptoms in diabetics, erectile dysfunction, depression, and can precipitate acute decompensated heart failure if initiated during acute HF exacerbation—should be started only in stable, compensated heart failure patients.
Contraindications/cautions: Severe bradycardia, high-degree AV block without pacemaker, decompensated heart failure, severe asthma/reactive airway disease (relatively cardioselective, so preferred beta-blocker in mild-moderate COPD/asthma if beta-blocker needed).
Pharmacokinetics: Extensively metabolized by CYP2D6, subject to significant first-pass metabolism; genetic polymorphisms in CYP2D6 affect drug levels.
Board relevance: Classic teaching point is distinguishing cardioselective (beta-1 selective: metoprolol, atenolol, esmolol, bisoprolol - mnemonic 'A BEAM') vs non-selective beta-blockers (propranolol, nadolol, timolol). Important to know beta-blocker overdose treatment (glucagon) and abrupt discontinuation risks (rebound tachycardia, hypertension, angina due to upregulated beta receptors).
Sources
- Katzung's Basic and Clinical Pharmacology
- First Aid for the USMLE Step 1
- Goodman & Gilman's The Pharmacological Basis of Therapeutics
- UpToDate: Beta blockers in the management of heart failure
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.