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:

• Hypertension • Heart Failure (HFrEF) • Arrhythmias • 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: Autonomic Receptors

Generations of Beta-Blockers

1st Generation – Nonselective (β1 + β2 Blockade)

Block both β1 and β2 receptors.

• ★ Propranolol • Nadolol • Timolol • Sotalol • Penbutolol • Carteolol

Clinical Notes:

• Avoid in asthma / severe COPD • Sotalol also has Class III antiarrhythmic activity

2nd Generation – Cardioselective (β1 Selective)

Primarily block β1 receptors.

• ★ Metoprolol • ★ Bisoprolol • ★ Atenolol • ★ Esmolol (IV, ultra short-acting) • Nebivolol • Acebutolol • Betaxolol • 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:

• ★ Carvedilol • ★ Labetalol

Nitric Oxide–Mediated:

• ★ Nebivolol

Less Common:

• 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
Propranolol 1st No No Lipophilic No Migraine, tremor, portal HTN
Sotalol 1st No No Hydrophilic No AF, ventricular arrhythmias
Metoprolol 2nd Yes No Lipophilic Only Succinate HTN, CAD, AF
Bisoprolol 2nd Yes No Moderate Yes HFrEF, HTN
Atenolol 2nd Yes No Hydrophilic No HTN (historical)
Esmolol 2nd Yes No Hydrophilic No ICU rate control
Carvedilol 3rd No Yes (alpha-1) Lipophilic Yes HFrEF, HTN
Labetalol 3rd No Yes (alpha-1) Moderate No HTN emergency, pregnancy
Nebivolol 3rd Yes Nitric Oxide-Mediated Lipophilic No HTN

Intrinsic Sympathomimetic Activity (ISA)

Partial agonist activity:

• Pindolol • Acebutolol • Penbutolol

Less commonly used in modern practice.

Evidence-Based Heart Failure Agents (Mortality Benefit)

• ★ Carvedilol • ★ Metoprolol Succinate • ★ Bisoprolol

→ 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

→ Hypertension Module

Arrhythmias: • Rate control in atrial fibrillation • SVT suppression

→ Dysrhythmias Module

Angina: • Reduce myocardial oxygen demand

→ Anti-Anginal Module

Hypertensive Emergency: • ★ Labetalol • ★ 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:

→ Hypertension Module → Heart Failure Module → Dysrhythmias Module → Return to Cardiovascular Modules