Beta blockers

Beta Blockers (β-blockers) are a class of medications that inhibit the effects of epinephrine (adrenaline) and norepinephrine at beta-adrenergic receptors, primarily in the heart, lungs, and vascular system. They are widely used in cardiovascular medicine, endocrinology, neurology, and sometimes psychiatry, with applications ranging from hypertension to migraine prevention and performance anxiety.

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Classification of Beta Blockers

Beta blockers are classified based on:

1. Selectivity

• Non-selective: Block both β1 and β2 receptors

  • e.g. Propranolol, Nadolol, Timolol

• Cardioselective (β1-selective): Preferentially block β1 receptors in the heart

  • e.g. Atenolol, Metoprolol, Bisoprolol, Nebivolol

• Third-generation (vasodilatory): β-blockers with additional vasodilating properties

  • Carvedilol (non-selective + α1-blocking)

  • Labetalol (non-selective + α1-blocking)

  • Nebivolol (β1-selective + NO-mediated vasodilation)

2. Intrinsic Sympathomimetic Activity (ISA)

Some β-blockers partially stimulate β-receptors while blocking them:

• e.g. Pindolol, Acebutolol

3. Lipid Solubility

• Determines CNS penetration and risk of side effects (e.g. nightmares, depression):

  • High lipid solubility: Propranolol

  • Low lipid solubility: Atenolol

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Mechanism of Action

Beta blockers inhibit the beta-adrenergic receptors:

• β1 receptors (primarily in the heart):

  • ↓ Heart rate (negative chronotropy)

  • ↓ Contractility (negative inotropy)

  • ↓ Cardiac output

  • ↓ Renin release from juxtaglomerular cells

• β2 receptors (found in lungs, skeletal muscle, liver, pancreas):

  • Blockade causes bronchoconstriction, vasoconstriction, and impaired glycogenolysis

• α1-receptor blockade (e.g. carvedilol): leads to vasodilation

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Therapeutic Uses

Cardiovascular Indications

• Hypertension (not first-line unless comorbid heart disease)

• Angina pectoris (chronic stable, unstable)

• Post-myocardial infarction (MI): Reduces mortality

• Heart failure (systolic dysfunction): e.g. carvedilol, bisoprolol, metoprolol succinate

• Arrhythmias: Supraventricular (e.g., atrial fibrillation), ventricular arrhythmias

• Hypertrophic obstructive cardiomyopathy (HOCM)

• Aortic dissection: Reduce shear stress

Non-Cardiac Indications

• Migraine prophylaxis: Propranolol, timolol

• Essential tremor: Propranolol

• Anxiety: Performance anxiety (propranolol)

• Hyperthyroidism: Acute management (propranolol inhibits T4→T3 conversion)

• Glaucoma (topical timolol, betaxolol): Decreases intraocular pressure

• Portal hypertension and variceal bleeding prophylaxis: Non-selective (propranolol, nadolol)

• Pheochromocytoma (in combination with alpha blockers)

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Dosage and Administration

Varies significantly by condition, agent, and route.

Examples:

• Propranolol: 40–320 mg/day (divided doses)

• Metoprolol tartrate: 50–100 mg twice daily

• Metoprolol succinate: 25–200 mg once daily (extended-release)

• Bisoprolol: 2.5–10 mg once daily

• Atenolol: 25–100 mg once daily

• Carvedilol: 3.125–25 mg twice daily

• Nebivolol: 5–10 mg once daily

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Contraindications

Absolute:

• Severe bradycardia

• Second or third-degree AV block (without pacemaker)

• Cardiogenic shock

• Decompensated heart failure

• Sick sinus syndrome (without pacemaker)

• Severe asthma or bronchospasm (non-selective β-blockers)

Relative:

• Peripheral arterial disease (PAD)

• Diabetes mellitus (masking of hypoglycemia)

• Depression (lipophilic β-blockers like propranolol)

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Precautions

• Tapering is essential when discontinuing to prevent rebound hypertension, angina, or arrhythmias.

• Monitor:

  • HR: Avoid <50 bpm unless clinically warranted.

  • BP: Watch for hypotension.

  • Glucose: May mask signs of hypoglycemia.

  • Lung function: In patients with COPD/asthma.

• Use with caution in elderly patients or those with renal impairment.

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Adverse Effects

Cardiovascular:

• Bradycardia

• Hypotension

• AV block

• Worsening of heart failure

Respiratory:

• Bronchospasm (non-selective agents)

CNS:

• Fatigue

• Depression

• Insomnia

• Nightmares (lipophilic β-blockers)

Metabolic:

• Masking of hypoglycemia symptoms

• Alteration of lipid profile (↑ triglycerides, ↓ HDL)

Sexual Dysfunction:

• Decreased libido

• Erectile dysfunction

Other:

• Cold extremities

• Raynaud's phenomenon

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Drug Interactions

Increased Effects / Toxicity:

• Other antihypertensives: Additive hypotension/bradycardia

• Verapamil / Diltiazem: ↑ risk of heart block and bradycardia (avoid IV combo)

• Digoxin: ↑ risk of bradycardia

• Clonidine: Avoid abrupt withdrawal; severe rebound hypertension if both stopped suddenly

• Anesthesia agents: Potentiation of myocardial depression

Decreased Efficacy:

• NSAIDs: May blunt antihypertensive effect

Metabolism:

• Hepatic enzyme inhibitors (e.g., cimetidine) may ↑ levels of propranolol/metoprolol.

• CYP2D6 polymorphisms affect metabolism of metoprolol and carvedilol.

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Examples of Common Beta Blockers

Drug	Selectivity	Other Properties	Use
Propranolol	Non-selective	Lipophilic	Migraine, tremor, thyrotoxicosis
Atenolol	β1-selective	Hydrophilic	Hypertension, angina
Metoprolol	β1-selective	Lipophilic, available in XR form	Heart failure, post-MI, arrhythmia
Bisoprolol	β1-selective	High β1 selectivity	Chronic heart failure
Carvedilol	Non-selective	Also blocks α1-receptors	Heart failure, hypertension
Labetalol	Non-selective	α1-blocking, used in IV form	Hypertensive emergencies, pregnancy HTN
Nebivolol	β1-selective	Vasodilatory via NO release	Hypertension
Nadolol	Non-selective	Long half-life	Portal hypertension, varices prophylaxis

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Use in Special Populations

Pregnancy

• Labetalol and metoprolol often used in gestational hypertension or preeclampsia.

• Avoid atenolol (associated with intrauterine growth restriction).

Lactation

• Most β-blockers excreted in breast milk; propranolol and labetalol preferred.

Pediatrics

• Used in certain pediatric arrhythmias, congenital heart disease.

Elderly

• Start low and go slow; increased sensitivity to bradycardia and hypotension.

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Clinical Guidelines and Recommendations

• Hypertension: β-blockers are not first-line unless there’s compelling indication (e.g., heart disease).

• Heart Failure: Carvedilol, bisoprolol, or metoprolol succinate shown to reduce mortality (per ACC/AHA/HFSA guidelines).

• Post-MI: β-blockers reduce reinfarction and improve survival (Class I recommendation).

• Arrhythmias: First-line for rate control in AF, SVTs.

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Patient Counseling Tips

• Take the medication at the same time daily.

• Do not stop suddenly without medical advice.

• Monitor pulse; report <50 bpm or symptoms like dizziness/fainting.

• Diabetics: Recognize non-heart rate signs of hypoglycemia (sweating, confusion).

• May cause cold hands/feet; dress warmly in winter.

• Report persistent fatigue, depression, or erectile dysfunction.

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Storage

• Store at room temperature (15–30°C), protected from moisture.

• Keep out of reach of children