1. Introduction
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Cardioselective beta-blockers are β1-adrenergic receptor antagonists that preferentially block β1 receptors in the heart over β2 receptors in the bronchi and peripheral vasculature.
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Also called β1-selective beta-blockers.
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At therapeutic doses, they reduce heart rate, myocardial contractility, and AV conduction with minimal β2 blockade.
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Selectivity is dose-dependent — at higher doses, β2 blockade becomes significant.
2. Mechanism of Action
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Competitive antagonism at β1-adrenergic receptors in cardiac tissue.
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Cardiac effects:
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↓ Heart rate (negative chronotropy).
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↓ Contractility (negative inotropy).
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↓ AV nodal conduction (negative dromotropy).
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↓ Myocardial oxygen demand.
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Renal effects:
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↓ Renin release from juxtaglomerular cells, reducing RAAS activation.
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3. Common Agents (β1-Selective)
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Atenolol
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Metoprolol (tartrate, succinate)
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Bisoprolol
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Esmolol (ultra-short-acting, IV use)
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Nebivolol (also causes NO-mediated vasodilation)
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Betaxolol (also used topically in glaucoma)
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Acebutolol (has intrinsic sympathomimetic activity — ISA)
4. Pharmacokinetics (General Trends)
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Oral bioavailability: varies (metoprolol moderate, atenolol higher).
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Metabolism:
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Hepatic (metoprolol, bisoprolol, nebivolol).
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Renal excretion largely unchanged (atenolol).
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Half-life: ranges from minutes (esmolol) to ~24 hours (bisoprolol, nebivolol).
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Dosing frequency: depends on formulation (e.g., metoprolol succinate once daily, tartrate twice daily).
5. Clinical Indications
Cardiovascular
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Hypertension (monotherapy or combination).
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Angina pectoris (chronic stable, exertional).
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Acute myocardial infarction and post-MI secondary prevention.
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Chronic heart failure with reduced ejection fraction (bisoprolol, metoprolol succinate, nebivolol).
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Supraventricular arrhythmias (rate control in atrial fibrillation/flutter, AV nodal re-entrant tachycardia).
Other
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Migraine prophylaxis (metoprolol, atenolol).
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Certain anxiety disorders (performance anxiety).
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Glaucoma (betaxolol topical).
6. Advantages of Cardioselectivity
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Lower risk of bronchoconstriction compared to non-selective beta-blockers — preferred in patients with mild to moderate asthma or COPD (but still used with caution).
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Less interference with β2-mediated peripheral vasodilation and metabolic effects.
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Better tolerability in patients with peripheral vascular disease or diabetes, although some β1 blockade still may mask hypoglycemia symptoms.
7. Contraindications
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Severe bradycardia.
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Second- or third-degree AV block without pacemaker.
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Cardiogenic shock.
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Severe decompensated heart failure (initiate only when stabilized).
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Known hypersensitivity to the drug.
8. Precautions
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Use cautiously in asthma/COPD — cardioselectivity is not absolute.
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Caution in diabetics — may mask adrenergic symptoms of hypoglycemia.
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Taper gradually when discontinuing to avoid rebound tachycardia, hypertension, or ischemia.
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Monitor for worsening peripheral circulation in severe peripheral artery disease.
9. Adverse Effects
Cardiac
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Bradycardia, hypotension.
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AV block, worsening heart failure (if started or titrated too quickly).
Respiratory
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Bronchospasm (rare at low doses, risk increases with higher doses).
Metabolic
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Masking of hypoglycemia symptoms (tremor, tachycardia).
Other
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Fatigue, dizziness, depression, sleep disturbances.
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Cold extremities, reduced exercise tolerance.
10. Drug Interactions
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Calcium channel blockers (non-DHPs: verapamil, diltiazem): additive negative chronotropy/inotropy → risk of bradycardia, AV block.
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Digoxin: additive effects on AV nodal conduction.
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Other antihypertensives: additive hypotensive effects.
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Drugs affecting CYP2D6 metabolism (for metoprolol, nebivolol): can alter plasma levels.
11. Monitoring
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Heart rate and blood pressure at baseline and during therapy.
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ECG for conduction abnormalities in long-term or high-risk patients.
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Signs and symptoms of worsening heart failure.
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In diabetics: monitor blood glucose more closely.
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