Generic Name

Labetalol

Mechanism

• α₁‑Blockade
• Competitive inhibition of α₁‑adrenergic receptors → vasodilation, ↓ systemic vascular resistance, ↓ blood pressure.
• β₁‑ and β₂‑Blockade
• β₁ inhibition → ↓ heart rate, ↓ contractility, ↓ myocardial oxygen demand.
• β₂ inhibition reduces β₂‑mediated vasodilation in skeletal muscle but the net effect is still vasodilation because α₁‑blockade dominates.
• Net Effect
• Rapid, controlled fall in blood pressure with minimal reflex tachycardia due to balanced adrenergic blockade.

Pharmacokinetics

• Absorption
• Oral: > 70 % bioavailability; peak plasma 30–60 min.
• IV: 100 % bioavailability; onset within 2–5 min.
• Distribution
• Protein binding ~ 50 %; distribution half‑life 30 min.
• CNS penetration limited but significant for β₂ blockade in central sites.
• Metabolism
• Primarily hepatic via oxidative pathways (CYP1A2, CYP3A4).

– Minor renal excretion (≈ 15 % unchanged).
• Elimination
• Half‑life 4–9 h (oral); 3 h (IV).
• Clearable in patients with moderate hepatic impairment; dose adjustments advised.
• Drug Interactions
• CYP2D6 inhibitors ↑ plasma levels; CYP3A4 inhibitors ↑ exposure slightly.
• Concurrent diuretics → ↑ risk of isolated systolic hypertension.

Indications

• Acute management of severe hypertension, hypertensive emergencies, and pre‑operative control of blood pressure.
• Adjunctive therapy in acute type A aortic dissection.
• Pre‑operative blood pressure management in patients undergoing aortic arch surgery.
• First‑line agent for preeclampsia‑eclampsia when rapid BP reduction is essential.

Contraindications

• Absolute Contraindications
• Severe sinoatrial node dysfunction; symptomatic bradycardia; third‑degree AV block.
• Uncontrolled severe asthma or COPD (due to β₂ blockade).
• Relative Warnings
• New‑onset heart failure (β‑blockade may exacerbate).
• Hypotension, low cardiac output states; avoid rapid IV loading.
• Pregnancy: Category C; use only if benefits outweigh risks.
• Breastfeeding: excretion in milk; caution advised.
• Precautions
• Patients with liver dysfunction: monitor β‑blockade effects.
• Concurrent β‑blockers or antiarrhythmics: monitor HR, BP.

Dosing

• IV infusion: start at low rate; incrementally increase 3–5 min intervals, monitor BP.
• Oral: gradual dose escalation minimizes reflex tachycardia.

Adverse Effects

• Common:
• Reflex tachycardia (rare), dizziness, headache, fatigue, hypotension.
• Insomnia, nausea, vomiting.
• Serious:
• Severe hypotension, bradycardia, heart block.
• Pulmonary edema in susceptible patients.
• Angioedema (rare).
• Allergic reactions (rash, urticaria).

Monitoring

• Hemodynamic:
• BP and HR every 5–10 min during IV initiation; hourly thereafter.
• Laboratory:
• Electrolytes if on diuretics; renal function if renal impairment.
• Cardiac Monitoring:
• Continuous ECG during IV therapy; watch for arrhythmias.
• Clinical Signs:
• Signs of pulmonary edema (dyspnea, crackles).

Clinical Pearls

• α/β Balance – Labetalol’s unique dual action makes it ideal for patients where catecholamine surge is driven by both α and β pathways, such as hypertensive emergencies.
• Avoid Abrupt Withdrawal – A sudden stop during IV infusion can precipitate rebound hypertension; taper over 20–30 min if discontinued.
• Use in Pregnancy – Limited data; if used, prefer short courses; monitor maternal BP closely.
• Drug Interaction Check – Concomitant CYP3A4 inhibitors (e.g., ketoconazole) may raise plasma levels; consider dose reduction.
• Dosing Flexibility – The same drug can act as a rapid IV infusion or a titrated oral regimen, reducing the transition time between inpatient and outpatient care.

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• *Labetalol* provides a versatile, well‑characterized option for clinicians dealing with challenging, life‑threatening hypertensive states while maintaining a favorable safety profile when dosed appropriately.