What are the effects of Labetalol (alpha- and beta-adrenergic blocker)?

From the Guidelines

Labetalol is a highly effective medication for managing high blood pressure and hypertensive emergencies, with its dual alpha and beta blocking mechanism providing balanced vasodilation and reducing the risk of severe bradycardia or bronchospasm. The effects of labetalol include lowering blood pressure by reducing heart rate, cardiac output, and peripheral vascular resistance 1. According to the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline, labetalol can be administered intravenously with an initial dose of 0.3-1.0 mg/kg (maximum 20 mg) slow IV injection every 10 min or 0.4-1.0 mg/kg/h IV infusion up to 3 mg/kg/h, with adjustments made up to a total cumulative dose of 300 mg 1.

Key Considerations

• Labetalol is contraindicated in patients with reactive airways disease or chronic obstructive pulmonary disease, and should be used cautiously in patients with asthma, COPD, heart failure, or diabetes 1.
• The medication is particularly useful in situations requiring rapid blood pressure control without excessive heart rate reduction, such as in pregnancy-related hypertension, pheochromocytoma, and perioperative settings.
• Common side effects of labetalol may include dizziness, fatigue, nausea, headache, and orthostatic hypotension.

Comparison with Other Antihypertensive Agents

• A meta-analysis of 147 randomized trials reported that beta-blockers, such as labetalol, have a similar effect to other agents in preventing coronary events and heart failure, but may be slightly inferior in preventing stroke 1.
• However, labetalol's dual blocking mechanism may provide a more balanced vasodilation compared to pure beta blockers, making it a useful option in certain clinical scenarios.
• The European guidelines on cardiovascular disease prevention in clinical practice recommend that beta-blockers, including labetalol, can be used as part of antihypertensive treatment, either as monotherapy or in combination with other agents 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Labetalol combines both selective, competitive alpha1-adrenergic blocking and nonselective, competitive beta-adrenergic blocking activity in a single substance. Labetalol beta1-receptor blockade in man was demonstrated by a small decrease in the resting heart rate, attenuation of tachycardia produced by isoproterenol or exercise, and by attenuation of the reflex tachycardia to the hypotension produced by amyl nitrite. Beta2-receptor blockade was demonstrated by inhibition of the isoproterenol-induced fall in diastolic blood pressure Labetalol produces dose-related falls in blood pressure without reflex tachycardia and without significant reduction in heart rate, presumably through a mixture of its alpha- and beta-blocking effects.

The effects of Labetalol (alpha- and beta-adrenergic blocker) include:

• Alpha1-adrenergic blocking activity: lowers blood pressure more in the standing than in the supine position
• Beta1-receptor blockade: small decrease in resting heart rate, attenuation of tachycardia
• Beta2-receptor blockade: inhibition of isoproterenol-induced fall in diastolic blood pressure
• Dose-related falls in blood pressure: without reflex tachycardia and without significant reduction in heart rate
• Hemodynamic effects: variable, with small nonsignificant changes in cardiac output and small decreases in total peripheral resistance 2
• Reduction in exercise-induced tachycardia: occurs within 2 hours after oral administration of labetalol HCl 3

From the Research

Effects of Labetalol on Blood Pressure

• Labetalol, a combined alpha- and beta-adrenergic receptor blocking agent, has been shown to reduce diastolic blood pressure by 30 mm Hg or more in patients with severe hypertension 4.
• The intravenous administration of labetalol produces a prompt but gradual reduction of arterial blood pressure without the induction of a reflex tachycardia 4, 5.
• Labetalol has been found to be effective in reducing blood pressure in patients with hypertensive emergencies, with a decrease in blood pressure of 55/33 mm Hg after the last dose of labetalol 5.

Hemodynamic Effects

• Labetalol reduces peripheral vascular resistance and blood pressure with little alteration in heart rate or cardiac output 6.
• The drug lowers peripheral vascular resistance by vasodilatation with little or no effect on cardiac output 7.
• Labetalol reduces blood pressure, heart rate, and peripheral resistance with almost no change in resting cardiac output or stroke volume 8.

Clinical Uses

• Labetalol is used in the treatment of hypertension, including essential hypertension, renal hypertension, pheochromocytoma, pregnancy hypertension, and hypertensive emergencies 6, 5, 8.
• The drug is also used in the management of ischemic heart disease and has been found to be safe in patients with coronary artery disease or after acute myocardial infarction 6, 8.

Side Effects

• The most troublesome side effect of labetalol therapy is posture-related dizziness 6.
• Other reported side effects of the drug include gastrointestinal disturbances, tiredness, headache, scalp tingling, skin rashes, urinary retention, and impotence 6.
• Labetalol may also cause side effects related to its beta-adrenoceptor blocking effect, including asthma, heart failure, and Raynaud's phenomenon, although these are rare 6.