Hydralazine

• Hypertension treatment
• Heart failure in African American patients (with isosorbide dinitrate)
• Hypertensive emergencies
• Alternative for patients intolerant to ACE inhibitors or ARBs

Hydralazine is a direct-acting arterial vasodilator used primarily in the treatment of hypertension and heart failure. By relaxing vascular smooth muscle in arterioles, it reduces peripheral vascular resistance and afterload, making it valuable for managing both conditions, particularly when combined with other agents such as nitrates in heart failure therapy.

Mechanism of Action

Hydralazine causes direct relaxation of arteriolar smooth muscle through a mechanism that is not completely understood but involves interference with calcium movements and alterations in cellular calcium metabolism. Unlike many other vasodilators, hydralazine primarily affects arterioles rather than veins, causing a reduction in peripheral vascular resistance without significant venodilation. This selective arteriolar effect results in decreased blood pressure and reduced cardiac afterload.

The blood pressure reduction triggers baroreceptor-mediated reflex responses including increased heart rate, cardiac output, and renin release. These compensatory mechanisms can limit the antihypertensive effect of hydralazine when used alone, which is why it is typically used in combination with beta-blockers (to control reflex tachycardia) and diuretics (to counteract sodium retention).

Available Formulations

Hydralazine is available in oral and injectable formulations. Oral tablets come in 10 mg, 25 mg, 50 mg, and 100 mg strengths. An injectable solution (20 mg/mL) is available for intravenous or intramuscular administration in acute hypertensive emergencies or when oral administration is not possible. A fixed-dose combination with isosorbide dinitrate (BiDil) is specifically approved for heart failure in African American patients.

FDA-Approved Indications

Hydralazine is FDA-approved for essential hypertension (oral formulation), severe essential hypertension when rapid blood pressure reduction is required (parenteral), and in combination with isosorbide dinitrate for heart failure in African American patients who remain symptomatic despite optimal therapy with ACE inhibitors and beta-blockers. The combination with nitrates leverages complementary mechanisms to improve outcomes in heart failure.

Dosing Guidelines

For hypertension, the usual starting dose is 10 mg orally four times daily for the first 2-4 days, then increased to 25 mg four times daily for the rest of the first week. Subsequent dosing is individualized based on response, with a usual maintenance dose of 50 mg four times daily. For hypertensive emergencies, 10-20 mg may be given IV, repeated as needed. For heart failure (as BiDil), the combination tablet is given three times daily.

Role in Heart Failure

The A-HeFT trial demonstrated that the combination of hydralazine and isosorbide dinitrate significantly reduces mortality and hospitalizations in African American patients with heart failure when added to standard therapy. This benefit appears related to enhanced nitric oxide bioavailability and neurohormonal modulation. The combination is recommended by heart failure guidelines for this population and may also be considered in patients of any race who cannot tolerate ACE inhibitors or ARBs.

Important Safety Considerations

Drug-induced lupus erythematosus is a significant concern with hydralazine, particularly with doses exceeding 200 mg daily or with prolonged therapy. Symptoms include arthralgia, myalgia, fever, and skin rash. Testing for antinuclear antibodies is recommended with prolonged use. The condition typically resolves after discontinuation. Hydralazine should be used with caution in patients with coronary artery disease due to reflex tachycardia, and in patients with rheumatic mitral valve disease due to increased pulmonary pressure.

Drug Interactions

NSAIDs may reduce the antihypertensive effect of hydralazine. Beta-blockers are often used together intentionally to counteract reflex tachycardia. Diuretics may be needed to manage fluid retention that can occur with hydralazine therapy. MAO inhibitors should be used with caution due to potential for enhanced hypotensive effects. The medication may enhance the hypotensive effects of other antihypertensive agents.

Special Populations

Hydralazine metabolism is affected by acetylator phenotype; slow acetylators may require lower doses and are at higher risk for lupus-like syndrome. Renal impairment may require dosage adjustment due to reduced clearance. Use during pregnancy is considered relatively safe and hydralazine is often used for hypertensive emergencies in pregnancy. Dose reduction may be needed in elderly patients due to increased sensitivity.

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