Hydralazine - Drug Monograph

Introduction

Hydralazine is a direct-acting vasodilator that has been used clinically since the 1950s. It is primarily indicated for the management of hypertension, either as monotherapy or in combination with other antihypertensive agents. Hydralazine remains particularly valuable in specific clinical scenarios, including hypertensive emergencies and heart failure management when combined with nitrates.

Mechanism of Action

Hydralazine exerts its pharmacological effects through direct relaxation of arteriolar smooth muscle. The drug causes vasodilation by activating guanylate cyclase, increasing cyclic guanosine monophosphate (cGMP) levels, and reducing intracellular calcium concentrations. This mechanism primarily affects arterial vasculature with minimal effect on venous capacitance vessels. The resulting reduction in peripheral vascular resistance leads to decreased blood pressure without significant effects on cardiac output or heart rate when used appropriately.

Indications

• Management of essential hypertension (usually as part of combination therapy)
• Hypertensive emergencies (acute severe hypertension)
• Heart failure (in combination with isosorbide dinitrate for African American patients with NYHA class III-IV heart failure)
• Perioperative hypertension

Dosage and Administration

• Initial dose: 10 mg four times daily for 2-4 days
• Maintenance dose: 25-100 mg daily in divided doses (maximum 300 mg/day)

• Initial IV/IM dose: 10-20 mg every 4-6 hours as needed
• May increase to 40 mg dose if necessary

• Renal impairment: Use with caution; may require dose adjustment
• Hepatic impairment: Use with caution; reduced metabolism may occur
• Geriatric patients: Start with lower doses due to increased sensitivity
• Pediatric patients: 0.75-3 mg/kg/day in 2-4 divided doses (maximum 200 mg/day)

Pharmacokinetics

Contraindications

• Hypersensitivity to hydralazine or any component of the formulation
• Coronary artery disease (relative contraindication due to reflex tachycardia)
• Mitral valvular rheumatic heart disease
• Dissecting aortic aneurysm
• Idiopathic systemic lupus erythematosus (SLE) or history of drug-induced lupus

Warnings and Precautions

• Lupus-like syndrome: May develop in 5-10% of patients receiving >200 mg/day for prolonged periods
• Peripheral neuritis: May occur due to pyridoxine deficiency
• Hypotension: May cause symptomatic hypotension, particularly in volume-depleted patients
• Reflex tachycardia: May precipitate angina in patients with coronary artery disease
• Blood dyscrasias: Neutropenia, agranulocytosis, anemia, and thrombocytopenia reported
• Hepatotoxicity: Rare cases of hepatitis and hepatic necrosis reported

Drug Interactions

• MAO inhibitors: Enhanced hypotensive effect
• Beta-blockers: Attenuate reflex tachycardia but may cause excessive hypotension
• Diuretics and other antihypertensives: Additive hypotensive effects
• Diazepam: Increased diazepam levels
• NSAIDs: May diminish antihypertensive effect
• Epinephrine: Reduced pressor response

Adverse Effects

• Headache
• Palpitations
• Tachycardia
• Nausea
• Angina pectoris
• Flushing

• Peripheral neuritis
• Edema
• Dizziness
• Dyspnea
• Anorexia

• Drug-induced lupus syndrome
• Blood dyscrasias
• Hepatitis
• Hypersensitivity reactions
• Depression

Monitoring Parameters

• Blood pressure (standing and supine)
• Heart rate and rhythm
• Complete blood count (baseline and periodically)
• Antinuclear antibody titers (if prolonged high-dose therapy)
• Liver function tests (periodically)
• Renal function
• Signs/symptoms of lupus-like syndrome
• Neurological examination for peripheral neuropathy

Patient Education

• Take medication exactly as prescribed; do not stop abruptly
• Rise slowly from sitting/lying position to minimize dizziness
• Report any unusual symptoms immediately: joint pain, fever, chest pain, rash, or numbness/tingling
• Regular blood pressure monitoring is essential
• Avoid alcohol as it may enhance hypotensive effects
• Inform all healthcare providers about hydralazine use
• Use effective contraception as safety in pregnancy is not well established
• Keep all follow-up appointments for monitoring

References

1. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. JAMA. 2014;311(5):507-520. 2. Taylor AL, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004;351(20):2049-2057. 3. Hydralazine hydrochloride [package insert]. U.S. Food and Drug Administration. 4. Brunton LL, et al. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 13th ed. McGraw-Hill Education; 2017. 5. McEvoy GK, ed. AHFS Drug Information. American Society of Health-System Pharmacists; 2023. 6. Cohn JN, et al. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345(23):1667-1675.