What are the potential reactions to hydralazine in patients with a history of hypertension or cardiovascular disease?

Potential Reactions to Hydralazine

Hydralazine causes several predictable adverse reactions including reflex tachycardia, sodium and water retention, and can provoke myocardial ischemia, particularly in patients with coronary artery disease, making it unsuitable as monotherapy in patients with ischemic heart disease. 1

Cardiovascular Reactions

Myocardial Ischemia and Angina

• Hydralazine can provoke anginal attacks and ECG changes of myocardial ischemia through myocardial stimulation. 2
• The drug has been implicated in the production of myocardial infarction and must be used with extreme caution in patients with suspected coronary artery disease. 2
• In patients with ischemic cardiomyopathy and severe heart failure, 23% experienced ischemic events (angina at rest or myocardial infarction) during initial hydralazine administration, typically occurring without significant tachycardia or hypotension. 3
• Monotherapy with hydralazine in ischemic heart disease is not recommended due to concerns about provoking angina. 1

Reflex Tachycardia

• Reflex tachycardia is a common and predictable side effect due to hydralazine's direct arterial vasodilatory mechanism. 4, 5
• This compensatory mechanism occurs as a baroreceptor-mediated response to vasodilation. 5
• Hydralazine should typically be combined with a beta-blocker to counteract reflex tachycardia. 6, 5

Hypotension

• Hydralazine causes significant and unpredictable blood pressure reductions with a prolonged duration of action (2-4 hours). 4
• Postural hypotension may occur, though it is less common than with ganglionic blocking agents. 2
• Profound hypotensive episodes can occur when hydralazine is used concomitantly with other potent antihypertensive drugs like diazoxide. 2
• In patients with pulmonary hypertension, mean arterial pressure fell markedly (17.5 mm Hg), with four patients becoming symptomatically hypotensive within 24 hours, two requiring pressors, and one death occurring. 7

Sodium and Water Retention

• Hydralazine is associated with sodium and water retention, which may counteract its antihypertensive effect. 4, 6
• This compensatory mechanism necessitates combination therapy with a diuretic. 6, 5

Hematologic Reactions

• Blood dyscrasias have been reported, including reduction in hemoglobin and red cell count, leukopenia, agranulocytosis, and purpura. 2
• If such abnormalities develop, therapy should be discontinued immediately. 2
• Hemolytic anemia has been documented in the literature. 8, 9

Immunologic Reactions

Drug-Induced Lupus-Like Syndrome

• A lupus-like syndrome can develop, particularly at higher doses and with prolonged therapy. 4
• Complete blood counts and antinuclear antibody titer determinations are indicated before and periodically during prolonged therapy, even in asymptomatic patients. 2
• A positive antinuclear antibody titer requires careful weighing of test results against the benefits of continued therapy. 2
• These studies are also indicated if the patient develops arthralgia, fever, chest pain, continued malaise, or other unexplained signs or symptoms. 2

Other Immunologic Manifestations

• Vasculitis and glomerulonephritis have been reported in the literature. 8, 9

Neurologic Reactions

• Peripheral neuritis, evidenced by paresthesia, numbness, and tingling, has been observed. 2
• Published evidence suggests an antipyridoxine effect, and pyridoxine should be added to the regimen if symptoms develop. 2

Specific Cardiovascular Conditions

Pulmonary Hypertension

• Hydralazine can have deleterious effects in patients with pulmonary hypertension. 7
• Despite marked decreases in systemic vascular resistance (40%), hydralazine produced only moderate decreases in pulmonary arteriolar resistance (21%) without improving stroke volume or pulmonary artery pressure. 7
• Progressive renal insufficiency and symptomatic decreases in systemic arterial oxygen saturation have occurred, both reversible upon drug discontinuation. 7

Mitral Valvular Disease

• The "hyperdynamic" circulation caused by hydralazine may increase pulmonary artery pressure in patients with mitral valvular disease. 2

Cerebrovascular Disease

• Hydralazine should be used with caution in patients with cerebral vascular accidents. 2

Pharmacokinetic Considerations

• Blood pressure typically begins to decrease within 10-30 minutes after administration, with effects lasting 2-4 hours. 4, 6
• The unpredictability of response and prolonged duration of action make hydralazine less desirable as a first-line agent for acute hypertension treatment. 4, 6
• Adverse effects are dependent on dose, duration, and acetylator status. 10

Drug Interactions

• MAO inhibitors should be used with caution in patients receiving hydralazine. 2
• Hydralazine may reduce the pressor responses to epinephrine. 2
• Administration with food results in higher plasma levels. 2

Carcinogenic Potential

• In lifetime studies in mice, there was a statistically significant increase in lung tumors at doses approximately 80 times the maximum recommended human dose. 2
• In rats, microscopic examination revealed increased benign neoplastic nodules in the liver and benign interstitial cell tumors of the testes at high doses. 2
• While long-term clinical observation has not suggested that human cancer is associated with hydralazine use, epidemiologic studies have been insufficient to arrive at conclusions. 2