What are the medical uses of hydrazine, particularly in cancer and hypertension treatment?

Hydralazine Medical Uses

Hydralazine is used primarily as a direct-acting vasodilator for treating hypertensive emergencies (particularly in pregnancy/eclampsia) and as combination therapy with isosorbide dinitrate for heart failure with reduced ejection fraction in African American patients, but it is NOT a first-line agent for most hypertensive emergencies due to unpredictable blood pressure response and prolonged duration of action. 1

Primary Medical Indications

Hypertensive Emergencies in Pregnancy

• Hydralazine is specifically indicated as first-line therapy for severe hypertension in pregnancy and eclampsia 1, 2, 3
• Initial dosing: 5 mg IV bolus, followed by 10 mg IV every 20-30 minutes to a maximum of 25 mg per episode 2, 4
• Treatment should be initiated within 60 minutes of onset 2, 4
• Onset of action occurs within 10-30 minutes, with duration of effect lasting 2-4 hours 1, 4, 3

Heart Failure with Reduced Ejection Fraction

• The combination of hydralazine plus isosorbide dinitrate demonstrates remarkable mortality benefit in self-identified African American patients with NYHA class III-IV heart failure who remain symptomatic despite optimal therapy 4
• This combination produces a 43% relative risk reduction in mortality with a number needed to treat of only 7 over 36 months 4
• Dosing for heart failure: Initial 37.5 mg three times daily, titrated to target dose of 75 mg three times daily 4
• Also recommended for patients with HFrEF who cannot tolerate ACE inhibitors or ARBs due to drug intolerance, hypotension, or renal insufficiency 4

Non-Obstetric Hypertensive Emergencies

Limited Role as Non-First-Line Agent

• Hydralazine should NOT be used as first-line therapy for most hypertensive emergencies due to unpredictability of response and prolonged duration of action 1, 2
• When used: Initial 10-20 mg via slow IV infusion (maximum initial dose 20 mg), repeated every 4-6 hours as needed 1, 3
• Blood pressure begins to decrease within 10-30 minutes, and the fall lasts 2-4 hours 1

Preferred Alternative Agents

• Nicardipine, clevidipine, or labetalol are preferred for most hypertensive emergencies due to more predictable titration and ability to immediately cease if blood pressure drops excessively 2, 4, 3
• Nicardipine: Initial 5 mg/h IV, increasing every 5 minutes by 2.5 mg/h to maximum 15 mg/h 1
• Clevidipine: Initial 1-2 mg/h, doubling every 90 seconds until BP approaches target 1
• Labetalol: Initial 0.3-1.0 mg/kg (maximum 20 mg) slow IV injection every 10 minutes 1

Critical Monitoring and Safety Considerations

Adverse Effects Requiring Management

• Reflex tachycardia is common and requires concomitant beta-blocker therapy 4, 3
• Fluid retention necessitates concomitant diuretic therapy 2, 4
• Common side effects include headache, palpitations, flushing, vomiting, dizziness, and gastrointestinal complaints 2, 4
• In pregnancy, side effects may mimic worsening preeclampsia 4

Monitoring Requirements

• Blood pressure should be checked at 10-30 minutes, 1 hour, and 2-4 hours after each dose 4, 3
• Continuous monitoring required for IV administration to prevent overshoot hypotension 4
• Overshoot hypotension cannot be reversed once it occurs 3

Drug-Induced Lupus Risk

• Risk of lupus-like syndrome increases significantly at cumulative doses >200 mg/day 2, 4
• Higher doses carry increased risk of drug-induced lupus 2

Absolute Contraindications

• Advanced aortic stenosis due to unpredictable blood pressure effects 1, 4
• Pregnancy (for chronic use) - though paradoxically it IS indicated for acute severe hypertension in pregnancy 1
• Acute myocardial infarction 1
• Bilateral renal artery stenosis 1
• Reactive airways disease when considering combination with beta-blockers 4

Historical Cancer-Related Research (Not Current Clinical Use)

Hydrazine Sulfate Investigation

• Hydrazine sulfate was investigated in the 1970s-1990s for potential antineoplastic activity in advanced cancer patients 5, 6
• A 1995 study of 740 patients with advanced solid tumors showed objective responses primarily in soft tissue sarcomas and desmoid tumors, with symptomatic benefit in 46.6% of cases 5
• However, a 1979 study of 25 patients showed no patient achieved 50% tumor size reduction 6
• This is NOT a current medical use - hydrazine compounds are highly carcinogenic, with over 80% of studied hydrazine class compounds demonstrating carcinogenicity 7

Important Distinction

• Hydralazine (the antihypertensive drug) is chemically distinct from hydrazine sulfate - hydralazine is 1-hydrazinophthalazine, while one of its metabolites is hydrazine, which has been shown to be carcinogenic in rats and mice 8
• A 1987 study of 3,419 women with breast cancer found no increased risk of breast cancer with hydralazine use (RR 0.9,95% CI 0.5-1.7) 8