What are the potential side effects of hydralazine (hypertension medication) in patients, including pregnant women and individuals with a history of hypertension?

Hydralazine Side Effects

Hydralazine causes significantly more maternal side effects than labetalol or nifedipine, including headache, palpitations, tachycardia, flushing, nausea, vomiting, and hypotension, and is associated with increased fetal distress, making it an acceptable but not preferred agent for hypertension management. 1, 2, 3

Common Cardiovascular Side Effects

• Reflex tachycardia and palpitations occur frequently due to hydralazine's direct vasodilatory action, with significantly higher rates compared to labetalol 1, 4
• Hypotension can develop, particularly when combined with other antihypertensive agents, and may be profound when used with diazoxide 5, 6
• Postural hypotension may occur, though less commonly than with ganglionic blocking agents 5
• Myocardial stimulation can precipitate anginal attacks, ECG changes of myocardial ischemia, and has been implicated in myocardial infarction, requiring caution in patients with suspected coronary artery disease 5

Gastrointestinal and Neurological Effects

• Headache, flushing, nausea, and vomiting are common, with vomiting occurring significantly more frequently than with nifedipine 1, 2
• Peripheral neuritis manifesting as paresthesia, numbness, and tingling has been observed, likely due to an antipyridoxine effect; pyridoxine supplementation should be added if symptoms develop 5

Serious Hematologic and Immunologic Complications

• Blood dyscrasias including reduction in hemoglobin and red cell count, leukopenia, agranulocytosis, and purpura have been reported; therapy should be discontinued if these develop 5
• Lupus-like syndrome can occur, particularly with prolonged use 4
• Hemolytic anemia, vasculitis, and glomerulonephritis have been documented 7, 4
• Complete blood counts and antinuclear antibody titers should be monitored before and periodically during prolonged therapy, even in asymptomatic patients 5

Pregnancy-Specific Concerns

In pregnant women, hydralazine poses specific maternal and fetal risks that make it less desirable than first-line agents:

• Maternal complications include greater risk of cesarean section, placental abruption, and maternal oliguria compared to labetalol or nifedipine 2
• Fetal distress occurs more frequently with hydralazine use 1, 2
• Abrupt maternal hypotension can cause acute uteroplacental insufficiency, compromising fetal perfusion 2, 3
• Side effects may mimic worsening pre-eclampsia (headache, visual disturbances), complicating clinical assessment 1, 2
• Despite these concerns, no short-term adverse effects have been reported from exposure to hydralazine in breastfeeding, and it is compatible with lactation 1

Drug Interactions and Contraindications

• MAO inhibitors should be used with caution in patients receiving hydralazine 5
• Profound hypotensive episodes may occur when diazoxide and hydralazine are used concomitantly; continuous observation for several hours is required 5
• Avoid combining nifedipine with magnesium sulfate when considering hydralazine as an alternative, due to risk of precipitous hypotension 1, 2
• Use with caution in patients with cerebral vascular accidents, advanced renal damage, or mitral valvular disease (may increase pulmonary artery pressure) 5

Carcinogenic Potential

• Animal studies showed statistically significant increases in lung tumors in mice at 80 times the maximum recommended human dose and benign liver nodules in rats at 5-20 times the recommended dose 5
• Mutagenic potential was demonstrated in bacterial systems and some in vitro DNA repair studies 5
• Long-term clinical observation has not suggested human cancer association, but epidemiologic studies remain insufficient 5

Clinical Monitoring Requirements

When hydralazine is used, intensive monitoring is mandatory:

• Blood pressure checks every 5-10 minutes during acute treatment 2, 3
• Continuous fetal heart rate monitoring throughout administration in pregnant patients 2, 3
• Close observation for signs of arthralgia, fever, chest pain, continued malaise, or other unexplained symptoms that may indicate lupus-like syndrome 5
• Laboratory monitoring including complete blood counts and antinuclear antibody titers, particularly if symptoms develop 5

Context for Use

Hydralazine should be reserved for specific situations:

• When first-line agents (labetalol or nifedipine) have failed to control blood pressure adequately 2, 3
• In low-resource settings where IV labetalol or immediate-release nifedipine are unavailable 2, 3
• When labetalol is contraindicated (asthma, heart block, bradycardia, decompensated heart failure) 2, 3
• For acute management of severe hypertension in pregnancy or severe preeclampsia, though not as first-line 1