Continuing Education Activity

Hydralazine is used orally as a therapeutic agent to treat essential hypertension and intravenously to lower blood pressure urgently or emergently. FDA-approved hydralazine is usually not used as a first-line agent for the treatment of essential hypertension due to the stimulation of the sympathetic system. It is used in combination with other hypertensives to treat persistently elevated blood pressure. This activity presents the indications, contraindications, and adverse effects of hydralazine so the interprofessional team can use and monitor this drug effectively.


  • List the indications for hydralazine.
  • Describe the mechanism of action of hydralazine.
  • Summarize the potential adverse effects of hydralazine.
  • Explain the importance of improving care coordination amongst the interprofessional team to enhance the delivery of care for patients with hypertension.


Hydralazine is used orally as a therapeutic agent to treat essential hypertension and intravenously to lower blood pressure urgently or emergently. FDA-approved hydralazine is usually not used as a first-line agent for the treatment of essential hypertension due to the stimulation of the sympathetic system.  It is used in combination with other hypertensives to treat persistently elevated blood pressure.[1][2]

Hydralazine is one of three drug options in eclampsia to control severe hypertension after magnesium is administered.[3][4]

The Vasodilator Heart Failure Study (V-HeFT),  a prospective study performed in 1986, did not demonstrate a decrease in the mortality of patients receiving vasodilator therapy. Certain subgroups were reexamined, and the A-HeFT (African-American Heart Failure Trial), published in 2004, demonstrated a significantly decreased mortality for African Americans on a fixed dose of isosorbide dinitrate and hydralazine for severe congestive heart failure (New York Heart Association Class III and IV). These studies have been replicated, and the results continue to demonstrate a decrease in mortality for African-American patients with known heart failure and a reduced ejection fraction who are prescribed both isosorbide dinitrate and hydralazine. The results have been criticized because the study was performed before the benefits of ACE inhibitors and beta-blockers were known. The Americal Heart Association does recommend ACE-inhibitors and beta-blockers as first-line therapy for patients with congestive heart failure.[5][6][7][8] For African Americans that cannot tolerate ACE-inhibitors and/or beta-blockers, hydralazine and isosorbide are used.[9][10][11]

Mechanism of Action

Hydralazine directly relaxes the arteriolar smooth muscle but not venous smooth muscle. The mechanism is not fully known but is theorized to be due to interference of calcium movement in the vascular smooth muscle, which is responsible for vasoconstriction. This results in lowering of blood pressure. Lowering blood pressure improves cardiac output. Also, hydralazine stimulates the sympathetic system, which can cause tachyphylaxis and tachycardia. Patients tend to tolerate this medication better when the hydralazine is given with a beta-blocker and/or diuretic.[1]

The drug is metabolized in the liver. Hydralazine undergoes polymorphic acetylation. Those that are slow acetylators require lower doses of the drug. Both the acetylated drug and unchanged drug are excreted in the urine and feces.[2]

The hypotensive effects occur 5 to 30 minutes after an intravenous dose. The duration is approximately 2 to 6 hours. The hypotensive effect occurs in 20 to 30 minutes after an oral dose, and the duration is approximately 2 to 4 hours.[1][2]


Dosage is 20 to 40 mg intravenously when treating emergent or urgent elevations of blood pressure. Dosage is 10 to  50 mg four times a day by mouth as part of a therapeutic plan in the treatment of essential hypertension. The initial dose orally should be 10 mg 4 times a day.   After 3 to 4 days, it can be increased to 25 mg for another 4 days. If the blood pressure is still not controlled, the hydralazine can be increased to 50 mg 4 times a day. The maximum oral dosage is 300 mg/day. After the maximum dosage is obtained, the drug frequency can be changed to twice a day.[12][13]

Adverse Effects

Patients may experience a headache, nausea, flushing, hypotension, palpitations, tachycardia, dizziness, and angina due to stimulation of the sympathetic system. The reflex tachycardia is a concern when given intravenously to patients that already have elevated heart rate.[14]

Immune phenomena such as drug-induced lupus erythematosus (DILE), serum sickness, hemolytic anemia, vasculitis, and glomerulonephritis are associated with the use of hydralazine. Usually, lupus syndrome occurs after the patient has been ingesting the drug for approximately 6 months.

The risk factors for developing this side effect are slow acetylator phenotype, family history of autoimmune disease, and decreased renal function. Patients with the genotype of HLA-DR4 with slow acetylator hepatic status are considered more prone to DILE. Discontinuing the hydralazine usually cures the lupus-like syndrome—patients with DILE test positive for antinuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA). Discontinuation of hydralazine is the treatment of DILE and other auto-immune phenomena that accompany DILE. Immunosuppression with prednisone and other immunosuppressants, such as cyclophosphamide, is controversial but has been attempted.[15][16][17][18][19]

Drug-induced liver injury (DILI) has also been noted to occur with the use of hydralazine. This adverse reaction can occur with the lupus syndrome or in isolation. Symptoms of DILI are those of hepatitis: nausea, vomiting, dark urine, jaundice, abdominal pain, and pruritis.  The treatment is similar to that of DILE.[20][21]

There have been rare cases of toxic epidermal necrolysis (TEN) reported in association with hydralazine ingestion.[22][23]

Paresthesias, numbness, and tingling of peripheral neuritis have been reported that are amenable to pyridoxine supplements.[24]


Contraindications include:

  • Allergy to the medication.
  • Coronary artery disease due to the increased oxygen demand by the heart due to stimulation of the sympathetic system.  There have been reports of angina and myocardial ischemia.[25]
  • Mitral valve rheumatic heart disease because hydralazine can increase pulmonary artery pressure.

Pregnancy risk category C: Hydralazine has not been studied in pregnant women. In rats, it has been known to cause cleft palate and malformations of facial and cranial bones.[26]

Lactation: It is not known if hydralazine is excreted in human milk.[26]


A complete blood count (CBC) and an antinuclear antibody (ANA)  titer determination should be performed before and periodically during therapy. A positive ANA titer must be considered before the patient starts this medication. The prescribing clinician must discuss the risks versus benefits with the patient before initiating therapy with hydralazine.[14]

If the patient develops arthralgias, fever, chest pain, continued malaise, or other unexplained signs or symptoms related to DILE, a complete blood count and ANA titer should be performed immediately, and the drug should be discontinued.[19][15]

If anemia, leukopenia, agranulocytosis, and/or purpura develop, the drug should be discontinued immediately. 


Toxicity symptoms include hypotension, tachycardia, headache, and generalized skin flushing. Patients have developed myocardial ischemia and subsequent myocardial infarction, cardiac arrhythmia, and shock from ingesting the drug. There is no specific treatment for an overdose other than supportive therapy. Fluids should be given, and if unsuccessful in restoring blood pressure to an adequate level, vasopressors can be administered. Tachycardia is treatable with beta-blockers with attention to the blood pressure before administration. No known recent deaths have been associated with this medication.[25]

Enhancing Healthcare Team Outcomes

Hydralazine is prescribed as an antihypertensive by nurse practitioners, obstetricians, internists, emergency department physicians, and intensivists. While the drug is relatively safe, it is important to be aware that it may cause a lupus-like syndrome in rare instances. This syndrome usually reverses upon discontinuation of the drug. An interprofessional team approach, including the clinicians mentioned, plus the nursing staff and pharmacists, can help monitor the patient's therapeutic results, watch for potential adverse events, and alert the prescriber. [Level 5]

Hydralazine is never the first choice for patients with essential hypertension but may be selected in African Americans who fail to respond to other antihypertensives.

Article Details

Article Author

Linda Herman

Article Author

Zachary Bruss

Article Editor:

Vijai Tivakaran


5/12/2021 6:05:36 PM

PubMed Link:




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