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.  
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 that were 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. For African Americans that cannot tolerate ACE-inhibitors and/or beta-blockers, hydralazine and isosorbide are used. 
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 an interference of calcium movement in the vascular smooth muscle which is responsible for vasoconstriction. This results in lowering of blood pressure. Lowering of 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. 
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.
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. 
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. Oral dosage maximum is 300 mg/day. After the maximum dosage is obtained, the drug frequency can be changed to twice a day.
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. 
Immune phenomenon such as drug-induced lupus erythematosus (DILE), serum sickness, hemolytic anemia, vasculitis, and glomerulonephritis are associated with the use of hydralazine. Usually, the 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, are controversial but have been attempted.
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. 
Paresthesias, numbness, and tingling of peripheral neuritis have been reported that are amenable to pyridoxine supplements. 
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. 
Lactation: It is not known if hydralazine is excreted in human milk. 
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. Risks versus benefits must be discussed with the patient before initiating therapy with hydralazine. 
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. 
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 ingestion of 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 can be treated with beta-blockers with attention to the blood pressure before administration. No known recent deaths have been associated with this medication. 
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 in the rare patient it may cause a lupus-like syndrome. This syndrome usually reverses upon discontinuation of the drug.
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.
|||Direct Vasodilators and Sympatholytic Agents., McComb MN,Chao JY,Ng TM,, Journal of cardiovascular pharmacology and therapeutics, 2016 Jan [PubMed PMID: 26033778]|
|||Kirsten R,Nelson K,Kirsten D,Heintz B, Clinical pharmacokinetics of vasodilators. Part I. Clinical pharmacokinetics. 1998 Jun; [PubMed PMID: 9646008]|
|||ACOG Committee Opinion No. 767: Emergent Therapy for Acute-Onset, Severe Hypertension During Pregnancy and the Postpartum Period. Obstetrics and gynecology. 2019 Feb; [PubMed PMID: 30575639]|
|||ACOG Committee Opinion No. 767 Summary: Emergent Therapy for Acute-Onset, Severe Hypertension During Pregnancy and the Postpartum Period. Obstetrics and gynecology. 2019 Feb; [PubMed PMID: 30681541]|
|||Combination of isosorbide dinitrate and hydralazine in blacks with heart failure., Taylor AL,Ziesche S,Yancy C,Carson P,D'Agostino R Jr,Ferdinand K,Taylor M,Adams K,Sabolinski M,Worcel M,Cohn JN,, The New England journal of medicine, 2004 Nov 11 [PubMed PMID: 15533851]|
|||Cohn JN,Archibald DG,Ziesche S,Franciosa JA,Harston WE,Tristani FE,Dunkman WB,Jacobs W,Francis GS,Flohr KH, Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. The New England journal of medicine. 1986 Jun 12; [PubMed PMID: 3520315]|
|||Cohn JN,Archibald DG,Francis GS,Ziesche S,Franciosa JA,Harston WE,Tristani FE,Dunkman WB,Jacobs W,Flohr KH, Veterans Administration Cooperative Study on Vasodilator Therapy of Heart Failure: influence of prerandomization variables on the reduction of mortality by treatment with hydralazine and isosorbide dinitrate. Circulation. 1987 May; [PubMed PMID: 3552302]|
|||Loeb HS,Johnson G,Henrick A,Smith R,Wilson J,Cremo R,Cohn JN, Effect of enalapril, hydralazine plus isosorbide dinitrate, and prazosin on hospitalization in patients with chronic congestive heart failure. The V-HeFT VA Cooperative Studies Group. Circulation. 1993 Jun; [PubMed PMID: 8500244]|
|||Yancy CW,Jessup M,Bozkurt B,Butler J,Casey DE Jr,Colvin MM,Drazner MH,Filippatos GS,Fonarow GC,Givertz MM,Hollenberg SM,Lindenfeld J,Masoudi FA,McBride PE,Peterson PN,Stevenson LW,Westlake C, 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Journal of the American College of Cardiology. 2017 Aug 8; [PubMed PMID: 28461007]|
|||The Paradox in Demonstrating Hydralazine-Nitrate Efficacy., Cohn JN,, JACC. Heart failure, 2017 Sep [PubMed PMID: 28711448]|
|||Clinical Effectiveness of Hydralazine-Isosorbide Dinitrate in African-American Patients With Heart Failure., Ziaeian B,Fonarow GC,Heidenreich PA,, JACC. Heart failure, 2017 Sep [PubMed PMID: 28711446]|
|||Rhoney D,Peacock WF, Intravenous therapy for hypertensive emergencies, part 2. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 2009 Aug 15; [PubMed PMID: 19667001]|
|||Whelton PK,Carey RM,Aronow WS,Casey DE Jr,Collins KJ,Dennison Himmelfarb C,DePalma SM,Gidding S,Jamerson KA,Jones DW,MacLaughlin EJ,Muntner P,Ovbiagele B,Smith SC Jr,Spencer CC,Stafford RS,Taler SJ,Thomas RJ,Williams KA Sr,Williamson JD,Wright JT Jr, 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension (Dallas, Tex. : 1979). 2018 Jun; [PubMed PMID: 29133356]|
|||Riddiough MA, Preventing, detecting and managing adverse reactions of antihypertensive agents in the ambulant patient with essential hypertension. American journal of hospital pharmacy. 1977 May; [PubMed PMID: 326040]|
|||Hydralazine-induced lupus syndrome presenting with large pericardial effusion., Chamsi-Pasha MA,Bassiouny M,Kim ES,, QJM : monthly journal of the Association of Physicians, 2014 Apr [PubMed PMID: 24194564]|
|||Hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis presenting with a vasculitic syndrome, acute nephritis and a puzzling skin rash: a case report., Keasberry J,Frazier J,Isbel NM,Van Eps CL,Oliver K,Mudge DW,, Journal of medical case reports, 2013 Jan 14 [PubMed PMID: 23316942]|
|||Hydralazine-induced pauci-immune glomerulonephritis: intriguing case series with misleading diagnoses., Babar F,Posner JN,Obah EA,, Journal of community hospital internal medicine perspectives, 2016 [PubMed PMID: 27124161]|
|||Hydralazine associated pauci-immune glomerulonephritis., Suneja M,Baiswar S,Vogelgesang SA,, Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 2014 Mar [PubMed PMID: 24561415]|
|||Hydralazine Induced Lupus Syndrome Presenting with Recurrent Pericardial Effusion and a Negative Antinuclear Antibody., Iyer P,Dirweesh A,Zijoo R,, Case reports in rheumatology, 2017 [PubMed PMID: 28194293]|
|||Hydralazine-Induced Autoimmune Hepatitis Precipitated by the Blood Transfusion., Amjad W,John G,Gulru S,, American journal of therapeutics, 2017 Oct 16 [PubMed PMID: 29045246]|
|||Acute Cholestatic Liver Injury From Hydralazine Intake., Harati H,Rahmani M,Taghizadeh S,, American journal of therapeutics, 2016 Sep-Oct [PubMed PMID: 26291593]|
|||A case report of hydralazine-induced skin reaction: Probable toxic epidermal necrolysis (TEN)., Mahfouz A,Mahmoud AN,Ashfaq PA,Siyabi KH,, The American journal of case reports, 2014 [PubMed PMID: 24719674]|
|||Hydralazine-induced toxic epidermal necrolysis in a patient on continuous ambulatory peritoneal dialysis., Chan JC,Yap DY,Yeung CK,, Journal of clinical pharmacy and therapeutics, 2014 Jun [PubMed PMID: 24588409]|
|||KIRKENDALL WM,PAGE EB, Polyneuritis occurring during hydralazine therapy; report of two cases and discussion of adverse reactions to hydralazine. Journal of the American Medical Association. 1958 May 24; [PubMed PMID: 13538717]|
|||Kandler MR,Mah GT,Tejani AM,Stabler SN,Salzwedel DM, Hydralazine for essential hypertension. The Cochrane database of systematic reviews. 2011 Nov 9; [PubMed PMID: 22071816]|
|||Hydralazine 2006; [PubMed PMID: 30000013]|