How is hydralazine used in treating hypertension. What are the primary indications for hydralazine therapy. How does hydralazine work to lower blood pressure. What are the key considerations for administering hydralazine. How can healthcare teams optimize hydralazine use for better patient outcomes.

Understanding Hydralazine: A Versatile Antihypertensive Agent

Hydralazine is a direct vasodilator that has been used for decades in the management of various cardiovascular conditions. Its primary use is in the treatment of hypertension, particularly in cases where other therapies have proven insufficient. While not considered a first-line agent for essential hypertension according to current guidelines, hydralazine continues to play a crucial role in specific clinical scenarios.

Key Indications for Hydralazine Use

• Essential hypertension refractory to other treatments
• Hypertensive urgency and emergency
• Eclampsia
• Heart failure with reduced ejection fraction (HFrEF) in combination with isosorbide dinitrate

Is hydralazine effective as an add-on medication for hypertension? Studies have shown that hydralazine can be effective when added to multidrug treatment regimens for hypertension. However, it is generally not as efficacious as first-line therapies such as calcium channel blockers, ACE inhibitors, angiotensin II receptor blockers, or thiazide diuretics.

The Mechanism of Action: How Hydralazine Lowers Blood Pressure

Understanding how hydralazine works is crucial for healthcare professionals to optimize its use in patient care. While the exact mechanism is not fully elucidated, several key processes have been identified.

Theorized Mechanisms of Hydralazine

1. Inhibition of inositol trisphosphate (IP3)-induced calcium release from smooth muscle cell sarcoplasmic reticulum
2. Inhibition of myosin phosphorylation within arterial smooth muscle
3. Reduction of peripheral vascular resistance
4. Stimulation of the sympathetic nervous system (leading to compensatory responses)

How does hydralazine’s mechanism of action affect its clinical use? The drug’s ability to stimulate the sympathetic nervous system can lead to tachyphylaxis and tachycardia. As a result, hydralazine is often administered in combination with beta-blockers or diuretics to improve patient tolerance and mitigate these side effects.

Administration and Pharmacokinetics of Hydralazine

Proper administration of hydralazine is crucial for achieving optimal therapeutic effects while minimizing adverse reactions. Healthcare providers should be familiar with the drug’s pharmacokinetics and dosing strategies.

Intravenous vs. Oral Administration

• Intravenous administration:
  • Onset of action: 5 to 30 minutes
  • Duration of effect: 2 to 6 hours
• Oral administration:
  • Onset of action: 20 to 30 minutes
  • Duration of effect: 2 to 4 hours

Why is understanding hydralazine’s pharmacokinetics important? Knowledge of the drug’s onset and duration of action allows healthcare providers to anticipate its effects, monitor patients appropriately, and adjust dosing schedules as needed to maintain consistent blood pressure control.

Hydralazine in Hypertensive Emergencies: A Double-Edged Sword

The use of intravenous hydralazine in hypertensive emergencies has increased in recent years, despite limited evidence of improved outcomes. This off-label use warrants careful consideration due to potential risks.

Challenges in Hypertensive Emergency Management

• Highly variable blood pressure changes
• Risk of adverse hypotensive episodes
• Limited evidence of improved outcomes in hospitalized patients

Should IV hydralazine be used routinely in hypertensive emergencies? While IV hydralazine can effectively lower blood pressure rapidly, its use should be carefully considered on a case-by-case basis. The potential for unpredictable blood pressure fluctuations and adverse hypotensive episodes necessitates close monitoring and individualized treatment plans.

Hydralazine in Pregnancy and Postpartum Hypertension

Hypertensive disorders of pregnancy pose significant risks to both mother and fetus. Hydralazine plays a crucial role in managing these conditions, particularly in acute settings.

First-Line Therapy for Severe Hypertension in Pregnancy

• IV hydralazine and IV labetalol are considered first-line treatments
• Recommended for acute-onset, severe hypertension during pregnancy and postpartum
• Should be administered if severe blood pressure persists for more than 15 minutes during intrapartum or postpartum periods

Why is rapid treatment of severe hypertension in pregnancy critical? Prompt management of severe hypertension during pregnancy and the postpartum period is essential to prevent potentially life-threatening complications such as stroke, eclampsia, and organ damage in the mother, as well as to protect fetal well-being.

Hydralazine in Heart Failure Management: A Targeted Approach

The use of hydralazine in heart failure treatment has evolved over time, with current guidelines recommending its use in specific patient populations.

Hydralazine and Isosorbide Dinitrate Combination Therapy

• Recommended for African-American patients with severe heart failure (NYHA Class III and IV) and reduced ejection fraction
• Can be added to standard therapy (ACE inhibitors/ARBs, beta-blockers) in African American patients
• Has demonstrated mortality benefit, although recent studies show less robust efficacy

How does the combination of hydralazine and isosorbide dinitrate benefit heart failure patients? This combination therapy is believed to improve nitric oxide availability and reduce oxidative stress, leading to improved endothelial function and myocardial performance. The specific benefit in African-American patients may be related to differences in nitric oxide biology and response to standard heart failure therapies.

Optimizing Hydralazine Therapy: Interprofessional Collaboration

Effective use of hydralazine requires a coordinated effort from various healthcare professionals to ensure optimal patient outcomes and minimize adverse effects.

Key Roles in Hydralazine Management

• Physicians: Prescribing, dose adjustment, and overall treatment planning
• Pharmacists: Medication review, drug interaction checks, and patient education
• Nurses: Administration, monitoring of vital signs and adverse effects
• Clinical pharmacologists: Guidance on dosing in special populations (e.g., slow acetylators)

How can interprofessional collaboration improve hydralazine therapy outcomes? By leveraging the expertise of various healthcare professionals, teams can ensure appropriate patient selection, optimize dosing regimens, monitor for adverse effects, and provide comprehensive patient education. This collaborative approach can lead to improved blood pressure control, reduced complications, and enhanced patient safety.

Adverse Effects and Monitoring Considerations for Hydralazine Therapy

While hydralazine can be an effective antihypertensive agent, it is associated with a range of potential adverse effects that require careful monitoring and management.

Common Adverse Effects of Hydralazine

• Tachycardia and palpitations
• Headache
• Fluid retention
• Gastrointestinal disturbances
• Lupus-like syndrome (with long-term use)

What strategies can be employed to mitigate hydralazine’s adverse effects? Combining hydralazine with beta-blockers can help counteract reflex tachycardia, while diuretics may be useful in managing fluid retention. Regular monitoring of blood pressure, heart rate, and symptoms is essential to identify and address adverse effects promptly.

Monitoring Parameters for Hydralazine Therapy

1. Blood pressure and heart rate
2. Renal function tests
3. Complete blood count
4. Antinuclear antibody (ANA) titers (for long-term use)
5. Signs and symptoms of fluid retention

Why is long-term monitoring crucial for patients on hydralazine? Long-term use of hydralazine, particularly at higher doses, has been associated with the development of a lupus-like syndrome. Regular monitoring of ANA titers and vigilance for symptoms such as joint pain, rash, or unexplained fever can help detect this rare but serious complication early.

Pharmacogenomics and Hydralazine: Tailoring Therapy to Individual Patients

Advances in pharmacogenomics have shed light on the importance of genetic factors in hydralazine metabolism and response, offering opportunities for personalized treatment approaches.

Acetylator Status and Hydralazine Dosing

• Hydralazine undergoes polymorphic acetylation in the liver
• Slow acetylators require lower doses of the drug
• Genetic testing can identify acetylator status

How does acetylator status impact hydralazine therapy? Patients who are slow acetylators may accumulate higher levels of hydralazine, potentially increasing the risk of adverse effects. Conversely, rapid acetylators may require higher doses to achieve therapeutic effects. Understanding a patient’s acetylator status can guide initial dosing and help optimize therapy.

Future Directions in Personalized Hydralazine Therapy

1. Development of point-of-care genetic tests for acetylator status
2. Investigation of other genetic factors influencing hydralazine response
3. Integration of pharmacogenomic data into clinical decision support systems

What potential benefits could pharmacogenomic-guided hydralazine therapy offer? By tailoring hydralazine dosing to individual genetic profiles, healthcare providers may be able to improve efficacy, reduce adverse effects, and enhance overall patient outcomes. This personalized approach could lead to more precise and effective hypertension management.

Hydralazine in Combination Therapy: Synergistic Approaches to Blood Pressure Control

While hydralazine can be effective as monotherapy in some cases, its use in combination with other antihypertensive agents often yields superior results and helps mitigate adverse effects.

Common Combination Strategies

• Hydralazine + Beta-blockers: Counteracts reflex tachycardia
• Hydralazine + Diuretics: Manages fluid retention and enhances blood pressure lowering
• Hydralazine + ACE inhibitors/ARBs: Complementary mechanisms of action
• Hydralazine + Isosorbide Dinitrate: Specifically for heart failure in African-American patients

How do combination therapies enhance the efficacy of hydralazine? By addressing multiple physiological pathways involved in blood pressure regulation, combination therapies can provide more comprehensive control. Additionally, using lower doses of multiple agents often results in fewer side effects compared to high-dose monotherapy.

Considerations for Combination Therapy

1. Patient comorbidities and risk factors
2. Potential drug interactions
3. Individual response and tolerability
4. Cost and accessibility of medications

What factors should guide the selection of combination therapy with hydralazine? The choice of combination therapy should be tailored to the individual patient, considering factors such as comorbid conditions (e.g., heart failure, diabetes), potential for drug interactions, and the patient’s overall cardiovascular risk profile. Regular follow-up and adjustment of the regimen based on response and tolerability are essential for optimal outcomes.

Hydralazine in Special Populations: Adapting Treatment to Unique Patient Needs

The use of hydralazine requires special considerations in certain patient populations due to altered pharmacokinetics, increased risks, or specific therapeutic benefits.

Hydralazine in Renal Impairment

• Dose adjustment may be necessary in moderate to severe renal impairment
• Increased risk of fluid retention and electrolyte imbalances
• Close monitoring of renal function and fluid status required

How should hydralazine dosing be approached in patients with renal impairment? In patients with reduced renal function, starting with lower doses and titrating slowly while monitoring for adverse effects is prudent. Collaboration with nephrology specialists may be beneficial in managing these complex cases.

Hydralazine in Elderly Patients

1. Increased sensitivity to blood pressure-lowering effects
2. Higher risk of orthostatic hypotension
3. Potential for drug interactions due to polypharmacy
4. Consideration of cognitive effects and fall risk

What precautions should be taken when using hydralazine in elderly patients? Starting with lower doses, monitoring for orthostatic hypotension, and assessing for potential drug interactions are crucial. Regular evaluation of cognitive function and fall risk is also important, as sudden drops in blood pressure can increase these risks in the elderly population.

Emerging Research and Future Directions in Hydralazine Therapy

While hydralazine has been in clinical use for decades, ongoing research continues to explore its potential in new therapeutic areas and refine its use in existing indications.

Novel Applications of Hydralazine

• Investigation of hydralazine’s epigenetic effects in cancer therapy
• Potential use in pulmonary hypertension
• Exploration of hydralazine’s role in vascular dementia prevention

How might hydralazine’s mechanisms extend beyond blood pressure control? Recent studies have suggested that hydralazine may have DNA demethylating properties, which could have implications in cancer treatment and other epigenetic-related disorders. Additionally, its vasodilatory effects are being explored in conditions such as pulmonary hypertension.

Advancing Precision Medicine in Hypertension Management

1. Development of biomarkers to predict hydralazine response
2. Integration of pharmacogenomics into routine clinical practice
3. Exploration of novel drug delivery systems for improved pharmacokinetics
4. Investigation of long-acting formulations for enhanced adherence

What potential improvements in hydralazine therapy can we anticipate in the future? Advances in precision medicine may allow for more targeted use of hydralazine based on individual patient characteristics and genetic profiles. Novel formulations and delivery systems could improve the drug’s pharmacokinetic profile, potentially reducing dosing frequency and enhancing patient adherence.

As research continues to uncover new insights into hydralazine’s mechanisms and potential applications, healthcare providers must stay informed about the latest developments to optimize patient care. The ongoing evolution of hydralazine therapy underscores the importance of lifelong learning and adaptability in clinical practice.

Hydralazine – StatPearls – NCBI Bookshelf

Continuing Education Activity

Hydralazine is a direct vasodilator used orally to treat essential hypertension, among other diseases, and intravenously to rapidly reduce blood pressure in hypertensive urgency or emergency. Per JNC 8 guidelines, it is not a first-line agent for the treatment of essential hypertension. This is due to hydralazine’s stimulation of the sympathetic nervous system, among several other adverse effects that make the current newer first-line agents more efficacious. This activity outlines the indications, mechanism of action, administration, contraindications, and adverse effects of hydralazine.

Objectives:

• Identify the indications for initiating hydralazine therapy.

• Summarize the theorized mechanism of action of hydralazine.

• Discuss the parameters of hydralazine administration.

• Outline how an interprofessional team can coordinate the use and monitoring of hydralazine to obtain the best patient outcomes.

Access free multiple choice questions on this topic.

Indications

Hydralazine is primarily used to treat hypertension and hypertensive urgency/emergency.[1] It has also been utilized in the treatment of eclampsia along with heart failure with reduced ejection fraction (HFrEF) when in combination with isosorbide dinitrate.[2] 

In current practice, oral hydralazine is used in essential hypertension refractory to other therapeutic agents.[2] Studies comparing its effects as an add-on medication to multidrug treatment for hypertension have proved effective but not as efficacious as other multi-modal first-line therapies (calcium channel blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, thiazides).[2] Per the JNC 8 guideline algorithm, hydralazine can be considered if initiation of first-line therapy titrated to its maximum dose and/or the addition of a second first-line agent does not meet blood pressure reduction goals. In these guidelines, hydralazine is categorized with other medications, including beta-blockers and aldosterone antagonists, that have more compelling additional indications when compared to hydralazine, such as their use in heart failure and pregnancy. [3]   

IV hydralazine has had increased off-label use in the setting of hypertensive emergencies. It is often given to hospitalized patients but has little evidence of improved outcomes. Reasons for this include highly variable blood pressure changes and adverse hypotensive episodes.[4]

IV hydralazine along with IV labetalol are considered first-line therapy for the treatment of acute-onset, severe hypertension in pregnancy and during the postpartum period. Either of these medications should be administered during the intrapartum or postpartum period if severe blood pressure persists for greater than 15 minutes.[5] 

For African-American patients with severe heart failure (New York Heart Association Class III and IV) with reduced ejection fraction (HFrEF), the American Heart Association recommends ACE inhibitors and beta-blockers as first-line therapy.[6] Within this population, the use of hydralazine in combination with isosorbide dinitrate has demonstrated a mortality benefit, although more recent studies have shown less robust efficacy. [7] Per the 2019 American College of Cardiology expert consensus guidelines, fixed-dose long-acting nitrates, and hydralazine can be added to African American people already receiving an ACE inhibitor, ARB, or ARNI plus a beta-blocker.[8]

Mechanism of Action

Hydralazine is a direct arteriole vasodilator. Although the mechanism is not completely understood, it is theorized to be associated with intracellular calcium homeostasis. Specifically, it acts to inhibit inositol trisphosphate (IP3)-induced release of calcium from the smooth muscle cells’ sarcoplasmic reticulum and inhibits myosin phosphorylation within the arterial smooth muscle.[2] This reduces peripheral vascular resistance and leads to a compensatory baroreceptor-mediated release of epinephrine and norepinephrine, which, as a result, increases venous return and cardiac output. Given hydralazine’s stimulation of the sympathetic nervous system, it consequently leads to tachyphylaxis and tachycardia. It is sometimes given with a beta-blocker or diuretic for better patient tolerance. [2]

Hydralazine is metabolized by the liver. It undergoes polymorphic acetylation. Slow acetylators require lower doses of the drug. Both the acetylated drug and unchanged drug are excreted in the urine and feces.[1]

For intravenous dosing, the blood-pressure-lowering effects occur within 5 to 30 minutes with a total duration of 2 to 6 hours. For oral dosing, the blood-pressure-lowering effects occur within 20 to 30 minutes with a total duration of 2 to 4 hours.[2]

Administration

For the treatment of hypertensive emergencies, hydralazine should be administered at a dosage of 10 mg via slow IV infusion with a maximum initial dose of 20 mg. This can be repeated every 4-6 hours as needed. Due to its unpredictable response and prolonged duration of action, hydralazine is not a desirable first-line agent for acute treatment.[9]

To treat essential hypertension, hydralazine should be initiated at a dosage of 10 mg orally four times daily for the first 2 to 4 days, then increased to 25 mg four times daily to complete 1 week of treatment. It can then be increased to 50 mg four times daily for maintenance therapy. The oral dosage maximum is 300 mg per day.[9] 

For the treatment of Stage C Heart Failure with Reduced Ejection Fraction (HFrEF), the recommended fixed initial dose combination of hydralazine and isosorbide dinitrate is 37.5 mg hydralazine/20 mg isosorbide dinitrate 3 times daily with a maximum dose of 75 mg hydralazine/40 mg isosorbide dinitrate 3 times daily.[10]

Adverse Effects

Hydralazine has been reported to cause headaches, nausea, flushing, hypotension, palpitations, tachycardia, dizziness, and angina.[11]

Immune phenomena such as drug-induced lupus erythematosus (DILE), serum sickness, hemolytic anemia, vasculitis, and glomerulonephritis have been reported using hydralazine.[12]

Hydralazine-related DILE, also known as hydralazine-induced lupus syndrome (HILS), usually occurs with greater than 6 months of exposure, and roughly 5-8% of hydralazine users are at risk of developing DILE. [12] The incidence of HILS is dose-dependent. The syndrome typically manifests with arthralgias, myalgias, serositis, and fevers; cardiac involvement is rare [13]. The risk factors for developing DILE include slow acetylator phenotype, family history of autoimmune disease, and decreased renal function. There have also been associations between DILE occurrence and certain human leukocyte antigens (HLA). Discontinuation of hydralazine usually resolves the lupus-like syndrome.[12]

Cases of drug-induced liver injury (DILI) have also been reported with the use of hydralazine. Symptoms of DILI are consistent with hepatitis and include nausea, vomiting, dark urine, jaundice, abdominal pain, and pruritus. Treatment entails discontinuation of hydralazine.[14]

There have been rare cases of toxic epidermal necrolysis (TEN) reported in association with hydralazine.[15][16]

There have also been rare cases reported of polyneuritis that are amenable to pyridoxine supplements.[17] 

Contraindications

Coronary artery disease: this is due to hydralazine’s stimulation of the sympathetic nervous system. This leads to increased cardiac output and oxygen demand, which can provoke myocardial ischemia.[18]

Lactation: use caution in breastfeeding women as it is unknown if hydralazine is excreted in human milk[19]

Aortic dissection:  it can increase aortic wall shear stress 

Monitoring

A complete blood count (CBC) and an antinuclear antibody (ANA) titer should be obtained prior to initiating therapy and periodically during therapy. In 95-100% of HILS, the serum ANA titer is positive. Abnormal hematologic findings to be aware of in HILS includes anemia, leukopenia, and/or agranulocytosis.[20] Risks versus benefits must be discussed with the patient with positive ANA titers before initiating therapy with hydralazine.[11]

If the patient develops arthralgias, fever, chest pain, continued malaise, hematologic findings mentioned above, or other unexplained signs or symptoms related to DILE, the drug should be discontinued immediately, and corticosteroids and/or immunosuppressive therapy should be considered in life-threatening cases. [13]

Toxicity

Published reports of toxicity with acute use of hydralazine are uncommon. Signs of toxicity include hypotension, tachycardia, headaches, and generalized flushing.[21] Chronic toxicity could lead to DILE.[22] There is no specific treatment for an overdose other than supportive therapy. Fluids should be given initially, followed by vasopressors should fluids fail to improve the hypotension. Tachycardia or ischemia can be treated with beta-blockers with attention to blood pressure prior to administration.[22]

Enhancing Healthcare Team Outcomes

Hydralazine should not be considered a first-line agent for essential hypertension but can be considered in hypertension refractory to other first-line medications. The newer hypertensive medications are more efficacious with fewer adverse effects. The recommended dosing of three to four times daily makes hydralazine patient compliance a challenge. Patients tend to tolerate this medication better when the hydralazine is given with a beta-blocker and/or diuretic. [2]

IV hydralazine has had increased off-label use for the treatment of hypertensive urgency or emergency.[4] However, it should not be considered for first-line therapy due to tachyphylaxis, highly variable blood pressure, and adverse hypotension.[2]

For African Americans with HFrEF, the combination of hydralazine and isosorbide dinitrate can be added to medication therapy if the patient is already receiving an ACE inhibitor, ARB, or ARNI and a beta-blocker.[6] In clinical practice, this combination has been used in heart failure patients as a preload and afterload reducer, especially in patients who cannot tolerate beta-blockers and ACE inhibitors or ARBs and would benefit from therapy reducing their systolic blood pressure.[8]

While hydralazine is relatively safe, it is important to be aware of some of its adverse effects, which, although rare, include triggering lupus-like syndrome.[11] This can usually be reversed upon discontinuation of the drug.[13] 

An interprofessional team approach involving clinicians, mid-level practitioners, and specialists, plus the nursing staff and pharmacists, can help monitor the patient’s therapeutic results, watch for potential adverse events, provide patient medication counseling regarding dosing and signs of toxicity, check for drug-drug interactions, and alert the prescriber. These types of interprofessional strategies will result in improved outcomes from hydralazine therapy. [Level 5]

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References

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Kirsten R, Nelson K, Kirsten D, Heintz B. Clinical pharmacokinetics of vasodilators. Part I. Clin Pharmacokinet. 1998 Jun;34(6):457-82. [PubMed: 9646008]

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Campbell P, Baker WL, Bendel SD, White WB. Intravenous hydralazine for blood pressure management in the hospitalized patient: its use is often unjustified. J Am Soc Hypertens. 2011 Nov-Dec;5(6):473-7. [PMC free article: PMC3218202] [PubMed: 21890447]

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Taylor AL, Ziesche S, Yancy C, Carson P, D’Agostino R, Ferdinand K, Taylor M, Adams K, Sabolinski M, Worcel M, Cohn JN., African-American Heart Failure Trial Investigators. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004 Nov 11;351(20):2049-57. [PubMed: 15533851]

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Ziaeian B, Fonarow GC, Heidenreich PA. Clinical Effectiveness of Hydralazine-Isosorbide Dinitrate in African-American Patients With Heart Failure. JACC Heart Fail. 2017 Sep;5(9):632-639. [PMC free article: PMC5581201] [PubMed: 28711446]

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Hollenberg SM, Warner Stevenson L, Ahmad T, Amin VJ, Bozkurt B, Butler J, Davis LL, Drazner MH, Kirkpatrick JN, Peterson PN, Reed BN, Roy CL, Storrow AB. 2019 ACC Expert Consensus Decision Pathway on Risk Assessment, Management, and Clinical Trajectory of Patients Hospitalized With Heart Failure: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2019 Oct 15;74(15):1966-2011. [PubMed: 31526538]

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Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC, Spencer CC, Stafford RS, Taler SJ, Thomas RJ, Williams KA, Williamson JD, Wright JT. 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. 2018 Jun;71(6):e13-e115. [PubMed: 29133356]

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WRITING COMMITTEE MEMBERS. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL., American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013 Oct 15;128(16):e240-327. [PubMed: 23741058]

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Riddiough MA. Preventing, detecting and managing adverse reactions of antihypertensive agents in the ambulant patient with essential hypertension. Am J Hosp Pharm. 1977 May;34(5):465-79. [PubMed: 326040]

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Mahfouz A, Mahmoud AN, Ashfaq PA, Siyabi KH. A case report of hydralazine-induced skin reaction: Probable toxic epidermal necrolysis (TEN). Am J Case Rep. 2014;15:135-8. [PMC free article: PMC3979803] [PubMed: 24719674]

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KIRKENDALL WM, PAGE EB. Polyneuritis occurring during hydralazine therapy; report of two cases and discussion of adverse reactions to hydralazine. J Am Med Assoc. 1958 May 24;167(4):427-32. [PubMed: 13538717]

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Rosendorff C, Lackland DT, Allison M, Aronow WS, Black HR, Blumenthal RS, Cannon CP, de Lemos JA, Elliott WJ, Findeiss L, Gersh BJ, Gore JM, Levy D, Long JB, O’Connor CM, O’Gara PT, Ogedegbe G, Oparil S, White WB., American Heart Association, American College of Cardiology, and American Society of Hypertension. Treatment of hypertension in patients with coronary artery disease: a scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. Hypertension. 2015 Jun;65(6):1372-407. [PubMed: 25828847]

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Arce C, Segura-Pacheco B, Perez-Cardenas E, Taja-Chayeb L, Candelaria M, Dueñnas-Gonzalez A. Hydralazine target: from blood vessels to the epigenome. J Transl Med. 2006 Feb 28;4:10. [PMC free article: PMC1413557] [PubMed: 16507100]

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Disclosure: Linda Herman declares no relevant financial relationships with ineligible companies.

Disclosure: Zachary Bruss declares no relevant financial relationships with ineligible companies.

Disclosure: Vijai Tivakaran declares no relevant financial relationships with ineligible companies.

Hydralazine: MedlinePlus Drug Information

pronounced as (hye dral’ a zeen)

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Hydralazine is used to treat high blood pressure. Hydralazine is in a class of medications called vasodilators. It works by relaxing the blood vessels so that blood can flow more easily through the body.

High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.

Hydralazine comes as a tablet to take by mouth. It usually is taken two to four a day. Take hydralazine at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take hydralazine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Hydralazine controls high blood pressure but does not cure it. Continue to take hydralazine even if you feel well. Do not stop taking hydralazine without talking to your doctor.

Hydralazine is also used after heart valve replacement and in the treatment of heart failure. Talk to your doctor about the possible risks of using this medication for your condition.

This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

Before taking hydralazine,

• tell your doctor and pharmacist if you are allergic to hydralazine, aspirin, tartrazine (a yellow dye in some processed foods and medications), any other medications, or any of the ingredients in hydralazine tablets. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: indomethacin (Indocin, Tivorbex), metoprolol (Lopressor, Toprol-XL, in Dutoprol), and propranolol (Inderal LA, Innopran XL, in Inderide).
• tell your doctor if you have ever had a heart attack, or have coronary artery disease, rheumatic heart disease, or heart, kidney or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking hydralazine, call your doctor.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking hydralazine.
• ask your doctor about the safe use of alcohol while you are taking hydralazine. Alcohol can make the side effects from hydralazine worse.

Take hydralazine with meals or a snack.

Your doctor may prescribe a low-salt or low-sodium diet. Follow these directions carefully.

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Hydralazine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• flushing
• headache
• upset stomach
• vomiting
• loss of appetite
• diarrhea
• constipation
• eye tearing
• stuffy nose
• rash

Some side effects can be serious.

If you experience any of the following symptoms, call your doctor immediately:

• fainting
• joint or muscle pain
• fever
• rapid heartbeat
• chest pain
• swollen ankles or feet
• numbing or tingling in hands or feet

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store at room temperature and away from excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA’s Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call emergency services at 911.

• Apresoline^®¶
• Dralzine^®¶

• Apresazide^® (containing Hydralazine, Hydrochlorothiazide)^¶
• Apresoline-Esidrix^® (containing Hydralazine, Hydrochlorothiazide)^¶
• BiDil^® (containing Hydralazine, Isosorbide Dinitrate)
• Dralserp^® (containing Hydralazine, Reserpine)^¶
• Hydra-Zide^® (containing Hydralazine, Hydrochlorothiazide)
• Hydrap-ES^® (containing Hydralazine, Hydrochlorothiazide, Reserpine)^¶
• Marpres^® (containing Hydralazine, Hydrochlorothiazide, Reserpine)^¶
• Ser-Ap-Es^® (containing Hydralazine, Hydrochlorothiazide, Reserpine)^¶
• Serathide^® (containing Hydralazine, Hydrochlorothiazide, Reserpine)^¶
• Serpazide^® (containing Hydralazine, Hydrochlorothiazide, Reserpine)^¶
• Serpex^® (containing Hydralazine, Hydrochlorothiazide, Reserpine)^¶
• Unipres^® (containing Hydralazine, Hydrochlorothiazide, Reserpine)^¶

^¶ This branded product is no longer on the market. Generic alternatives may be available.

Last Revised – 06/15/2017

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Hydralazine – description of the substance, pharmacology, use, contraindications, formula

Contents

• Structural formula

• Russian name

• English title

• Latin name

• chemical name

• Gross formula

• Pharmacological group of the substance Hydralazine

• Nosological classification

• CAS code

• pharmachologic effect

• Characteristic

• Pharmacology

• Application of the substance Hydralazine

• Contraindications

• Side effects of Hydralazine

• Dosage and administration

• Precautionary measures

• special instructions

Structural formula

Russian name

Hydralazine

English name

Hydralazine

Latin name

Hydralazinum (born ) Hydralazini)

Chemical name

1(2H)-Phthalazinonhydrazone (as base and monohydrochloride )

Gross formula

C ₈ H ₈ N ₄

Pharmacological group of the substance Hydralazine

Vasodilators

Nosological classification

ICD-10 code list

• I10 Essential (primary) hypertension

• I15 Secondary hypertension

• I50. 0 Congestive heart failure

• O15 Eclampsia

CAS code

86-54-4

Pharmacological action

Pharmacological action –

vasodilator , antihypertensive .

Characteristics

White crystalline powder. Let’s dissolve in water in the ratio 4,4:100, it is a little — in alcohol.

Pharmacology

Inhibits calcium transport into arteriole myofibril cells and/or releases intracellular ions. A decrease in blood pressure is accompanied by a reflex increase in the tone of the sympathetic nervous system, an increase in cardiac output; increases renal blood flow.

Use of the substance Hydralazine

Arterial hypertension, hypertensive crisis, congestive heart failure with high afterload, eclampsia.

Contraindications

Hypersensitivity, severe arterial atherosclerosis, systemic lupus erythematosus, peripheral neuropathies.

Side effects of the substance Hydralazine

Headache, dizziness, fever, hypotension, tachycardia, cardialgia, angina pectoris, hot flashes, sweating, lacrimation, nausea, vomiting, lupus-like syndrome.

Dosage and administration

Inside, after meals, starting with 10-25 mg 2-4 times a day, with a gradual increase to 100-200 mg/day (in 4 divided doses). Higher doses: single – 100 mg, daily – 300 mg. Course 2-4 weeks; repeated course – after 3-5 months.

Precautions

Use with caution in coronary insufficiency.

Special instructions

Forms colored complexes with iron, and therefore contact of the moistened preparation or its solutions with iron objects should be avoided.

Information for healthcare professionals only.
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Hydralazine for cats and dogs

11/24/2022 Medicines323

Product Information

General Description

Hydralazine is a medicine that opens blood vessels, treats high blood pressure, and helps treat congestive heart failure.

Dosage

The veterinarian determines the dosage of the medicine for a particular living creature, based on a variety of data – the weight and age of the animal, previous diseases, medications taken, and much more.

Do not self-medicate unless you want to lose your pet! Contact your veterinarian!

How it works

Hydralazine relaxes the smooth muscles of the blood vessels. Nerve signals trigger the release of calcium, which contracts the muscles. Without calcium, muscles cannot contract and blood vessels cannot constrict. When hydralazine inhibits the movement of calcium, the blood vessels are forced to relax, reducing the pressure within them.

Storage Information

Read the product label for storage information.

Missed dose?

Give the dose as soon as possible. If it’s almost time for your next dose, skip the missed dose and continue as usual. Do not give your pet two doses at once.

Side effects and drug reactions

Hydralazine may cause the following side effects:

• Hypotension
• Vomiting
• Diarrhea
• Lethargy
• Conjunctivitis
• Increased water or urinary pressure
• Constipation

Hydralazine may react with these drugs:

• ta-blockers
• Sympathomimetic
• Digoxin
• Furosemide

USE THIS WITH CAUTION DRUG FOR ANIMALS WITH KIDNEY OR HEART DISEASE.