Hydralazine Hydrochloride

Hydralazine is a vasodilator medication that was first introduced in the 1950s for the treatment of hypertension and heart failure. It works by relaxing the smooth muscle in the walls of blood vessels, which helps to reduce peripheral vascular resistance, thereby lowering blood pressure and decreasing the heart's workload. Hydralazine is approved by the U.S. Food and Drug Administration (FDA) for managing high blood pressure and as an adjunct treatment for heart failure, especially in combination with other medications. It is commonly used when other antihypertensive drugs are not sufficient. Additionally, a combination of hydralazine and isosorbide dinitrate has been specifically approved for heart failure in certain populations.

BRAND NAMES

Apresoline: It is used to lower blood pressure in patients with hypertension and as part of combination therapy for heart failure to reduce the heart’s workload.

MECHANISM OF ACTION

Hydralazine works by directly relaxing the smooth muscle in the walls of blood vessels, primarily the arteries. This leads to vasodilation, or the widening of the blood vessels, which reduces peripheral vascular resistance and lowers blood pressure. The reduction in vascular resistance helps decrease the workload on the heart, making it easier for the heart to pump blood. 

PHARMACOKINETICS

Absorption: Hydralazine is well absorbed from the gastrointestinal tract after oral administration, though its bioavailability is variable, ranging from 25% to 50%.

Distribution: It is widely distributed throughout the body, including to the heart, liver, and kidneys. Hydralazine is moderately protein-bound (about 70%).

Metabolism: Hydralazine undergoes extensive hepatic metabolism via acetylation. The rate of metabolism can vary depending on genetic factors.

Excretion: The metabolites are primarily excreted through the urine. Only a small fraction of the drug is eliminated unchanged. The elimination half-life of hydralazine is about 2–8 hours, which supports its dosing schedule.

DOSAGE AND ADMINISTRATION

• Hypertension: Start with 10 mg 4 times a day, increase to 25 mg 4 times a day. Max dose: 300 mg/day.
• Heart Failure: Start with 25 mg 3–4 times a day, increase as tolerated. Max dose: 300 mg/day (often with isosorbide dinitrate).
• Take orally with or without food. Adjust for elderly or liver impairment.

DRUG INTERACTIONS

• Other antihypertensives: Increased risk of low blood pressure.
• NSAIDs: May reduce hydralazine’s effectiveness.
• Beta-blockers: Can enhance hypotension.
• Corticosteroids: May decrease hydralazine's effect.
• Antidiabetic drugs: May alter blood sugar levels.
• MAO inhibitors: Risk of increased blood pressure.

CONTRAINDICATIONS

• Hypersensitivity: Allergy to hydralazine.
• Lupus erythematosus: Can worsen or cause symptoms.
• Coronary artery disease: Not recommended for severe cases.
• Mitral valve disease: Avoid in severe cases.
• Pregnancy: Only use if necessary (e.g., severe hypertension or pre-eclampsia).

SIDE EFFECTS

Common:

• Headache
• Dizziness or lightheadedness
• Tachycardia (increased heart rate)
• Fluid retention (edema)
• Nausea and vomiting

Serious:

• Lupus-like syndrome (joint pain, rashes, fever)
• Hypotension (low blood pressure)
• Angina or worsening chest pain
• Heart failure exacerbation in some cases

TOXICITY

• Severe hypotension: Overdose can cause dangerously low blood pressure, leading to dizziness, fainting, or shock.
• Reflex tachycardia: Excessive vasodilation can result in a rapid heart rate, which may worsen heart conditions.
• Fluid retention: May lead to edema and worsen heart failure.
• Lupus-like symptoms: Prolonged use or overdose can trigger lupus-like reactions (joint pain, skin rashes, fever).

Treatment:

In case of overdose, supportive care with intravenous fluids, vasopressors, and monitoring for signs of hypotension and electrolyte imbalances may be needed. Discontinuation of the drug may be necessary if severe reactions occur.