|Trade names||Apresoline, BiDil, others|
|Main uses||High blood pressure (including in pregnancy)|
|By mouth, intravenous|
|Onset of action||5 to 30 min|
|Duration of action||2 to 6 hrs|
|Defined daily dose||100 mg|
|Elimination half-life||2–8 hours, 7–16 hours (renal impairment)|
|Chemical and physical data|
|Molar mass||160.180 g·mol−1|
|3D model (JSmol)|
Hydralazine, sold under the brand name Apresoline among others, is a medication used to treat high blood pressure and heart failure. This includes high blood pressure in pregnancy and very high blood pressure resulting in symptoms. It has been found to be particularly useful in heart failure, together with isosorbide dinitrate, for treatment of people of African descent. It is given by mouth or by injection into a vein. Effects usually begin around 15 minutes and last up to six hours.
Common side effects include headache and fast heart rate. It is not recommended in people with coronary artery disease or in those with rheumatic heart disease that affects the mitral valve. In those with kidney disease a low dose is recommended. Hydralazine is in the vasodilator family of medications and is believed to work by causing the dilation of blood vessels.
Hydralazine was discovered while scientists at Ciba were looking for a treatment for malaria. It was patented in 1949. It is on the World Health Organization's List of Essential Medicines. The wholesale cost in the developing world is about US$2.78–9.11 per month. In the United States treatment costs about $50–100 per month. In 2017, it was the 105th most commonly prescribed medication in the United States, with more than seven million prescriptions.
Hydralazine is not used as a primary drug for treating hypertension because it elicits a reflex sympathetic stimulation of the heart (the baroreceptor reflex). The sympathetic stimulation may increase heart rate and cardiac output, and in people with coronary artery disease may cause angina pectoris or myocardial infarction. Hydralazine may also increase plasma renin concentration, resulting in fluid retention. To prevent these undesirable side effects, hydralazine is usually prescribed in combination with a β-blocker (e.g., propranolol) and a diuretic. Beta-blockers licensed to treat heart failure in the UK include bisoprolol, carvedilol, and nebivolol.
Hydralazine is used to treat severe hypertension, but again, it is not a first-line therapy for essential hypertension. However, hydralazine is often used to treat hypertension in pregnancy, with methyldopa.
Hydralazine is commonly used in combination with isosorbide dinitrate for the treatment of congestive heart failure in self-identified African American populations. This preparation, isosorbide dinitrate/hydralazine, was the first race-based prescription drug.
The defined daily dose is 100 mg by injection. For high blood pressure in pregnancy it can be given as 5 mg over about 3 minutes by injection into a vein. If after 20 minutes the BP is not improved the dose can be repeated up to 20 mg total. It can also be given as an infusion starting at 200 to 300 micrograms/minute and than decreased to 50 to 150 micrograms/minute.
Common (1–10% frequency) side effects include flushing, hypotension, anginal symptoms, aching or swelling joints, muscle aches, positive tests for ANP, stomach upset, diarrhea, nausea, and vomiting, and swelling (sodium and water retention).
It may potentiate the antihypertensive effects of:
Drugs subject to a strong first-pass effect such as β-blockers may increase the bioavailability of hydralazine. Epinephrine (adrenaline)'s heart rate-accelerating effects are increased by hydralazine, hence may lead to toxicity.
Mechanism of action
It is a direct-acting smooth muscle relaxant and acts as a vasodilator primarily in resistance arterioles; the molecular mechanism involves inhibition of inositol trisphosphate-induced Ca2+ release from the sarcoplasmic reticulum in arterial smooth muscle cells. By relaxing vascular smooth muscle, vasodilators act to decrease peripheral resistance, thereby lowering blood pressure and decreasing afterload.
The antihypertensive activity of hydralazine was discovered by scientists at Ciba who were trying to discover drugs to treat malaria; it was initially called C-5968 and 1-hydrazinophthalazine; Ciba's patent application was filed in 1945 and issued in 1949, and the first scientific publications of its blood-pressure lowering activities appeared in 1950. It was approved by the FDA in 1953.
It was one of the first antihypertensive medications that could be taken by mouth.
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