Hydralazine


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. In 2017, it was the 105th most commonly prescribed medication in the United States, with more than seven million prescriptions.

Medical use

Hydralazine is not used as a primary drug for treating hypertension because it elicits a reflex sympathetic stimulation of the heart. 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 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.
It should not be used in people with tachycardia, heart failure, who have constrictive pericarditis, who have lupus, a dissecting aortic aneurysm, or porphyria.

Adverse effects

Prolonged treatment may cause a syndrome similar to lupus which can become fatal if the symptoms are not noticed and drug treatment stopped.
Very common side effects include headache, high heart rate, and palpitations.
Common 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.

Interactions

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 '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.

Chemistry

Hydralazine belongs to the hydrazinophthalazine class of drugs.

History

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.

Research

Hydralazine has also been studied as a treatment for myelodysplastic syndrome in its capacity as a DNA methyltransferase inhibitor.