Hydralazine

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 is commonly used in combination with isosorbide dinitrate for the treatment of congestive heart failure in black populations. This preparation, isosorbide dinitrate/hydralazine, was the first race-based prescription drug. It should not be used in people who have tachycardia, heart failure, constrictive pericarditis, 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. Common (1–10% frequency) side effects include flushing, hypotension, anginal symptoms, aching or swelling joints, muscle aches, positive tests for atrial natriuretic peptide, stomach upset, diarrhea, nausea and vomiting, and swelling (sodium and water retention). == Interactions ==

Hydralazine may potentiate the antihypertensive effects of: • ACE inhibitors • Antihypertensives • Antipsychotics • Calcium antagonists • Diazoxide • Diuretics • Ethanol (alcohol) • Tricyclic antidepressants • Vasodilators Drugs subject to a strong first-pass effect, such as beta blockers, may increase the bioavailability of hydralazine. The heart rate-accelerating effects of epinephrine (adrenaline) are increased by hydralazine, and coadministration may lead to toxicity. == Mechanism of action ==

Hydralazine is a direct-acting smooth muscle relaxant and acts as a vasodilator primarily in resistance arterioles, also known as the smooth muscle of the arterial bed. 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 exact mechanism of action of hydralazine is unknown, at least as of 1981. Metabolic products include the N-acetyl derivative, pyruvic acid hydrazone, and acetone hydrazone, each of which may also contribute to reducing blood pressure. ==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. == References ==