Hydralazine

Hydralazine (apresoline) is a direct-acting smooth muscle relaxant used to treat hypertension by acting as a vasodilator primarily in arteries and arterioles. By relaxing vascular smooth muscle, vasodilators act to decrease peripheral resistance, thereby lowering blood pressure and decreasing afterload.

However, this only has a short term effect on blood pressure, as the system will reset to the previous, high blood pressure necessary to maintain pressure in the kidney necessary for natriuresis. The long term effect of antihypertensive drugs comes from their effects on the pressure natriuresis curve.

Mechanism of action
Hydralazine increases guanosine monophosphate levels, decreasing the action of the second messenger IP3, limiting calcium release from the sarcoplasmic reticulum of smooth muscle. This results in an vessel relaxation. It dilates arterioles more than veins.

It recently has been identified as a nitric oxide donor.

Activation of hypoxia-inducible factors has been suggested as a mechanism.

Clinical use
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 patients with coronary artery disease may cause angina pectoris or myocardial infarction. Hydralazine may also increase plasma renin concentration, resulting in fluid retention. In order to prevent these undesirable side-effects, hydralazine is usually prescribed in combination with a beta-blocker (e.g., propranolol) and a diuretic.

Hydralazine is used to treat severe hypertension, but again, it is not a first-line therapy for essential hypertension. However, hydralazine is the first-line therapy for hypertension in pregnancy, with methyldopa.

Pre-clinical research
Multiple sclerosis: Due to its ability to damage myelin nerve sheaths, acrolein may be a factor in the development of multiple sclerosis. Hydralazine, a known scavenger of acrolein, was found to reduce myelin damage and significantly improve behavioral outcomes in a mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis).

Side effects
Common side-effects include:
 * Diarrhea
 * Compensatory tachycardia due to baroreceptor reflex ->Angina
 * Headache
 * Loss of appetite
 * Nausea or vomiting
 * Depression
 * Pounding heartbeat
 * Vitamin B6 deficiency
 * Drug-Induced Lupus Erythematosus
 * ANCA-associated Vasculitis - Generally MPO-ANCA positive

Patients given hydralazine over a period of six months may develop a lupus-like syndrome or other immune-related diseases that, in general, are reversible with withdrawal. Hydralazine is differentially acetylated by fast and slow acetylator phenotypes, hence incidence of lupus-like disease in slow acetylators.