hydralazine

Hydralazine
Systematic (IUPAC) name
1-hydrazinylphthalazine
Identifiers
CAS number	86-54-4
ATC code	C02DB02
PubChem	3637
ChemSpider	3511
Chemical data
Formula	C8H8N4
Mol. mass	160.176 g/mol
Pharmacokinetic data
Bioavailability	26-55%
Metabolism	Hepatic
Half life	2-4 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	C Commonly used to treat severe PIH
Legal status
Routes	Oral, intravenous

Hydralazine hydrochloride (1-hydrazinophthalazine monohydrochloride; trade name 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.^[1]

Mechanism

The mechanism of action of hydralazine is not well known. It interferes with the action of the second messenger IP₃, limiting calcium release from the sarcoplasmic reticulum of smooth muscle. This results in an arterial and arteriolar relaxation.^[2]

It recently has been identified as a nitric oxide donor.^[3]

Activation of hypoxia-inducible factors has been suggested as a mechanism.^[4]

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 may cause angina pectoris or myocardial infarction.^[1] 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.^[1]

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.^[5]

Side-effects

Common side-effects include:

• Diarrhea
• Compensatory tachycardia due to baroreceptor reflex
• Headache
• Loss of appetite
• Nausea or vomiting
• Depression
• Pounding heartbeat
• Drug-Induced Lupus Erythematosus^[6]

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.^[1] Hydralazine is differentially acetylated by fast and slow acetylator phenotypes, hence incidence of lupus-like disease in slow acetylators.

References