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Hydralazine

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Hydralazine chemical structure
Hydralazine

1-hydrazinylphthalazine
IUPAC name
CAS number
86-54-4
ATC code

C02DB02

PubChem
3637
DrugBank
[1]
Chemical formula {{{chemical_formula}}}
Molecular weight 160.176 g/mol
Bioavailability
Metabolism Hepatic
Elimination half-life 2-4 hours
Excretion Renal
Pregnancy category C
Commonly used to treat severe PIH
Legal status
Routes of administration 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]

MechanismEdit

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

An exam revision source declares that hydralazine works through a cGMP-mediated mechanism, resulting in smooth muscle relaxation.[3]

It recently has been identified as a nitric oxide donor.[4]

Activation of hypoxia-inducible factors has been suggested as a mechanism.[5]

Clinical UseEdit

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 generally 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.[3]

Side effectsEdit

Common side effects include:

Patients given hydralazine over a period of six months may develop a lupus-like syndrome or other immune related diseases that generally are reversible with withdrawal.[1] Hydralazine is differentially acetylated by fast and slow acetylator phenotypes thus incidence of lupus-like disease in slow acetylators.

ReferencesEdit

  1. 1.0 1.1 1.2 1.3 Harvey, Richard A., Pamela A. Harvey, and Mark J. Mycek. Lippincott's Illustrated Reviews: Pharmacology. 2nd ed. Philadelphia: Lipincott, Williams & Wilkins, 2000. 190.
  2. Rang, Dale, Ritter and Flower. Pharmacology. 6th Ed, 2007.
  3. 3.0 3.1 Bhushan, Vikas, Tao T. Lee, and Ali Ozturk. First Aid for the USMLE Step 1. New York: McGraw-Hill Medical, 2007. 251.
  4. antihtn. URL accessed on 2008-10-05.
  5. Knowles HJ, Tian YM, Mole DR, Harris AL (July 2004). Novel mechanism of action for hydralazine: induction of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and angiogenesis by inhibition of prolyl hydroxylases. Circ. Res. 95 (2): 162–9.

Template:Antihypertensives and diuretics


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