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Hydralazine

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Revision as of 19:20, 18 May 2011 by 128.172.94.70 (talk) (→Side effects)(diff) ← Previous revision | Latest revision (diff) | Newer revision → (diff) Pharmaceutical compound
Hydralazine
Clinical data
Pregnancy
category
  • C
    Commonly used to treat severe PIH
Routes of
administration		Oral, intravenous
ATC code
Pharmacokinetic data
Bioavailability26-55%
MetabolismHepatic
Elimination half-life2-4 hours
ExcretionRenal
Identifiers
IUPAC name
  • 1-hydrazinylphthalazine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.001.528 Edit this at Wikidata
Chemical and physical data
FormulaC8H8N4
Molar mass160.176 g/mol g·mol
3D model (JSmol)
SMILES
  • n2nc(c1ccccc1c2)NN
InChI
  • InChI=1S/C8H8N4/c9-11-8-7-4-2-1-3-6(7)5-10-12-8/h1-5H,9H2,(H,11,12)
  • Key:RPTUSVTUFVMDQK-UHFFFAOYSA-N
  (verify)

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:

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.

See also

References

  1. ^ Harvey, Richard A., Pamela A. Harvey, and Mark J. Mycek. Lippincott's Illustrated Reviews: Pharmacology. 2nd ed. Philadelphia: Lipincott, Williams & Wilkins, 2000. 190.
  2. Le, Bhushan and Vasan. First Aid for the USMLE Step 1. 20th Anniv. Ed, 2010.
  3. "antihtn". Retrieved 2008-10-05.
  4. Knowles HJ, Tian YM, Mole DR, Harris AL (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. doi:10.1161/01.RES.0000134924.89412.70. PMID 15192023. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. Bhushan, Vikas, Tao T. Lee, and Ali Ozturk. First Aid for the USMLE Step 1. New York: McGraw-Hill Medical, 2007. 251.
  6. Leung, G (2010). "Anti-acrolein treatment improves behavioral outcome and alleviates myelin damage in experimental autoimmune enchephalomyelitis mouse". Neuroscience. 173: 150. doi:10.1016/j.neuroscience.2010.11.018. PMC 3034379. PMID 21081153. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  7. http://query.nytimes.com/gst/fullpage.html?res=9807E7DF163FF935A35755C0A9669D8B63&n=Top/Features/Magazine/Columns/Diagnosis&pagewanted
  8. Schoonen WM,et al. Do selected drugs increase the risk of lupus? A matched case-control study. Br J Clin Pharmacol. 2010 Oct;70(4):588-96. doi: 10.1111/j.1365-2125.2010.03733.x.
  9. Mazari L, Ouarzane M, Zouali M (2007). "Subversion of B lymphocyte tolerance by hydralazine, a potential mechanism for drug-induced lupus". Proc. Natl. Acad. Sci. U.S.A. 104 (15): 6317–22. doi:10.1073/pnas.0610434104. PMC 1851062. PMID 17404230. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
Nonsympatholytic vasodilatory antihypertensives (C02)
Nitrovasodilator (arterioles and venules)
Hydrazinophthalazines (arterioles)
Potassium channel openers (arterioles)
Calcium channel blockers (arterioles)
Hydrazines


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