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definitions - Hydralazine

hydralazine (n.)

1.an antihypertensive drug (trade name Apresoline) that dilates blood vessels; used (often with a diuretic) to treat hypertension and congestive heart failure

Hydralazine (n.)

1.(MeSH)A direct-acting vasodilator that is used as an antihypertensive agent.

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Hydralazine

                   
Hydralazine
Systematic (IUPAC) name
1-hydrazinylphthalazine
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a682246
Pregnancy cat. C
Commonly used to treat severe PIH
Legal status  ?
Routes Oral, intravenous
Pharmacokinetic data
Bioavailability 26-55%
Metabolism Hepatic
Half-life 2-4 hours
Excretion Renal
Identifiers
CAS number 86-54-4 YesY
ATC code C02DB02
PubChem CID 3637
DrugBank DB01275
ChemSpider 3511 YesY
UNII 26NAK24LS8 YesY
KEGG D08044 YesY
ChEBI CHEBI:5775 YesY
ChEMBL CHEMBL276832 YesY
Chemical data
Formula C8H8N4 
Mol. mass 160.176 g/mol
 YesY (what is this?)  (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.[1]

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.

It belongs to the hydrazinophthalazine class of drugs.[2]

Contents

  Mechanism of action

Hydralazine increases cyclic guanosine monophosphate (cGMP) levels, decreasing the phosphorylaton of smooth muscle myosin light chains. This results in blood vessel relaxation. It dilates arterioles more than veins.[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 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.[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.[6]

  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).[7]

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

  See also

  References

  1. ^ a b c d Harvey, Richard A., Pamela A. Harvey, and Mark J. Mycek. Lippincott's Illustrated Reviews: Pharmacology. 2nd ed. Philadelphia: Lipincott, Williams & Wilkins, 2000. 190.
  2. ^ Bourreli, B.; Pinaud, M.; Passuti, N.; Gunst, J. P.; Drouet, J. C.; Remi, J. P. (1988). "Additive effects of dihydralazine during enflurane or isoflurane hypotensive anaesthesia for spinal fusion". Canadian Journal of Anaesthesia 35 (3): 242–248. doi:10.1007/BF03010617. PMID 3383316.  edit
  3. ^ Le, Bhushan and Vasan. First Aid for the USMLE Step 1. 20th Anniv. Ed, 2010.
  4. ^ "antihtn". http://faculty.swosu.edu/scott.long/phcl/antihtn.htm. Retrieved 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. doi:10.1161/01.RES.0000134924.89412.70. PMID 15192023. http://circres.ahajournals.org/cgi/pmidlookup?view=long&pmid=15192023. 
  6. ^ Bhushan, Vikas, Tao T. Lee, and Ali Ozturk. First Aid for the USMLE Step 1. New York: McGraw-Hill Medical, 2007. 251.
  7. ^ Leung, G; Sun W, Zheng L, Brookes S, Tully M, Shi R (2010). "Anti-acrolein treatment improves behavioral outcome and alleviates myelin damage in EAE mouse". Neuroscience 173: 150–5. doi:10.1016/j.neuroscience.2010.11.018. PMC 3034379. PMID 21081153. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3034379. 
  8. ^ Sanders, Lisa (2010-06-06). "DIAGNOSIS; Dizzying Symptoms". The New York Times. http://query.nytimes.com/gst/fullpage.html?res=9807E7DF163FF935A35755C0A9669D8B63&n=Top/Features/Magazine/Columns/Diagnosis&pagewanted. 
  9. ^ 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.
  10. ^ Mazari L, Ouarzane M, Zouali M (April 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. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=17404230. 
 
               

 

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