Hydralazine

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Hydralazine
Skeletal formula of hydralazine
Ball-and-stick model of the hydralazine molecule
Clinical data
Trade namesApresoline, BiDil, others
AHFS/Drugs.comMonograph
MedlinePlusa682246
License data
Pregnancy
category
  • AU: C
Routes of
administration		By mouth, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability26–50%
Protein binding85–90%
MetabolismLiver
Onset of action5 to 30 min[1]
Elimination half-life2–8 hours, 7–16 hours (renal impairment)
Duration of action2 to 6 hrs[1]
ExcretionUrine
Identifiers
  • 1-hydrazinylphthalazine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.001.528 Edit this at Wikidata
Chemical and physical data
FormulaC8H8N4
Molar mass160.176 g/mol g·mol−1
3D model (JSmol)
  • n2nc(c1ccccc1c2)NN
  • InChI=1S/C8H8N4/c9-11-8-7-4-2-1-3-6(7)5-10-12-8/h1-5H,9H2,(H,11,12) checkY
  • Key:RPTUSVTUFVMDQK-UHFFFAOYSA-N checkY
  (verify)

Hydralazine, sold under the brand name Apresoline among others, is a medication used to treat high blood pressure and heart failure.[1] This includes high blood pressure in pregnancy and very high blood pressure resulting in symptoms.[2] It has been found to be particularly useful in heart failure together with isosorbide dinitrate in people of African descent.[1] It is given by mouth or by injection into a vein.[2] Effects usually begin around 15 minutes and last up to six hours.[1]

Common side effects include headache and fast heart rate.[1] It is not recommended in people with coronary artery disease or rheumatic heart disease that is affecting the mitral valve.[1] In those with kidney problems a low dose is recommended.[2] Hydralazine is in the vasodilator family of medications and is believed to work by causing the dilation of blood vessels.[1]

Hydralazine was discovered while scientists at Ciba were looking for a treatment for malaria.[3] It was patented in 1949.[4] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[5] The wholesale cost in the developing world is about 2.78 to 9.11 USD per month.[6] In the United States treatment costs about 50 to 100 USD per month.[7]

Medical 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).[8] The sympathetic stimulation may increase heart rate and cardiac output, and in people with coronary artery disease may cause angina pectoris or myocardial infarction.[9] Hydralazine may also increase plasma renin concentration, resulting in fluid retention. To prevent these undesirable side effects, hydralazine is usually prescribed in combination with a β-blocker (e.g., propranolol) and a diuretic.[9] Beta-blockers licensed to treat heart failure in the UK include bisoprolol, carvedilol, and nebivolol.[citation needed]

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.[10]

Hydralazine is commonly used in combination with isosorbide dinitrate for the treatment of congestive heart failure in self-identified African American populations. This preparation, isosorbide dinitrate/hydralazine, was the first race-based prescription drug.[11]

It should not be used in people with tachycardia, heart failure, who have constrictive pericarditis, who have lupus, a dissecting aortic aneurism, or porphyria.[12]

Adverse effects

Prolonged treatment may cause a syndrome similar to lupus which can become fatal if the symptoms are not noticed and drug treatment stopped.[12]

Very common (>10% frequency) side effects include headache, high heart rate, and palpitations.[12]

Common (1–10% frequency) side effects include flushing, hypotension, anginal symptoms, aching or swelling joints, muscle aches, positive tests for ANP, stomach upset, diarrhea, nausea, and vomiting, and swelling (sodium and water retention).[12]

Interactions

It may potentiate the antihypertensive effects of:[12]

Drugs subject to a strong first-pass effect such as β-blockers may increase the bioavailability of hydralazine.[12] Epinephrine (adrenaline)'s heart rate-accelerating effects are increased by hydralazine, hence may lead to toxicity.[12]

Mechanism of action

It is a direct-acting smooth muscle relaxant and acts as a vasodilator primarily in resistance arterioles; the molecular mechanism was unknown as of 2011.[8][13] By relaxing vascular smooth muscle, vasodilators act to decrease peripheral resistance, thereby lowering blood pressure and decreasing afterload.[9]

Chemistry

Hydralazine belongs to the hydrazinophthalazine class of drugs.[14]

History

The antihypertensive activity of hydralazine was discovered by scientists at Ciba who were trying to discover drugs to treat malaria; it was initially called C-5968 and 1-hydrazinophthalazine; Ciba's patent application was filed in 1945 and issued in 1949,[15][16][17] and the first scientific publications of its blood-pressure lowering activities appeared in 1950.[3][14][18] It was approved by the FDA in 1953.[19]

It was one of the first antihypertensive medications that could be taken by mouth.[8]

Research

Hydralazine has also been studied as a treatment for myelodysplastic syndrome in its capacity as a DNA methyltransferase inhibitor.[20]

See also

References

  1. ^ a b c d e f g h "Hydralazine Hydrochloride". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  2. ^ a b c WHO Model Formulary 2008 (PDF). World Health Organization. 2009. p. 280. ISBN 9789241547659. Archived from the original (PDF) on 13 December 2016. Retrieved 8 December 2016. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  3. ^ a b Wermuth, Camille Georges (2011-05-02). The Practice of Medicinal Chemistry. Academic Press. p. 12. ISBN 9780080568775. Archived from the original on 2017-02-26. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  4. ^ Progress in Drug Research/Fortschritte der Arzneimittelforschung/Progrés des recherches pharmaceutiques. Birkhäuser. 2013. p. 206. ISBN 9783034870948. Archived from the original on 2016-12-20. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  5. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived from the original (PDF) on 13 December 2016. Retrieved 8 December 2016. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  6. ^ "Hydralazine". International Drug Price Indicator Guide. Retrieved 8 December 2016.
  7. ^ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 145. ISBN 9781284057560.
  8. ^ a b c Kandler, MR; Mah, GT; Tejani, AM; Stabler, SN; Salzwedel, DM (9 November 2011). "Hydralazine for essential hypertension". The Cochrane database of systematic reviews (11): CD004934. doi:10.1002/14651858.CD004934.pub4. PMID 22071816.
  9. ^ a b c Harvey, Richard A., Pamela A. Harvey, and Mark J. Mycek. Lippincott's Illustrated Reviews: Pharmacology. 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2000. 190.
  10. ^ Bhushan, Vikas, Tao T. Lee, and Ali Ozturk. First Aid for the USMLE Step 1. New York: McGraw-Hill Medical, 2007. 251.
  11. ^ Ferdinand, KC; Elkayam, U; Mancini, D; Ofili, E; Piña, I; Anand, I; Feldman, AM; McNamara, D; Leggett, C (1 July 2014). "Use of isosorbide dinitrate and hydralazine in African-Americans with heart failure 9 years after the African-American Heart Failure Trial". The American journal of cardiology. 114 (1): 151–9. PMID 24846808.
  12. ^ a b c d e f g "Hydralazine Tablets 50mg". UK Electronic Medicines Compendium. September 7, 2016. Archived from the original on February 27, 2017. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  13. ^ Cohn, JN; McInnes, GT; Shepherd, AM (September 2011). "Direct-acting vasodilators". Journal of clinical hypertension (Greenwich, Conn.). 13 (9): 690–2. doi:10.1111/j.1751-7176.2011.00507.x. PMID 21896152. Archived from the original on 2012-09-30. {{cite journal}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  14. ^ a b Schroeder, NA (January 1952). "The effect of 1-hydrasinophthalasine in hypertension". Circulation. 5 (1): 28–37. PMID 14896450. Archived from the original on 2017-02-26. {{cite journal}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  15. ^ "Hydralazine". Drugbank. Archived from the original on 4 March 2017. Retrieved 4 March 2017. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  16. ^ "hydralazine". PubChem. Archived from the original on 4 March 2017. Retrieved 4 March 2017. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  17. ^ US2484029; see Example 1
  18. ^ Reubi, FC (January 1950). "Renal hyperemia induced in man by a new phthalazine derivative". Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine. 73 (1): 102. PMID 15402536.
  19. ^ "New Drug Application (NDA) 008303 Company: NOVARTIS Drug Name(s): Apresoline". FDA. Archived from the original on 26 February 2017. Retrieved 26 February 2017. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  20. ^ Singh, V; Sharma, P; Capalash, N (May 2013). "DNA methyltransferase-1 inhibitors as epigenetic therapy for cancer". Current Cancer Drug Targets. 13 (4): 379–99. doi:10.2174/15680096113139990077. PMID 23517596.
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