Hydralazine

Hydralazine
Skeletal formula of hydralazine
Ball-and-stick model of the hydralazine molecule
Clinical data
Trade names Apresoline, BiDil, others
AHFS/Drugs.com Monograph
MedlinePlus a682246
License data
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
Routes of
administration		 By mouth, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 26–50%
Protein binding 85–90%
Metabolism Liver
Onset of action 5 to 30 min[1]
Biological half-life 2–8 hours, 7–16 hours (renal impairment)
Duration of action 2 to 6 hrs[1]
Excretion Urine
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.001.528
Chemical and physical data
Formula C8H8N4
Molar mass 160.176 g/mol
3D model (JSmol)
  (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. 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.

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. 1 2 3 4 5 6 7 "Hydralazine Hydrochloride". The American Society of Health-System Pharmacists. Retrieved 8 December 2016.
  2. 1 2 3 WHO Model Formulary 2008 (PDF). World Health Organization. 2009. p. 280. ISBN 9789241547659. Retrieved 8 December 2016.
  3. 1 2 Wermuth, Camille Georges. The Practice of Medicinal Chemistry. Academic Press. p. 12. ISBN 9780080568775.
  4. ↑ Progress in Drug Research/Fortschritte der Arzneimittelforschung/Progrés des recherches pharmaceutiques. Birkhäuser. 2013. p. 206. ISBN 9783034870948.
  5. ↑ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Retrieved 8 December 2016.
  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. 1 2 3 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. PMID 22071816. doi:10.1002/14651858.CD004934.pub4.
  9. 1 2 3 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. 1 2 3 4 5 6 7 "Hydralazine Tablets 50mg". UK Electronic Medicines Compendium. September 7, 2016.
  13. ↑ Cohn, JN; McInnes, GT; Shepherd, AM (September 2011). "Direct-acting vasodilators.". Journal of clinical hypertension (Greenwich, Conn.). 13 (9): 690–2. PMID 21896152.
  14. 1 2 Schroeder, NA (January 1952). "The effect of 1-hydrasinophthalasine in hypertension.". Circulation. 5 (1): 28–37. PMID 14896450.
  15. ↑ "Hydralazine". Drugbank. Retrieved 4 March 2017.
  16. ↑ "hydralazine". PubChem. Retrieved 4 March 2017.
  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 (New York, N.Y.). 73 (1): 102. PMID 15402536.
  19. ↑ "New Drug Application (NDA) 008303 Company: NOVARTIS Drug Name(s): Apresoline". FDA. Retrieved 26 February 2017.
  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. PMID 23517596. doi:10.2174/15680096113139990077.
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