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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 black people.[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]

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 (Jmol)
  (verify)

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]

Contents

Medical 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).[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 effectsEdit

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 Edema (sodium and water retention).[12]

InteractionsEdit

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 actionEdit

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]

ChemistryEdit

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

HistoryEdit

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]

ResearchEdit

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

See alsoEdit

ReferencesEdit

  1. ^ a b c d e f g "Hydralazine Hydrochloride". The American Society of Health-System Pharmacists. Retrieved 8 December 2016. 
  2. ^ a b c WHO Model Formulary 2008 (PDF). World Health Organization. 2009. p. 280. ISBN 9789241547659. Retrieved 8 December 2016. 
  3. ^ a b 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. ^ 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. PMID 22071816. doi:10.1002/14651858.CD004934.pub4. 
  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. 
  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. ^ a b 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. ^ Candelaria, M; Herrera, A; Labardini, J; González-Fierro, A; Trejo-Becerril, C; Taja-Chayeb, L; Pérez-Cárdenas, E; Cruz-Hernández, E; Arias-Bofill, D; Vidal, S; Cervera, E; Dueñas-Gonzalez, A (5 October 2010). "Hydralazine and magnesium valproate as epigenetic treatment for myelodysplastic syndrome. Preliminary results of a phase-II trial". Annals of Hematology. 90 (4): 379–387. PMID 20922525. doi:10.1007/s00277-010-1090-2.