Hydralazine

Source: Wikipedia, the free encyclopedia.
Not to be confused with hydrazine.

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[2]
Elimination half-life2–8 hours, 7–16 hours (renal impairment)
Duration of action2 to 6 hrs[2]
ExcretionUrine
Identifiers
  • 1-hydrazinylphthalazine
JSmol)
  • NNc1c2ccccc2cnn1
  • 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

by injection into a vein.[3] Effects usually begin around 15 minutes and last up to six hours.[2]

Common side effects include

vasodilator family of medications, so it is believed to work by causing the dilation of blood vessels.[2]

Hydralazine was discovered while scientists at Ciba were looking for a treatment for malaria.[4] It was patented in 1949.[5] It is on the World Health Organization's List of Essential Medicines.[6] In 2021, it was the 106th most commonly prescribed medication in the United States, with more than 6 million prescriptions.[7][8]

Medical use

Hydralazine is not used as a primary drug for treating hypertension because it elicits a reflex

angina pectoris or myocardial infarction.[10] 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 beta blocker (e.g., propranolol) and a diuretic.[10] Beta-blockers licensed to treat heart failure in the UK include bisoprolol, carvedilol, and nebivolol.[11][12][13]

Hydralazine is used to treat severe hypertension, but is not a first-line therapy for essential hypertension. Hydralazine is often used to treat hypertension in pregnancy, though, with either labetalol and/or methyldopa.[14]

Hydralazine is commonly used in combination with

isosorbide dinitrate/hydralazine, was the first race-based prescription drug.[15]

It should not be used in people who have tachycardia, heart failure, constrictive pericarditis, lupus, a dissecting aortic aneurysm, or porphyria.[16]

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.[16] Hydralazine is within the top three drugs that is known to induce systemic lupus and this adverse drug event is dose dependent yet significant.

Very common (>10% frequency) side effects include headache, tachycardia, and palpitations.[16]

Common (1–10% frequency) side effects include flushing, hypotension, anginal symptoms, aching or swelling joints, muscle aches, positive tests for atrial natriuretic peptide, stomach upset, diarrhea, nausea and vomiting, and swelling (sodium and water retention).[16]

Interactions

It may potentiate the antihypertensive effects of:[16]

Drugs subject to a strong first-pass effect such as beta blockers may increase the

epinephrine (adrenaline) are increased by hydralazine, and coadministration may lead to toxicity.[16]

Mechanism of action

Hydralazine is a direct-acting

peripheral resistance, thereby lowering blood pressure and decreasing afterload.[10]

Metabolic products include the N-

acetyl derivative, pyruvic acid hydrazone, and acetone hydrazone, each of which may also contribute to reducing blood pressure.[19]

Chemistry

Hydralazine belongs to the hydrazinophthalazine class of drugs.[20]

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,[21][22][23] and the first scientific publications of its blood pressure-lowering activities appeared in 1950.[4][20][24] It was approved by the FDA in 1953.[25]

It was one of the first antihypertensive medications that could be taken by mouth.[9]

Research

Hydralazine has also been studied as a treatment for myelodysplastic syndrome in its capacity as a DNA methyltransferase inhibitor.[26]

References

  1. ^ "Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 30 March 2024.
  2. ^ 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.
  3. ^
    ISBN 9789241547659
    .
  4. ^
    ISBN 9780080568775. Archived
    from the original on 26 February 2017.
  5. ISBN 9783034870948. Archived
    from the original on 20 December 2016.
  6. hdl:10665/325771
    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  7. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  8. ^ "Hydralazine - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  9. ^
    PMID 22071816
    .
  10. ^ a b c Harvey RA, Harvey PA, Mycek MJ (2000). Lippincott's Illustrated Reviews: Pharmacology (2nd ed.). Philadelphia: Lippincott Williams & Wilkins. p. 190.
  11. ^ Joint Formulary Committee. "Bisoprolol fumarate". British National Formulary (online). London: BMJ Group and Pharmaceutical Press. Retrieved 13 March 2023.
  12. ^ Joint Formulary Committee. "Carvedilol". British National Formulary (online). London: BMJ Group and Pharmaceutical Press. Retrieved 13 March 2023.
  13. ^ Joint Formulary Committee. "Nebivolol". British National Formulary (online). London: BMJ Group and Pharmaceutical Press. Retrieved 13 March 2023.
  14. ^ Bhushan V, Lee TT, Ozturk A (2007). First Aid for the USMLE Step 1. New York: McGraw-Hill Medical. p. 251.
  15. PMID 24846808
    .
  16. ^ a b c d e f g "Hydralazine Tablets 50mg". UK Electronic Medicines Compendium. 7 September 2016. Archived from the original on 27 February 2017.
  17. PMID 7712024
    .
  18. PMID 11588117
    .
  19. PMID 21896152
    .
  20. ^
    PMID 14896450
    .
  21. ^ "Hydralazine". Drugbank. Archived from the original on 4 March 2017. Retrieved 4 March 2017.
  22. ^ "hydralazine". PubChem. Archived from the original on 4 March 2017. Retrieved 4 March 2017.
  23. ^ US2484029; see Example 1
  24. S2CID 32603042
    .
  25. ^ "New Drug Application (NDA) 008303 Company: NOVARTIS Drug Name(s): Apresoline". FDA. Archived from the original on 26 February 2017. Retrieved 26 February 2017.
  26. PMID 23517596
    .
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