Jump to content

Hydralazine: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
remove content added by sock of blocked user Nuklear
Falconerd (talk | contribs)
110 edits
m changed word for readability
Line 58: Line 58:
'''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.<ref name=Harvey>Harvey, Richard A., Pamela A. Harvey, and Mark J. Mycek. Lippincott's Illustrated Reviews: Pharmacology. 2nd ed. Philadelphia: Lipincott, Williams & Wilkins, 2000. 190.</ref>
'''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.<ref name=Harvey>Harvey, Richard A., Pamela A. Harvey, and Mark J. Mycek. Lippincott's Illustrated Reviews: Pharmacology. 2nd ed. Philadelphia: Lipincott, Williams & Wilkins, 2000. 190.</ref>


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.<ref name=Bourreli1988>{{cite pmid|3383316}}</ref>
However, this only has a short term effect on blood pressure, as the system will reset to the previous, high blood pressure needed 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.<ref name=Bourreli1988>{{cite pmid|3383316}}</ref>


<!-- Society and culture -->
<!-- Society and culture -->

Revision as of 18:06, 11 March 2015

Hydralazine
Clinical data
Trade namesApresoline
AHFS/Drugs.comMonograph
MedlinePlusa682246
License data
Pregnancy
category
  • AU: C
Routes of
administration		Oral, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability26-50%
Protein binding85-90%
MetabolismHepatic
Elimination half-life2-8 hours, 7-16 hours (renal impairment)
ExcretionRenal
Identifiers
  • 1-hydrazinylphthalazine
CAS Number
PubChem CID
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 (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 needed 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]

It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[3]

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). 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. To prevent these undesirable side effects, hydralazine is usually prescribed in combination with a beta-blocker (e.g., propranolol) and a diuretic.[1] In the UK, labetalol tends to be the first-line beta-blocker.

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.[4] It has also been used successfully as a treatment for myelodysplastic syndrome in its capacity as a DNA methyltransferase inhibitor.[5]

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

Side effects

Very common (>10% frequency) side effects include:[6]

Common (1-10% frequency) side effects include:[6][7]

  • Flushing
  • Hypotension
  • Anginal symptoms
  • Joint ache
  • Positive test for ANF
  • Gastrointestinal disturbances
  • Diarrhoea
  • Nausea
  • Vomiting
  • Joint swelling
  • Muscle aches
  • Oedema (sodium and water retention)

Uncommon (0.1-1% frequency) side effects include:[6][7]

  • Nasal congestion
  • Heart failure
  • Dizziness
  • Rash
  • Lupus-like syndrome
  • Protein in the urine
  • Increased plasma creatinine
  • Blood in the urine
  • Glomerulonephritis
  • Jaundice
  • Liver enlargement
  • Hepatitis
  • Agitation
  • Weight loss
  • Appetite loss
  • Anxiety
  • Blood dyscrasias
  • Increased lacrimation
  • Conjunctivitis
  • Nasal congestion
  • Dyspnoea
  • Pleural pain
  • Fever
  • Malaise
  • Hypersensitivity reactions

Rare (<0.1% frequency) side effects include:[6][7]

  • Paradoxical pressor responses
  • Pins and needles (might be reversed by pyridoxine administration)
  • Peripheral neuritis
  • Polyneuritis
  • Tremor
  • Paralysed bowel
  • Acute kidney failure
  • Urinary retention
  • Depression
  • Hallucinations
  • Haemolytic anaemia
  • Leucocytosis
  • Lymphadenopathy
  • Pancytopenia
  • Splenomegaly
  • Agranulocytosis
  • Exophthalmos
  • Retroperitoneal fibrosis

Contraindications

Contraindications include:[6]

  • Known hypersensitivity to hydralazine or dihydralazine
  • Idiopathic systemic lupus erythematosus and related diseases
  • Severe tachycardia and heart failure with a high cardiac output (e.g. in thyrotoxicosis)
  • Myocardial insufficiency due to mechanical obstruction (e.g. in the presence of aortic or

mitral stenosis or constrictive pericarditis).

  • Isolated right-ventricular heart failure due to pulmonary hypertension (cor pulmonale)
  • Dissecting aortic aneurysm

Interactions

It may potentiate the antihypertensive effects of:[6]

  • Vasodilators
  • Calcium antagonists
  • ACE inhibitors
  • Diuretics
  • Antihypertensives
  • Tricyclic antidepressants
  • Major tranquillisers
  • Ethanol (alcohol)
  • Diazoxide

Drugs subject to a strong first-pass effect such as beta-blockers may increase the bioavailability of hydralazine.[6] Epinephrine (adrenaline)'s heart rate-accelerating effects are increased by hydralazine, hence may lead to toxicity.[6]

Mechanism of action

Hydralazine binds to and activates gated potassium channels on vascular smooth muscle. The result is an efflux of potassium and a subsequent hyperpolarization of the cell. This prevents calcium-mediated activation and constriction of the smooth muscle, resulting in vasodilation. However, this induced vasodilation triggers the baroreflex resulting in tachycardia and vasoconstriction. Hydralazine is, therefore, not a great candidate for control of hypertension alone. It is often coadministered with a beta blocker to mitigate the effects of the baroreflex.

Hydralazine requires the endothelium to provide nitric oxide,[8] thus only causes vasodilation in vivo with functional endothelium. Hydralazine will not cause vasodilation in vitro in an isolated blood vessel.

Activation of hypoxia-inducible factors has been suggested as a mechanism.[9]

See also

References

  1. ^ a b c Harvey, Richard A., Pamela A. Harvey, and Mark J. Mycek. Lippincott's Illustrated Reviews: Pharmacology. 2nd ed. Philadelphia: Lipincott, Williams & Wilkins, 2000. 190.
  2. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 3383316, please use {{cite journal}} with |pmid=3383316 instead.
  3. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
  4. ^ Bhushan, Vikas, Tao T. Lee, and Ali Ozturk. First Aid for the USMLE Step 1. New York: McGraw-Hill Medical, 2007. 251.
  5. ^ Candelaria, M (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. doi:10.1007/s00277-010-1090-2. PMID 20922525. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  6. ^ a b c d e f g h "PRODUCT INFORMATION APRESOLINE® (hydralazine hydrochloride 20 mg powder for injection ampoule)" (PDF). TGA eBusiness Services. Link Medical Products Pty Ltd. 27 March 2005. Retrieved 13 February 2014.
  7. ^ a b c Template:Cite isbn
  8. ^ "antihtn". Retrieved 2008-10-05.
  9. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
Retrieved from "https://en.wikipedia.org/w/index.php?title=Hydralazine&oldid=650932294"