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			{{Short description|Anti-hypertension medication}}
	{{drugbox | verifiedrevid = 407838852
			{{Distinguish|hydrazine}}
	|
			{{Use dmy dates|date=October 2022}}
	| IUPAC_name = 1-hydrazinylphthalazine
			{{Drugbox
			| verifiedrevid = 443859600
	| image = Hydralazine.svg		| image = Hydralazine.svg
			| alt = Skeletal formula of hydralazine
	| CASNo_Ref = {{cascite|correct|CAS}}
			| width = 125
			| image2 = Hydralazine-based-on-xtals-3D-bs-17.png
			| alt2 = Ball-and-stick model of the hydralazine molecule
			<!-- Clinical data -->
			| tradename = Apresoline, BiDil, others
			| Drugs.com = {{drugs.com|monograph|hydralazine-hydrochloride}}
			| MedlinePlus = a682246
			| DailyMedID = Hydralazine
			| pregnancy_AU = C
			| routes_of_administration = ], ]
			| ATC_prefix = C02
			| ATC_suffix = DB02
			| legal_AU = S4
			| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024}}</ref>
			| legal_CA = Rx-only
			| legal_UK = POM
			| legal_US = Rx-only
			<!-- Pharmacokinetic data -->
			| bioavailability = 26–50%
			| protein_bound = 85–90%
			| metabolism = ]
			| elimination_half-life = 2–8 hours, 7–16 hours (renal impairment)
			| excretion = ]
			| onset = 5 to 30 min<ref name=AHFS2016/>
			| duration_of_action = 2 to 6 hrs<ref name=AHFS2016/>
			<!-- Identifiers -->
			| CAS_number_Ref = {{cascite|correct|??}}
			| CAS_number = 86-54-4
			| PubChem = 3637
			| IUPHAR_ligand = 7326
			| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
			| DrugBank = DB01275
			| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
			| ChemSpiderID = 3511
	| UNII_Ref = {{fdacite|correct|FDA}}		| UNII_Ref = {{fdacite|correct|FDA}}
	| UNII = 26NAK24LS8		| UNII = 26NAK24LS8
			| KEGG_Ref = {{keggcite|correct|kegg}}
	| InChI = 1/C8H8N4/c9-11-8-7-4-2-1-3-6(7)5-10-12-8/h1-5H,9H2,(H,11,12)
			| KEGG = D08044
	| smiles = n2nc(c1ccccc1c2)NN
			| ChEBI_Ref = {{ebicite|correct|EBI}}
	| InChIKey = RPTUSVTUFVMDQK-UHFFFAOYAB
			| ChEBI = 5775
	| ChEMBL_Ref = {{ebicite|correct|EBI}}		| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 276832		| ChEMBL = 276832
			<!--Chemical data-->
			| IUPAC_name = 1-hydrazinylphthalazine
			| C=8 | H=8 | N=4
			| smiles = NNc1c2ccccc2cnn1
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C8H8N4/c9-11-8-7-4-2-1-3-6(7)5-10-12-8/h1-5H,9H2,(H,11,12)		| StdInChI = 1S/C8H8N4/c9-11-8-7-4-2-1-3-6(7)5-10-12-8/h1-5H,9H2,(H,11,12)
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}		| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChIKey = RPTUSVTUFVMDQK-UHFFFAOYSA-N		| StdInChIKey = RPTUSVTUFVMDQK-UHFFFAOYSA-N
	| CAS_number = 86-54-4
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 3511
	| ATC_prefix = C02
	| ATC_suffix = DB02
	| PubChem = 3637
	| DrugBank =
	| KEGG_Ref = {{keggcite|correct|kegg}}
	| KEGG = D08044
	| C=8 | H=8 | N=4
	| molecular_weight = 160.176 g/mol
	| bioavailability = 26-55%
	| protein_bound =
	| metabolism = Hepatic
	| elimination_half-life = 2-4 hours
	| excretion = Renal
	| pregnancy_category = C<br/>Commonly used to treat severe ]
	| legal_status =
	| routes_of_administration = Oral, ]
	}}		}}
			<!-- Definition and medical uses -->
			'''Hydralazine''', sold under the brand name '''Apresoline''' among others, is a medication used to treat ] and ].<ref name=AHFS2016>{{cite web|title=Hydralazine Hydrochloride|url=https://www.drugs.com/monograph/hydralazine-hydrochloride.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221010517/https://www.drugs.com/monograph/hydralazine-hydrochloride.html|archive-date=21 December 2016}}</ref> This includes ] and ].<ref name=WHO2008/> It has been found to be particularly useful in heart failure, together with ], for treatment of ].<ref name=AHFS2016/> It is given by mouth or ].<ref name=WHO2008>{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 9789241547659 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | hdl-access=free |page=280}}</ref> Effects usually begin around 15 minutes and last up to six hours.<ref name=AHFS2016/>
			<!-- Side effects and mechanism -->
	'''Hydralazine''' ('''Apresoline''') is a direct-acting ] relaxant used to treat ] by acting as a ] primarily in ] and ]. By relaxing ], vasodilators act to decrease ], thereby lowering ] 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>
			Common side effects include ] and ].<ref name=AHFS2016/> It is not recommended in people with ] or in those with ] that affects the ].<ref name=AHFS2016/> In those with ] a low dose is recommended.<ref name=WHO2008/> Hydralazine is in the ] family of medications, so it is believed to work by causing the ].<ref name=AHFS2016/>
			<!-- Society and culture -->
	== Mechanism of action ==
			Hydralazine was discovered while scientists at ] were looking for a treatment for malaria.<ref name=Wermuth>{{cite book | vauthors = Wermuth CG | author-link = Camille Georges Wermuth|title=The Practice of Medicinal Chemistry|publisher=Academic Press|isbn=9780080568775|page=12|url=https://books.google.com/books?id=Qmt1_DQkCpEC&pg=PA12|language=en|url-status=live|archive-url=https://web.archive.org/web/20170226131556/https://books.google.com/books?id=Qmt1_DQkCpEC&pg=PA12|archive-date=26 February 2017|date=2 May 2011}}</ref> It was patented in 1949.<ref>{{cite book|title=Progress in Drug Research/Fortschritte der Arzneimittelforschung/Progrés des recherches pharmaceutiques|date=2013|publisher=Birkhäuser|isbn=9783034870948|page=206|url=https://books.google.com/books?id=i8LzBwAAQBAJ&pg=PA206|language=en|url-status=live|archive-url=https://web.archive.org/web/20161220130333/https://books.google.ca/books?id=i8LzBwAAQBAJ&pg=PA206|archive-date=20 December 2016}}</ref> It is on the ].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> In 2022, it was the 121st most commonly prescribed medication in the United States, with more than 5{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Hydralazine Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Hydralazine | access-date = 30 August 2024 }}</ref>
	Hydralazine increases ] levels, decreasing the action of the ] ], limiting ] from the ] of smooth muscle. This results in an vessel relaxation. It dilates arterioles more than veins.<ref name="First Aid">Le, Bhushan and Vasan. First Aid for the USMLE Step 1. 20th Anniv. Ed, 2010.</ref>
			== Medical use ==
	It recently has been identified as a ] donor.<ref name="urlantihtn">{{cite web |url=http://faculty.swosu.edu/scott.long/phcl/antihtn.htm |title=antihtn |work= |accessdate=2008-10-05}}</ref>
			Hydralazine is not used as a primary drug for treating hypertension because it elicits a reflex ] stimulation of the heart (the ]).<ref name=Cochrane2011rev>{{cite journal | vauthors = Kandler MR, Mah GT, Tejani AM, Stabler SN, Salzwedel DM | title = Hydralazine for essential hypertension | journal = The Cochrane Database of Systematic Reviews | issue = 11 | pages = CD004934 | date = November 2011 | pmid = 22071816 | doi = 10.1002/14651858.CD004934.pub4 }}</ref> The sympathetic stimulation may increase heart rate and ], and in people with coronary artery disease may cause ] or ].<ref name=Harvey/> Hydralazine may also increase ] ] concentration, resulting in fluid retention. To prevent these undesirable side effects, hydralazine is usually prescribed in combination with a ] (e.g., ]) and a ].<ref name=Harvey/>
			Hydralazine is used to treat severe hypertension, but is not a first-line therapy for ]. Hydralazine is often used to treat hypertension in pregnancy, though, with either labetalol and/or ].<ref name=Bhushan>{{cite book | vauthors = Bhushan V, Lee TT, Ozturk A | title = First Aid for the USMLE Step 1. | location = New York | publisher = McGraw-Hill Medical | date = 2007 | page = 251 }}</ref>
	Activation of ] has been suggested as a mechanism.<ref name="pmid15192023">{{cite journal |author=Knowles HJ, Tian YM, Mole DR, Harris AL |title=Novel mechanism of action for hydralazine: induction of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and angiogenesis by inhibition of prolyl hydroxylases |journal=Circ. Res. |volume=95 |issue=2 |pages=162–9 |year=2004 |month=July |pmid=15192023 |doi=10.1161/01.RES.0000134924.89412.70 |url=http://circres.ahajournals.org/cgi/pmidlookup?view=long&pmid=15192023}}</ref>
			Hydralazine is commonly used in combination with ] for the treatment of ] in black populations. This preparation, ], was the first race-based prescription drug.<ref name=Ferdinand2014rev>{{cite journal | vauthors = Ferdinand KC, Elkayam U, Mancini D, Ofili E, Piña I, Anand I, Feldman AM, McNamara D, Leggett C | display-authors = 6 | title = Use of isosorbide dinitrate and hydralazine in African-Americans with heart failure 9 years after the African-American Heart Failure Trial | journal = The American Journal of Cardiology | volume = 114 | issue = 1 | pages = 151–9 | date = July 2014 | pmid = 24846808 | doi = 10.1016/j.amjcard.2014.04.018 | url = http://www.ajconline.org/article/S0002-9149(14)00975-8/pdf | doi-access = free }}</ref>
	== Clinical Use ==
	Hydralazine is not used as a primary drug for treating hypertension because it elicits a reflex ] stimulation of the heart (the ]). The sympathetic stimulation may increase heart rate and ], and in patients with coronary artery disease may cause ] or ].<ref name=Harvey/> Hydralazine may also increase ] ] concentration, resulting in fluid retention. In order to prevent these undesirable side-effects, hydralazine is usually prescribed in combination with a beta-blocker (e.g., ]) and a ].<ref name=Harvey/>
			It should not be used in people who have ], heart failure, constrictive ], ], a dissecting ], or ].<ref name=UKlabel2016/>
	Hydralazine is used to treat severe hypertension, but again, it is not a first-line therapy for essential ]. However, hydralazine is the first-line therapy for hypertension in pregnancy, with ].<ref name=Bhushan>Bhushan, Vikas, Tao T. Lee, and Ali Ozturk. First Aid for the USMLE Step 1. New York: McGraw-Hill Medical, 2007. 251.</ref>
			== Adverse effects ==
	===Pre-clinical research===
			Prolonged treatment may cause a ], which can become fatal if the symptoms are not noticed and drug treatment stopped.<ref name =UKlabel2016/> Hydralazine is within the top three drugs that is known to induce systemic lupus and this adverse drug event is dose dependent yet significant.
	Multiple sclerosis: Due to its ability to damage ] nerve sheaths, acrolein may be a factor in the development of ]. Hydralazine, a known scavenger of acrolein, was found to reduce myelin damage and significantly improve behavioral outcomes in a mouse model of multiple sclerosis (]).<ref>{{cite journal | last =Leung | first =G | coauthors =Sun W, Zheng L, Brookes S, Tully M, Shi R | title =Anti-acrolein treatment improves behavioral outcome and alleviates myelin damage in experimental autoimmune enchephalomyelitis mouse| journal = Neuroscience | volume =173 | pages =150| year =2010 | pmid =21081153 | doi=10.1016/j.neuroscience.2010.11.018 }}</ref>
			Very common (>10% frequency) side effects include headache, tachycardia, and ].<ref name=UKlabel2016>{{cite web|title=Hydralazine Tablets 50mg|url=https://www.medicines.org.uk/emc/medicine/24412|work=UK Electronic Medicines Compendium|date=7 September 2016|language=en|url-status=live|archive-url=https://web.archive.org/web/20170227063940/https://www.medicines.org.uk/emc/medicine/24412|archive-date=27 February 2017}}</ref>
	== Side effects ==
	Common side-effects include:
	* ]
	* Compensatory ] due to baroreceptor reflex ->Angina
	* ]
	* ]
	* ] or ]
	* ]
	* ]
	* ]<ref>Schoonen WM,et al. Do selected drugs increase the risk of lupus? A matched case-control study. Br J Clin Pharmacol. 2010 Oct;70(4):588-96. doi: 10.1111/j.1365-2125.2010.03733.x.
	</ref><ref name="pmid17404230">{{cite journal |author=Mazari L, Ouarzane M, Zouali M |title=Subversion of B lymphocyte tolerance by hydralazine, a potential mechanism for drug-induced lupus |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=104 |issue=15 |pages=6317–22 |year=2007 |month=April |pmid=17404230 |pmc=1851062 |doi=10.1073/pnas.0610434104 |url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=17404230}}</ref>
	* ] - Generally MPO-ANCA positive
			Common (1–10% frequency) side effects include ], ], anginal symptoms, aching or swelling joints, muscle aches, positive tests for ], stomach upset, diarrhea, nausea and vomiting, and ] (sodium and water retention).<ref name =UKlabel2016/>
	Patients given hydralazine over a period of six months may develop a ]-like syndrome or other ]s that, in general, are reversible with withdrawal.<ref name=Harvey/> Hydralazine is differentially acetylated by fast and slow ] phenotypes, hence incidence of lupus-like disease in slow acetylators.{{Citation needed|date=May 2010}}
	== See also ==		== Interactions ==
			It may potentiate the antihypertensive effects of:<ref name =UKlabel2016/>
	* ]
			{{div col|colwidth=22em}}
	* ]
			* ]
	* ]
			* ]s
			* ]s
			* ]s
			* ]
			* ]s
			* ]
			* ] (])
			* ]
			{{div col end}}
			Drugs subject to a strong first-pass effect such as beta blockers may increase the ] of hydralazine.<ref name =UKlabel2016/> The heart rate-accelerating effects of ] (adrenaline) are increased by hydralazine, and coadministration may lead to toxicity.<ref name =UKlabel2016/>
			== Mechanism of action ==
			Hydralazine is a direct-acting ] relaxant and acts as a ] primarily in ], also known as the smooth muscle of the arterial bed. The molecular mechanism involves inhibition of inositol trisphosphate-induced Ca<sup>2+</sup> release from the sarcoplasmic reticulum in arterial smooth muscle cells.<ref name="BJP Allam">{{Cite journal| vauthors = Gurney AM, Allam M | title = Inhibition of calcium release from the sarcoplasmic reticulum of rabbit aorta by hydralazine | journal = British Journal of Pharmacology | volume = 114 | issue = 1 | pages = 238–244 | date = January 1995 | pmid = 7712024 | pmc = 1510175 | doi = 10.1111/j.1476-5381.1995.tb14931.x }}</ref><ref name="BJP Ellershaw">{{Cite journal| vauthors = Ellershaw DC, Gurney AM| title = Mechanisms of hydralazine induced vasodilation in rabbit aorta and pulmonary artery | journal = British Journal of Pharmacology | volume = 134 | issue = 3 | pages = 621–631 | date = October 2001 | pmid = 11588117 | pmc = 1572994 | doi = 10.1038/sj.bjp.0704302 }}</ref> By relaxing ], vasodilators act to decrease ], thereby lowering ] and decreasing afterload.<ref name=Harvey>{{cite book | vauthors = Harvey RA, Harvey PA, Mycek MJ | title = Lippincott's Illustrated Reviews: Pharmacology. | edition = 2nd | location = Philadelphia | publisher = Lippincott Williams & Wilkins | date = 2000 | page = 190 }}</ref> The exact ] of hydralazine is unknown, at least as of 1981.<ref name="Reece1981">{{cite journal | vauthors = Reece PA | title = Hydralazine and related compounds: chemistry, metabolism, and mode of action | journal = Med Res Rev | volume = 1 | issue = 1 | pages = 73–96 | date = 1981 | pmid = 7050561 | doi = 10.1002/med.2610010105 | url = }}</ref>
			Metabolic products include the ''N''-] derivative, ], and ], each of which may also contribute to reducing blood pressure.<ref>{{cite journal |title= Direct-acting vasodilators |vauthors= Cohn JN, McInnes GT, Shepherd AM |journal= Journal of Clinical Hypertension |year= 2011 |volume= 13 |issue= 9 |pages= 690–692 |doi= 10.1111/j.1751-7176.2011.00507.x |pmid= 21896152 |pmc= 8108999 }}</ref>
			==Chemistry==
			Hydralazine belongs to the ] class of drugs.<ref name=Schroeder>{{cite journal | vauthors = Schroeder NA | title = The effect of 1-hydrasinophthalasine in hypertension | journal = Circulation | volume = 5 | issue = 1 | pages = 28–37 | date = January 1952 | pmid = 14896450 | doi = 10.1161/01.cir.5.1.28 | doi-access = free }}</ref>
			==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,<ref>{{cite web|title=Hydralazine|url=https://www.drugbank.ca/drugs/DB01275|publisher=Drugbank|access-date=4 March 2017|url-status=live|archive-url=https://web.archive.org/web/20170304114322/https://www.drugbank.ca/drugs/DB01275|archive-date=4 March 2017}}</ref><ref>{{cite web|title=hydralazine|url=https://pubchem.ncbi.nlm.nih.gov/compound/hydralazine#section=Physical-Description|publisher=PubChem|access-date=4 March 2017|language=en|url-status=live|archive-url=https://web.archive.org/web/20170304115216/https://pubchem.ncbi.nlm.nih.gov/compound/hydralazine#section=Physical-Description|archive-date=4 March 2017}}</ref><ref>; see Example 1</ref> and the first scientific publications of its blood pressure-lowering activities appeared in 1950.<ref name=Wermuth/><ref name=Schroeder/><ref>{{cite journal | vauthors = Reubi FC | title = Renal hyperemia induced in man by a new phthalazine derivative | journal = Proceedings of the Society for Experimental Biology and Medicine | volume = 73 | issue = 1 | pages = 102–103 | date = January 1950 | pmid = 15402536 | doi = 10.3181/00379727-73-17591 | s2cid = 32603042 }}</ref> It was approved by the FDA in 1953.<ref>{{cite web|title=New Drug Application (NDA) 008303 Company: NOVARTIS Drug Name(s): Apresoline|url=http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=008303|publisher=FDA|access-date=26 February 2017|url-status=live|archive-url=https://web.archive.org/web/20170226135437/http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=008303|archive-date=26 February 2017}}</ref>
			It was one of the first antihypertensive medications that could be taken by mouth.<ref name=Cochrane2011rev/>
			==Research==
			Hydralazine has also been studied as a treatment for ] in its capacity as a ] inhibitor.<ref>{{cite journal | vauthors = Singh V, Sharma P, Capalash N | title = DNA methyltransferase-1 inhibitors as epigenetic therapy for cancer | journal = Current Cancer Drug Targets | volume = 13 | issue = 4 | pages = 379–99 | date = May 2013 | pmid = 23517596 | doi = 10.2174/15680096113139990077 }}</ref>
	== References ==		== References ==
	{{Reflist|2}}		{{Reflist}}
	{{Nonsympatholytic vasodilatory antihypertensives}}		{{Nonsympatholytic vasodilatory antihypertensives}}
			{{Monoamine metabolism modulators}}
	{{Hydrazines}}		{{Hydrazines}}
			{{Portal bar|Medicine}}
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	{{antihypertensive-stub}}
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