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Revision as of 14:09, 5 December 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,071 edits Saving copy of the {{drugbox}} taken from revid 462521453 of page Prazosin for the Chem/Drugbox validation project (updated: 'DrugBank').		Latest revision as of 19:53, 30 December 2024 edit Alfa-ketosav (talk | contribs)Extended confirmed users2,310 edits wanted only to remove the double close
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			{{Short description|Antihypertensive drug}}
	{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
			{{Use dmy dates|date=January 2020}}
	{{Drugbox		{{Drugbox
	| Verifiedfields = changed		| Watchedfields = changed
	| verifiedrevid = 415358823		| verifiedrevid = 464213473
			| image = ]
	| IUPAC_name = 2--6,7-dimethoxyquinazolin-4-amine
	| image = Prazosin.svg		| width = 250
			| image2 = ]
	| width = 300
			| width2 = 250
	<!--Clinical data-->		<!-- Clinical data -->
	| tradename = Minipress		| pronounce =
			| tradename = Minipress, others
	| Drugs.com = {{drugs.com|monograph|prazosin-hydrochloride}}		| Drugs.com = {{drugs.com|monograph|prazosin-hydrochloride}}
	| MedlinePlus = a682245		| MedlinePlus = a682245
			| DailyMedID = Prazosin
	| pregnancy_category =
	| legal_UK = POM		| pregnancy_AU = B2
			| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Prazosin (Minipress) Use During Pregnancy | website=Drugs.com | date=26 November 2019 | url=https://www.drugs.com/pregnancy/prazosin.html | access-date=30 January 2020}}</ref>
	| routes_of_administration = Oral
			| pregnancy_category=
			| routes_of_administration = ]
			| class = ]
			| ATC_prefix = C02
			| ATC_suffix = CA01
			| ATC_supplemental =
			<!-- Legal status -->
			| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
			| legal_AU_comment =
			| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
			| legal_BR_comment =
			| legal_CA = Rx-only
			| legal_CA_comment =
			| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
			| legal_DE_comment =
			| legal_NZ = <!-- Class A, B, C -->
			| legal_NZ_comment =
			| legal_UK = POM
			| legal_UK_comment = <ref>{{cite web | title=Hypovase Tablets 0.5mg - Summary of Product Characteristics (SmPC) | website=(emc) | date=26 April 2021 | url=https://www.medicines.org.uk/emc/product/1068 | access-date=5 February 2023}}</ref>
			| legal_US = Rx-only
			| legal_US_comment = <ref name="Minipress FDA label">{{cite web | title=Minipress- prazosin hydrochloride capsule | website=DailyMed | date=19 July 2021 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=36c4da56-502e-4da1-acf7-8e81ee453dcc | access-date=5 February 2023}}</ref>
			| legal_EU =
			| legal_EU_comment =
			| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
			| legal_UN_comment =
			| legal_status = Rx-only
	<!--Pharmacokinetic data-->		<!-- Pharmacokinetic data -->
	| bioavailability = ~60%		| bioavailability = ~60%
	| protein_bound = 97%		| protein_bound = 97%<ref name=ppa/>
	| metabolism =		| metabolism =
			| metabolites =
	| elimination_half-life = 2–3 hours
			| onset = 30–90&nbsp;minutes<ref name="pmid761333">{{cite journal | vauthors = Packer M, Meller J, Gorlin R, Herman MV | title = Hemodynamic and clinical tachyphylaxis to prazosin-mediated afterload reduction in severe chronic congestive heart failure | journal = Circulation | volume = 59 | issue = 3 | pages = 531–539 | date = March 1979 | pmid = 761333 | doi = 10.1161/01.cir.59.3.531 | doi-access = free | title-link = doi }}</ref>
			| elimination_half-life = 2–3 hours<ref name=ppa/>
			| duration_of_action = 10–24&nbsp;hours<ref name=ppa>{{cite web|title=Prazosin|work=drugs.com|url=https://www.drugs.com/ppa/prazosin.html|access-date=15 March 2020}}</ref>
			| excretion =
	<!--Identifiers-->		<!-- Identifiers -->
	| CASNo_Ref = {{cascite|correct|CAS}}
	| CAS_number_Ref = {{cascite|correct|??}}		| CAS_number_Ref = {{cascite|correct|??}}
	| CAS_number = 19216-56-9		| CAS_number = 19216-56-9
	| ATC_prefix = C02		| CAS_supplemental =
	| ATC_suffix = CA01
	| ATC_supplemental =
	| PubChem = 4893		| PubChem = 4893
	| IUPHAR_ligand = 503		| IUPHAR_ligand = 503
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	| KEGG_Ref = {{keggcite|correct|kegg}}		| KEGG_Ref = {{keggcite|correct|kegg}}
	| KEGG = D08411		| KEGG = D08411
	| ChEBI_Ref = {{ebicite|changed|EBI}}		| ChEBI_Ref = {{ebicite|correct|EBI}}
	| ChEBI = 8364		| ChEBI = 8364
	| ChEMBL_Ref = {{ebicite|correct|EBI}}		| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 2		| ChEMBL = 2
			| NIAID_ChemDB =
			| PDB_ligand =
			| synonyms =
	<!--Chemical data-->		<!-- Chemical and physical data -->
			| IUPAC_name = (2-furyl)methanone
	| C=19 | H=21 | N=5 | O=4
			| C=19 | H=21 | N=5 | O=4
	| molecular_weight = 383.401 g/mol
	| smiles = O=C(N3CCN(c2nc1cc(OC)c(OC)cc1c(n2)N)CC3)c4occc4		| SMILES = O=C(N3CCN(c2nc1cc(OC)c(OC)cc1c(n2)N)CC3)c4occc4
	| InChI = 1/C19H21N5O4/c1-26-15-10-12-13(11-16(15)27-2)21-19(22-17(12)20)24-7-5-23(6-8-24)18(25)14-4-3-9-28-14/h3-4,9-11H,5-8H2,1-2H3,(H2,20,21,22)
	| InChIKey = IENZQIKPVFGBNW-UHFFFAOYAU
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C19H21N5O4/c1-26-15-10-12-13(11-16(15)27-2)21-19(22-17(12)20)24-7-5-23(6-8-24)18(25)14-4-3-9-28-14/h3-4,9-11H,5-8H2,1-2H3,(H2,20,21,22)		| StdInChI = 1S/C19H21N5O4/c1-26-15-10-12-13(11-16(15)27-2)21-19(22-17(12)20)24-7-5-23(6-8-24)18(25)14-4-3-9-28-14/h3-4,9-11H,5-8H2,1-2H3,(H2,20,21,22)
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	| StdInChIKey = IENZQIKPVFGBNW-UHFFFAOYSA-N		| StdInChIKey = IENZQIKPVFGBNW-UHFFFAOYSA-N
	}}		}}
			<!-- Definition and medical uses -->
			'''Prazosin''', sold under the brand name '''Minipress''' among others, is a ] used to treat ], symptoms of an ], and ]s related to ] (PTSD).<ref name=AHFS2019/> It is an ].<ref name=AHFS2019/> It is a less preferred treatment of high blood pressure.<ref name=AHFS2019/> Other uses may include ] and ].<ref name=BNF76/> It is taken ].<ref name=AHFS2019>{{cite web |title=Prazosin Hydrochloride Monograph for Professionals |url=https://www.drugs.com/monograph/prazosin-hydrochloride.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=18 March 2019 }}</ref>
			<!-- Side effect and mechanism -->
			Common ]s include ], ], ], and ]s.<ref name=AHFS2019/> Serious side effects may include ] and ].<ref name=AHFS2019/><ref name=BNF76>{{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=766|edition=76}}</ref> Prazosin is a ] ] of the ]s.<ref name=AHFS2019/> It works to decrease blood pressure by dilating ] and helps with an enlarged prostate by relaxing the outflow of the ].<ref name=AHFS2019/> How it works in PTSD is not entirely clear.<ref name=AHFS2019/>
			<!-- Society and culture -->
			Prazosin was patented in 1965 and came into medical use in 1974.<ref>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=455 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA455 }}</ref> It is available as a ].<ref name=AHFS2019/> In 2021, it was the 183rd most commonly prescribed medication in the United States, with more than 2{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2021 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=14 January 2024 | archive-date=15 January 2024 | archive-url=https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Prazosin - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Prazosin | access-date = 14 January 2024}}</ref>
			==Medical uses==
			Prazosin is active after taken by mouth and has a minimal effect on cardiac function due to its ] ]. When prazosin is started, however, heart rate and contractility can increase in order to maintain the pre-treatment blood pressures because the body has reached ] at its abnormally high blood pressure. The blood pressure lowering effect becomes apparent when prazosin is taken for longer periods of time. The heart rate and contractility go back down over time and blood pressure decreases.
			The ] characteristics of prazosin make it a second-line choice for the treatment of high blood pressure.<ref name=pharmnemonics>{{Cite book | vauthors = Shen H | title=Illustrated Pharmacology Memory Cards: PharMnemonics | year=2008 | publisher=Minireview | isbn=978-1-59541-101-3 | page=13}}</ref>
			Prazosin is also useful in treating urinary hesitancy associated with ], blocking α<sub>1</sub>-adrenergic receptors, which control constriction of both the ] and ]. Although not a first-line choice for either hypertension or benign prostatic hyperplasia, it is a choice for people who present with both problems concomitantly.<ref name=pharmnemonics />
			During its use for urinary hesitancy in military veterans in the 1990s, Murray A. Raskind and colleagues discovered that prazosin appeared to be effective in reducing ]s. Subsequent reviews indicate prazosin is effective in improving sleep quality and treating nightmares related to ] (PTSD).<ref>{{cite journal | vauthors = Zhang Y, Ren R, Sanford LD, Yang L, Ni Y, Zhou J, Zhang J, Wing YK, Shi J, Lu L, Tang X | display-authors = 6 | title = The effects of prazosin on sleep disturbances in post-traumatic stress disorder: a systematic review and meta-analysis | journal = Sleep Medicine | volume = 67 | pages = 225–231 | date = March 2020 | pmid = 31972510 | pmc = 6986268 | doi = 10.1016/j.sleep.2019.06.010 }}</ref><ref>{{cite journal | vauthors = Reist C, Streja E, Tang CC, Shapiro B, Mintz J, Hollifield M | title = Prazosin for treatment of post-traumatic stress disorder: a systematic review and meta-analysis | journal = CNS Spectrums | volume = 26 | issue = 4 | pages = 338–344 | date = August 2021 | pmid = 32362287 | doi = 10.1017/S1092852920001121 | s2cid = 218492349 }}</ref>
			Prazosin is used ] in the treatment of ] for its ] effects.<ref name="pmid26600112">{{cite journal | vauthors = Krystal AD | title = New Developments in Insomnia Medications of Relevance to Mental Health Disorders | journal = The Psychiatric Clinics of North America | volume = 38 | issue = 4 | pages = 843–860 | date = December 2015 | pmid = 26600112 | pmc = 5972036 | doi = 10.1016/j.psc.2015.08.001 }}</ref><ref name="pmid29487083">{{cite journal |author3-link=Gabriella Gobbi |vauthors=Atkin T, Comai S, Gobbi G |date=April 2018 |title=Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery |journal=Pharmacological Reviews |volume=70 |issue=2 |pages=197–245 |doi=10.1124/pr.117.014381 |pmid=29487083 |s2cid=3578916 |doi-access=free |title-link=doi}}</ref> Prazosin is an ] at α<sub>1</sub>-adrenergic receptors;<ref name="pmid29487083" /> these receptors are expressed on ] that ] neurons ] onto in the brain. Some of the noradrenergic pathways in the ] form part of the ], which promotes arousal when stimulated.<ref name="ARAS">{{cite journal | vauthors = Iwańczuk W, Guźniczak P | title = Neurophysiological foundations of sleep, arousal, awareness and consciousness phenomena. Part 1 | journal = Anaesthesiol Intensive Ther | volume = 47 | issue = 2 | pages = 162–167 | date = 2015 | pmid = 25940332 | doi = 10.5603/AIT.2015.0015| doi-access = }}</ref><ref name="Nestler chapter 13">{{Cite book |title=Molecular Neuropharmacology: A Foundation for Clinical Neuroscience |vauthors=Malenka RC, Nestler EJ, Hyman SE, Holtzman DM |publisher=McGraw-Hill Medical |year=2015 |isbn=9780071827706 |edition=3rd |pages=521 |chapter=Chapter 13: Sleep and Arousal}}</ref> Prazosin inhibits the output neurons of the noradrenergic pathways in that system, in turn causing sedation.<ref name="pmid29487083" />
			The drug is usually recommended for severe stings from the ].<ref name="bawaskar&bawaskar2008">{{cite journal | vauthors = Bawaskar HS, Bawaskar PH |title=Scorpion sting: A study of the clinical manifestations and treatment regimes |journal=Current Science |date=2008 |volume=95 |issue=9 |pages=1337–1341 |jstor=24103245 }}</ref><ref name=bawaskar&bawaskar2007>{{cite journal | vauthors = Bawaskar HS, Bawaskar PH | title = Utility of scorpion antivenin vs prazosin in the management of severe Mesobuthus tamulus (Indian red scorpion) envenoming at rural setting | journal = The Journal of the Association of Physicians of India | volume = 55 | pages = 14–21 | date = January 2007 | pmid = 17444339 | url = https://japi.org/u294e484/utility-of-scorpion-antivenin-vs-prazosin-in-the-management-of-severe-mesobuthus-tamulus-indian-red-scorpion-envenoming-at-rural-setting | citeseerx = 10.1.1.1038.366 }}</ref><ref>{{cite journal | vauthors = Pandi K, Krishnamurthy S, Srinivasaraghavan R, Mahadevan S | title = Efficacy of scorpion antivenom plus prazosin versus prazosin alone for Mesobuthus tamulus scorpion sting envenomation in children: a randomised controlled trial | journal = Archives of Disease in Childhood | volume = 99 | issue = 6 | pages = 575–580 | date = June 2014 | pmid = 24550184 | doi = 10.1136/archdischild-2013-305483 | s2cid = 37215729 }}</ref>
			==Adverse effects==
			Common (4–10% frequency) side effects of prazosin include ], ], ], ], ], ], and ].<ref name="Minipress FDA label" /> Less frequent (1–4%) side effects include ], ], ], ], ], ], ], ], ], ], ], and ].<ref name="Minipress FDA label" /> A very rare side effect of prazosin is ].<ref name="Minipress FDA label" /><ref name="pmid519276">{{cite journal | vauthors = Bhalla AK, Hoffbrand BI, Phatak PS, Reuben SR | title = Prazosin and priapism | journal = British Medical Journal | volume = 2 | issue = 6197 | pages = 1039 | date = October 1979 | pmid = 519276 | pmc = 1596841 | doi = 10.1136/bmj.2.6197.1039 }}</ref> One phenomenon associated with prazosin is known as the "]", in which the side effects of the drug {{emdash}} specifically orthostatic hypotension, dizziness, and drowsiness {{emdash}} are especially pronounced in the first dose.<ref name="Minipress FDA label" />
			Orthostatic hypotension and syncope are associated with the body's poor ability to control blood pressure without active α-adrenergic receptors. The nasal congestion is exacerbated by changing body positions, because α<sub>1</sub>-adrenergic receptors also control nasal vascular blood flow and alpha blockers inhibit this, in the same way that alpha-adrenergic agonists have the opposite effect of being a decongestant.<ref>{{cite journal | vauthors = Riechelmann H, Krause W | title = Autonomic regulation of nasal vessels during changes in body position | journal = European Archives of Oto-Rhino-Laryngology | volume = 251 | issue = 4 | pages = 210–213 | date = 1994-01-01 | pmid = 7917253 | doi = 10.1007/BF00628425 | s2cid = 24405406 }}</ref><ref>{{cite journal | vauthors = Johnson DA, Hricik JG | title = The pharmacology of alpha-adrenergic decongestants | journal = Pharmacotherapy | volume = 13 | issue = 6 Pt 2 | date = 1993 | pages = 110S-115S; discussion 143S-146S | pmid = 7507588 | doi = 10.1002/j.1875-9114.1993.tb02779.x | s2cid = 70981730 | url=https://accpjournals.onlinelibrary.wiley.com/doi/10.1002/j.1875-9114.1993.tb02779.x }}</ref>
			==Pharmacology==
			===Pharmacodynamics===
			Prazosin is an ] that acts as a ] ] at ]s, including of the ], ], and ]s.<ref name="Prazosin biological activity">{{cite web|title=Prazosin: Biological activity|url=http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=503|website=IUPHAR|publisher=International Union of Basic and Clinical Pharmacology|access-date=3 June 2016}}</ref> It binds to these receptors with ] (K<sub>i</sub>) values of 0.13 to 1.0&nbsp;nM for the α<sub>1Α</sub>-adrenergic receptor, 0.06 to 0.62&nbsp;nM for the α<sub>1B</sub>-adrenergic receptor, and 0.06 to 0.38&nbsp;nM for the α<sub>1D</sub>-adrenergic receptor.<ref name="DrugBank">{{Cite web|url=https://go.drugbank.com/drugs/DB00457|title = Prazosin | work = DrugBank }}</ref><ref name="IUPHAR">{{Cite web|url=https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=503|title = Prazosin Ligand page | work = IUPHAR/BPS Guide to PHARMACOLOGY }}</ref> It has much lower affinity for the ]s (K<sub>i</sub> = 210–5,012&nbsp;nM for the ], 13–398&nbsp;nM for the ], and 10–200&nbsp;nM for the ]).<ref name="DrugBank" /><ref name="IUPHAR" /> The α<sub>1</sub>-adrenergic receptors are found in ], where they are responsible for the ] action of ].<ref name="Prazosin clinical data">{{cite web|title=Prazosin: Clinical data|url=http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=clinical&ligandId=503|website=IUPHAR|publisher=International Union of Basic and Clinical Pharmacology|access-date=3 June 2016}}</ref> They are also found throughout the ].<ref name="pmid9285356">{{cite journal | vauthors = Day HE, Campeau S, Watson SJ, Akil H | title = Distribution of alpha 1a-, alpha 1b- and alpha 1d-adrenergic receptor mRNA in the rat brain and spinal cord | journal = Journal of Chemical Neuroanatomy | volume = 13 | issue = 2 | pages = 115–139 | date = July 1997 | pmid = 9285356 | doi = 10.1016/S0891-0618(97)00042-2 | s2cid = 28007564 }}</ref> α<sub>1</sub>-Adrenergic receptors have additionally been found on ]s, where ] binding can stimulate and enhance ] production.<ref>{{cite journal | vauthors = Heijnen CJ, Rouppe van der Voort C, Wulffraat N, van der Net J, Kuis W, Kavelaars A | title = Functional alpha 1-adrenergic receptors on leukocytes of patients with polyarticular juvenile rheumatoid arthritis | journal = Journal of Neuroimmunology | volume = 71 | issue = 1–2 | pages = 223–226 | date = December 1996 | pmid = 8982123 | doi = 10.1016/s0165-5728(96)00125-7 | s2cid = 53151786 }}</ref><ref name="Konig"/>
			===Pharmacokinetics===
			Prazosin has an ] of 30 to 90&nbsp;minutes,<ref name="pmid761333" /> the ] of prazosin is 2 to 3&nbsp;hours,<ref name=ppa /> and its ] is 10 to 24&nbsp;hours.<ref name=ppa />
			==Research==
			Prazosin has been said to be the only selective α<sub>1</sub>-adrenergic receptor antagonist which has been used in the treatment of insomnia to any significant degree.<ref name="pmid26600112" /> It is used at doses of 1 to 12&nbsp;mg for this purpose.<ref name="pmid26600112" /> The combination of prazosin and the ] ] may produce greater sedative effects than either of them alone.<ref name="pmid29487083" />
			Prazosin has been shown to prevent death in animal models of ].<ref>{{cite journal | vauthors = Staedtke V, Bai RY, Kim K, Darvas M, Davila ML, Riggins GJ, Rothman PB, Papadopoulos N, Kinzler KW, Vogelstein B, Zhou S | display-authors = 6 | title = Disruption of a self-amplifying catecholamine loop reduces cytokine release syndrome | journal = Nature | volume = 564 | issue = 7735 | pages = 273–277 | date = December 2018 | pmid = 30542164 | pmc = 6512810 | doi = 10.1038/s41586-018-0774-y | bibcode = 2018Natur.564..273S }}</ref> As a repurposed drug, prazosin is being investigated for the prevention of cytokine storm syndrome and complications of ] where it is thought to decrease ] dysregulation.<ref>{{Cite web|title=Preventing 'Cytokine Storm' May Ease Severe COVID-19 Symptoms|url=https://www.hhmi.org/news/preventing-cytokine-storm-may-ease-severe-covid-19-symptoms|website=HHMI.org|access-date=2020-05-24}}</ref><ref name="Konig">{{cite journal | vauthors = Konig MF, Powell M, Staedtke V, Bai RY, Thomas DL, Fischer N, Huq S, Khalafallah AM, Koenecke A, Xiong R, Mensh B, Papadopoulos N, Kinzler KW, Vogelstein B, Vogelstein JT, Athey S, Zhou S, Bettegowda C | display-authors = 6 | title = Preventing cytokine storm syndrome in COVID-19 using α-1 adrenergic receptor antagonists | journal = The Journal of Clinical Investigation | volume = 130 | issue = 7 | pages = 3345–3347 | date = July 2020 | pmid = 32352407 | pmc = 7324164 | doi = 10.1172/JCI139642 | doi-access = free | title-link = doi | author-link9 = Allison Koenecke }}</ref><ref>{{ClinicalTrialsGov|NCT04365257|Prazosin to Prevent COVID-19 (PREVENT-COVID Trial) (PREVENT)}}</ref>
			{{clear}}
			== References ==
			{{Reflist}}
			{{Antihypertensives and diuretics}}
			{{Anxiolytics}}
			{{Peripheral vasodilators}}
			{{Adrenergic receptor modulators}}
			{{Portal bar | Medicine}}
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