Hydroxyzine: Difference between revisions
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| image2 = Hydroxyzine-3d-sticks.png | | image2 = Hydroxyzine-3d-sticks.png | ||
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| alt2 = <!--Clinical data--> | | alt2 = <!--Clinical data--> | ||
| pronounce = {{IPAc-en|h|aɪ|ˈ|d|r|ɒ|k|s|ᵻ|z|iː|n}} | | pronounce = {{IPAc-en|h|aɪ|ˈ|d|r|ɒ|k|s|ᵻ|z|iː|n}} | ||
| tradename = Atarax,<ref>{{cite web | title=Atarax: FDA-Approved Drugs | publisher=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=010392 | access-date=25 March 2023}}</ref> Vistaril,<ref>{{cite web|title=Vistaril: FDA-Approved Drugs|url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=011459|archive-url=https://web.archive.org/web/20170501033938/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=011459 | | tradename = Atarax,<ref>{{cite web | title=Atarax: FDA-Approved Drugs | publisher=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=010392 | access-date=25 March 2023}}</ref> Vistaril,<ref>{{cite web|title=Vistaril: FDA-Approved Drugs|url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=011459|archive-url=https://web.archive.org/web/20170501033938/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=011459|archive-date=1 May 2017|access-date=5 August 2020|publisher=U.S. [[Food and Drug Administration]] (FDA) }}</ref> others | ||
| Drugs.com = {{drugs.com|monograph|hydroxyzine-hydrochloride}} | | Drugs.com = {{drugs.com|monograph|hydroxyzine-hydrochloride}} | ||
| MedlinePlus = a682866 | | MedlinePlus = a682866 | ||
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| pregnancy_AU_comment = | | pregnancy_AU_comment = | ||
| pregnancy_category = | | pregnancy_category = | ||
| dependency_liability = | | dependency_liability = Very Low <ref> https://carolinacenterforrecovery.com/addiction-blog/what-is-the-difference-between-hydroxyzine-and-xanax/#:~:text=Addiction-,Medical%20experts%20believe%20hydroxyzine,psychological%20dependence%20on%20hydroxyzine,-.%20They </ref><ref> https://addictionwellness.com/hydroxyzine-addiction-warning-signs/ </ref> | ||
| addiction_liability = None-Very Low <ref> https://carolinacenterforrecovery.com/addiction-blog/what-is-the-difference-between-hydroxyzine-and-xanax/#:~:text=Addiction-,Medical%20experts%20believe%20hydroxyzine,psychological%20dependence%20on%20hydroxyzine,-.%20They </ref><ref> https://addictionwellness.com/hydroxyzine-addiction-warning-signs/ </ref> | |||
| routes_of_administration = [[Oral administration|By mouth]], [[intramuscular injection|intramuscular]] | | routes_of_administration = [[Oral administration|By mouth]], [[intramuscular injection|intramuscular]] | ||
| class = [[First-generation antihistamine]]<ref name=Chem2020/> | | class = [[First-generation antihistamine]]<ref name=Chem2020/> | ||
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<!-- Side effects and mechanism --> | <!-- Side effects and mechanism --> | ||
Hydroxyzine works by blocking the effects of [[histamine]].<ref name="BNF74">{{cite book |title=British national formulary : BNF 74 |date=2017 |publisher=British Medical Association |isbn=978- | Hydroxyzine works by blocking the effects of [[histamine]].<ref name="BNF74">{{cite book |title=British national formulary: BNF 74 |date=2017 |publisher=British Medical Association |isbn=978-0-85711-298-9 |edition=74 |page=X}}</ref> It is a [[first-generation antihistamine]] in the [[piperazine]] family of chemicals.<ref name="AHSF2018" /><ref name="Chem2020">{{cite web |title=Hydroxyzine |url=https://pubchem.ncbi.nlm.nih.gov/compound/Hydroxyzine |access-date=4 March 2020 |publisher=[[United States National Library of Medicine]] (NLM)}}</ref> Common side effects include [[sleepiness]], [[headache]], and [[dry mouth]].<ref name=AHSF2018/><ref name=BNF74/> Serious side effects may include [[QT prolongation]].<ref name=BNF74/> It is unclear if use during pregnancy or breastfeeding is safe.<ref name=AHSF2018/> | ||
<!-- History and culture --> | <!-- History and culture --> | ||
It was first [[chemical synthesis|made]] by [[Union Chimique Belge]] in 1956 and was approved for sale by [[Pfizer]] in the United States later that year.<ref name=AHSF2018/><ref name=Shor2009>{{cite book|url=https://books.google.com/books?id=8VaYF8pIPxgC&q=hydroxyzine%201956&pg=PR13|title=Before Prozac: the troubled history of mood disorders in psychiatry|vauthors=Shorter E|publisher=Oxford University Press|year=2009|isbn= | It was first [[chemical synthesis|made]] by [[Union Chimique Belge]] in 1956 and was approved for sale by [[Pfizer]] in the United States later that year.<ref name=AHSF2018/><ref name=Shor2009>{{cite book|url=https://books.google.com/books?id=8VaYF8pIPxgC&q=hydroxyzine%201956&pg=PR13|title=Before Prozac: the troubled history of mood disorders in psychiatry|vauthors=Shorter E|publisher=Oxford University Press|year=2009|isbn=978-0-19-536874-1|location=Oxford [Oxfordshire]}}</ref> In 2023, it was the 39th most commonly prescribed medication in the United States, with more than 15{{nbsp}}million prescriptions.<ref name="Top300Drugs">{{cite web | title=Top 300 of 2023 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=12 August 2025 | archive-date=12 August 2025 | archive-url=https://web.archive.org/web/20250812130026/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Hydroxyzine Drug Usage Statistics, United States, 2013 - 2023 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Hydroxyzine | access-date = 18 August 2025 }}</ref> | ||
==Medical uses== | ==Medical uses== | ||
{{Primary source|date=December 2023}}Hydroxyzine is used in the treatment of [[itchiness]], [[anxiety]], and [[nausea]] due to [[motion sickness]].<ref name=AHSF2018/> | {{Primary source|date=December 2023}}Hydroxyzine is used in the treatment of [[itchiness]], [[anxiety]], and [[nausea]] due to [[motion sickness]].<ref name=AHSF2018/> | ||
A [[systematic review]] concluded that hydroxyzine outperforms [[placebo]] in treating [[generalized anxiety disorder]]. Insufficient data were available to compare the drug with [[benzodiazepines]] and [[buspirone]].<ref>{{cite journal | vauthors = Guaiana G, Barbui C, Cipriani A | title = Hydroxyzine for generalised anxiety disorder | journal = The Cochrane Database of Systematic Reviews | issue = 12 | | A [[systematic review]] concluded that hydroxyzine outperforms [[placebo]] in treating [[generalized anxiety disorder]]. Insufficient data were available to compare the drug with [[benzodiazepines]] and [[buspirone]].<ref>{{cite journal | vauthors = Guaiana G, Barbui C, Cipriani A | title = Hydroxyzine for generalised anxiety disorder | journal = The Cochrane Database of Systematic Reviews | issue = 12 | article-number = CD006815 | date = December 2010 | pmid = 21154375 | doi = 10.1002/14651858.CD006815.pub2 }}</ref> | ||
Hydroxyzine can also be used for the treatment of [[allergy|allergic conditions]], such as chronic [[urticaria]], [[atopic dermatitis|atopic]] or [[contact dermatitis|contact dermatoses]], and [[histamine]]-mediated [[pruritus]].{{medcn|date=March 2023}} These have also been confirmed in both recent and past studies to have no adverse effects on the liver, blood, nervous system, or urinary tract.<ref name="fda_vistaril">United States Food & Drug Administration (2004), p. 1</ref>{{Better source|date=March 2023}} | Hydroxyzine can also be used for the treatment of [[allergy|allergic conditions]], such as chronic [[urticaria]], [[atopic dermatitis|atopic]] or [[contact dermatitis|contact dermatoses]], and [[histamine]]-mediated [[pruritus]].{{medcn|date=March 2023}} These have also been confirmed in both recent and past studies to have no adverse effects on the liver, blood, nervous system, or urinary tract.<ref name="fda_vistaril">United States Food & Drug Administration (2004), p. 1</ref>{{Better source|date=March 2023}} | ||
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Use of hydroxyzine for [[premedication]] as a [[sedative]] has no effects on [[tropane alkaloid]]s, such as [[atropine]], but may, following general anesthesia, potentiate [[pethidine|meperidine]] and [[barbiturate]]s, and use in pre-anesthetic [[adjunctive therapy]] should be modified depending upon the state of the individual.<ref name="fda_vistaril" /> | Use of hydroxyzine for [[premedication]] as a [[sedative]] has no effects on [[tropane alkaloid]]s, such as [[atropine]], but may, following general anesthesia, potentiate [[pethidine|meperidine]] and [[barbiturate]]s, and use in pre-anesthetic [[adjunctive therapy]] should be modified depending upon the state of the individual.<ref name="fda_vistaril" /> | ||
Doses of hydroxyzine hydrochloride used for sleep range from 25 to 100 mg.<ref name="pmid27486547">{{cite journal | vauthors = Smith E, Narang P, Enja M, Lippmann S | title = Pharmacotherapy for Insomnia in Primary Care | journal = The Primary Care Companion for CNS Disorders | volume = 18 | issue = 2 | date = 2016 | pmid = 27486547 | pmc = 4956432 | doi = 10.4088/PCC.16br01930 }}</ref><ref name="pmid28671376">{{cite journal | vauthors = Matheson E, Hainer BL | title = Insomnia: Pharmacologic Therapy | journal = American Family Physician | volume = 96 | issue = 1 | pages = 29–35 | date = July 2017 | pmid = 28671376 | doi = }}</ref><ref name="pmid12701339">{{cite journal | vauthors = Lippmann S, Yusufzie K, Nawbary MW, Voronovitch L, Matsenko O | title = Problems with sleep: what should the doctor do? | journal = Comprehensive Therapy | volume = 29 | issue = 1 | pages = 18–27 | date = 2003 | pmid = 12701339 | doi = 10.1007/s12019-003-0003-x | s2cid = 1508856 }}</ref> As with other antihistamine sleep aids, hydroxyzine is usually only prescribed for short term or "as-needed" use since [[Drug tolerance|tolerance]] to the [[central nervous system]] (CNS) effects of hydroxyzine can develop in as little as a few days.<ref name="tolerance">{{cite journal | vauthors = Levander S, Ståhle-Bäckdahl M, Hägermark O | title = Peripheral antihistamine and central sedative effects of single and continuous oral doses of cetirizine and hydroxyzine | journal = European Journal of Clinical Pharmacology | volume = 41 | issue = 5 | pages = 435–439 | date = 1 September 1991 | pmid = 1684750 | doi = 10.1007/BF00626365 | s2cid = 25249362 }}</ref>{{Primary source inline|date=December 2023}} A major systematic review and [[network meta-analysis]] of medications for the treatment of [[insomnia]] published in 2022 found little evidence to inform the use of hydroxyzine for insomnia.<ref name="pmid35843245">{{cite journal | vauthors = De Crescenzo F, D'Alò GL, Ostinelli EG, Ciabattini M, Di Franco V, Watanabe N, Kurtulmus A, Tomlinson A, Mitrova Z, Foti F, Del Giovane C, Quested DJ, Cowen PJ, Barbui C, Amato L, Efthimiou O, Cipriani A | title = Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis | journal = Lancet | volume = 400 | issue = 10347 | pages = 170–184 | date = July 2022 | pmid = 35843245 | doi = 10.1016/S0140-6736(22)00878-9 | s2cid = 250536370 | url = | doi-access = free | hdl = 11380/1288245 | hdl-access = free }}</ref> A 2023 meta-review concludes that hydroxyzine is effective for inducing [[sleep onset]] but less effective for maintaining sleep for eight hours.<ref>{{cite journal | vauthors = Burgazli CR, Rana KB, Brown JN, Tillman F | title = Efficacy and safety of hydroxyzine for sleep in adults: Systematic review | journal = Human Psychopharmacology | volume = 38 | issue = 2 | | Doses of hydroxyzine hydrochloride used for sleep range from 25 to 100 mg.<ref name="pmid27486547">{{cite journal | vauthors = Smith E, Narang P, Enja M, Lippmann S | title = Pharmacotherapy for Insomnia in Primary Care | journal = The Primary Care Companion for CNS Disorders | volume = 18 | issue = 2 | date = 2016 | pmid = 27486547 | pmc = 4956432 | doi = 10.4088/PCC.16br01930 }}</ref><ref name="pmid28671376">{{cite journal | vauthors = Matheson E, Hainer BL | title = Insomnia: Pharmacologic Therapy | journal = American Family Physician | volume = 96 | issue = 1 | pages = 29–35 | date = July 2017 | pmid = 28671376 | doi = }}</ref><ref name="pmid12701339">{{cite journal | vauthors = Lippmann S, Yusufzie K, Nawbary MW, Voronovitch L, Matsenko O | title = Problems with sleep: what should the doctor do? | journal = Comprehensive Therapy | volume = 29 | issue = 1 | pages = 18–27 | date = 2003 | pmid = 12701339 | doi = 10.1007/s12019-003-0003-x | s2cid = 1508856 }}</ref> As with other antihistamine sleep aids, hydroxyzine is usually only prescribed for short term or "as-needed" use since [[Drug tolerance|tolerance]] to the [[central nervous system]] (CNS) effects of hydroxyzine can develop in as little as a few days.<ref name="tolerance">{{cite journal | vauthors = Levander S, Ståhle-Bäckdahl M, Hägermark O | title = Peripheral antihistamine and central sedative effects of single and continuous oral doses of cetirizine and hydroxyzine | journal = European Journal of Clinical Pharmacology | volume = 41 | issue = 5 | pages = 435–439 | date = 1 September 1991 | pmid = 1684750 | doi = 10.1007/BF00626365 | s2cid = 25249362 }}</ref>{{Primary source inline|date=December 2023}} A major systematic review and [[network meta-analysis]] of medications for the treatment of [[insomnia]] published in 2022 found little evidence to inform the use of hydroxyzine for insomnia.<ref name="pmid35843245">{{cite journal | vauthors = De Crescenzo F, D'Alò GL, Ostinelli EG, Ciabattini M, Di Franco V, Watanabe N, Kurtulmus A, Tomlinson A, Mitrova Z, Foti F, Del Giovane C, Quested DJ, Cowen PJ, Barbui C, Amato L, Efthimiou O, Cipriani A | title = Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis | journal = Lancet | volume = 400 | issue = 10347 | pages = 170–184 | date = July 2022 | pmid = 35843245 | doi = 10.1016/S0140-6736(22)00878-9 | s2cid = 250536370 | url = | doi-access = free | hdl = 11380/1288245 | hdl-access = free }}</ref> A 2023 meta-review concludes that hydroxyzine is effective for inducing [[sleep onset]] but less effective for maintaining sleep for eight hours.<ref>{{cite journal | vauthors = Burgazli CR, Rana KB, Brown JN, Tillman F | title = Efficacy and safety of hydroxyzine for sleep in adults: Systematic review | journal = Human Psychopharmacology | volume = 38 | issue = 2 | article-number = e2864 | date = March 2023 | pmid = 36843057 | doi = 10.1002/hup.2864 | doi-access = free | title-link = doi }}</ref> | ||
==Contraindications== | ==Contraindications== | ||
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Other contraindications include the administration of hydroxyzine alongside [[depressant]]s and other compounds that affect the [[central nervous system]];<ref name="fda_vistaril_2" /> if necessary, it should only be administered concomitantly in small doses.<ref name="fda_vistaril_2" /> If administered in small doses with other substances, as mentioned, then patients should refrain from using dangerous machinery, motor vehicles, or any other practice requiring absolute concentration, under safety laws.<ref name="fda_vistaril_2" /> | Other contraindications include the administration of hydroxyzine alongside [[depressant]]s and other compounds that affect the [[central nervous system]];<ref name="fda_vistaril_2" /> if necessary, it should only be administered concomitantly in small doses.<ref name="fda_vistaril_2" /> If administered in small doses with other substances, as mentioned, then patients should refrain from using dangerous machinery, motor vehicles, or any other practice requiring absolute concentration, under safety laws.<ref name="fda_vistaril_2" /> | ||
Studies have also been conducted which show that long-term prescription of hydroxyzine can lead to [[tardive dyskinesia]] after years of use, but effects related to [[dyskinesia]] have also anecdotally been reported after periods of 7.5 months,<ref name="clark_phen">{{cite journal | vauthors = Clark BG, Araki M, Brown HW | title = Hydroxyzine-associated tardive dyskinesia | journal = Annals of Neurology | volume = 11 | issue = 4 | | Studies have also been conducted which show that long-term prescription of hydroxyzine can lead to [[tardive dyskinesia]] after years of use, but effects related to [[dyskinesia]] have also anecdotally been reported after periods of 7.5 months,<ref name="clark_phen">{{cite journal | vauthors = Clark BG, Araki M, Brown HW | title = Hydroxyzine-associated tardive dyskinesia | journal = Annals of Neurology | volume = 11 | issue = 4 | page = 435 | date = April 1982 | pmid = 7103423 | doi = 10.1002/ana.410110423 | s2cid = 41117995 }}</ref> such as continual head rolling, lip licking, and other forms of [[athetoid]] movement. In certain cases, elderly patients' previous interactions with [[phenothiazine]] derivatives or pre-existing [[neuroleptic]] treatment may have contributed to dyskinesia at the administration of hydroxyzine due to hypersensitivity caused by prolonged treatment,<ref name="clark_phen" /> and therefore some contraindication is given for short-term administration of hydroxyzine to those with previous phenothiazine use.<ref name="clark_phen" /> | ||
==Side effects== | ==Side effects== | ||
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Hydroxyzine exhibits [[anxiolytic]] and [[sedative]] properties in many psychiatric patients. One study showed that patients reported very high levels of subjective sedation when first taking the drug, but that levels of reported sedation decreased markedly over 5–7 days, likely due to CNS receptor desensitization. Other studies have suggested that hydroxyzine acts as an acute [[hypnotic]], reducing [[sleep onset latency]] and increasing sleep duration—also showing that some drowsiness did occur. This was observed more in female patients, who also had greater hypnotic responses.<ref name="hydroxy_sleep">{{cite journal |vauthors=Alford C, Rombaut N, Jones J, Foley S, Idzikowski C, Hindmarch I|date=1992|title=Acute effects of hydroxyzine on nocturnal sleep and sleep tendency the following day: A C-EEG study|journal=Human Psychopharmacology|volume=7|issue=1|pages=25–35|doi=10.1002/hup.470070104|s2cid=143580519}}</ref> The use of sedating drugs alongside hydroxyzine can cause oversedation and confusion if administered at high doses—any form of hydroxyzine treatment alongside sedatives should be done under the supervision of a doctor.<ref name="calif_dolan">{{cite journal | vauthors = Dolan CM | title = Management of emotional disturbances; use of hydroxyzine (atarax) in general practice | journal = California Medicine | volume = 88 | issue = 6 | pages = 443–444 | date = June 1958 | pmid = 13536863 | pmc = 1512309 }}</ref><ref name="fda_vistaril_3" /> | Hydroxyzine exhibits [[anxiolytic]] and [[sedative]] properties in many psychiatric patients. One study showed that patients reported very high levels of subjective sedation when first taking the drug, but that levels of reported sedation decreased markedly over 5–7 days, likely due to CNS receptor desensitization. Other studies have suggested that hydroxyzine acts as an acute [[hypnotic]], reducing [[sleep onset latency]] and increasing sleep duration—also showing that some drowsiness did occur. This was observed more in female patients, who also had greater hypnotic responses.<ref name="hydroxy_sleep">{{cite journal |vauthors=Alford C, Rombaut N, Jones J, Foley S, Idzikowski C, Hindmarch I|date=1992|title=Acute effects of hydroxyzine on nocturnal sleep and sleep tendency the following day: A C-EEG study|journal=Human Psychopharmacology|volume=7|issue=1|pages=25–35|doi=10.1002/hup.470070104|s2cid=143580519}}</ref> The use of sedating drugs alongside hydroxyzine can cause oversedation and confusion if administered at high doses—any form of hydroxyzine treatment alongside sedatives should be done under the supervision of a doctor.<ref name="calif_dolan">{{cite journal | vauthors = Dolan CM | title = Management of emotional disturbances; use of hydroxyzine (atarax) in general practice | journal = California Medicine | volume = 88 | issue = 6 | pages = 443–444 | date = June 1958 | pmid = 13536863 | pmc = 1512309 }}</ref><ref name="fda_vistaril_3" /> | ||
Because of the potential for more severe side effects, this drug is on the list to avoid in the elderly.<ref>{{cite web|url=http://www.ncqa.org/Portals/0/Newsroom/SOHC/Drugs_Avoided_Elderly.pdf|title=NCQA's HEDIS Measure: Use of High Risk Medications in the Elderly|date=2008|website=NCQA.org|archive-url=https://web.archive.org/web/20100201113909/http://www.ncqa.org/Portals/0/Newsroom/SOHC/Drugs_Avoided_Elderly.pdf|archive-date=1 February 2010 | Because of the potential for more severe side effects, this drug is on the list to avoid in the elderly.<ref>{{cite web|url=http://www.ncqa.org/Portals/0/Newsroom/SOHC/Drugs_Avoided_Elderly.pdf|title=NCQA's HEDIS Measure: Use of High Risk Medications in the Elderly|date=2008|website=NCQA.org|archive-url=https://web.archive.org/web/20100201113909/http://www.ncqa.org/Portals/0/Newsroom/SOHC/Drugs_Avoided_Elderly.pdf|archive-date=1 February 2010|access-date=22 February 2010}}</ref> | ||
==Pharmacology== | ==Pharmacology== | ||
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| [[D2 receptor|D<sub>2</sub>]] || 378<br />560 ({{abbr|IC<sub>50</sub>|Half-maximal inhibitory concentration}}) || Mouse<br />Rat || <ref name="pmid9193868" /><br /><ref name="pmid1979798" /> | | [[D2 receptor|D<sub>2</sub>]] || 378<br />560 ({{abbr|IC<sub>50</sub>|Half-maximal inhibitory concentration}}) || Mouse<br />Rat || <ref name="pmid9193868" /><br /><ref name="pmid1979798" /> | ||
|- | |- | ||
| [[Histamine H1 receptor|H<sub>1</sub>]] || '''2.0–19'''<br />'''6.4'''<br />100 ({{abbr|IC<sub>50</sub>|Half-maximal inhibitory concentration}}) || '''Human'''<br />'''Bovine'''<br />Rat || <ref name="pmid11809864">{{cite journal | vauthors = Gillard M, Van Der Perren C, Moguilevsky N, Massingham R, Chatelain P | title = Binding characteristics of cetirizine and levocetirizine to human H(1) histamine receptors: contribution of Lys(191) and Thr(194) | journal = Molecular Pharmacology | volume = 61 | issue = 2 | pages = 391–399 | date = February 2002 | pmid = 11809864 | doi = 10.1124/mol.61.2.391 | url = http://pdfs.semanticscholar.org/1c73/c896c9b25e9a529643851696f51672f07640.pdf | | [[Histamine H1 receptor|H<sub>1</sub>]] || '''2.0–19'''<br />'''6.4'''<br />100 ({{abbr|IC<sub>50</sub>|Half-maximal inhibitory concentration}}) || '''Human'''<br />'''Bovine'''<br />Rat || <ref name="pmid11809864">{{cite journal | vauthors = Gillard M, Van Der Perren C, Moguilevsky N, Massingham R, Chatelain P | title = Binding characteristics of cetirizine and levocetirizine to human H(1) histamine receptors: contribution of Lys(191) and Thr(194) | journal = Molecular Pharmacology | volume = 61 | issue = 2 | pages = 391–399 | date = February 2002 | pmid = 11809864 | doi = 10.1124/mol.61.2.391 | url = http://pdfs.semanticscholar.org/1c73/c896c9b25e9a529643851696f51672f07640.pdf | s2cid = 13075815 | archive-url = https://web.archive.org/web/20190219231925/http://pdfs.semanticscholar.org/1c73/c896c9b25e9a529643851696f51672f07640.pdf | archive-date = 19 February 2019 }}</ref><ref name="pmid15947036">{{cite journal | vauthors = Lim HD, van Rijn RM, Ling P, Bakker RA, Thurmond RL, Leurs R | title = Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 314 | issue = 3 | pages = 1310–1321 | date = September 2005 | pmid = 15947036 | doi = 10.1124/jpet.105.087965 | s2cid = 24248896 }}</ref><ref name="pmid12167464">{{cite journal | vauthors = Anthes JC, Gilchrest H, Richard C, Eckel S, Hesk D, West RE, Williams SM, Greenfeder S, Billah M, Kreutner W, Egan RE | title = Biochemical characterization of desloratadine, a potent antagonist of the human histamine H(1) receptor | journal = European Journal of Pharmacology | volume = 449 | issue = 3 | pages = 229–237 | date = August 2002 | pmid = 12167464 | doi = 10.1016/s0014-2999(02)02049-6 }}</ref><br /><ref name="pmid2884340" /><br /><ref name="pmid1979798" /> | ||
|- | |- | ||
| [[Histamine H2 receptor|H<sub>2</sub>]] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} | | [[Histamine H2 receptor|H<sub>2</sub>]] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} | ||
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Hydroxyzine's predominant [[mechanism of action]] is as a [[potency (pharmacology)|potent]] and [[binding selectivity|selective]] [[histamine]] [[H1 receptor|H<sub>1</sub> receptor]] [[inverse agonist]].<ref name="SzepietowskiWeisshaar2016">{{cite book|url=https://books.google.com/books?id=IlgDDQAAQBAJ&pg=RA1-PA80|title=Itch - Management in Clinical Practice|vauthors=Szepietowski J, Weisshaar E|publisher=Karger Medical and Scientific Publishers|year=2016|isbn= | Hydroxyzine's predominant [[mechanism of action]] is as a [[potency (pharmacology)|potent]] and [[binding selectivity|selective]] [[histamine]] [[H1 receptor|H<sub>1</sub> receptor]] [[inverse agonist]].<ref name="SzepietowskiWeisshaar2016">{{cite book|url=https://books.google.com/books?id=IlgDDQAAQBAJ&pg=RA1-PA80|title=Itch - Management in Clinical Practice|vauthors=Szepietowski J, Weisshaar E|publisher=Karger Medical and Scientific Publishers|year=2016|isbn=978-3-318-05889-5|veditors=Itin P, Jemec GB|series=Current Problems in Dermatology|volume=50|pages=1–80}}</ref><ref name="LadislavMichal2017">{{cite book|url=https://books.google.com/books?id=bD9UDgAAQBAJ&pg=PA364|title=Psychiatry and Pedopsychiatry|vauthors=Hosák L, Hrdlička M|publisher=Charles University in Prague, Karolinum Press|year=2017|isbn=978-80-246-3378-7|page=364 }}</ref> This action is responsible for its [[antihistamine]] and [[sedative]] effects.<ref name="SzepietowskiWeisshaar2016" /><ref name="LadislavMichal2017" /> Unlike many other first-generation antihistamines, hydroxyzine has a lower [[affinity (pharmacology)|affinity]] for the [[muscarinic acetylcholine receptor]]s, and in accordance, has a lower risk of [[anticholinergic]] side effects.<ref name="pmid2884340" /><ref name="LadislavMichal2017" /><ref name="Berger1957">{{cite journal | vauthors = Berger FM | title = The chemistry and mode of action of tranquilizing drugs | journal = Annals of the New York Academy of Sciences | volume = 67 | issue = 10 | pages = 685–700 | date = May 1957 | pmid = 13459139 | doi = 10.1111/j.1749-6632.1957.tb46006.x | s2cid = 12702714 | bibcode = 1957NYASA..67..685B }}</ref><ref name="Tripathi2013">{{cite book|url=https://books.google.com/books?id=FfG8AQAAQBAJ&pg=PA165|title=Essentials of Medical Pharmacology|vauthors=Tripathi KD|publisher=JP Medical Ltd|year=2013|isbn=978-93-5025-937-5|page=165}}</ref> In addition to its antihistamine activity, hydroxyzine has also been shown to act more weakly as an [[receptor antagonist|antagonist]] of the [[serotonin]] [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]], the [[dopamine]] [[D2 receptor|D<sub>2</sub> receptor]], and the [[alpha-1 adrenergic|α<sub>1</sub>-adrenergic receptor]].<ref name="pmid1979798" /><ref name="SzepietowskiWeisshaar2016" /> Similarly to the [[atypical antipsychotic]]s, the comparably weak [[antiserotonergic]] effects of hydroxyzine likely underlie its usefulness as an [[anxiolytic]].<ref name="isbn1-58562-254-0">{{cite book|url=https://books.google.com/books?id=quQY1R8vsZcC&q=hydroxyzine%20serotonin&pg=PA196|title=Textbook of Anxiety Disorders|publisher=American Psychiatric Publishing, Inc|year=2009|isbn=978-1-58562-254-2|veditors=Stein DJ, Hollander E, Rothbaum BO|page=196}}</ref> Other antihistamines without such properties have not been found to be effective in the treatment of [[anxiety]].<ref name="pmid15388291">{{cite journal | vauthors = Lamberty Y, Gower AJ | title = Hydroxyzine prevents isolation-induced vocalization in guinea pig pups: comparison with chlorpheniramine and immepip | journal = Pharmacology, Biochemistry, and Behavior | volume = 79 | issue = 1 | pages = 119–124 | date = September 2004 | pmid = 15388291 | doi = 10.1016/j.pbb.2004.06.015 | s2cid = 23593514 }}</ref> | ||
Hydroxyzine crosses the [[blood–brain barrier]] easily and exerts effects in the [[central nervous system]].<ref name="SzepietowskiWeisshaar2016" /> A [[positron emission tomography]] (PET) study found that brain occupancy of the H<sub>1</sub> receptor was 67.6% for a single 30 mg dose of hydroxyzine.<ref name="pmid19697300">{{cite journal | vauthors = Tashiro M, Kato M, Miyake M, Watanuki S, Funaki Y, Ishikawa Y, Iwata R, Yanai K | title = Dose dependency of brain histamine H(1) receptor occupancy following oral administration of cetirizine hydrochloride measured using PET with [11C]doxepin | journal = Human Psychopharmacology | volume = 24 | issue = 7 | pages = 540–548 | date = October 2009 | pmid = 19697300 | doi = 10.1002/hup.1051 | s2cid = 5596000 }}</ref> In addition, subjective sleepiness correlated well with the brain H<sub>1</sub> receptor occupancy.<ref name="pmid19697300" /> PET studies with antihistamines have found that brain H<sub>1</sub> receptor occupancy of more than 50% is associated with a high prevalence of [[somnolence]] and [[cognitive decline]], whereas brain H<sub>1</sub> receptor occupancy of less than 20% is considered to be non-sedative.<ref name="pmid16890992">{{cite journal | vauthors = Yanai K, Tashiro M | title = The physiological and pathophysiological roles of neuronal histamine: an insight from human positron emission tomography studies | journal = Pharmacology & Therapeutics | volume = 113 | issue = 1 | pages = 1–15 | date = January 2007 | pmid = 16890992 | doi = 10.1016/j.pharmthera.2006.06.008 }}</ref> | Hydroxyzine crosses the [[blood–brain barrier]] easily and exerts effects in the [[central nervous system]].<ref name="SzepietowskiWeisshaar2016" /> A [[positron emission tomography]] (PET) study found that brain occupancy of the H<sub>1</sub> receptor was 67.6% for a single 30 mg dose of hydroxyzine.<ref name="pmid19697300">{{cite journal | vauthors = Tashiro M, Kato M, Miyake M, Watanuki S, Funaki Y, Ishikawa Y, Iwata R, Yanai K | title = Dose dependency of brain histamine H(1) receptor occupancy following oral administration of cetirizine hydrochloride measured using PET with [11C]doxepin | journal = Human Psychopharmacology | volume = 24 | issue = 7 | pages = 540–548 | date = October 2009 | pmid = 19697300 | doi = 10.1002/hup.1051 | s2cid = 5596000 }}</ref> In addition, subjective sleepiness correlated well with the brain H<sub>1</sub> receptor occupancy.<ref name="pmid19697300" /> PET studies with antihistamines have found that brain H<sub>1</sub> receptor occupancy of more than 50% is associated with a high prevalence of [[somnolence]] and [[cognitive decline]], whereas brain H<sub>1</sub> receptor occupancy of less than 20% is considered to be non-sedative.<ref name="pmid16890992">{{cite journal | vauthors = Yanai K, Tashiro M | title = The physiological and pathophysiological roles of neuronal histamine: an insight from human positron emission tomography studies | journal = Pharmacology & Therapeutics | volume = 113 | issue = 1 | pages = 1–15 | date = January 2007 | pmid = 16890992 | doi = 10.1016/j.pharmthera.2006.06.008 }}</ref> | ||
Hydroxyzine also acts as a functional inhibitor of [[acid sphingomyelinase]].<ref name=":0">{{cite journal | vauthors = Sánchez-Rico M, Limosin F, Vernet R, Beeker N, Neuraz A, Blanco C, Olfson M, Lemogne C, Meneton P, Daniel C, Paris N, Gramfort A, Lemaitre G, De La Muela P, Salamanca E, Bernaux M, Bellamine A, Burgun A, Hoertel N | title = Hydroxyzine Use and Mortality in Patients Hospitalized for COVID-19: A Multicenter Observational Study | journal = Journal of Clinical Medicine | volume = 10 | issue = 24 | | Hydroxyzine also acts as a functional inhibitor of [[acid sphingomyelinase]].<ref name=":0">{{cite journal | vauthors = Sánchez-Rico M, Limosin F, Vernet R, Beeker N, Neuraz A, Blanco C, Olfson M, Lemogne C, Meneton P, Daniel C, Paris N, Gramfort A, Lemaitre G, De La Muela P, Salamanca E, Bernaux M, Bellamine A, Burgun A, Hoertel N | title = Hydroxyzine Use and Mortality in Patients Hospitalized for COVID-19: A Multicenter Observational Study | journal = Journal of Clinical Medicine | volume = 10 | issue = 24 | page = 5891 | date = December 2021 | pmid = 34945186 | doi = 10.3390/jcm10245891 | pmc = 8707307 | doi-access = free }}</ref> | ||
===Pharmacokinetics=== | ===Pharmacokinetics=== | ||
Hydroxyzine can be administered orally or via intramuscular injection. | Hydroxyzine can be administered orally or via intramuscular injection. In both cases it is rapidly absorbed and distributed. It is metabolized in the liver and the main metabolite (45%), [[cetirizine]] is formed through oxidation of the alcohol moiety to a carboxylic acid by [[alcohol dehydrogenase]]. Overall effects are observed within one hour of administration. | ||
Higher concentrations are found in the skin than in the plasma. Cetirizine, although less sedating, is non-[[Dialysis (chemistry)|dialyzable]] and possesses similar antihistamine properties. Metabolites identified include an ''N''-dealkylated metabolite and an ''O''-dealkylated 1/16 metabolite with a plasma half-life of 59 hours. These pathways are mediated principally by [[CYP3A4]] and [[CYP3A5]].<ref>{{cite web|url=http://www.imb.ie/images/uploaded/swedocuments/LicenseSPC_PA0891-005-001_16082013162208.pdf|title=Ucerax (hydroxyzine hydrochloride) 25 mg film-coated tablets. Summary of product characteristics|date=2013|publisher=Irish Medicines Board|archive-url=https://web.archive.org/web/20140222041846/http://www.imb.ie/images/uploaded/swedocuments/LicenseSPC_PA0891-005-001_16082013162208.pdf|archive-date=22 February 2014|access-date=9 February 2014}}</ref><ref>{{cite book|title=Foye's principles of medicinal chemistry|date=2013|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins| vauthors = Foye WO, Lemke TL, Williams DA |isbn=978-1-60913-345-0|edition=7th |location=Philadelphia|oclc=748675182}}</ref> The N-dealykylated metabolite, norchlorcyclizine, bears some structural similarities to [[trazodone]], but it has not been established whether it is pharmacologically active.<ref>{{cite journal | vauthors = Thavundayil JX, Hambalek R, Kin NM, Krishnan B, Lal S | title = Prolonged penile erections induced by hydroxyzine: possible mechanism of action | journal = Neuropsychobiology | volume = 30 | issue = 1 | pages = 4–6 | date = 1994 | pmid = 7969858 | doi = 10.1159/000119126 }}</ref><ref>{{cite journal | vauthors = Malcolm MJ, Cody TE |title=Hydroxyzine and Possible Metabolites |journal=Canadian Society of Forensic Science Journal |date=January 1994 |volume=27 |issue=2 |pages=87–92 |doi=10.1080/00085030.1994.10757029}}</ref> In animals, hydroxyzine and its metabolites are excreted in feces primarily through biliary elimination.<ref>{{cite web|url=http://www.pfizer.com/pfizer/download/uspi_vistaril.pdf|title=Vistaril (hydroxyzine pamoate) Capsules and Oral Suspension|date=2006|website=pfizer.com|archive-url=https://web.archive.org/web/20070703074852/http://www.pfizer.com/pfizer/download/uspi_vistaril.pdf|archive-date=3 July 2007|access-date=7 March 2007|quote=This paper says "The extent of renal excretion of Vistaril has not been determined"}}</ref><ref name="rats">{{cite journal | vauthors = Pong SF, Huang CL | title = Comparative studies on distribution, excretion, and metabolism of hydroxyzine-3H and its methiodide-14C in rats | journal = Journal of Pharmaceutical Sciences | volume = 63 | issue = 10 | pages = 1527–1532 | date = October 1974 | pmid = 4436782 | doi = 10.1002/jps.2600631008 | bibcode = 1974JPhmS..63.1527P | doi-access = free }}</ref> In rats, less than 2% of the drug is excreted unchanged.<ref name="rats" /> | |||
The time to reach maximum concentration ([[Tmax (pharmacology)|T<sub>max</sub>]]) of hydroxyzine is about 2.0 hours in both adults and children and its [[elimination half-life]] is around 20.0 hours in adults (mean age 29.3 years) and 7.1 hours in children.<ref name="pmid2866055">{{cite journal | vauthors = Paton DM, Webster DR | title = Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines) | journal = Clinical Pharmacokinetics | volume = 10 | issue = 6 | pages = 477–497 | date = 1985 | pmid = 2866055 | doi = 10.2165/00003088-198510060-00002 | s2cid = 33541001 }}</ref><ref name="pmid6141198">{{cite journal | vauthors = Simons FE, Simons KJ, Frith EM | title = The pharmacokinetics and antihistaminic of the H1 receptor antagonist hydroxyzine | journal = The Journal of Allergy and Clinical Immunology | volume = 73 | issue = 1 Pt 1 | pages = 69–75 | date = January 1984 | pmid = 6141198 | doi = 10.1016/0091-6749(84)90486-x | doi-access = free }}</ref> Its elimination half-life is shorter in children compared to adults.<ref name="pmid2866055" /> In another study, the elimination half-life of hydroxyzine in elderly adults was 29.3 hours.<ref name="pmid2562944">{{cite journal | vauthors = Simons KJ, Watson WT, Chen XY, Simons FE | title = Pharmacokinetic and pharmacodynamic studies of the H1-receptor antagonist hydroxyzine in the elderly | journal = Clinical Pharmacology and Therapeutics | volume = 45 | issue = 1 | pages = 9–14 | date = January 1989 | pmid = 2562944 | doi = 10.1038/clpt.1989.2 | s2cid = 24571876 }}</ref> One study found that the elimination half-life of hydroxyzine in adults was as short as 3 hours, but this may have just been due to methodological limitations.<ref name="Kacew1989">{{cite book|url=https://books.google.com/books?id=3eruIjPYbC8C&pg=PA257|title=Drug Toxicity & Metabolism In Pediatrics|vauthors=Kacew S|publisher=CRC Press|year=1989|isbn= | The time to reach maximum concentration ([[Tmax (pharmacology)|T<sub>max</sub>]]) of hydroxyzine is about 2.0 hours in both adults and children and its [[elimination half-life]] is around 20.0 hours in adults (mean age 29.3 years) and 7.1 hours in children.<ref name="pmid2866055">{{cite journal | vauthors = Paton DM, Webster DR | title = Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines) | journal = Clinical Pharmacokinetics | volume = 10 | issue = 6 | pages = 477–497 | date = 1985 | pmid = 2866055 | doi = 10.2165/00003088-198510060-00002 | s2cid = 33541001 }}</ref><ref name="pmid6141198">{{cite journal | vauthors = Simons FE, Simons KJ, Frith EM | title = The pharmacokinetics and antihistaminic of the H1 receptor antagonist hydroxyzine | journal = The Journal of Allergy and Clinical Immunology | volume = 73 | issue = 1 Pt 1 | pages = 69–75 | date = January 1984 | pmid = 6141198 | doi = 10.1016/0091-6749(84)90486-x | doi-access = free }}</ref> Its elimination half-life is shorter in children compared to adults.<ref name="pmid2866055" /> In another study, the elimination half-life of hydroxyzine in elderly adults was 29.3 hours.<ref name="pmid2562944">{{cite journal | vauthors = Simons KJ, Watson WT, Chen XY, Simons FE | title = Pharmacokinetic and pharmacodynamic studies of the H1-receptor antagonist hydroxyzine in the elderly | journal = Clinical Pharmacology and Therapeutics | volume = 45 | issue = 1 | pages = 9–14 | date = January 1989 | pmid = 2562944 | doi = 10.1038/clpt.1989.2 | s2cid = 24571876 }}</ref> One study found that the elimination half-life of hydroxyzine in adults was as short as 3 hours, but this may have just been due to methodological limitations.<ref name="Kacew1989">{{cite book|url=https://books.google.com/books?id=3eruIjPYbC8C&pg=PA257|title=Drug Toxicity & Metabolism In Pediatrics|vauthors=Kacew S|publisher=CRC Press|year=1989|isbn=978-0-8493-4564-7|page=257}}</ref> Although hydroxyzine has a long elimination half-life and acts, in-vivo, as an antihistamine for as long as 24 hours, the predominant CNS effects of hydroxyzine and other antihistamines with long half-lives seem to diminish after 8 hours.<ref name="EstelleSimons1994">{{cite journal | vauthors = Simons FE | title = H1-receptor antagonists. Comparative tolerability and safety | journal = Drug Safety | volume = 10 | issue = 5 | pages = 350–380 | date = May 1994 | pmid = 7913608 | doi = 10.2165/00002018-199410050-00002 | s2cid = 12749971 }}</ref> | ||
Administration in geriatrics differs from the administration of hydroxyzine in younger patients; according to the FDA, there have not been significant studies made (2004), which include population groups over 65, which provide a distinction between elderly aged patients and other younger groups. Hydroxyzine should be administered carefully in the elderly with consideration given to possible reduced elimination.<ref name="fda_vistaril_3">United States Food & Drug Administration (2004), p. 3</ref>{{Better source|date=March 2023}} | Administration in geriatrics differs from the administration of hydroxyzine in younger patients; according to the FDA, there have not been significant studies made (2004), which include population groups over 65, which provide a distinction between elderly aged patients and other younger groups. Hydroxyzine should be administered carefully in the elderly with consideration given to possible reduced elimination.<ref name="fda_vistaril_3">United States Food & Drug Administration (2004), p. 3</ref>{{Better source|date=March 2023}} | ||
Latest revision as of 07:53, 21 December 2025
Template:Short description Template:Use dmy dates Template:Cs1 config Template:Drugbox
Hydroxyzine, sold under the brand names Atarax and Vistaril among others, is an antihistamine medication.[1] It is used in the treatment of itchiness, anxiety, insomnia, and nausea (including that due to motion sickness).[1] It is used either by mouth or injection into a muscle.[1]
Hydroxyzine works by blocking the effects of histamine.[2] It is a first-generation antihistamine in the piperazine family of chemicals.[1][3] Common side effects include sleepiness, headache, and dry mouth.[1][2] Serious side effects may include QT prolongation.[2] It is unclear if use during pregnancy or breastfeeding is safe.[1]
It was first made by Union Chimique Belge in 1956 and was approved for sale by Pfizer in the United States later that year.[1][4] In 2023, it was the 39th most commonly prescribed medication in the United States, with more than 15Script error: No such module "String".million prescriptions.[5][6]
Medical uses
Template:Primary sourceHydroxyzine is used in the treatment of itchiness, anxiety, and nausea due to motion sickness.[1]
A systematic review concluded that hydroxyzine outperforms placebo in treating generalized anxiety disorder. Insufficient data were available to compare the drug with benzodiazepines and buspirone.[7]
Hydroxyzine can also be used for the treatment of allergic conditions, such as chronic urticaria, atopic or contact dermatoses, and histamine-mediated pruritus.Template:Medcn These have also been confirmed in both recent and past studies to have no adverse effects on the liver, blood, nervous system, or urinary tract.[8]Template:Better source
Use of hydroxyzine for premedication as a sedative has no effects on tropane alkaloids, such as atropine, but may, following general anesthesia, potentiate meperidine and barbiturates, and use in pre-anesthetic adjunctive therapy should be modified depending upon the state of the individual.[8]
Doses of hydroxyzine hydrochloride used for sleep range from 25 to 100 mg.[9][10][11] As with other antihistamine sleep aids, hydroxyzine is usually only prescribed for short term or "as-needed" use since tolerance to the central nervous system (CNS) effects of hydroxyzine can develop in as little as a few days.[12]Template:Primary source inline A major systematic review and network meta-analysis of medications for the treatment of insomnia published in 2022 found little evidence to inform the use of hydroxyzine for insomnia.[13] A 2023 meta-review concludes that hydroxyzine is effective for inducing sleep onset but less effective for maintaining sleep for eight hours.[14]
Contraindications
Hydroxyzine is contraindicated for subcutaneous or intra-articular administration.[15]
The administration of hydroxyzine in large amounts by ingestion or intramuscular administration during the onset of pregnancy can cause fetal abnormalities. When administered to pregnant rats, mice, and rabbits, hydroxyzine caused abnormalities such as hypogonadism with doses significantly above that of the human therapeutic range.[16]Template:Better source
In humans, a significant dose has not yet been established in studies, and, by default, the US Food and Drug Administration (FDA) has introduced contraindication guidelines regarding hydroxyzine.[16] Use by those at risk for or showing previous signs of hypersensitivity is also contraindicated.[16]
Other contraindications include the administration of hydroxyzine alongside depressants and other compounds that affect the central nervous system;[16] if necessary, it should only be administered concomitantly in small doses.[16] If administered in small doses with other substances, as mentioned, then patients should refrain from using dangerous machinery, motor vehicles, or any other practice requiring absolute concentration, under safety laws.[16]
Studies have also been conducted which show that long-term prescription of hydroxyzine can lead to tardive dyskinesia after years of use, but effects related to dyskinesia have also anecdotally been reported after periods of 7.5 months,[17] such as continual head rolling, lip licking, and other forms of athetoid movement. In certain cases, elderly patients' previous interactions with phenothiazine derivatives or pre-existing neuroleptic treatment may have contributed to dyskinesia at the administration of hydroxyzine due to hypersensitivity caused by prolonged treatment,[17] and therefore some contraindication is given for short-term administration of hydroxyzine to those with previous phenothiazine use.[17]
Side effects
Several reactions have been noted in manufacturer guidelines—deep sleep, incoordination, sedation, and dizziness have been reported in children and adults, as well as others such as hypotension, tinnitus, and headaches.[18]Template:Medical citation needed Gastrointestinal effects have also been observed, as well as less serious effects such as dryness of the mouth and constipation caused by the mild antimuscarinic properties of hydroxyzine.[18]Template:Medical citation needed
Central nervous system effects such as hallucinations or confusion have been observed in rare cases, attributed mostly to overdosage.[19][18] Such properties have been attributed to hydroxyzine in several cases, particularly in patients treated for neuropsychological disorders, as well as in cases where overdoses have been observed. While there are reports of hallucinogenic effects from use of hydroxyzine, several clinical data trials have not reported such side effects from the sole consumption of hydroxyzine, but rather, have described its overall calming effect described through the stimulation of areas within the reticular formation. The hallucinogenic or hypnotic properties have been described as being an additional effect from overall central nervous system suppression by other CNS agents, such as lithium or ethanol.[20]
Hydroxyzine exhibits anxiolytic and sedative properties in many psychiatric patients. One study showed that patients reported very high levels of subjective sedation when first taking the drug, but that levels of reported sedation decreased markedly over 5–7 days, likely due to CNS receptor desensitization. Other studies have suggested that hydroxyzine acts as an acute hypnotic, reducing sleep onset latency and increasing sleep duration—also showing that some drowsiness did occur. This was observed more in female patients, who also had greater hypnotic responses.[21] The use of sedating drugs alongside hydroxyzine can cause oversedation and confusion if administered at high doses—any form of hydroxyzine treatment alongside sedatives should be done under the supervision of a doctor.[22][19]
Because of the potential for more severe side effects, this drug is on the list to avoid in the elderly.[23]
Pharmacology
Pharmacodynamics
| Site | Ki (nM) | Species | Ref |
|---|---|---|---|
| 5-HT2A | 170 (IC50) | Rat | [25] |
| 5-HT2C | ND | ND | ND |
| α1 | 460 (IC50) | Rat | [25] |
| D1 | 10000+ | Mouse | [26] |
| D2 | 378 560 (IC50) |
Mouse Rat |
[26] [25] |
| H1 | 2.0–19 6.4 100 (IC50) |
Human Bovine Rat |
[27][28][29] [30] [25] |
| H2 | ND | ND | ND |
| H3 | ND | ND | ND |
| H4 | 10000+ | Human | [28] |
| mACh | 4600 10000+ 10000+ (IC50) 6310 (pA2) 3800 |
Human Mouse Rat Guinea pig Bovine |
[31] [26] [25] [32] [30] |
| VDCC | 3400+ (IC50) | Rat | [25] |
| Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site. | |||
Hydroxyzine's predominant mechanism of action is as a potent and selective histamine H1 receptor inverse agonist.[33][34] This action is responsible for its antihistamine and sedative effects.[33][34] Unlike many other first-generation antihistamines, hydroxyzine has a lower affinity for the muscarinic acetylcholine receptors, and in accordance, has a lower risk of anticholinergic side effects.[30][34][35][36] In addition to its antihistamine activity, hydroxyzine has also been shown to act more weakly as an antagonist of the serotonin 5-HT2A receptor, the dopamine D2 receptor, and the α1-adrenergic receptor.[25][33] Similarly to the atypical antipsychotics, the comparably weak antiserotonergic effects of hydroxyzine likely underlie its usefulness as an anxiolytic.[37] Other antihistamines without such properties have not been found to be effective in the treatment of anxiety.[38]
Hydroxyzine crosses the blood–brain barrier easily and exerts effects in the central nervous system.[33] A positron emission tomography (PET) study found that brain occupancy of the H1 receptor was 67.6% for a single 30 mg dose of hydroxyzine.[39] In addition, subjective sleepiness correlated well with the brain H1 receptor occupancy.[39] PET studies with antihistamines have found that brain H1 receptor occupancy of more than 50% is associated with a high prevalence of somnolence and cognitive decline, whereas brain H1 receptor occupancy of less than 20% is considered to be non-sedative.[40]
Hydroxyzine also acts as a functional inhibitor of acid sphingomyelinase.[41]
Pharmacokinetics
Hydroxyzine can be administered orally or via intramuscular injection. In both cases it is rapidly absorbed and distributed. It is metabolized in the liver and the main metabolite (45%), cetirizine is formed through oxidation of the alcohol moiety to a carboxylic acid by alcohol dehydrogenase. Overall effects are observed within one hour of administration. Higher concentrations are found in the skin than in the plasma. Cetirizine, although less sedating, is non-dialyzable and possesses similar antihistamine properties. Metabolites identified include an N-dealkylated metabolite and an O-dealkylated 1/16 metabolite with a plasma half-life of 59 hours. These pathways are mediated principally by CYP3A4 and CYP3A5.[42][43] The N-dealykylated metabolite, norchlorcyclizine, bears some structural similarities to trazodone, but it has not been established whether it is pharmacologically active.[44][45] In animals, hydroxyzine and its metabolites are excreted in feces primarily through biliary elimination.[46][47] In rats, less than 2% of the drug is excreted unchanged.[47]
The time to reach maximum concentration (Tmax) of hydroxyzine is about 2.0 hours in both adults and children and its elimination half-life is around 20.0 hours in adults (mean age 29.3 years) and 7.1 hours in children.[48][49] Its elimination half-life is shorter in children compared to adults.[48] In another study, the elimination half-life of hydroxyzine in elderly adults was 29.3 hours.[50] One study found that the elimination half-life of hydroxyzine in adults was as short as 3 hours, but this may have just been due to methodological limitations.[51] Although hydroxyzine has a long elimination half-life and acts, in-vivo, as an antihistamine for as long as 24 hours, the predominant CNS effects of hydroxyzine and other antihistamines with long half-lives seem to diminish after 8 hours.[52]
Administration in geriatrics differs from the administration of hydroxyzine in younger patients; according to the FDA, there have not been significant studies made (2004), which include population groups over 65, which provide a distinction between elderly aged patients and other younger groups. Hydroxyzine should be administered carefully in the elderly with consideration given to possible reduced elimination.[19]Template:Better source
Chemistry
Hydroxyzine is a member of the diphenylmethylpiperazine class of antihistamines.Template:Medcn
Hydroxyzine is supplied mainly as a dihydrochloride salt (hydroxyzine hydrochloride) but also to a lesser extent as an embonate salt (hydroxyzine pamoate).[53][54][55] The molecular weights of hydroxyzine, hydroxyzine dihydrochloride, and hydroxyzine pamoate are 374.9 g/mol, 447.8 g/mol, and 763.3 g/mol, respectively.[3] Due to their differences in molecular weight, 1 mg hydroxyzine dihydrochloride is equivalent to about 1.7 mg hydroxyzine pamoate.[56]
Analogues
Script error: No such module "Unsubst". Analogues of hydroxyzine include buclizine, cetirizine, cinnarizine, cyclizine, etodroxizine, meclizine, and pipoxizine among others.[57]
Society and culture
Brand names
Script error: No such module "Unsubst". Hydroxyzine preparations require a doctor's prescription. The drug is available in two formulations, the pamoate and the dihydrochloride or hydrochloride salts. Vistaril, Equipose, Masmoran, and Paxistil are preparations of the pamoate salt, while Atarax, Alamon, Aterax, Durrax, Tran-Q, Orgatrax, Quiess, and Tranquizine are of the hydrochloride salt.
See also
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References
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- ↑ a b c d e f g h Script error: No such module "citation/CS1".
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- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ a b United States Food & Drug Administration (2004), p. 1
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ a b c d e f United States Food & Drug Administration (2004), p. 2
- ↑ a b c Script error: No such module "Citation/CS1".
- ↑ a b c UCB South-Africa, et al., (2004)
- ↑ a b c United States Food & Drug Administration (2004), p. 3
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ a b c d e f g Script error: No such module "Citation/CS1".
- ↑ a b c Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ a b Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ a b c Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ a b c d Script error: No such module "citation/CS1".
- ↑ a b c Script error: No such module "citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ a b Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ a b Script error: No such module "Citation/CS1".
- ↑ a b Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "citation/CS1".
Script error: No such module "Check for unknown parameters".
Script error: No such module "navboxes". Script error: No such module "Navbox".
Script error: No such module "Navbox". Template:Sedatives Script error: No such module "navbox".Script error: No such module "navboxes".Script error: No such module "Check for unknown parameters". Script error: No such module "navboxes". Template:Adrenergic receptor modulators Template:Dopamine receptor modulators Template:Histamine receptor modulators Template:Serotonin receptor modulatorsScript error: No such module "navboxes".Script error: No such module "Check for unknown parameters".
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