Talk:Hydroxyzine: Difference between revisions

'''Hydroxyzine''' is a first-generation [[psychoactive class::antihistamine]] substance of the [[chemical class::diphenylmethylpiperazine/ethano-piperidine]] class. It acts primarily as a potent and selective H1 receptor antagonist,<ref>Szepietowski J, Weisshaar E (2016). Itin P, Jemec GB (eds.). Itch - Management in Clinical Practice. Current Problems in Dermatology. 50. Karger Medical and Scientific Publishers. pp. 1–80. ISBN 9783318058895.</ref><ref>Hosák L, Hrdlička M, et al. (2017). Psychiatry and Pedopsychiatry. Charles University in Prague, Karolinum Press. p. 364. ISBN 9788024633787.</ref> with anxiolytic effects attributable to weak antiserotonergic effects.<ref>Snowman AM, Snyder SH (December 1990). "Cetirizine: actions on neurotransmitter receptors". The Journal of Allergy and Clinical Immunology. 86 (6 Pt 2): 1025–1028. doi:10.1016/S0091-6749(05)80248-9. PMID 1979798.</ref>

It belongs to the [[psychoactive class::piperazine/ethanopiperidine]] family of chemicals.<ref>"Hydroxyzine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 21 Nov 2018.</ref> Hydroxyzine is often used in the treatment of [[itchiness]], [[anxiety]], [[insomnia]], and [[nausea]] from motion sickness.<ref>"Hydroxyzine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 21 Nov 2018.</ref> Unlike many other first-generation antihistamines, hydroxyzine has low affinity for muscarinic acetylcholine receptors, and thus does not produce strong anticholinergic side effects responsible for the deliriant properties of drugs such as [[diphenhydramine]].<ref>Kubo N, Shirakawa O, Kuno T, Tanaka C (March 1987). "Antimuscarinic effects of antihistamines: quantitative evaluation by receptor-binding assay". Japanese Journal of Pharmacology. 43 (3): 277–282. doi:10.1254/jjp.43.277. PMID 2884340.</ref>

Hydroxyzine sees little recreational use, limited mostly to where stronger anxiolytics, such as [[benzodiazepines]] or [[alcohol]], are not available. Unlike more commonly abused [[depressants]], it does not impact the [[neurotransmitter]] [[GABA]], and acts by antagonizing adrenergic, dopaminergic, and serotonergic receptors. It is effective in the treatment of [[generalized anxiety disorder]] (due to its [[anxiolytic]] effects), short-term treatment of [[insomnia]] (due to its [[sedative]] effects), and allergic reactions (due to its [[antihistamine]] effects).<ref>Rosario B. Hidalgo, David V. Sheehan, in Handbook of Clinical Neurology, 2012</ref> Despite having limited abuse potential, combining hydroxyzine with other [[depressants]] can lead to [[respiratory depression]]. Like other antihistamines, high doses of hydroxyzine can prolong the QT interval, which may lead to the development of [[torsades de pointes]], a potentially fatal arrhythmia.<ref>British national formulary : BNF 74 (74 ed.). British Medical Association. 2017. p. X. ISBN 978-0857112989.</ref> It is highly advised to use [[harm reduction practices]] if using this substance.

It was first made by Union Chimique Belge in 1956 and was approved for sale by Pfizer in the United States later that year. Originally mostly given for nausea and allergies, it was transitioned over to its anxiolytic purposes in medicine. It is commonly given as a substitute to an anxiolytic Benzodiazepine in surgeries to decrease anxiety and act as an anesthetic. <ref>"Hydroxyzine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 21 Nov 2018.</ref><ref>Shorter E (2009). Before Prozac: the troubled history of mood disorders in psychiatry. Oxford [Oxfordshire]: Oxford University Press. ISBN 9780195368741.</ref> In the United Kingdom 28 doses cost less than a pound.<ref>British national formulary : BNF 74 (74 ed.). British Medical Association. 2017. p. X. ISBN 978-0857112989.</ref> In the United States the wholesale cost in 2018 was about 0.05 USD per dose.<ref>"NADAC as of 2018-11-21". Centers for Medicare and Medicaid Services. Retrieved 21 Nov 2018.</ref> In the United States about 8 million prescriptions were written for hydroxyzine in 2016.<ref>British national formulary : BNF 74 (74 ed.). British Medical Association. 2017. p. X. ISBN 978-0857112989.</ref>

Hydroxyzine is a member of the diphenylmethylpiperazine and ethano-piperidine class of drugs.

 

Analogues of hydroxyzine include buclizine, cetirizine, cinnarizine, cyclizine, etodroxizine, meclizine, and pipoxizine among others.

 

Hydroxyzine is synthesized by the alkylation of 1-(4-chlorobenzhydryl)piperazine with 2-(2-Chloroethoxy)ethanopiperidine<ref>H. Morren, U.S. Patent 2,899,436 (1959); H. Morren, DE 1049383 (1954); H. Morren, DE 1061786 (1954); H. Morren, DE 1068262 (1954); H. Morren, DE 1072624 (1954); H. Morren, DE 1075116 (1954).</ref>

Hydroxyzine acts primarily as a potent [[histamine]] H1 receptor [[antagonist]].<ref>Szepietowski J, Weisshaar E (2016). Itin P, Jemec GB (eds.). Itch - Management in Clinical Practice. Current Problems in Dermatology. 50. Karger Medical and Scientific Publishers. pp. 1–80. ISBN 9783318058895.</ref><ref>Hosák L, Hrdlička M, et al. (2017). Psychiatry and Pedopsychiatry. Charles University in Prague, Karolinum Press. p. 364. ISBN 9788024633787.</ref> Hydroxyzine is notable for having lower affinity for muscarinic acetylcholine receptor, responsible for the deliriant action of other first-generation antihistamines, like [[diphenhydramine]] - subsequently, hydroxyzine is less liable to cause hallucinatory states or delirium. In addition to antihistaminergic activity, hydroxyzine acts as an antagonist for [[5-HT2A]] receptors (responsible for its [[anxiolytic]] effects), [[D2]] receptors, and [[A1]] receptors (responsible for the emotional numbing hydroxyzine causes - this is a similar mechanism as [[antipsychotics]], although notably weaker). Hydroxyzine is unique among first-generation antihistamines in that acts as an anxiolytic, likely attributable to its [[5-HT2A]] antagonism. Hydroxyzine easily crosses the blood-brain barrier. Low doses of hydroxyzine (where less than 20% of H1 receptors are bound to) are not associated with [[somnolence]], but high doses (where 50% or more of H1 receptors are bound to) cause [[sedation]].<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 is metabolized rapidly and crosses the blood-brain barrier with ease. When taken orally, it is rapidly absorbed through the gastrointestinal tract and is metabolized in the liver. Effects typically begin within 15-30 minutes. Peak concentration of hydroxyzine occurs at approximatively two hours after administration. Hydroxyzine and its metabolites have long half-lives, but the sedative effects typically at around 4-6 hours. In adults, the elimination half-life of hydroxyzine is 20 hours.