Talk:Hydroxyzine: Difference between revisions

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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. It 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's chemical structure features a diphenylmethylpiperazine core, consisting of a piperazine ring bonded to a diphenylmethyl group. This structure is integral to its pharmacological effects, including its antihistaminic and anxiolytic properties.

==Pharmacology==

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 relative to other first-generation antihistamines, like [[diphenhydramine]] - subsequently, hydroxyzine is less liable to cause hallucinatory states or delirium. In addition to antihistamine activity, hydroxyzine acts as an antagonist towards [[5-HT2A]] receptors (likely responsible for its [[anxiolytic]] effects), dopamine D2 receptors, and α1-adrenergic receptors. Hydroxyzine is unique among first-generation antihistamines with regards to its anxiolytic properties.

~~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. Low doses of hydroxyzine (where less than 20% of H1 receptors are bound) are not associated with [[somnolence]], but high doses (where 50% or more of H1 receptors are bound) 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>

In terms of its pharmacokinetics, 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, with peak plasma concentrations occurring approximately two hours post-administration. Hydroxyzine and its metabolites have relatively long half-lives; however, the sedative effects generally last around 4-6 hours. In adults, the elimination half-life of hydroxyzine is approximately 20 hours.<ref>Jensen, C., & Mehta, N. (2016). Pharmacokinetics and Pharmacodynamics of Hydroxyzine. Journal of Pain and Symptom Management, 51(5), 872-877.</ref>

Low doses of hydroxyzine (where less than 20% of H1 receptors are bound) are not associated with [[somnolence]], but high doses (where 50% or more of H1 receptors are bound) 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 also exhibits anticholinergic and sedative properties, which can be beneficial in treating conditions like anxiety and tension. The anticholinergic properties of hydroxyzine are due to its ability to block muscarinic acetylcholine receptors, which can help reduce muscle spasms and other symptoms related to excessive cholinergic activity. The sedative properties of hydroxyzine are primarily due to its antagonism of central H1 receptors and, to a lesser extent, its antagonism of serotonin 5-HT2A receptors. These combined actions contribute to its efficacy in managing anxiety and promoting relaxation.<ref>Howland RH. (2015). Hydroxyzine for anxiety. Journal of Psychosocial Nursing and Mental Health Services, 53(10), 21-24.</ref>

Hydroxyzine is also used to manage nausea and vomiting, primarily through its antihistamine effects. The drug's action on H1 receptors helps alleviate symptoms of motion sickness and other vestibular disorders that can cause nausea. Additionally, hydroxyzine's antagonistic effects on dopamine D2 receptors in the chemoreceptor trigger zone (CTZ) contribute to its antiemetic properties.<ref>Gan, T. J. (2017). Mechanisms underlying postoperative nausea and vomiting and neurotransmitter receptor antagonist-based pharmacotherapy. CNS Drugs, 21(11), 813-833.</ref>

As an antihistamine, hydroxyzine is effective in treating allergic reactions such as urticaria (hives) and chronic pruritus (itching). By blocking H1 receptors, hydroxyzine reduces the effects of histamine release, which includes vasodilation, increased vascular permeability, and sensory nerve stimulation that causes itching.<ref>Kaplan AP. (2013). Chronic urticaria: Pathogenesis and treatment. Journal of Allergy and Clinical Immunology, 131(3), 594-602.</ref>

==Subjective effects==

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{{effects/physical|

*'''[[Effect::Sedation]]''' ~~- Hydroxyzine has milder sedative effects than other first-generation antihistamines, such as [[diphenhydramine]]. Tolerance to its sedative effects builds rapidly.~~

*'''[[Effect::Sedation]]'''

*'''[[Effect::Motor control loss]]'''

*'''[[Effect::Respiratory depression]]'''

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==Legal status==

'''United States''': Hydroxyzine is available by prescription only.

*'''Austria''': Hydroxyzine is available by prescription only.

*'''Brazil''': Hydroxyzine can be bought without a prescription, over the counter. <ref>Anvisa. (2016). PARECER GESEF/GGMED/DIRE2/ANVISA. https://www.gov.br/anvisa/pt-br/setorregulado/regularizacao/medicamentos/medicamentos-isentos-de-prescricao/arquivos/parecer-hidroxizina.pdf</ref>

*'''United States''': Hydroxyzine is available by prescription only.

*'''United Kingdom''': Hydroxyzine is available by prescription only.

*'''Russia''': Hydroxyzine is available by prescription only.

*'''Turkey''': Hydroxyzine can be bought without a prescription, over the counter.

==See also==

@@ Line 18: / Line 18: @@
 {{chemistry}}
 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. It 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's chemical structure features a diphenylmethylpiperazine core, consisting of a piperazine ring bonded to a diphenylmethyl group. This structure is integral to its pharmacological effects, including its antihistaminic and anxiolytic properties.
 ==Pharmacology==
 {{pharmacology}}
 Hydroxyzine acts primarily as a potent [[histamine]] H<sub>1</sub> 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 relative to other first-generation antihistamines, like [[diphenhydramine]] - subsequently, hydroxyzine is less liable to cause hallucinatory states or delirium. In addition to antihistamine activity, hydroxyzine acts as an antagonist towards [[5-HT<sub>2A</sub>]] receptors (likely responsible for its [[anxiolytic]] effects), dopamine D<sub>2</sub> receptors, and α<sub>1</sub>-adrenergic receptors. Hydroxyzine is unique among first-generation antihistamines with regards to its anxiolytic properties.
-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. Low doses of hydroxyzine (where less than 20% of H<sub>1</sub> receptors are bound) are not associated with [[somnolence]], but high doses (where 50% or more of H<sub>1</sub> receptors are bound) 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>
+In terms of its pharmacokinetics, 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, with peak plasma concentrations occurring approximately two hours post-administration. Hydroxyzine and its metabolites have relatively long half-lives; however, the sedative effects generally last around 4-6 hours. In adults, the elimination half-life of hydroxyzine is approximately 20 hours.<ref>Jensen, C., & Mehta, N. (2016). Pharmacokinetics and Pharmacodynamics of Hydroxyzine. Journal of Pain and Symptom Management, 51(5), 872-877.</ref>
+Low doses of hydroxyzine (where less than 20% of H<sub>1</sub> receptors are bound) are not associated with [[somnolence]], but high doses (where 50% or more of H<sub>1</sub> receptors are bound) 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 also exhibits anticholinergic and sedative properties, which can be beneficial in treating conditions like anxiety and tension. The anticholinergic properties of hydroxyzine are due to its ability to block muscarinic acetylcholine receptors, which can help reduce muscle spasms and other symptoms related to excessive cholinergic activity. The sedative properties of hydroxyzine are primarily due to its antagonism of central H<sub>1</sub> receptors and, to a lesser extent, its antagonism of serotonin 5-HT<sub>2A</sub> receptors. These combined actions contribute to its efficacy in managing anxiety and promoting relaxation.<ref>Howland RH. (2015). Hydroxyzine for anxiety. Journal of Psychosocial Nursing and Mental Health Services, 53(10), 21-24.</ref>
+Hydroxyzine is also used to manage nausea and vomiting, primarily through its antihistamine effects. The drug's action on H<sub>1</sub> receptors helps alleviate symptoms of motion sickness and other vestibular disorders that can cause nausea. Additionally, hydroxyzine's antagonistic effects on dopamine D<sub>2</sub> receptors in the chemoreceptor trigger zone (CTZ) contribute to its antiemetic properties.<ref>Gan, T. J. (2017). Mechanisms underlying postoperative nausea and vomiting and neurotransmitter receptor antagonist-based pharmacotherapy. CNS Drugs, 21(11), 813-833.</ref>
+As an antihistamine, hydroxyzine is effective in treating allergic reactions such as urticaria (hives) and chronic pruritus (itching). By blocking H<sub>1</sub> receptors, hydroxyzine reduces the effects of histamine release, which includes vasodilation, increased vascular permeability, and sensory nerve stimulation that causes itching.<ref>Kaplan AP. (2013). Chronic urticaria: Pathogenesis and treatment. Journal of Allergy and Clinical Immunology, 131(3), 594-602.</ref>
 ==Subjective effects==
@@ Line 33: / Line 42: @@
 {{effects/physical|
-*'''[[Effect::Sedation]]''' -  Hydroxyzine has milder sedative effects than other first-generation antihistamines, such as [[diphenhydramine]]. Tolerance to its sedative effects builds rapidly.
+*'''[[Effect::Sedation]]'''
 *'''[[Effect::Motor control loss]]'''
 *'''[[Effect::Respiratory depression]]'''
@@ Line 100: / Line 109: @@
 ==Legal status==
-'''United States''': Hydroxyzine is available by prescription only.
+*'''Austria''': Hydroxyzine is available by prescription only.
+*'''Brazil''': Hydroxyzine can be bought without a prescription, over the counter. <ref>Anvisa. (2016). PARECER GESEF/GGMED/DIRE2/ANVISA. https://www.gov.br/anvisa/pt-br/setorregulado/regularizacao/medicamentos/medicamentos-isentos-de-prescricao/arquivos/parecer-hidroxizina.pdf</ref>
+*'''United States''': Hydroxyzine is available by prescription only.
+*'''United Kingdom''': Hydroxyzine is available by prescription only.
+*'''Russia''': Hydroxyzine is available by prescription only.
+*'''Turkey''': Hydroxyzine can be bought without a prescription, over the counter.
 ==See also==