Talk:Hydroxyzine
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| Summary sheet: Hydroxyzine |
| Hydroxyzine | |||||||||||||||||||||||||||||
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| Chemical Nomenclature | |||||||||||||||||||||||||||||
| Common names | Vistaril, Atarax | ||||||||||||||||||||||||||||
| Substitutive name | Hydroxyzine | ||||||||||||||||||||||||||||
| Systematic name | 2-[2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]ethanol | ||||||||||||||||||||||||||||
| Class Membership | |||||||||||||||||||||||||||||
| Psychoactive class | Depressant | ||||||||||||||||||||||||||||
| Chemical class | Diphenylmethylpiperazine | ||||||||||||||||||||||||||||
| Routes of Administration | |||||||||||||||||||||||||||||
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Hydroxyzine is a first-generation antihistamine substance of the diphenylmethylpiperazine/ethano-piperidine class.[1] It acts primarily as a potent and selective histamine H1 receptor antagonist,[2][3] with anxiolytic effects likely attributable to weak antiserotonergic effects.[4]
Hydroxyzine is often used in the treatment of itchiness, anxiety, insomnia, and nausea from motion sickness.[5] 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.[6]
Hydroxyzine sees little recreational use, limited mostly to where stronger anxiolytics, such as benzodiazepines or alcohol, are not available.[citation needed] Unlike more commonly abused depressants, it does not impact the neurotransmitter GABA, instead acting via potent inverse agonism of the histamine H1 receptor, which is responsible for its antihistamine and sedative effects.[7][8] In addition to its antihistamine activity, it has been shown to act as a weak antagonist towards the serotonin 5-HT2A receptor, the dopamine D2 receptor, and the α1-adrenergic receptor. It is prescribed for the treatment of generalized anxiety disorder, short-term treatment of insomnia, and allergic reactions .[9] 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.[10] Combining hydroxyzine with other depressants such as benzodiazepines or alcohol can cause extreme symptoms such as dizziness or drowsiness, and as such it is recommended to use harm reduction practices if using this substance.
Tolerance to the CNS effects of hydroxyzine develops rapidly, often in as few as 3-7 days.[11] Tolerance to its sedative effects builds faster than tolerance to its anxiolytic effects. Such, it is indicated for use in short-term or as-needed insomnia treatment.
History and Culture
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This History and culture section is a stub. As a result, it may contain incomplete or wrong information. You can help by expanding it. |
Hydroxyzine was first synthesized by Union Chimique Belge in 1956 and was approved for sale by Pfizer in the United States later that year.[12][13] Originally mostly given for nausea and allergies, it later began to be used in medicine for its anxiolytic properties. It is sometimes given as a substitute to benzodiazepines in surgeries to decrease anxiety and act as an anesthetic. In the United Kingdom 28 doses cost less than a pound.[14] In the United States the wholesale cost in 2018 was about 0.05 USD per dose.[15] In the United States about 8 million prescriptions were written for hydroxyzine in 2016.[16]
Chemistry
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This chemistry section is incomplete. You can help by adding to it. |
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[17] 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
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This pharmacology section is incomplete. You can help by adding to it. |
Hydroxyzine acts primarily as a potent histamine H1 receptor antagonist.[18][19] 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.
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.[20]
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.[21]
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.[22]
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.[23]
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.[24]
Subjective effects
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This subjective effects section is a stub. As such, it is still in progress and may contain incomplete or wrong information. You can help by expanding or correcting it. |
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠. {{effects/base
Physical effects 
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- Sedation
- Motor control loss
- Respiratory depression
- Perception of bodily heaviness
- Dizziness
- Abnormal heartbeat
- Increased heart rate
- Difficulty urinating
- Itchiness - Itchiness is suppressed in low doses but increased in high doses.
- Nausea suppression - Hydroxyzine is indicated for treatment of nausea.
- Dehydration
- Cough suppression
- Tactile hallucinations - This effect only occurs at dangerously high doses, such as intentional overdoses.
Visual effects 
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- Visual acuity suppression - Like many depressants, hydroxyzine is known to cause blurred or otherwise suppressed visual acuity in high doses. This is less likely to occur than other depressants, however it can still present itself at higher doses, or if the user has a low tolerance.
- External hallucinations - This effect is nowhere near as pronounced as diphenhydramine and only occurs in extremely high doses or when combined with other CNS depressants, such as lithium, valproate, antipsychotics, or ethanol.[25] These experiences are often reported by individuals with psychiatric comorbidities who are prescribed mood stabilizers, antipsychotics, or tricylic/tetracyclic antidepressants.
Paradoxical effects 
- Paradoxical reactions to hydroxyzine occur mostly in high doses and can include nausea, itchiness, agitation, restlessness, and muscle spasms. Extremely high doses can result in seizures, vomiting, uncontrollable shaking, and other effects typical of an antihistamine overdose.
Cognitive effects 
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The general head space of hydroxyzine is described by many as one of mild to moderate sedation.
The most prominent of these cognitive effects generally include:
- Anxiety suppression - This effect is mild compared to benzodiazepines.
- Disinhibition - This effect is mild compared to benzodiazepines.
- Thought deceleration
- Analysis suppression
- Amnesia - This only occurs in very high doses and is less pronounced than other depressants.
- Emotion suppression - Antagonizing dopamine, adrenaline, and serotonin receptors, hydroxyzine exhibits similar emotional suppression to antipsychotics, but far less pronounced.
- Language suppression - This only occurs in very high doses and may be indictive of an overdose.
- Confusion
- Creativity suppression
- Decreased libido
After effects 
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- Rebound anxiety - Rebound anxiety is a commonly observed effect with anxiety relieving substances like hydroxyzine. It typically corresponds to the total duration spent under the substance's influence along with the total amount consumed in a given period, an effect which can easily lend itself to cycles of dependence and addiction. Because hydroxyzine is a weak anxiolytic compared to benzodiazepines, addiction is extremely rare, but physical dependence is possible with frequent use.
- Residual sleepiness - While hydroxyzine can be used as an effective sleep-inducing aid, its effects may persist into the morning afterward, which may lead users to feeling "groggy" or "dull" for up to a few hours.
- Thought deceleration
- Thought disorganization
Experience reports
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
Toxicity, Harm Potential, and Dangerous Interactions
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This toxicity and harm potential section is a stub. As a result, it may contain incomplete or even dangerously wrong information! You can help by expanding upon or correcting it. |
It is strongly recommended that one use harm reduction practices when using this substance. It can cause extreme drowsiness and lack of coordination, and can increase the sedating effects of alcohol and other CNS depressants.
Hydroxyzine is contraindicated in patients with risk factors for QT prolongation, a cardiac electrical disturbance which causes the heart muscles longer than normal to recharge between beats. Excessive QT prolongation can trigger tachycardias such as torsades de pointes (TdP), which can be fatal. Caution is recommended during the concomitant use of drugs known to prolong the QT interval, which include quinidine, antiarrhythmics, certain antipsychotics (e.g., ziprasidone, iloperidone, clozapine, quetiapine, chlorpromazine), certain antidepressants (e.g., citalopram, fluoxetine), certain antibiotics (e.g., azithromycin, erythromycin, clarithromycin, gatifloxacin, moxifloxacin); and others (e.g., pentamidine, methadone, ondansetron, droperidol).[26]
Tolerance and addiction potential
As discussed, hydroxyzine interacts with a variety of receptors and can cause a variety of effects. At very high doses, it may cause delirium, similar to other antihistamines like diphenhydramine. Its sedating, anxiolytic effects can be habit forming and result in psychological addiction, tolerance, and dependence. Tolerance to Hydroxyzine can develop fast and psychological addiction can be common in patients treated for anxiety and insomnia with hydroxizine.[citation needed]
Legal status
- Austria: Hydroxyzine is available by prescription only.
- Brazil: Hydroxyzine can be bought without a prescription, over the counter. [27]
- 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
External links
Literature
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References
- ↑ "Hydroxyzine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 21 Nov 2018.
- ↑ 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.
- ↑ Hosák L, Hrdlička M, et al. (2017). Psychiatry and Pedopsychiatry. Charles University in Prague, Karolinum Press. p. 364. ISBN 9788024633787.
- ↑ 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.
- ↑ "Hydroxyzine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 21 Nov 2018.
- ↑ 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.
- ↑ 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.
- ↑ Hosák L, Hrdlička M, et al. (2017). Psychiatry and Pedopsychiatry. Charles University in Prague, Karolinum Press. p. 364. ISBN 9788024633787.
- ↑ Rosario B. Hidalgo, David V. Sheehan, in Handbook of Clinical Neurology, 2012
- ↑ British national formulary : BNF 74 (74 ed.). British Medical Association. 2017. p. X. ISBN 978-0857112989.
- ↑ Levander S, Ståhle-Bäckdahl M, Hägermark O (1 September 1991). "Peripheral antihistamine and central sedative effects of single and continuous oral doses of cetirizine and hydroxyzine". European Journal of Clinical Pharmacology. 41 (5): 435–439. doi:10.1007/BF00626365. PMID 1684750. S2CID 25249362.
- ↑ "Hydroxyzine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 21 Nov 2018.
- ↑ Shorter E (2009). Before Prozac: the troubled history of mood disorders in psychiatry. Oxford [Oxfordshire]: Oxford University Press. ISBN 9780195368741.
- ↑ British national formulary : BNF 74 (74 ed.). British Medical Association. 2017. p. X. ISBN 978-0857112989.
- ↑ "NADAC as of 2018-11-21". Centers for Medicare and Medicaid Services. Retrieved 21 Nov 2018.
- ↑ British national formulary : BNF 74 (74 ed.). British Medical Association. 2017. p. X. ISBN 978-0857112989.
- ↑ 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).
- ↑ 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.
- ↑ Hosák L, Hrdlička M, et al. (2017). Psychiatry and Pedopsychiatry. Charles University in Prague, Karolinum Press. p. 364. ISBN 9788024633787.
- ↑ Jensen, C., & Mehta, N. (2016). Pharmacokinetics and Pharmacodynamics of Hydroxyzine. Journal of Pain and Symptom Management, 51(5), 872-877.
- ↑ Yanai K, Tashiro M (January 2007). "The physiological and pathophysiological roles of neuronal histamine: an insight from human positron emission tomography studies". Pharmacology & Therapeutics. 113 (1): 1–15. doi:10.1016/j.pharmthera.2006.06.008. PMID 16890992.
- ↑ Howland RH. (2015). Hydroxyzine for anxiety. Journal of Psychosocial Nursing and Mental Health Services, 53(10), 21-24.
- ↑ Gan, T. J. (2017). Mechanisms underlying postoperative nausea and vomiting and neurotransmitter receptor antagonist-based pharmacotherapy. CNS Drugs, 21(11), 813-833.
- ↑ Kaplan AP. (2013). Chronic urticaria: Pathogenesis and treatment. Journal of Allergy and Clinical Immunology, 131(3), 594-602.
- ↑ Anderson PO, Knoben JE, Troutman WG (2002). Handbook of Clinical Drug Data. pp. 794-6. ISBN 9780071363624. PMC 1875767. PMID 20313924.
- ↑ Vistaril® (hydroxyzine pamoate) [package insert]. New York, New York: Pfizer Labs; 2016.
- ↑ 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