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. It acts primarily as a potent and selective H1 receptor antagonist,[1][2] with anxiolytic effects attributable to weak antiserotonergic effects.[3]
It belongs to the piperazine/ethanopiperidine family of chemicals.[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. 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).[7] 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.[8] It is highly advised 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.[9] 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. |
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. [10][11] In the United Kingdom 28 doses cost less than a pound.[12] In the United States the wholesale cost in 2018 was about 0.05 USD per dose.[13] In the United States about 8 million prescriptions were written for hydroxyzine in 2016.[14]
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.
Hydroxyzine is synthesized by the alkylation of 1-(4-chlorobenzhydryl)piperazine with 2-(2-Chloroethoxy)ethanopiperidine[15]
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.[16][17] 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.[18]
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.
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 ☠.
Physical effects 
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- Sedation - Hydroxyzine has milder sedative effects than other first-generation antihistamines, such as diphenhydramine. Tolerance to its sedative effects builds rapidly.
- 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.[19] 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 and harm potential
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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.
Lethal dosage
Tolerance and addiction potential
Hydroxyzine works in multiple ways and can cause a variety of effects. It is only proven to affect histamine but has been shown to effect Acetylcholine, Glutamate, and GABA. Being a dissociative at very high doses, it can act more similarly to Ketamine and PCP (structural relative)in comparison to other antihistamines like Diphenhydramine (a deliriant). Most abuse of this drug happens at lower doses with the desired effect being sedation. Being a relaxant sedative, it can become habit forming. Its sedative effects are found to be more powerful than that of Diphenhydramine or Doxylamine, and happens to have more of an anxiolytic/anticonvulsant effect than that of those named above. Because of this, it can be a safer substitute to Benzodiazepines and GABAergics, and can provide a similar effect. Tolerance to Hydroxyzine can develop fast and psychological addiction can be common in patients treated for anxiety and insomnia with Hydroxizine. Physical addiction and dependence is present but not common - much of the addiction is psychological. Safe use is recommended with this medication.
Dangerous interactions
This medication can interact with many other substances in dangerous and even lethal ways. Being a CNS depressant, it can be potentiated by other depressant drugs. Alcohol should always be avoided as well as other GABA active drugs like Benzodiazepines (Ex. Alprazolam, Diazepam), Barbiturates (Ex. Secobarbital, Sodium Thiopental), and Anticonvulsants (Ex. Gabapentin, Pregabalin, Carisoprodol, Baclofen). Other depressant drugs that can interact with this are opiates. Opiates can be potentiated by this drug and can increase risk for overdose. Phencyclidine is a piperidine similar in structure to this drug and can basically double dose you. Be careful with any depressant when taking this medication.
Legal status
United States: Hydroxyzine is available by prescription but is not scheduled due to its low abuse concern
See also
External links
Literature
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References
- ↑ 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.
- ↑ "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.
- ↑ 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.
- ↑ 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.
- ↑ Anderson PO, Knoben JE, Troutman WG (2002). Handbook of Clinical Drug Data. pp. 794-6. ISBN 9780071363624. PMC 1875767. PMID 20313924.