Hydroxyzine
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| Pronunciation | /haɪˈdrɒksɪziːn/ |
| Trade names | Atarax,[1] Vistaril,[2] others |
| Other names | UCB-4492 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682866 |
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First generation antihistamine[4] | |
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| Bioavailability | High |
| Protein binding | 93% |
| Metabolism | Liver |
| Metabolites | Cetirizine, others |
| Elimination half-life | Adults: 20.0 hours[5][6] Elderly: 29.3 hours[7] Children: 7.1 hours[5] |
| Excretion | Urine, feces |
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Hydroxyzine, sold under the brand names Atarax and Vistaril among others, is an
Common side effects include sleepiness, headache, and a
It was first
Medical uses
A Hydroxyzine can also be used for the treatment of better source needed ]
Use of hydroxyzine for adjunctive therapy should be modified depending upon the state of the individual.[14]
Doses of hydroxyzine hydrochloride used for sleep range from 25 to 100 mg. GabasyncGabasync, a treatment consisting of a combination of hydroxyzine and two other medications (gabapentin and flumazenil) as well as therapy, is an ineffective treatment promoted for methamphetamine addiction, though it had also been claimed to be effective for dependence on alcohol or cocaine.[21] It was marketed as PROMETA. While the individual drugs had been approved by the FDA, their off-label use for addiction treatment has not.[22] Gabasync was marketed by Hythiam, Inc. which is owned by Terren Peizer, a former bond salesman who has since been indicted for securities fraud relative to another company.[23][24] Hythiam charges up to $15,000 per patient to license its use (of which half goes to the prescribing physician, and half to Hythiam).[25] In November 2011, the results of a double-blind, placebo-controlled study (financed by Hythiam and carried out at peer-reviewed journal Addiction. It concluded that Gabasync is ineffective: "The PROMETA protocol, consisting of flumazenil, gabapentin and hydroxyzine, appears to be no more effective than placebo in reducing methamphetamine use, retaining patients in treatment or reducing methamphetamine craving."[26]
ContraindicationsHydroxyzine is contraindicated for The administration of hydroxyzine in large amounts by ingestion or intramuscular administration during the onset of pregnancy can cause better source needed ]
In humans, a significant dose has not yet been established in studies and, by default, the Food and Drug Administration (FDA) has introduced contraindication guidelines in regard to hydroxyzine.[29] Use by those at risk for or showing previous signs of hypersensitivity is also contraindicated.[29] Other contraindications include the administration of hydroxyzine alongside depressants and other compounds which affect the central nervous system;[29] if absolutely necessary, it should only be administered concomitantly in small doses.[29] 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, in accordance with safety laws.[29] Studies have also been conducted which show that long-term prescription of hydroxyzine can lead to neuroleptic treatment may have contributed to dyskinesia at the administration of hydroxyzine due to hypersensitivity caused by prolonged treatment,[30] and therefore some contraindication is given for short-term administration of hydroxyzine to those with previous phenothiazine use.[30]
Side effectsSeveral reactions have been noted in manufacturer guidelines—deep sleep, incoordination, sedation, calmness, and dizziness have been reported in children and adults, as well as others such as antimuscarinic properties of hydroxyzine.[31]
 Central nervous system effects such as hallucinations or confusion have been observed in rare cases, attributed mostly to overdosage. 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 response.[34] 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 supervision of a doctor.[35][32] Because of the potential for more severe side effects, this drug is on the list to avoid in the elderly.[36] PharmacologyPharmacodynamics
Hydroxyzine's predominant antiserotonergic effects of hydroxyzine likely underlie its usefulness as an anxiolytic.[50] Other antihistamines without such properties have not been found to be effective in the treatment of anxiety.[51]
Hydroxyzine crosses the cognitive decline, whereas brain H1 receptor occupancy of less than 20% is considered to be non-sedative.[53]
Hydroxyzine also acts as a functional inhibitor of Acid sphingomyelinase.[54] PharmacokineticsHydroxyzine can be administered orally or via intramuscular injection. When given orally, hydroxyzine is rapidly absorbed from the gastrointestinal tract. Hydroxyzine is rapidly absorbed and distributed with oral and intramuscular administration, and is metabolized in the liver; the main metabolite (45%), cetirizine, is formed through oxidation of the alcohol moiety to a carboxylic acid by alcohol dehydrogenase, and 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. The other metabolites identified include a 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.[55][56] The N-dealykylated metabolite, norchlorcyclizine, bears some structural similarities to trazodone, but it has not been established whether it is pharmacologically active.[57][58] In animals, hydroxyzine and its metabolites are excreted in feces primarily through biliary elimination.[59][60] In rats, less than 2% of the drug is excreted unchanged.[60] The time to reach maximum concentration ( elimination half-life is around 20.0 hours in adults (mean age 29.3 years) and 7.1 hours in children.[5][6] Its elimination half-life is shorter in children compared to adults.[5] In another study, the elimination half-life of hydroxyzine in elderly adults was 29.3 hours.[7] 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.[61] 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.[62]
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. ChemistryHydroxyzine is a member of the diphenylmethylpiperazine class of antihistamines.[medical citation needed] Hydroxyzine is supplied mainly as a molecular weights of hydroxyzine, hydroxyzine dihydrochloride, and hydroxyzine pamoate are 374.9 g/mol, 447.8 g/mol, and 763.3 g/mol, respectively.[4] Due to their differences in molecular weight, 1 mg hydroxyzine dihydrochloride is equivalent to about 1.7 mg hydroxyzine pamoate.[66]
Analogues
Analogues of hydroxyzine include buclizine, cetirizine, cinnarizine, cyclizine, etodroxizine, meclizine, and pipoxizine among others. Society and cultureBrand names
Hydroxyzine 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.
References
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