Hydroxyzine, sold under the brand names Atarax and Vistaril among others, is an antihistamine medication.[
]
Hydroxyzine works by blocking the effects of histamine.[ Serious side effects may include QT prolongation.][ It is unclear if use during pregnancy or breastfeeding is safe.][
]
It was first made by Union Chimique Belge in 1956 and was approved for sale by Pfizer in the United States later that year.
Medical uses
Hydroxyzine is used in the treatment of itchiness, anxiety, and nausea due to motion sickness.[
]
A systematic review concluded that hydroxyzine outperforms placebo in treating generalized anxiety disorder. Insufficient data were available to compare the drug with benzodiazepines and buspirone.
Hydroxyzine can also be used for the treatment of allergy, such as chronic urticaria, atopic or contact dermatoses, and histamine-mediated pruritus. These have also been confirmed in both recent and past studies to have no adverse effects on the liver, blood, nervous system, or urinary tract.[United States Food & Drug Administration (2004), p. 1]
Use of hydroxyzine for premedication as a sedative has no effects on , such as atropine, but may, following general anesthesia, potentiate pethidine and , and use in pre-anesthetic adjunctive therapy should be modified depending upon the state of the individual.
Doses of hydroxyzine hydrochloride used for sleep range from 25 to 100 mg.
Contraindications
Hydroxyzine is contraindicated for subcutaneous or intra-articular administration.
The administration of hydroxyzine in large amounts by ingestion or intramuscular administration during the onset of pregnancy can cause fetal abnormalities. When administered to pregnant rats, mice, and rabbits, hydroxyzine caused abnormalities such as hypogonadism with doses significantly above that of the human therapeutic range.[United States Food & Drug Administration (2004), p. 2]
In humans, a significant dose has not yet been established in studies, and, by default, the US Food and Drug Administration (FDA) has introduced contraindication guidelines regarding hydroxyzine.
Other contraindications include the administration of hydroxyzine alongside and other compounds that affect the central nervous system;
Studies have also been conducted which show that long-term prescription of hydroxyzine can lead to tardive dyskinesia after years of use, but effects related to dyskinesia have also anecdotally been reported after periods of 7.5 months,
Side effects
Several reactions have been noted in manufacturer guidelines—deep sleep, Ataxia, sedation, and dizziness have been reported in children and adults, as well as others such as hypotension, tinnitus, and Headache.[UCB South-Africa, et al., (2004)] Gastrointestinal effects have also been observed, as well as less serious effects such as dryness of the mouth and constipation caused by the mild antimuscarinic properties of hydroxyzine.
Central nervous system effects such as Hallucination 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 responses.
Because of the potential for more severe side effects, this drug is on the list to avoid in the elderly.
Pharmacology
Pharmacodynamics
+Hydroxyzine |
|
|
| |
|
|
|
|
| |
| |
|
|
|
| Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site. |
Hydroxyzine's predominant mechanism of action is as a potent and selective histamine H1 receptor inverse agonist.
Hydroxyzine crosses the blood–brain barrier easily and exerts effects in the central nervous system.
Hydroxyzine also acts as a functional inhibitor of acid sphingomyelinase.
Pharmacokinetics
Hydroxyzine 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.
The time to reach maximum concentration (Tmax) of hydroxyzine is about 2.0 hours in both adults and children and its elimination half-life is around 20.0 hours in adults (mean age 29.3 years) and 7.1 hours in children.
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.[United States Food & Drug Administration (2004), p. 3]
Chemistry
Hydroxyzine is a member of the diphenylmethylpiperazine class of antihistamines.
Hydroxyzine is supplied mainly as a dihydrochloride salt (hydroxyzine hydrochloride) but also to a lesser extent as an embonate salt (hydroxyzine pamoate).
Analogues
Analogues of hydroxyzine include buclizine, cetirizine, cinnarizine, cyclizine, etodroxizine, meclizine, and pipoxizine among others.
Society and culture
Brand names
Hydroxyzine drug form require a doctor's prescription. The drug is available in two , the pamoate and the 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.
See also
