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Hydroxyzine, sold under the brand names Atarax among others, is a medication of the antihistamine type.
Common side effects include sleepiness, headache, and a dry mouth.
It was first made by Union Chimique Belge in 1956 and was approved for sale by Pfizer in the United States later that year.
Contents
1 Medical uses
2 Contraindications
3 Side effects
4 Pharmacology
4.1 Pharmacodynamics
4.2 Pharmacokinetics
5 Chemistry
5.1 Analogues
5.2 Synthesis
6 Brand names
7 References
8 External links
Medical uses
Hydroxyzine is used in the treatment of itchiness, anxiety, and nausea including that due to motion sickness.
Hydroxyzine is prescribed when the onset of an organic disease state manifests through anxiety, as generalized anxiety disorder, or in other more serious cases as psychoneurosis, and is therefore prescribed as a means of regulating normal function. Hydroxyzine has shown to be as effective as the benzodiazepine drug bromazepam in the treatment of generalised anxiety disorder.
Hydroxyzine can also be used for the treatment of allergic conditions, 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.
Use of hydroxyzine for premedication as a sedative has no effects on tropane alkaloids, such as atropine, but may, following general anesthesia, potentiate meperidine and barbiturates, and use in pre-anesthetic adjunctive therapy should be modified depending upon the state of the individual.
In other cases, the usage of hydroxyzine is as a form of non-barbiturate tranquilizer
Contraindications
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. Hydroxyzine is contraindicated for intravenous (IV) injection, as it has shown to cause hemolysis.
Other contraindications include the administration of hydroxyzine alongside depressants and other compounds which 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, incoordination, sedation, calmness, and dizziness have been reported in children and adults, as well as others such as hypotension, tinnitus, and headaches.
Central nervous system problems such as hallucinations or confusion have been observed in rare cases, attributed mostly to overdosage.
The effect of hydroxyzine has also been tested on the ability of humans in the registration and storage of memory, and was used in comparison with relatively safe drugs, such as lorazepam, to illustrate the effects of benzodiazepines, which are thought to have adverse effects on the capacity of memory storage. Hydroxyzine was found to have no adverse effects on memory in relation to lorazepam, which caused several deficiencies in the capacity of memory storage.
In a comparative study with lorazepam on memory effects, patients who had taken hydroxyzine experienced sedative effects like drowsiness, but recalled that they felt capable, attentive and able to continue with a memory test under these conditions.
Somnolence with or without vivid dreams or nightmares may occur in users with antihistamine sensitivities in combination with other CNS depressants. Hydroxyzine exhibits anxiolytic and sedative properties in many psychiatric patients. 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.
Because of potential for more severe side effects, this drug is on the list to avoid in the elderly.
In 2015, the European Medicines Agency (EMA) announced a small but definite risk of QT prolongation associated with the use of hydroxyzine.
This side effect is more likely to occur in people with pre-existing cardiac disease, or with the use of other medicines known to prolong the QT interval.
Pharmacology
Pharmacodynamics
Hydroxyzine
Site
K i (nM)
Species
Ref
5-HT 2A
170 ( IC 50 )
Rat
5-HT 2C
ND
ND
ND
α 1
460 ( IC 50 )
Rat
D 1
>10,000
Mouse
D 2
378 560 ( IC 50 )
Mouse Rat
H 1
2.0–19 6.4 100 ( IC 50 )
Human Bovine Rat
H 2
ND
ND
ND
H 3
ND
ND
ND
H 4
>10,000
Human
mACh
4,600 10,000 10,000 ( IC 50 ) 6,310 (pA 2 ) 3,800
Human Mouse Rat Guinea pig Bovine
VDCC
≥3,400 ( IC 50 )
Rat
Values are K i (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 H 1 receptor inverse agonist.
Hydroxyzine crosses the blood–brain barrier easily and exerts effects in the central nervous system.
Pharmacokinetics
Hydroxyzine can be administered orally or via intramuscular injection. When given orally, hydroxyzine is rapidly absorbed from the gastrointestinal tract. The effect of hydroxyzine is notable in 30 minutes.
Pharmacokinetically, hydroxyzine is rapidly absorbed and distributed in 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 anti-histaminergic 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.
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.
Similarly, the use of sedating drugs alongside hydroxyzine can cause oversedation and confusion if administered in large amounts—any form of treatment alongside sedatives should be done under supervision of a doctor.
The T max of hydroxyzine is about 2.0 hours in both adults and children and its elimination half-life is around 20.0 hours in adults and 7.1 hours in children.
Chemistry
Hydroxyzine is a member of the diphenylmethylpiperazine class of antihistamines.
Analogues
Analogues of hydroxyzine include buclizine, cetirizine, cinnarizine, cyclizine, etodroxizine, meclizine, and pipoxizine among others.
Synthesis
Hydroxyzine is synthesized by the alkylation of 1-(4-chlorobenzohydril)piperazine with 2-(2-hydroxyethoxy)ethylchloride:
Brand names
Hydroxyzine preparations require a doctor’s prescription. The drug is available in two formulations, 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.

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