Hydroxyzine

Absorption

The absolute bioavailability of hydroxyzine has not been ascertained, as intravenous formulations are unavailable due to a risk of hemolysis. Hydroxyzine is rapidly absorbed from the gastrointestinal tract upon oral administration, reaching its maximum plasma concentration (Tmax) approximately 2 hours following administration.

Toxicity

The oral LD50 is 840 mg/kg in rats and 400 mg/kg in mice.
Overdose from hydroxyzine is most commonly characterized by hypersedation, but may also manifest as convulsions, stupor, nausea, and vomiting. In cases of overdose, consider the induction of vomiting and the use of gastric lavage. Other treatment should involve general symptomatic and supportive care. Hypotension may be controlled by intravenous fluids and pressors, and caffeine and sodium benzoate injection may be used to counteract any observed CNS depressant effects. Hemodialysis is unlikely to provide any benefit in the treatment hydroxyzine overdose.

Description

Hydroxyzine is an antihistamine drug with M-cholinoblocking properties and expressed action on the CNS. It suppresses subcortical regions of the CNS including the limbic system and reticular formation. It potentiates the effect of narcotic analgesics and exhibits sedative effects.

Chemical properties

Yellow Oil

Originator

Atarax,UCB,France,1956

The Uses of Hydroxyzine

Hydroxyzine is intended for the symptomatic treatment of anxiety and stress associated with neurosis as well as with conditions of organic illness. This drug has muscle relaxant, antihistimine, analgesic, local anesthetic, and antiemetic action as well as a wide therapeutic effect. It is mainly used in premedication and following general anesthesia, during which it potentiates the action of meperidine and barbiturates. It is frequently used in pediatrics as a mild sedative drug.

The Uses of Hydroxyzine

H1 receptor antagonist. Anxiolytic. Antihistaminic.

The Uses of Hydroxyzine

It is used as a sympthomatic drug for atopic dermatitis as a sedative drug before and after operational interventions, for preventing vomiting and diarrhea, and for relieving agitation and emotional disorders. Synonyms of this drug are atarax, durrax, and vistaril.

Indications

Hydroxyzine is indicated for the symptomatic relief of anxiety and tension associated with psychoneuroses, and as an adjunct in organic disease states in which anxiety is manifested. It is also indicated in the treatment of histamine-mediated pruritus and pruritus due to allergic conditions such as chronic urticaria.
Canadian labeling states that hydroxyzine is also indicated in adults and children as a premedication prior to medical procedures, such as dental surgery. It is also used in the control of nausea and vomiting, excluding nausea and vomiting of pregnancy.

Background

Hydroxyzine is a first-generation histamine H1-receptor antagonist of the dephenylmethane and piperazine classes that exhibits sedative, anxiolytic, and antiemetic properties. It was first developed in 1955, and has since remained a relatively common treatment for allergic conditions such as pruritus, urticaria, dermatoses, and histamine-mediated pruritus. The active metabolite of hydroxyzine, cetirizine, is also available as an active ingredient in allergic medications, and is responsible for much of its hydroxyzine's antihistaminic effect. Hydroxyzine is also used for generalized anxiety disorder, tension caused by psychoneurosis, and other conditions with manifestations of anxiety.

What are the applications of Application

Hydroxyzine is an H1 receptor antagonist

Definition

ChEBI: A N-alkylpiperazine that is piperzine in which the nitrogens atoms are substituted by 2-(2-hydroxyethoxy)ethyl and (4-chlorophenyl)(phenyl)methyl groups respectively.

Indications

Drugs of choice for the treatment of dermatographism and cholinergic urticaria. They are also effective alone or in combination with other antihistamines in the management of acute and chronic urticaria, atopic and contact dermatoses, and histamine-induced pruritus. It may be used alone or with other antihistamines, and dosage should be pushed to the limit of tolerance or to subsidence of symptoms.

Manufacturing Process

A mixture of 0.1 mol of N-mono-1-p-chlorobenzohydrylpiperazine and 0.1 mol of 1-chloro-2-(2-hydroxy-ethoxy)-ethane is heated for 3 hours to 150°C. The mass is then taken up in 100 ml of benzene and 100 ml of a 10% aqueous solution of NaOH; decanting takes place, and the benzene solution is washed with water and the solvent is evaporated. Vacuum distilling of the residue yields 1-p-chlorobenzohydryl-4-[2-(2-hydroxy-ethoxy)-ethyl]-piperazine, BP 220°C/0.5 mm Hg.
The corresponding dihydrochloride is prepared by dissolving this base in about twice its weight of alcohol, by treating it with excess of gaseous HCl and by precipitating it with ether. The solvent is decanted and the residue, dissolved in a minimum of alcohol, crystallizes on the addition of ether, MP 193°C.

brand name

Amplimexon (Amplimed).

Therapeutic Function

Tranquilizer

Pharmacokinetics

Hydroxyzine blocks the activity of histamine to relieve allergic symptoms such as pruritus. Activity at off-targets also allows for its use as a sedative anxiolytic and an antiemetic in certain disease states.
Hydroxyzine is relatively fast-acting, with an onset of effect that occurs between 15 and 60 minutes and a duration of action between 4-6 hours. Hydroxyzine may potentiate the effects of central nervous system (CNS) depressants following general anesthesia - patients maintained on hydroxyzine should receive reduced doses of any CNS depressants required. Hydroxyzine is reported to prolong the QT/QTc interval based on postmarketing reports of rare events of Torsade de Pointes, cardiac arrest, and sudden death, and should be used with caution in patients with an increased baseline risk for QTc prolongation.

Safety Profile

Poison by intravenous and intraperitoneal routes. Moderately toxic by ingestion. Experimental teratogenic and reproductive effects. When heated to decomposition it emits very toxic fumes of Cland NOx.

Synthesis

Hydroxyzine, 2-[2-[4-(p-chloro-|á-phenylbenzyl)-1-piperazinyl]-ethoxy] ethanol (5.2.6), is synthesized by the alkylation of 1-(4-chlorobenzohydril)piperazine with 2-(2-hydroxyotoxy)ethylchloride [56¨C61].

Metabolism

Hydroxyzine is metabolized in the liver by CYP3A4 and CYP3A5. While the precise metabolic fate of hydroxyzine is unclear, its main and active metabolite (~45 to 60% of an orally administered dose), generated by oxidation of its alcohol moiety to a carboxylic acid, is the second-generation antihistamine cetirizine. Hydroxyzine is likely broken down into several other metabolites, though specific structures and pathways have not been elucidated in humans.

Dosage forms

25 mg, three to four times a day.