Histan Mechanism of Action

Pharmacology: Pharmacodynamics: Hydroxyzine is a piperazine-derivative antihistamine. It is a first-generation antihistamine which binds nonselectively to central and peripheral H₁ receptors. Hydroxyzine is a sedating antihistamine with antimuscarinic and significant sedative properties. Its main use is as an anxiolytic. It is also used as an adjunct to premedication and in the management of pruritus and urticaria.
Hydroxyzine appears to be the most potent antihistamine in alleviating IgE-mediated pruritus and urticaria.
Hydroxyzine suppresses the wheal-and-flare response in the skin for greater than 24 hours.
The sedative and tranquilizing effects of Hydroxyzine are thought to result principally from suppression of activity at subcortical levels of the CNS; the drug does not have cortical depressant activity.
Pharmacokinetics: Absorption: Hydroxyzine is rapidly absorbed from the gastrointestinal tract. The peak plasma level (C_max) is reached approximately 2 hours after oral intake. The sedative effects begin approximately 15-30 minutes after oral intake and the sedative effect lasts for 4-6 hours.
Distribution: Hydroxyzine is widely distributed into most body tissues and fluids with highest generally concentration in the liver, lung, spleen, kidney and adipose tissue. The apparent volume of distribution is 16 L/kg in adults.
Metabolism: Hydroxyzine is metabolized in the liver by alcohol dehydrogenase and cytochrome P450 isoenzymes CYP3A4 and CYP3A5. The major metabolite of Hydroxyzine is cetirizine, which is a carboxylic acid metabolite. This metabolite has significant peripheral H₁-antagonist properties and long-acting antihistamine.
Elimination: Hydroxyzine and antihistamine metabolites (including small amounts of unchanged drug) are excreted in the urine. An elimination half-life of about 20 and 25 hours have been reported for Hydroxyzine and cetirizine, respectively.