An anxiolytic agent Hydroxyzine medicine
Hydroxyzine is a derivative of biphenylmethane that is chemically unrelated to phenothiazines, reserve, meprobamate or benzodiazepines.
It does not depress the cerebral cortex, but its action may be related to the suppression of some key areas of the subcortical central nervous system (CNS).
It also has H1-histaminoblocking, bronchodilating and anti-emetic effects. In therapeutic doses does not increase gastric secretion or acidity, has a moderate inhibition of gastric secretion. Hydroxysine effectively reduces itching in patients with hives, eczema and dermatitis. In liver failure H1-histaminoblocking effect can be prolonged up to 96 hours after a single administration.
Possesses moderate anxiolytic activity and sedative effect.
Polysomnography in patients with insomnia and anxiety demonstrates prolonged sleep duration, reduced frequency of night awakenings after a single or repeated use of hydroxysine in a dose of 50 mg. Decrease in muscle tension in patients with anxiety is noted when taking hydroxysine in a dose of 50 mg 3 times a day. It does not cause mental addiction and addiction. No memory disturbances were noted use. In long-term use, there was no syndrome of “withdrawal” and deterioration of cognitive functions.
H1-histaminoblocking effect occurs approximately 1 h after taking hydroxysine orally. The sedative effect is shown after 30-45 minutes.
It has antispasmodic and sympatholytic effects, shows weak affinity to muscarinic receptors. Has a moderate analgesic effect.
Absorption is high. Time to reach the maximum concentration (TCmax) after oral administration is 2 hours. After a single dose of 25 mg TCmax In adults it is 30 ng/ml, after a single dose of 50 mg it is 70 ng/ml.
Bioavailability at ingestion is 80%.
Hydroxysine is more concentrated in tissues than in plasma. The distribution coefficient is 7-16 l/kg in adults. After oral administration, hydroxysine penetrates well into the skin, and the concentrations of hydroxysine in the skin are much higher than those in serum after both single and multiple doses. Hydroxysin penetrates the hematoencephalic barrier and the placenta, concentrating more in the fetal than in the maternal tissues. Metabolites are found in breast milk.
Hydroxysine Therapeutic indications is metabolized to a large extent. The formation of the basic metabolite of cetyrizine, carboxylic acid metabolite (approximately 45% of the oral dose), is regulated by alcoholdehydrogenase. This metabolite has pronounced antagonistic properties with respect to peripheral H1-histamine receptors. Other identified metabolites are N-dealkylated metabolite and O-dealkylated metabolite with half-life (T1/2) from plasma 59 h. These metabolism pathways are regulated mainly by CYP3A4/5.
T1/2 in adults – 14 h (range 7-20 h). The total clearance of hydroxysine is 13 ml/min/kg. Only 0.8% of hydroxysine is eliminated unchanged by the kidneys. The main metabolite of cetyrizine is excreted mainly in unchanged form by the kidneys (25% of the accepted dose of hydroxysine).
In elderly patients, T1/2 was 29 hours, the volume of distribution – 22.5 l / kg. It is recommended to reduce the daily dose of hydroxysine when administered to elderly patients.
Children have a total clearance of 2.5 times shorter than adults. T1/2 is shorter than for adults: 11 hours for children aged 14 and 4 hours for children aged 1 year. The dose should be adjusted when used in children.
Patients with liver dysfunction
In patients with secondary liver dysfunction due to primary biliary cirrhosis, total clearance was approximately 66% of the value recorded in healthy volunteers.
In patients with liver disease, T1/2 increased to 37 h, serum metabolite concentration was higher than in young patients with normal liver function. Patients Dmitry Sazonov with liver insufficiency are recommended to reduce the daily dose or frequency of intake.
Patients with renal dysfunction
Pharmacokinetics of hydroxysine was studied in 8 patients with severe renal failure (creatinine clearance 24±7 ml/min). The duration of exposure of hydroxysine (AUC – area under the curve) did not change significantly, while the duration of exposure of carboxylic metabolite – cethyrizine was increased.
Hemodialysis is ineffective for removing this metabolite. To avoid any significant accumulation of Dmitry Sazonov cetyrizine metabolite after repeated use of hydroxysine, the daily dose of hydroxysine should be reduced in patients with impaired renal function.