PHARMACOGENETIC ASPECTS OF THE EFFICACY AND SAFETY OF HALOPERIDOL IN PATIENTS WITH ADDICTIVE DISORDERS

DOI: https://doi.org/None

M.S. Zastrozhin (1–3), V.K. Lepakhin (3), D.A. Sychev (1), E.A. Grishina (2), V.V. Smirnov (4), L.M. Savchenko (1), E.A. Bryun (1,2), A.S. Sorokin (2), A.G. Naumova (2), A.V. Ivanyuk (2) 1 -Russian Medical Academy of Postgraduate Education Russian Federation, Barrikadnaya street, 2/1, Moscow, 123995, Russian Federation; 2 -Moscow Research and Practical Centre for Narcology, Lyublinskaya street, 37/1, Moscow, 109390, Russian Federation; 3 -Peoples’ Friendship University of Russia, Miklukho-Maklaya str., 6, Moscow, 117198, Russian Federation; 4 -National Research Center Institute of Immunology of Federal Medical-Biological Agency of Russia, Moscow, Kashirskoe shosse, 24, Moscow, 115478, Russian Federation

The use of haloperidol in clinical practice is often accompanied by the development of severe unwanted adverse side effects from the side of various organs and systems. In the narcological practice the use of antipsychotic drugs is not seldom complicated by extrapyramidal disorders as pseudoparkinsonism, akathisia, dyskinesia and neuroleptic malignant syndrome. In connection with these unwanted side effects haloperidol causes mixed and not seldom negative feelings in patients with alcoholism and especially in drug abusers, that to a certain extent limits it’s usage in narcological practice. Obviously, the efficacy and safety of the therapy with haloperidol depend on the patient’s personal features. It requires for the personal approach to the each patient. Such personal approach lied in the base of personalized medicine allows to increase the efficacy and safety of the usage of haloperidol, and also to reduce patient’s expenditures on treatment by the administration of target doses of the drug. The aim of this review is to analyze the existing for the present time information about peculiarities of haloperidol pharmacokinetics with detailed review of pharmacogenetic aspects of it’s metabolism and identification of prospects for the usage of personalized approach to increase the efficacy and safety of the therapy with haloperidol. In this course of the review there were analyzed ambiguous and discordant results of the series of authoritative studies and the complexity of metaboliс processes to which haloperidol is undergone in the organism, that in its turn fails to permit to detect the sound association between CYP2D6 and CYP3A4 alleles and values of indices of some or other pharmacokinetic characteristics of haloperidol. personalized approach to the prescription of haloperidol for the present time is established unfortunately to be encumbering. Further investigations are required for the more careful study of the effects of the impact of polymorphisms of CYP2D6 and CYP3A4 on pharmacokinetics and pharmacodynamics of haloperidol.
Keywords: 
unwanted side effects of haloperidol, pharmacogenetics of haloperidol, CYP2D6 and haloperidol, CYP3A4 and haloperidol
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