Yakovleva O. A., Semenenko S. I., Zhamba A. O., Hoina-Kardasevich O. Yu.

STRUCTURAL POLYMORPHISM OF CYP2D6 AND CYP2C19 GENES MODIFIES THE EFFICACY AND TOXICITY OF PHARMACOTHERAPY FOR DEPRESSIVE STATES

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About the author:

Yakovleva O. A., Semenenko S. I., Zhamba A. O., Hoina-Kardasevich O. Yu.

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LITERATURE REVIEWS

Type of article:

Scientific article

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Nature has created protective systems on against the entry of drugs, for metabolism in the human body. Structure of biotransformation systems is formed through the expression of genetic regulators – cytochrome P450 (CYP) enzymes, which have individual allele variability. CYP2D6 and CYP2C19 are active for the antidepressants’ metabolism (substrates). Against the background of different alleles (there are more than 140 for CYP2D6), different enzyme activity occurs, it varies from maximally slow to ultrarapid, destroying the drug. Enzyme speed options are different in countries and regions of the Earth. The history of differences began in the late 1970s, the frequency of adverse drug reactions (ADRs) from antidepressants analyzed. The CYP2D6 activity covers more than 300 substrates, so the results of pharmacotherapy differ significantly, depending on the cytochromes’ genetic polymorphism. Discrepancies increase with the drugs’ interaction (cytochromes’ inhibitors or inducers) in conditions of polypharmacy and comorbidity. Such variants of interaction are given, and the list of NLRs varies significantly for both cytochromes, because they are represented in different organs of the body. The frequency of depressive states in the world and in Ukraine should emphasize attention to the competent use of antidepressants: a promising tactic of genetic testing is proposed for the drug’s selection and prescription, with the aim of timely forecasting the effectiveness and prevention of the dangers of therapy.

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Bibliography:

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Publication of the article:

«Bulletin of problems biology and medicine», 2024 Issue 1, 172, 82-87 pages, index UDC 615.015.4:612.8

DOI:

10.29254/2077-4214-2024-1-172-82-87