References

ssmu

Бюллетень сибирской медицины

Bulletin of Siberian Medicine

1682-03631819-3684

Siberian State Medical University, the Ministry of Healthcare of the Russian Federation

10.20538/1682-0363-2017-4-30-41

ssmu-1022

Research Article

ОБЗОРЫ И ЛЕКЦИИ

REVIEW AND LECTURES

Механизмы развития антипсихотик-индуцированных метаболических нарушений: фармакогенетический аспект

Mechanisms of development of antipsychotic-induced metabolic disorders: pharmacogenetic aspect

Насырова

Р. Ф.

Nasyrova

R. F.

д-р мед. наук, вед. науч. сотрудник, руководитель

отделение персонализированной психиатрии и неврологии

192019, г. Санкт-Петербург, ул. Бехтерева, 3/1

DM, Leading Researcher, Head of the Department of Personalized Psychiatry and Neurology

3, Bekhtereva Str., St.-Petersburg, 192019

reginaf@bekhterev.ru

Толмачев

М. Ю.

Tolmachev

M. Yu.

мл. науч. сотрудник

отделение персонализированной психиатрии и неврологии

192019, г. Санкт-Петербург, ул. Бехтерева, 3/1

Junior Researcher, Department of Personalized Psychiatry and Neurology

3, Bekhtereva Str., St.-Petersburg, 192019

Сычев

Д. А.

Sychev

D. A.

д-р мед. наук, профессор, член-корр. РАН, зав. кафедрой

кафедра клинической фармакологии и терапии

125993, г. Москва, ул. Баррикадная, 2/1/1

DM, Professor, Corresponding Member of RAS, Head of the Department of Clinical Pharmacology and Therapy

2/1, Barrikadnaya Str., Moscow, 125993

Яхин

К. К.

Yakhin

K. K.

д-р мед. наук, профессор, зав. кафедрой

кафедра психиатрии с курсом наркологии

420012, г. Казань, ул. Бутлерова, 49

DM, Professor, Head of the Department of Psychiatry and Narcology

49, Butlerova Str., Kazan, 420012

Незнанов

Н. Г.

Neznanov

N. G.

д-р мед. наук, профессор, директор

192019, г. Санкт-Петербург, ул. Бехтерева, 3/1

DM, Professor, Director

3, Bekhtereva Str., St.-Petersburg, 192019

Национальный медицинский исследовательский центр психиатрии и неврологии имени В.М. БехтереваРоссияV.M. Bekhterev National Medical Research Centre for Psychiatry and NeurologyRussian Federation

Российская медицинская академия непрерывного профессионального образованияРоссияRussian Medical Academy of Continuous Professional EducationRussian Federation

Казанский государственный медицинский университетРоссияKazan State Medical UniversityRussian Federation

2017

02012018

1643041

2018

Насырова Р.Ф., Толмачев М.Ю., Сычев Д.А., Яхин К.К., Незнанов Н.Г.

Nasyrova R.F., Tolmachev M.Y., Sychev D.A., Yakhin K.K., Neznanov N.G.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://bulletin.ssmu.ru/jour/article/view/1022

Антипсихотики являются основными лекарственными препаратами в терапии расстройств шизофренического спектра. Антипсихотические препараты требуют длительного применения, обладают узкой терапевтической широтой, большим спектром и выраженностью нежелательных лекарственных реакций, проявление которых во многом определяется генотипом пациента. Выраженность нежелательных лекарственных реакций у препаратов первой и второй генераций антипсихотиков различна.

Применение атипичных антипсихотиков, в отличие от типичных, реже вызывает экстрапирамидные расстройства, но индуцирует, прежде всего, метаболические нарушения: изменение веса, дизрегуляцию метаболизма глюкозы, дислипидемию. Перечисленные нежелательные лекарственные реакции в значительной мере снижают приверженность пациентов к терапии и могут привести к серьезным осложнениям в дальнейшем. Клинический опыт применения антипсихотиков показал, что выраженность нежелательных реакций одного препарата, принимаемого различными пациентами, является вариабельным показателем в связи с полиморфизмом генов фармакокинетических и фармакодинамических факторов, задействованных в реализации фармакологического действия антипсихотиков. В связи с этим изучение влияния различных комбинаций полиморфных вариантов генов фармакокинетических и фармакодинамических факторов на развитие антипсихотик-индуцированных метаболических нарушений является приоритетной задачей персонализированной психиатрии.

Antipsychotics are the main drug group in the treatment of disorders of the schizophrenic spectrum. At the same time, this drug group requires long-term use, has a narrow therapeutic breadth and a large spectrum and high severity of undesirable drug reactions, the manifestation of which is largely determined by the patient’s genotype. In this connection, the severity of undesirable drug reactions in drugs of the first and second generation of antipsychotics is different. Atypical antipsychotics, unlike typical antipsychotics, have a significantly lower chance of causing extrapyramidal disorders, though they primarily induce metabolic side effects, consisting of significant weight changes, glucose metabolism dysregulation, and dyslipidemia. These unwanted drug reactions significantly reduce adherence to therapy and can lead to serious complications in the future. At the same time, experience with the use of atypical antipsychotics has shown that the severity of unwanted reactions differs within the group of atypical antipsychotics and, more importantly, even for one drug taken by different patients, is a variable index. The reason for this phenomenon lies is in the polymorphism of the pharmacokinetic and pharmacodynamic factors involved in the metabolism of atypical antipsychotics and the different chemical structure of the drugs. The study of the effect of various combinations of polymorphic variants of the pharmacokinetic and pharmacodynamics factors on the development of antipsychotic-induced metabolic disorders is a complex and high-priority task of personalized medicine.

фармакогенетикаантипсихотикиметаболические нарушениянабор весафармакодинамические факторыфармакокинетические факторы

pharmacogeneticsantipsychoticsmetabolic disordersweight gainpharmacodynamics factorpharmacokinetic factor

Работа выполнена при финансовой поддержке гранта Президента Российской Федерации для государственной поддержки молодых российских ученых - докторов наук (МД-7471.2016.7).

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The authors declare that there are no conflicts of interest present.