Genetic Risk Factors for Adverse Drug Reactions

The use of medicines may in some cases be associated with the development of drug-induced diseases (DIDs) аnd other adverse drug reactions (ADRs), which leads to an increase in morbidity/mortality rates, and/or symptoms forcing a patient to seek medical attention or resulting in hospitalisation. ADR...

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Main Authors: D. A. Sychev, M. S. Chernyaeva, O. D. Ostroumova
Format: Article
Language:Russian
Published: Ministry of Health of the Russian Federation, Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» 2022-04-01
Series:Безопасность и риск фармакотерапии
Subjects:
Online Access:https://www.risksafety.ru/jour/article/view/245
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author D. A. Sychev
M. S. Chernyaeva
O. D. Ostroumova
author_facet D. A. Sychev
M. S. Chernyaeva
O. D. Ostroumova
author_sort D. A. Sychev
collection DOAJ
description The use of medicines may in some cases be associated with the development of drug-induced diseases (DIDs) аnd other adverse drug reactions (ADRs), which leads to an increase in morbidity/mortality rates, and/or symptoms forcing a patient to seek medical attention or resulting in hospitalisation. ADRs may develop due to changes in a patient’s genotype, which entail an inadequate pharmacological response. The aim of the study was to analyse and summarise literature data on genetic risk factors that cause DIDs аnd other ADRs. It was shown that the polymorphism of genes encoding enzymes of drug metabolism (CYP, UGT, NAT, TPMT, EPHX, GST, etc.) or carriers (transporters) of drugs (P-gp, BCRP, MRP, OATP, OCT, etc.) can change the pharmacokinetics of drugs, affecting their activity. Polymorphism of RYR1, CACNA1S, MT-RNR1, VKORC1, and other genes encoding receptors targeted by drugs, and human leukocyte antigen (HLA) gene, may affect drug pharmacodynamics by modifying drug targets or changing the sensitivity of biological pathways to pharmacological effects of medicines. Changes in drug pharmacokinetics and pharmacodynamics may cause DIDs аnd other ADRs. The use of pharmacogenetic tests will allow a personalised approach to patients’ treatment and prevention or timely detection of potential ADRs during therapy. Before prescribing some medicines, clinicians should use recommendations on their dosing based on pharmacogenetic tests, which are posted on the official websites of Pharmacogenomics Research Network (PGRN), Pharmacogenomics Knowledgebase (PharmGKB), and Clinical Pharmacogenetics Implementation Consortium (CPIC). The results of ongoing clinical studies on the effect of gene polymorphism on drug safety will soon allow for higher personalisation of the choice of pharmacotherapy and prevention of many ADRs, including DIDs.
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spelling doaj.art-fc9bee954551487cb4ea66ee065e64bf2024-04-03T17:56:37ZrusMinistry of Health of the Russian Federation, Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products»Безопасность и риск фармакотерапии2312-78212619-11642022-04-01101486410.30895/2312-7821-2022-10-1-48-64212Genetic Risk Factors for Adverse Drug ReactionsD. A. Sychev0M. S. Chernyaeva1O. D. Ostroumova2Russian Medical Academy of Continuous Professional EducationCentral State Medical AcademyRussian Medical Academy of Continuous Professional Education; I.M. Sechenov First Moscow State Medical University (Sechenov University)The use of medicines may in some cases be associated with the development of drug-induced diseases (DIDs) аnd other adverse drug reactions (ADRs), which leads to an increase in morbidity/mortality rates, and/or symptoms forcing a patient to seek medical attention or resulting in hospitalisation. ADRs may develop due to changes in a patient’s genotype, which entail an inadequate pharmacological response. The aim of the study was to analyse and summarise literature data on genetic risk factors that cause DIDs аnd other ADRs. It was shown that the polymorphism of genes encoding enzymes of drug metabolism (CYP, UGT, NAT, TPMT, EPHX, GST, etc.) or carriers (transporters) of drugs (P-gp, BCRP, MRP, OATP, OCT, etc.) can change the pharmacokinetics of drugs, affecting their activity. Polymorphism of RYR1, CACNA1S, MT-RNR1, VKORC1, and other genes encoding receptors targeted by drugs, and human leukocyte antigen (HLA) gene, may affect drug pharmacodynamics by modifying drug targets or changing the sensitivity of biological pathways to pharmacological effects of medicines. Changes in drug pharmacokinetics and pharmacodynamics may cause DIDs аnd other ADRs. The use of pharmacogenetic tests will allow a personalised approach to patients’ treatment and prevention or timely detection of potential ADRs during therapy. Before prescribing some medicines, clinicians should use recommendations on their dosing based on pharmacogenetic tests, which are posted on the official websites of Pharmacogenomics Research Network (PGRN), Pharmacogenomics Knowledgebase (PharmGKB), and Clinical Pharmacogenetics Implementation Consortium (CPIC). The results of ongoing clinical studies on the effect of gene polymorphism on drug safety will soon allow for higher personalisation of the choice of pharmacotherapy and prevention of many ADRs, including DIDs.https://www.risksafety.ru/jour/article/view/245adverse drug reactionsdrug-induced diseasesrisk factorsmedicinespharmacogeneticspharmacokineticspharmacodynamicspolymorphismclinical pharmacogenetics implementation consortium
spellingShingle D. A. Sychev
M. S. Chernyaeva
O. D. Ostroumova
Genetic Risk Factors for Adverse Drug Reactions
Безопасность и риск фармакотерапии
adverse drug reactions
drug-induced diseases
risk factors
medicines
pharmacogenetics
pharmacokinetics
pharmacodynamics
polymorphism
clinical pharmacogenetics implementation consortium
title Genetic Risk Factors for Adverse Drug Reactions
title_full Genetic Risk Factors for Adverse Drug Reactions
title_fullStr Genetic Risk Factors for Adverse Drug Reactions
title_full_unstemmed Genetic Risk Factors for Adverse Drug Reactions
title_short Genetic Risk Factors for Adverse Drug Reactions
title_sort genetic risk factors for adverse drug reactions
topic adverse drug reactions
drug-induced diseases
risk factors
medicines
pharmacogenetics
pharmacokinetics
pharmacodynamics
polymorphism
clinical pharmacogenetics implementation consortium
url https://www.risksafety.ru/jour/article/view/245
work_keys_str_mv AT dasychev geneticriskfactorsforadversedrugreactions
AT mschernyaeva geneticriskfactorsforadversedrugreactions
AT odostroumova geneticriskfactorsforadversedrugreactions