Clinical pharmacogenetics of ibuprofen enantiomers after lower third molar surgeries

Detalhes bibliográficos
Autor(a) principal: Weckwerth, Giovana Maria
Data de Publicação: 2020
Tipo de documento: Tese
Idioma: eng
Título da fonte: Biblioteca Digital de Teses e Dissertações da USP
Texto Completo: https://www.teses.usp.br/teses/disponiveis/25/25149/tde-22102021-123302/
Resumo: Non-steroidal anti-inflammatory drugs (NSAIDs) are over-the-counter agents frequently consumed by the population in order to control chronic pain and also acute pain after inflammatory processes. Extraction of lower third molars is recommended for evaluation of the NSAIDs effect since it generates pain, swelling and trismus. Metabolism of NSAIDs is mainly dependent on the family of cytochrome P450 (CYP), more precisely CYP2C8 and CYP2C9 genes. In this context, pharmacogenetics, which studies the contribution of polymorphisms and genetic factors to the individual variability of responses to drug metabolism, is growing and starting to show results regarding the clinical use of drugs. In addition, the possible influence of genetic and tissue biomarkers at the descending inhibitory system of pain, may also impact the response and effects of NSAIDS, and this inhibitory system could be checked through the modulation of conditioned pain. In this aspect, the OPRM1 opioid receptor has been widely studied by pharmacogenetics, due to the structural variation, and its function in a variety of painful disorders. The -opioid receptor (MOR), encoded by the OPRM1 gene naturally regulates the analgesic response to pain. Genetic variabilities in the OPRM1 gene, particularly A118G SNP have been associated with a number of functional purposes. Thus, the aim of this study was assess the link between the different haplotypes of CYP2C8, CYP2C9 CYP1A2, CYP3A4 and CYP3A5 genes and the clinical efficacy of ibuprofen after lower third molar extractions regarding pain, swelling and trismus, adverse reactions, the amount of pain medication used, the patients satisfaction with the drug and the influence of the ability on preoperative modulation of conditioned pain. The relationship between the different haplotypes of the OPRM1 and COMT gene was also evaluated, the salivary concentrations of the pro-inflammatory cytokines (IL-2, IL-6, IFN-g and TNF-), and the modulation of pre- operative. The genetic sequencing of 200 Brazilian patients was carried out, with genomic DNA extracted from their saliva, from the genes CYP2C8, CYP2C9 CYP1A2, CYP3A4, CYP3A5, OPRM1 and COMT, using MiSeq® System (Illumina®) instruments with a 2 x 78bp read length, to check for possible new correlations of these genes with postoperative pain and modulation of pain, at Kailos Genetics, Inc. in Huntsville, Alabama, United States of America.
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spelling Clinical pharmacogenetics of ibuprofen enantiomers after lower third molar surgeriesFarmacogenética clínica dos enantiômeros do ibuprofeno após exodontias de terceiros molares inferioresCirurgia BucalDor FacialFacial PainFarmacogenéticaIbuprofenIbuprofenoOral SurgeryPharmacogeneticsTerceiro molarThird MolarNon-steroidal anti-inflammatory drugs (NSAIDs) are over-the-counter agents frequently consumed by the population in order to control chronic pain and also acute pain after inflammatory processes. Extraction of lower third molars is recommended for evaluation of the NSAIDs effect since it generates pain, swelling and trismus. Metabolism of NSAIDs is mainly dependent on the family of cytochrome P450 (CYP), more precisely CYP2C8 and CYP2C9 genes. In this context, pharmacogenetics, which studies the contribution of polymorphisms and genetic factors to the individual variability of responses to drug metabolism, is growing and starting to show results regarding the clinical use of drugs. In addition, the possible influence of genetic and tissue biomarkers at the descending inhibitory system of pain, may also impact the response and effects of NSAIDS, and this inhibitory system could be checked through the modulation of conditioned pain. In this aspect, the OPRM1 opioid receptor has been widely studied by pharmacogenetics, due to the structural variation, and its function in a variety of painful disorders. The -opioid receptor (MOR), encoded by the OPRM1 gene naturally regulates the analgesic response to pain. Genetic variabilities in the OPRM1 gene, particularly A118G SNP have been associated with a number of functional purposes. Thus, the aim of this study was assess the link between the different haplotypes of CYP2C8, CYP2C9 CYP1A2, CYP3A4 and CYP3A5 genes and the clinical efficacy of ibuprofen after lower third molar extractions regarding pain, swelling and trismus, adverse reactions, the amount of pain medication used, the patients satisfaction with the drug and the influence of the ability on preoperative modulation of conditioned pain. The relationship between the different haplotypes of the OPRM1 and COMT gene was also evaluated, the salivary concentrations of the pro-inflammatory cytokines (IL-2, IL-6, IFN-g and TNF-), and the modulation of pre- operative. The genetic sequencing of 200 Brazilian patients was carried out, with genomic DNA extracted from their saliva, from the genes CYP2C8, CYP2C9 CYP1A2, CYP3A4, CYP3A5, OPRM1 and COMT, using MiSeq® System (Illumina®) instruments with a 2 x 78bp read length, to check for possible new correlations of these genes with postoperative pain and modulation of pain, at Kailos Genetics, Inc. in Huntsville, Alabama, United States of America.Os anti-inflamatórios não esteroidais estão disponíveis no mercado e são altamente consumidos pela população para o controle de processos inflamatórios dolorosos crônicos e agudos. A extração de terceiros molares inferiores é o modelo preconizado para a avaliação do efeito de fármacos, pois esse procedimento gera dor, edema e trismo. A família do citocromo P450 (CYP) principalmente os genes CYP2C8 e CYP2C9 são responsáveis pela metabolização dos AINES. Nesse contexto a farmacogenética, área da farmacologia que estuda a contribuição de polimorfismos e fatores genéticos para a variabilidade das respostas individuais ao metabolismo dos fármacos, vem crescendo e obtendo resultados com sua utilização clínica. Além da possível influência de biomarcadores genéticos e teciduais, o sistema inibitório descendente da dor também pode impactar na resposta e efeitos dos AINES, e uma maneira de verificar seu funcionamento é por meio da modulação da dor condicionada. Nesse aspecto, o receptor opióide OPRM1, tem sido vastamente estudado pela farmacogenética, devido à sua variação estrutural, e sua função em uma variedade de desordens dolorosas. O receptor opióide - (MOR), codificado pelo gene OPRM1, regula naturalmente a resposta analgésica à dor. Variabilidades genéticas no gene OPRM1, particularmente o SNP A118G, têm sido associados a um número de efeitos funcionais. O objetivo deste estudo foi avaliar o elo entre os diferentes haplótipos dos genes CYP2C8, CYP2C9, CYP1A2, CYP3A4 e CYP3A5 e a eficácia clínica do ibuprofeno, após exodontias de terceiros molares inferiores em relação à dor, edema e trismo, reações adversas, necessidade de utilização de medicação analgésica de socorro e satisfação do paciente em relação ao medicamento com a sua capacidade de modulação de dor condicionada pré-operatória. Avaliou-se também, a relação entre os diferentes haplótipos do gene OPRM1 e COMT as concentrações salivares das citocinas pró-inflamatórias (IL-2, IL-6, IFN-g e TNF-), e a modulação de dor condicionada pré-operatória. Foi feito o sequenciamento genético dos 200 pacientes brasileiros, com DNA genômico extraído de sua saliva, dos genes CYP2C8, CYP2C9 CYP1A2, CYP3A4, CYP3A5, OPRM1 e COMT, utilizando o instrumento MiSeq® System (Illumina®) com um comprimento de leitura de 2 x 78bp, para verificação de possíveis novas correlações destes genes com a dor pós-operatória e modulação de dor, na Kailos Genetics, Inc. em Huntsville, Alabama, Estados Unidos da América.Biblioteca Digitais de Teses e Dissertações da USPBonjardim, Leonardo RigoldiSantos, Carlos Ferreira dosWeckwerth, Giovana Maria2020-09-17info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttps://www.teses.usp.br/teses/disponiveis/25/25149/tde-22102021-123302/reponame:Biblioteca Digital de Teses e Dissertações da USPinstname:Universidade de São Paulo (USP)instacron:USPLiberar o conteúdo para acesso público.info:eu-repo/semantics/openAccesseng2024-08-02T13:09:02Zoai:teses.usp.br:tde-22102021-123302Biblioteca Digital de Teses e Dissertaçõeshttp://www.teses.usp.br/PUBhttp://www.teses.usp.br/cgi-bin/mtd2br.plvirginia@if.usp.br|| atendimento@aguia.usp.br||virginia@if.usp.bropendoar:27212024-08-02T13:09:02Biblioteca Digital de Teses e Dissertações da USP - Universidade de São Paulo (USP)false
dc.title.none.fl_str_mv Clinical pharmacogenetics of ibuprofen enantiomers after lower third molar surgeries
Farmacogenética clínica dos enantiômeros do ibuprofeno após exodontias de terceiros molares inferiores
title Clinical pharmacogenetics of ibuprofen enantiomers after lower third molar surgeries
spellingShingle Clinical pharmacogenetics of ibuprofen enantiomers after lower third molar surgeries
Weckwerth, Giovana Maria
Cirurgia Bucal
Dor Facial
Facial Pain
Farmacogenética
Ibuprofen
Ibuprofeno
Oral Surgery
Pharmacogenetics
Terceiro molar
Third Molar
title_short Clinical pharmacogenetics of ibuprofen enantiomers after lower third molar surgeries
title_full Clinical pharmacogenetics of ibuprofen enantiomers after lower third molar surgeries
title_fullStr Clinical pharmacogenetics of ibuprofen enantiomers after lower third molar surgeries
title_full_unstemmed Clinical pharmacogenetics of ibuprofen enantiomers after lower third molar surgeries
title_sort Clinical pharmacogenetics of ibuprofen enantiomers after lower third molar surgeries
author Weckwerth, Giovana Maria
author_facet Weckwerth, Giovana Maria
author_role author
dc.contributor.none.fl_str_mv Bonjardim, Leonardo Rigoldi
Santos, Carlos Ferreira dos
dc.contributor.author.fl_str_mv Weckwerth, Giovana Maria
dc.subject.por.fl_str_mv Cirurgia Bucal
Dor Facial
Facial Pain
Farmacogenética
Ibuprofen
Ibuprofeno
Oral Surgery
Pharmacogenetics
Terceiro molar
Third Molar
topic Cirurgia Bucal
Dor Facial
Facial Pain
Farmacogenética
Ibuprofen
Ibuprofeno
Oral Surgery
Pharmacogenetics
Terceiro molar
Third Molar
description Non-steroidal anti-inflammatory drugs (NSAIDs) are over-the-counter agents frequently consumed by the population in order to control chronic pain and also acute pain after inflammatory processes. Extraction of lower third molars is recommended for evaluation of the NSAIDs effect since it generates pain, swelling and trismus. Metabolism of NSAIDs is mainly dependent on the family of cytochrome P450 (CYP), more precisely CYP2C8 and CYP2C9 genes. In this context, pharmacogenetics, which studies the contribution of polymorphisms and genetic factors to the individual variability of responses to drug metabolism, is growing and starting to show results regarding the clinical use of drugs. In addition, the possible influence of genetic and tissue biomarkers at the descending inhibitory system of pain, may also impact the response and effects of NSAIDS, and this inhibitory system could be checked through the modulation of conditioned pain. In this aspect, the OPRM1 opioid receptor has been widely studied by pharmacogenetics, due to the structural variation, and its function in a variety of painful disorders. The -opioid receptor (MOR), encoded by the OPRM1 gene naturally regulates the analgesic response to pain. Genetic variabilities in the OPRM1 gene, particularly A118G SNP have been associated with a number of functional purposes. Thus, the aim of this study was assess the link between the different haplotypes of CYP2C8, CYP2C9 CYP1A2, CYP3A4 and CYP3A5 genes and the clinical efficacy of ibuprofen after lower third molar extractions regarding pain, swelling and trismus, adverse reactions, the amount of pain medication used, the patients satisfaction with the drug and the influence of the ability on preoperative modulation of conditioned pain. The relationship between the different haplotypes of the OPRM1 and COMT gene was also evaluated, the salivary concentrations of the pro-inflammatory cytokines (IL-2, IL-6, IFN-g and TNF-), and the modulation of pre- operative. The genetic sequencing of 200 Brazilian patients was carried out, with genomic DNA extracted from their saliva, from the genes CYP2C8, CYP2C9 CYP1A2, CYP3A4, CYP3A5, OPRM1 and COMT, using MiSeq® System (Illumina®) instruments with a 2 x 78bp read length, to check for possible new correlations of these genes with postoperative pain and modulation of pain, at Kailos Genetics, Inc. in Huntsville, Alabama, United States of America.
publishDate 2020
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