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Clin Pharmacol Ther ; 79(4): 316-24, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16580900

RESUMO

OBJECTIVE: The aim of this study was to investigate the respective influence of genetic and nongenetic factors on morphine dose requirements and adverse effects after colorectal surgery. METHODS: Seventy-four patients who planned to undergo colorectal surgery were included in this pilot study. The cumulative 24-hour postoperative dose of morphine and postoperative nausea or vomiting requiring the antiemetic ondansetron were the 2 clinical end points. The association of patient characteristics, A118G mu-opioid receptor (OPRM1) single-nucleotide polymorphism (SNP); T802C uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7) SNP; and 2 adenosine triphosphate-binding cassette, subfamily B, member 1 (ABCB1) (multidrug resistance 1 [MDR1]) exonic SNPs (G2677T/A and C3435T) with study end points was investigated. RESULTS: Age, creatinine clearance, and the regular use of psychotropic agents were found to be significantly associated with postoperative morphine dose requirements by univariate analysis. Multivariate analysis identified that age (P = .01) and the use of psychotropic agents before surgery (P = .03) were positively associated with a higher rate of morphine consumption. A higher weight (P = .05) and the ABCB1 homozygous GG-CC diplotype (P = .03) were significantly associated with fewer morphine side effects by univariate analysis. The homozygous ABCB1 diplotype (GG-CC) conferred an odds ratio of 0.12 (95% confidence interval, 0.01-0.98) with regard to the use of ondansetron for postoperative nausea or vomiting. Multivariate analysis identified that the ABCB1 GG-CC diplotype was the only borderline-significant (P = .07) predictive factor of morphine side effects. CONCLUSION: Age and prior use of psychotropic agents are associated with postoperative morphine dose requirements. Whether ABCB1 polymorphisms might predict morphine side effects remains to be determined.


Assuntos
Analgésicos Opioides/farmacologia , Morfina/farmacologia , Receptores Opioides mu/efeitos dos fármacos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/efeitos dos fármacos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Analgésicos Opioides/administração & dosagem , Cirurgia Colorretal , Feminino , Glucuronosiltransferase/efeitos dos fármacos , Glucuronosiltransferase/genética , Humanos , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Medição da Dor , Dor Pós-Operatória/patologia , Dor Pós-Operatória/prevenção & controle , Projetos Piloto , Polimorfismo de Nucleotídeo Único , Náusea e Vômito Pós-Operatórios/patologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Período Pós-Operatório , Receptores Opioides mu/genética
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