Influence of Cytochrome P-450 Genetic Polymorphisms on the Main and Side Effects of Tramadol in the Postoperative Period

Abstract

One of the approaches to increasing the effectiveness and safety of postoperative analgesia can be its personification. The goal of the study was to evaluate the efficacy of tramadol analgesia depending on the polymorphisms of the CYP2D6 gene, the cytochrome P-450 isoenzyme, involved in drug biotransformation into the active metabolite. 96 patients with elective endoscopic gynecology procedures were examined. Polymorphisms G1846A and C100T, which reduce the activity of the isoenzyme CYP2D6, were detected, and the intensity of postoperative pain, the autonomic nervous system state by cardiointervalography and hemostasis using rotational thromboelastometry were evaluated. Polymorphisms were detected in 29 (30.2%) patients, united in the 1-st group. The second group consisted of 67 patients without gene polymorphisms. Patients with polymorphisms have a higher pain scores; the frequency of postoperative nausea and vomiting, on the contrary, was significantly lower. According to cardiointervalography, sympathicotonia was observed in Group 1 patients after surgery, while in Group 2 patients the indices did not change significantly compared to baseline. The parameters of hemostasis in patients of the 2nd group were characterized by moderate hypercoagulability (shortening of clotting time and clot formation time), whereas in the firsts group, relative hypocoagulation (decrease in α angle, and clot firmness) was noted. Conclusion. In female carriers of G1846A and C100T polymorphisms of the CYP2D6 gene, the effectiveness of post-operative analgesia based on tramadol is reduced. They have a lower incidence of postoperative nausea and vomiting, and moderate hypocoagulation. Probably, these phenomena are associated with a change in the ratio between the drug and its active metabolite - O-desmethyltramadol.