Potential impact of CYP2D6 genotyping on postoperative analgesia with tramadol in patients undergoing hip and knee arthroplasty

Abstract

Tramadol is an analgesic drug indicated for the treatment of pain of moderate to severe intensity. It is a drug largely used for postoperative analgesia in orthopedic surgery, where it is included in the standard prescription protocol as rescue medication for standard programmed analgesia. Tramadol exerts its analgesic action acting synergistically as an opioid agonist and as an inhibitor of the reuptake of serotonin and noradrenaline. Its metabolization occurs mainly by O-demethylation and N-demethylation, as well as by the conjugation of O-demethylated derivatives with glucuronic acid. The first two reactions are mediated by cytochrome P450 (CYP2D6 and CYP3A4, respectively) and originate two active metabolites M1 and M2. The M1 metabolite is a high affinity ligand and produces a more potent analgesic effect than that of the starting compound. It is estimated that about 80% of the tramadol dose is metabolized by this CYP2D6 mediated pathway. CYP2D6 is a highly polymorphic gene and there are a number of described variations that condition the activity of the enzyme. Thus, the objective of this study is to evaluate the phenotypic and genotypic distribution of CYP2D6 in the study population and to analyze its impact on the immediate postoperative analgesic effect of tramadol in knee and hip orthopedic surgeries. (AU)