Impact of CYP Enzyme Polymorphisms on Opioid Response in Anesthesia and Pain Medicine

Opioids serve as the cornerstone for anesthesia, postoperative analgesia, and chronic pain management. However, significant interindividual variations exist in their efficacy and safety, posing substantial challenges to clinical practice. Genetic polymorphisms of Cytochrome P450 (CYP) enzymes, particularly CYP2D6 and CYP3A4/5, represent one of the primary contributors to these differences. This review aims to elucidate the mechanisms by which CYP enzyme gene polymorphisms influence opioid metabolism and discuss their clinical implications. Key conclusions indicate that the CYP2D6 genotype significantly influences the bioactivation of precursor drugs such as codeine and tramadol; ultrarapid metabolizers (UMs) are at substantial risk of toxicity when using codeine, whereas slow metabolizers (PM) are at increased risk of inadequate analgesia. Polymorphisms in CYP3A4/5 primarily affect the metabolism of agents such as fentanyl and sufentanil via drug-drug interactions, although evidence supporting genotype-guided dose adjustments independent of clinical factors remains insufficient. Additionally, CYP2B6 polymorphisms are critical for methadone metabolism. Although integrating pharmacogenomic testing into clinical practice holds significant potential, current evidence supports selective testing in specific clinical scenarios rather than routine implementation across all opioid prescriptions.