Opioid-Related Genetic Polymorphisms of Cytochrome P450 Enzyme After Total Joint Arthroplasty: A Focus on Drug-Drug-Gene Interaction with Commonly Co-Prescribed Medications


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Research Mentor Name

Khaled J. Saleh

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Institution / Department

Wayne State University School of Medicine

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Research Abstract

Research Type


Level of Research



Genetic polymorphisms in the CYP 450 enzyme system correlates to immense variability observed in opioid analgesic metabolism and its consequent sequelae. However, the impact of CYP polymorphisms on opioid metabolism following TJA, both in terms of drug efficacy and associated side effects, has yet to be delineated. This article focuses on three categories of CYP metabolizers (EM: extensive metabolizers, PM: poor metabolizers, and NM: non-metabolizers), in terms of drug efficacy and adverse reactions witnessed in the use of various pain analgesics and other commonly prescribed drugs [1]. This paper hopes to highlight the necessity of pharmacogenomic testing as a part of orthopedist’s pre- and postoperative pain management repertoire for TJA. Utilization of genetic testing may serve clinical utility in minimizing adverse drug reactions while maximizing response rates for hopes in improving postoperative patient satisfaction.

Although the theoretical link between drug interaction and genetic polymorphisms is tangible, evidence-based relevance is limited. However, some clinical cases have been reported and with increasing knowledge of pharmacogenomics it may soon be possible to identify subgroups of patients at greater risk of adverse reactions and poor response rates to certain medications. We hope that the orthopaedic community can benefit from our analysis by understanding the genetic basis of pain response and the opioid interaction. We aim to provide the reader with a greater understanding of the etiological complexity associated with drug-gene interactions in order to develop evidence-based approach to prescribing opioids.


Medicinal and Pharmaceutical Chemistry | Medicine and Health Sciences | Orthopedics | Patient Safety

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