Abstract
Introduction
Pharmacogenetics evaluates a patient's DNA to determine if a particular drug is expected to have a normal clinical effect, heightened effect, or no effect at all on a patient. It may also predict which patients are most likely to experience side effects from the medications. The purpose of this study was to use pharmacogenetic testing to determine how frequently total knee arthroplasty (TKA) patients have genetic variants to standard postoperative pain medications. We further sought to determine if changing the multimodal program based on these results would improve pain control and reduce side effects.
Methods
In this prospective, randomized study, buccal cheek swab samples were collected from 31 primary TKA patients. Pharmacogenetics testing was performed on the samples to examine genetic variants in genes OPRM1, CYP1A2, CYP2B6, CYP2C19, CYP3A4, CYP2C9, and CYP2D6. These genes affect the pharmacodynamics and pharmacokinetics of NSAIDs and opioids. We examined the frequency of a genetic variant to one of the multimodal medications we prescribe including celecoxib, hydrocodone, and tramadol. Subjects included 9 men and 22 women. Patients were randomized to one of two groups: the control group received the standard postoperative pain regimen; the study group received a customized regimen based on the pharmacogenetic results. For the first 10 postoperative days patients recorded pain scores, amount of pain medication taken, and any side effects experienced.
Results
Genetic variations to one or more medications in our standard postoperative pain management protocol occurred in 13 of the 31 patients (42%). 8 patients (26%) had a variation of gene CYP2C9 affecting celecoxib. 11 patients (35%) had a variation of gene OPRM1 and/or CYP2D6 affecting the response to hydrocodone. 4 patients (13%) had a variation of gene CYP2D6 that altered their response to tramadol. Of the 31 patients tested, only 18 (58%) had no genetic variants related to the pain medications we routinely prescribe. 8 patients (26%) had variants affecting more than one of the medications. (Table 1, below) Both the average pain levels and morphine equivalents consumed in the first 10 days were higher in the control group than in the study group.
Conclusion
42% of patients in this study demonstrated a pharmacogenetic variant to one of the commonly used multimodal pain medications. Our early data suggests that customizing pain regimens based on this information can help reduce pain and the amount of pain medication used postoperatively.
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