ORLANDO — Pharmacogenetic testing may determine which patients will respond well to conventional drugs or who may need alternative drugs during orthopedic surgery, according to a presenter at the Current Concepts in Joint Replacement Winter Meeting.
“We know that your DNA affects your response to drugs, and there is a test now that can distinguish different people and how they may respond to specific medications,” William G. Hamilton, MD, said in his presentation.
According to Hamilton, cytochrome P-450 enzymes in the liver, such as CYP2D6 and CYP3A4, metabolize drugs into an active drug or a pro-drug.
“An active drug is one in which the molecule itself is the active metabolite and when you take it during metabolism it is inactivated,” he said. “A pro-drug is a molecule that has no activity and it only becomes active until it is metabolized by the appropriate enzyme.”
Hamilton noted patients can have normal metabolic activity, reduced metabolic activity, increased metabolic activity or poor metabolic activity, which can affect how pro-drugs are converted.
To perform pharmacogenetic testing, he said physicians collect a cheek swab from the patient and send it for DNA analysis for the patient’s specific genotype. The physician will then receive a report that indicates which medications may and may not work based on the patient’s genes, according to Hamilton.
In a prospective, randomized trial, Hamilton and colleagues performed pharmacogenetic testing in 50 patients, half of whom received a standard medication profile and half received a customized medication profile based on the pharmacologic test results. More than 40% of patients had at least one genetic variant to medications commonly used in a multimodal protocol, according to Hamilton.
“In 13 patients, we executed a total of 21 medication changes. When we looked at the 10-day pain logs, we saw ... patients who had genetic variants where we changed their medications appeared to have the lowest pain scores and lowest morphine intake,” Hamilton said. – by Casey Tingle
Hamilton WG. Paper 117. Presented at: Current Concepts in Joint Replacement Winter Meeting; Dec. 11-14, 2019; Orlando.
Disclosure: Hamilton reports he receives consulting fees and royalties for consulting and product design from DePuy Synthes and Total Joint Orthopedics.