LAS VEGAS—“How do we know how a patient will respond to a certain medication or if they will have an adverse effect to that medication?” Brett B. Snodgrass, MSN, APRN, FNP-C, asked attendees at PAINWeek 2014. The answer, she said, is that we couldn’t – until now.
Pharmacogenomic testing can identify how genetic variations affect drug responses, and help guide treatment strategies for patients suffering from chronic pain, according to Snodgrass.Genomics offers “improved diagnostic and prescribing accuracy and speed,” Snodgrass said, decreasing healthcare costs and better personalizing treatment plans. On the research front, pharmacogenomics also promises to hasten rational drug design and the development of gene therapies, she added.
For example, more than 50 enzymes in the cytochrome P450 (CYP450) super-family have been identified in humans. These enzymes are found in the liver, mucosal surfaces and intestines, and play “important roles in the biosynthesis and metabolism of endogenous and exogenous compounds,” she explained. Seven of these metabolize more than 90% of the clinically most-important drugs, Snodgrass noted.
“CYP2D6 is involved in the metabolism of 25% to 30% of all prescribed drugs,” she said. “CYP2C19 is involved in metabolizing 15%.” Gene variations in CYP2D6 and CYP2C19 genes “result in markedly increased or decreased drug metabolism, leading to wide variations in clinical effect,” she explained. In addition to allelic variation, there are gene copy-number polymorphisms that may affect drug metabolism, she reported.
Genotyping patients allows identification of those likely to respond normally to a given drug therapy, and those who are less likely to benefit or who might be at increased risk for toxic adverse events, she said.“For example, codeine is metabolized into the active morphine,” she explained. “Poor metabolizers would not achieve a full therapeutic response. Ultra-rapid metabolizers metabolize codeine quickly into morphine, potentially leading to a toxic effect.” Among nursing mothers, ultra-rapid codeine metabolism could lead to morphine overdose in their breast-fed infants.
Similarly, patients may metabolize hydrocodone into hydromorphone too quickly or too inefficiently, risking significant side-effects or poor pain relief, respectively, she said.“If a patient is complaining about a drug not being effective, or about side effects, genomics testing can guide your therapy,” Snodgrass said.
Pharmacogenomic tests should be used in pain management when pharmacotherapies fail to relieve pain at an appropriate dose, or when a patient complains of significant side-effects and pain is not controlled, she advised.Pharmacogenomic tests should be considered before prescribing when patients say that “nothing works” to alleviate their pain or that “everything makes me feel horrible,” Snodgrass added.
Genetic analyses for pain management planning are available for genes affecting metabolism of codeine, fentanyl, oxycodone, methadone, morphine, and tramadol.Results of such tests are probabilistic; a smaller or larger number of patients with a particular gene variation are likely to be non-responders for a particular drug, for example. That information can significantly improve the odds that a particular treatment strategy will help a patient, Snodgrass concluded.