Gwen McMillin presented an overview of the developing field of pharmacogenomics as part of the CCTS-supported Foundations in Personalized Health Care course, which was designed to introduce students to many facets of this emerging field.
Adverse drug reactions, or harmful side effects from medications, are the fourth-leading cause of death in the United States. According to Gwen McMillin, PhD, professor in the Department of Pathology at the University of Utah Health and a medical director at ARUP Laboratories, 60 percent of these incidents could be prevented if the medical community could link a patient’s genome to a drug response.
McMillin explained that each patient’s unique genetic make-up produces an individualized response to a particular drug. “It is part magic and part luck of the draw, but we are learning all the time how our genetics can be used to predict or explain our response to a drug,” she said. Understanding these differences is the key to preventing negative side effects.
Aligning a person’s genome and the resulting drug response is the basis of the rapidly developing field of pharmacogenetics, which builds on two principles: pharmacokinetics and pharmacodynamis. According to McMillin, pharmacokinetics aims to get the right drug to the right place at the right time, while pharmacodynamics focuses on the properties that make a drug effective.
In essence, your genome influences how the drug is metabolized and transported through your body.
“In reality, the medical community does not understand how most drugs interact at the genetic level and finding the relevant genes is difficult,” she said. While gene-drug interactions are very important to consider, there are many barriers to this approach, including limitations in gene testing, lack of clinical guidance for gene-drug pairs, and cost.
Pharmacogenetics has shown some success. In instances where one gene has been identified and paired with a drug response, pre-therapeutic genetic testing can be beneficial for care. “An ultra-rapid metabolizer and a poor metabolizer will respond to the same drug dose very differently,” said McMillin.
To help clinicians interpret lab results, a national organization called the Clinical Pharmacogenetics Implementation Consortium (CPIC) was established to design and publish guidelines to help clinicians optimize drug therapy.
Using the CPIC guidance, clinicians can follow a flow chart for a particular therapy to determine whether a drug would be beneficial, as well as identify patients at high risk of a serious adverse drug reaction or patients unlikely to respond to treatment. Clinicians can optimize dosing by taking into account a patient’s sensitivity or resistivity to a drug.
She pointed to codeine, an opioid pain medication commonly prescribed to treat mild to moderately severe pain, to illustrate this point. The drug has little to no activity on its own, but when activated, it converts to morphine. “If you are an ultra-rapid metabolizer, you could produce way more morphine than expected and are vulnerable to overdose,” she said. To limit this negative outcome, codeine now has a black box warning to prevent its use in pregnant women and children until an individual’s genotype/phenotype is known she explained.
While pharmacogenomics may help guide drug and dose selection for an individual patient, McMillin cautions that this field is still evolving and should not replace dose optimization or clinical monitoring. “We see pharmacogenomics as a complement to existing tools that doctors already use,” said McMillin.