Know what you don't know - a lesson in pharmacogenomics

Written by: Alicia A. Timko, PharmD.  Consultant Pharmacist Long Term Care Rx Pharmacy

Those of us in the field of medicine and health care have studied the sciences for years. As a pharmacy student, I spent hours building and rebuilding molecular structures with my molecular model kit for Organic chemistry and many more hours studying molecular pathways of metabolism in Medicinal chemistry.

Science can seem rigid and firm. It can seem certain and true. But we know that that the practice of medicine is an art, right? What does that mean? On the surface, we may accept that the practice of medicine is more gray and fluid and creative like art, but do we really? Do we accept that there are huge gaps in our knowledge of how these molecular structures interact with the unique blueprints within each person?

Practicing pharmacists can sound so certain about their knowledge of side effects of medications, so certain that “You really couldn’t be having that side effect. It isn’t in the package insert.” or “That medication HAS to be working especially at THAT dose!”. We doubt the patient. We are skeptical of their pronouncement of how this medicine is working in their body. “It couldn’t be. It can’t.” The world of pharmacogenomics is here to change all that.

Pharmacogenomics is the study of how human genes affect drug response. This field is no longer the Star Wars of pharmacy, some farfetched, futuristic potential in medicine. It is happening here and now. You may not have laid eyes on the results of any genomic lab tests, but the knowledge of specific genes and their effect on specific medications is well documented and laid out.  

Let’s take the pain medication codeine. Pharmacology has long taught us that codeine gets largely metabolized to morphine which has a 200-fold stronger affinity for pain receptors in the body vs codeine. Pharmacogenomics now reveals that individuals can have variations in their genes that cause them to have varying effects. Some can be considered “Ultra-rapid metabolizers” (convert lots of codeine to morphine), “Extensive or Intermediate metabolizers” (convert “normal” or slightly lower amounts of codeine to morphine) or “Poor metabolizers” (convert much less codeine to morphine). It is believed that approximately 5%-10% of the population are “Poor metabolizers” of codeine to morphine. Thus, not getting the pain relief the rest of us would experience. And approximately 1%-2% of the population are “Ultra-rapid metabolizers,” leading to toxic levels at doses considered “normal.” Morphine is a recommended alternative because it does not follow the same metabolic pathway.

Pharmacogenomics is helping to reveal why medicine is an art. Helping us accept the outliers. Helping to create personalized medicine over empiric medicine. A seismic shift.

So, do we need to memorize all the genes and their effects on medications? Probably not just yet. But we do owe it to our patients to know what we don’t know. Believe them when they say that this drug is just not giving them any pain relief. Try a recommended alternative (there really are published guidelines to follow! Google CPIC Guidelines*). You may not know whether your patient is an Ultra-metabolizer or Poor metabolizer but you will have an intelligent alternative to try if they are failing the empiric drug of choice.


*CPIC- Clinical Pharmacogenetic Implementation Consortium Guidelines.