With so many people taking so many drugs, providers need information that will increase effectiveness of needed therapies, avoid cost and patient frustration by eliminating ineffective therapy, and prevent or minimize adverse drug reactions.
Would you like to know more about understanding your patient's personal drug response to help guide prescribing?
Before we get any further, it's important to understand some of the commonly used vocabulary, including pharmacogenomics, pharmacokinetics and pharmacodynamics. By definition, pharmacogenomics is the study of how genes affect a person's response to drugs. This relatively new field combines pharmacology — the science of drugs — and genomics — the study of genes and their functions — to develop effective, safe medications and doses that will be tailored to a person's genetic makeup.
A person's genes can affect pharmacokinetics, or how the body absorbs, metabolizes, distributes and excretes drugs, and the concentration of the drug in your body over time. A person's genes can also affect pharmacodynamics, or the effect a drug has on the body. A person's genetic makeup may result in a lack of desired effect or even adverse drug reactions at normal concentrations.
To illustrate how pharmacogenomics can be important, let's review the following case study. Dan went to see a doctor because of his history of major depressive disorder. He told his doctor that in the past his antidepressant medications did not work. His doctor prescribed 75 milligrams of venlafaxine daily.
After two weeks, Dan still had unresolved symptoms. So his physician increased the dose to 150 milligrams daily. Even with the increased dose, he continued to struggle with his symptoms, and it was affecting his job. His physician decided to order pharmacogenomic testing.
Dan's pharmacogenomic test result showed that he was a CYP2D6 poor metabolizer, indicating that he couldn't metabolize the prodrug venlafaxine into its active form. So his physician changed the prescription to an antidepressant not metabolized by the CYP2D6 pathway. And Dan's symptoms improved.
"Poor metabolizer," "prodrug," "CYP2D6." Let's explore what these terms mean and what this all means for Dan. Cytochrome P450, often referred to as CYP or "sip," is a family of enzymes responsible for the metabolism of many drugs. In fact, the P450 enzyme CYP2D6 is involved in the metabolism of approximately 25% of all the drugs used clinically.
Venlafaxine is a prodrug, which means it must be metabolized or activated before it will have the desired effect. Dan's CYP2D6 phenotype showed he was a poor metabolizer. This means that for prodrugs like venlafaxine, metabolized by CYP2D6, he can't fully activate the prodrug into its active form, which is why he did not get the desired therapeutic effect. On the other hand, a patient who is an ultrarapid metabolizer activates the prodrug too quickly, resulting in too high of a concentration of the active form. This may result in adverse drug reactions.
Patients with the form of the enzyme that works too slowly or too quickly may require dose adjustment or even alternative medications. Let's contrast the previous example of a prodrug with the effective CYPs in active drugs that don't need to be metabolized to have the desired effect. For example, the drug fluoxetine is an active drug, that is metabolized to its inactive form by CYP2D6.
Because Dan is a CYP2D6 poor metabolizer, he may end up with too high of drug levels and be at a greater risk of adverse drug reactions. In contrast, someone who was a CYP2D6 ultrarapid metabolizer would inactivate the drug too quickly and may not reach therapeutic levels.
It is important to note that most recommendations for drug dosing assume that patients metabolize or react to drugs normally. "Ultrarapid metabolizer" isn't just a description of enzyme activity. It's also the technical term used for describing one of the phenotypic results. "Poor metabolizer" is the term used to describe those variants that metabolize the slowest. The term used for the normal form of the enzyme is less intuitive. A person with normal enzyme function is known as an "extensive metabolizer."
Dan's case illustrates that using pharmacogenomics information in clinical practice can help prescribe the right drug at the right dose and at the right time for patients. At this point, you should have a better understanding of key pharmacogenomics vocabulary and concepts, how pharmacogenomics can impact your practice, and how to identify resources for additional information.