Genomics - Pharmacogenomics: Nursing

Nurse Marta works in a primary care office and is caring for a client, Juan, who was recently diagnosed with HIV. Juan has come to the office for genetic counseling after testing positive for the HLA B*5701 allele. While Nurse Marta is documenting Juan’s admission information, Juan says, “So I know I can’t take certain HIV drugs because of my genes, but I don’t really know why.” Nurse Marta responds, “Some people with HIV can develop a serious reaction to the medication abacavir if they have a genetic variation called the HLA B∗5701 allele.” Juan nods his head but looks puzzled. He tells Nurse Marta, “I’m not following. Is there something wrong with me?” Nurse Marta assures Juan that they’ll work together to understand how his genes impact his response to this medication. Nurse Marta will use what she knows about pharmacogenomics to support, educate, and assess Juan during this process.

Pharmacogenomics combines genomics and pharmacology to understand how a client’s genetic variations affect their response to medication. It examines the genetic factors that play a role in the effectiveness of medication therapy to provide individualized and safe care to clients.

Now, most medication metabolism depends on a family of CYP450 enzymes. And there are a number of genes that code for these enzymes. So, one way a variant in one of these genes can modify a client’s response to medications is by altering the medication’s metabolism. Depending on the genetic variant, when a client takes a certain medication, it can either cause an exaggerated response, leading to possible toxicity, or a muted response, leading to a reduction in the effect of the medication.

For example, some clients have a form of the CYP450 enzyme CYP2D6, that is unable to convert codeine into morphine, which is the active form of codeine. So, when codeine is administered to a client with this altered enzyme, the medication is ineffective because it doesn't reduce the client’s pain. Likewise, some clients have another form of CYP2D6 that’s unable to metabolize venlafaxine, a serotonin and norepinephrine uptake inhibitor, or SNRI, leading to decreased medication effectiveness.

Next, genetic variants can also modify a client’s response to medications by altering medication targets around the body. An example of this can be seen with the anticoagulant, warfarin, which works by inhibiting the vitamin K epoxide reductase complex 1, or VKORC1, which is an important enzyme in the vitamin K-dependent clotting pathway. Some clients produce a gene variant of VKORC1 which alters the structure of the enzyme, causing clients to be more sensitive to the effects of warfarin. In this situation, clients will need much smaller doses of warfarin to achieve a safe level of anticoagulation while preventing excessive bleeding.

Genetic variants can also affect receptors on cells that are targets of medications, such as those found on cancer cells. For example, cetuximab is a cancer medication that is only successful in treating tumors that express the epidermal growth factor receptor, or EGFR. This means tumors that don’t have this receptor aren’t responsive to cetuximab and another medication must be given instead.