Concepts
Pharmacogenomics: study of how genes affect drug response. Pharmacogenetics: study of single gene effects. Goal: right drug, right dose, right patient. Genes affect: drug metabolism (CYP enzymes), transport, receptors, targets, immune response. Polymorphisms: common genetic variations affecting enzyme activity. Phenotypes: ultra-rapid metabolizer (UM), extensive/normal (EM), intermediate (IM), poor (PM). Result: drug toxicity, lack of efficacy, or altered response. Genetic testing can guide medication selection and dosing.
Clinical Applications
CYP2D6: codeine (UM convert to morphine rapidly — toxicity risk in children/breastfed infants), tamoxifen (PM less effective), antidepressants, antipsychotics. CYP2C19: clopidogrel (PM less effective — increased stent thrombosis risk), PPIs, antidepressants. CYP2C9/VKORC1: warfarin (affects dosing — lower dose in PM). HLA-B*5701: abacavir hypersensitivity (contraindicated if positive). HLA-B*1502: carbamazepine SJS/TEN (Asian ancestry). TPMT: 6-mercaptopurine/azathioprine (PM risk of severe myelosuppression). DPD: 5-FU toxicity. UGT1A1: irinotecan toxicity.
Nursing Implications
Identify patients who may benefit from pharmacogenomic testing (before starting high-risk drugs, history of drug reactions, unusual drug response). Educate: why testing is done, what results mean, implications. Document genotype and pharmacist/MD recommendations. Monitor: therapeutic effect, side effects, toxicity — especially before results available. Advocate for testing when appropriate. Recognize limitations: not all drug response is genetic (interactions, organ function, age, diet). Pharmacogenomics is one tool — not the only tool. Stay current: new applications emerging rapidly. Resources: CPIC, PharmGKB, FDA labeling.
Important Notes
- Codeine is contraindicated in breastfeeding mothers and children — CYP2D6 ultra-rapid metabolizers convert codeine to morphine rapidly, causing fatal overdose.
- Clopidogrel response varies by CYP2C19 genotype — poor metabolizers have increased risk of stent thrombosis; consider alternative (ticagrelor, prasugrel).
Clinical Tips
- HLA-B*5701 testing required before abacavir — positive predicts fatal hypersensitivity reaction.
- Warfarin dosing affected by CYP2C9 and VKORC1 genotype — pharmacogenomic-guided dosing reduces bleeding and thrombosis risk.
Summary
Pharmacogenomics uses genetic testing to guide drug selection and dosing — nurses must identify candidates, educate, monitor response, and advocate for testing.
