Pharmacogenomics
Context:
Pharmacogenomics is currently transforming medication prescribing from a traditional trial-and-error approach to precision medication.
It addresses the limitations of the one-size-fits-all model.
It is shifting healthcare from reactive care to proactive prevention.
What is Pharmacogenomics?
Pharmacogenetics (sometimes called pharmacogenomics) is a field of research that studies how a person’s genes affect how he or she responds to medications.
Its long-term goal is to help doctors select the drugs and doses best suited for each person
It determines whether a drug will be effective, ineffective, or dangerous for a specific person.
It is part of the field of precision medicine, which aims to treat each patient individually.
Studies indicate that approximately 90% of people carry at least one actionable pharmacogenetic variant
Goal of Pharmacogenetics:
Maximize drug efficacy
Minimize drug toxicity
Predict patients who will respond to intervention
Aid in new drug development
Key Scientific Mechanisms:
Role of Enzymes:
Variability in drug response largely arises from differences in drug-metabolizing enzymes (particularly the cytochrome P450 (CYP) family) which processes about 75% of commonly prescribed medications.
Metabolizer Phenotypes:
Genetic variations result in different metabolizer types:
Poor Metabolizers: These have low functional enzyme activity, leading to the accumulation of toxic drug levels from standard doses.
Ultrarapid Metabolizers: These have enhanced enzyme activity, often resulting in no therapeutic benefit from standard doses.
Clinical Examples:
Warfarin:
It is a widely prescribed blood thinner with a notoriously narrow therapeutic window.
Genetic variants in CYP2C9 and VKORC1 genes account for significant variation in dosing requirements.
Clopidogrel:
It is a cornerstone antiplatelet drug used after heart attacks and stenting.
Patients with loss-of-function CYP2C19 variants may experience reduced drug activation and higher cardiovascular risk.