Syllabus: Bio-technology
Introduction
- Pharmacogenomics studies how genetic variations influence an individual’s response to medicines.
- It moves healthcare from population-based prescribing to precision medication, reducing trial-and-error treatment.
- Genetic differences, especially in cytochrome P450 (CYP) enzymes, significantly alter drug metabolism and safety.
Genetic Variability and Drug Response
- CYP enzymes metabolise nearly 75% of commonly prescribed drugs.
- Variants produce distinct metaboliser phenotypes such as poor, intermediate, normal and ultrarapid metabolisers.
- Poor metabolisers risk toxic accumulation, while ultrarapid metabolisers may receive insufficient benefit.
- Studies indicate around 90% of people carry at least one actionable pharmacogenetic variant.
- Genetic factors contribute substantially to adverse drug reactions (ADRs), a major cause of hospitalisation and mortality.
Clinical Applications
- Warfarin: CYP2C9 and VKORC1 variants explain ~50% of dosing variability; genetic-guided dosing improves safety and reduces bleeding.
- Clopidogrel: Requires CYP2C19 activation; loss-of-function variants (e.g., CYP2C192*) raise risks of stent thrombosis.
- CPIC 2022 guidelines recommend alternative antiplatelet drugs for CYP2C19 poor metabolisers.
- Psychiatry: Variants in CYP2D6 and CYP2C19 impact antidepressant and antipsychotic drug levels, influencing side-effects and outcomes.
- Oncology increasingly integrates pharmacogenomic-guided treatments.
Economic Considerations
- Genetic test costs have declined from thousands to $200–500 for comprehensive panels.
- Cost-effectiveness depends on variant frequency, drug alternatives, severity of ADRs, and duration of therapy.
- Preventing even one serious ADR may offset testing costs across multiple patients.
Challenges in Implementation
- Major barrier is limited provider knowledge on interpreting test results.
- Electronic health records often lack integrated decision-support tools.
- Insurance coverage for tests remains inconsistent across jurisdictions.
- Varying regulatory guidance: over 100 FDA drug labels now include pharmacogenomic information with differing levels of actionability.
- Institutional resistance requires strong frameworks, administrative support, and clinical champions.
Way Forward
- Future lies in pre-emptive pharmacogenomic testing, enabling lifelong access to genetic data for personalised prescribing.
- It marks a shift from reactive care to proactive precision medicine, ensuring safer and more effective therapies.