12. Pharmacogenetics dose determination and immune response Flashcards
What are the 3 main reasons for pharmacogenomics?
- Minimise adverse drug reactions
- Determine most effective drug
- Determine appropriate dose
What are the benefits of PGx?
Safer dosing = fewer ADRs
Ensure maximum efficacy of drugs
Reduce healthcare costs
Which genes contribute to variation in warfarin response?
CYP2C9 and VKORC1
When is TPMT testing used?
In ALL patients treated with 6-mercaptopurine
What is 5-fluorouracil used to treat?
Variety of solid tumours including CRC, breast, pancreatic
What is the role of DPD?
Dihydropyrimidine dehydrogenase
Inactivates 5-FU in the liver
What is the consequence of reduced DPD activity?
Diarrhoea, vomiting, cardiac problems, neurological problems and in some cases fatality
How do 5-FUs work?
Work as antimetabolites & prevent cellular proliferation by blocking DNA synthesis
How does DPYD diplotype impact dosing of 5-FUs?
Intermediate metaboliser = reduce by 50%, dose then titrated based on toxicity
Poor metaboliser = alternative treatment
What does CYP2C19 metabolise?
Mavacamten - oHCM patients
Clopidegrol - antiplatelet drug for stroke patients
