4.2.2 Pharmacogenetics Flashcards
Why is pharmacogenetics important?
Poor drug efficacy presents substantial problems in medicine
Majority of commonly prescribed drugs only effective in 30-50% of individuals
What is pharmacogenetics?
Study of how genes affect our response to drugs
What are the 4 Ps in precision medicine?
Prediction and prevention of disease
Precise diagnoses
Personalised and targeted interventions
Participatory role for patients
What factors contribute to variability in drug response?
- Age
- Race/ethnicity
- Weight
- Gender
- Concomitant Diseases
- Concomitant Drugs
- Compliance
- Social factors
- Biomarkers
- GENETICS
How does genetic variability affect PK and PD?
Pharmacokinetics
ADME
Absorption, distribution, metabolism and excretion
Pharmacodynamics
RITE +DNA
Receptors
Ion channels
Transporters
Enzymes
DNA
Why should pharmacogenetics be integrated into the NHS?
Give patients safer and more appropriate therapies
Avoid wasting time and money on treatments that will be at best ineffective and at worse harmful
Move away from one size fits all medicine
What are the 4Ps (again)?
Prediction and prevention
Precision
Personalised
Participatory
Clinical example of pharmacogenetics
Believed renin typically lower in African Caribbean populations so ACEi/ARB not primary choice for lowering BP, but may actually be negligible difference
Angioedema more prevalent in African Caribbean populations than in young white
What is the problem with classifying people by race?
Less homogeneity now, no longer as relevant and can lead to more harm than good by not giving treatments
How has HLA alleles led to screening?
Human leukocyte antigen cause a 5-8% risk of Stevens Johnson syndrome reaction to abacavir and carbamazepine (increased frequency in south east asians)
People screened for antigen before recieving drugs
CYP2D6 pharmacogenetics example
CYP2D6 isofrom responsible for metabolising ~25% of drugs
Variability in population with this enzyme
8% of population lack the enzyme
2% have more than 2 copies and are ultra metabolisers, codeine does no work in these patients
How does warfarin work?
Inhibits Vitamin K epoxide reductase
Why do warfarin doses vary between people?
10-20 fold variation, need to measure INR
Polymorphisms in genes for VKOR and is metabolised by CYP2C9
Clotting activation and breakdown of warfarin can vary between patients, makes dosing difficult
Simvastatin pharmacogenetics
Some patients have different gene variations, increased risk of myopathy and rhabdomyolysis
Reduced function of OATP transort proteins, these usually transport statins to liver to be metabolised
Personalised cancer vaccine example
