S15) Pharmacogenetics Flashcards
What is pharmacogenetics?
- Pharmacogenetics is the science of understanding how different individual genotypes relate to different drugs
- It enables physicians to know which drugs will therefore be safe and effective for an individual patient
What is pharmacogenomics?
Pharmacogenomics is pharmacogenetics applied to an entire genome
What are the potential risk factors for drug inefficacy or toxicity?
- Drug-drug interactions
- Age
- Renal and liver function
- Concurrent illness
- Genetic variation
- Lifestyle variables e.g. smoking and alcohol consumption
Explain the variation in genetics and the Renin-Angiotensin System
An individual’s response to ACEi / ARB is dependent on their own RAS activity:
- Young Caucasians have higher RAS activity – ACEi / ARB treatment will lower BP more effectively
- Older and Afro-caribbean patients have lower RASS activity – first line therapy is thiazide diuretics and CCBS
Compare and contrast Type A and B adverse drug reactions based on the following characteristics:
- Dose dependency
- Predictable
- Frequency
- Severity
- Host factors
- Clinical burden
- %ADRs
Identify where genetic polymorphisms might affect the pharmacokinetics of a drug
- Absorption
- Distribution
- Metabolism
- Excretion
Identify where genetic polymorphisms might affect the pharmacodynamics of a drug
- Receptors
- Ion channels
- Enzymes
- Immune systems
Illustrate how efficacy and toxicity vary with different combinations of the images below:
For the following P450 enzymes, identify the affected drug and resulting adverse reactions:
- CYP 1A2
- CYP 2C9
- CYP 2C19
- CYP 2D6
- CYP 3A4
Absent/reduced CYP 2D6 activity can lead to ADRs by three mechanisms.
Describe them
- Decreased first pass metabolism and drug elimination e.g. metoprolol and bradycardia
- Accumulation of drug as a result of reduced metabolism e.g. perhexilene and hepatotoxicity
- Re-routing of metabolism e.g. paracetamol and methaemoglobinaemia
For the following Phase II enzymes, identify the affected drug and resulting adverse reactions:
- N-acetyltransferase
- Thiopurine methyltransferase
- Dihydropyrimidine dehydrogenase
For the following enzyme defects, identify the affected drug and resulting adverse reactions:
- Glucose-6-phosphate dehydrogenase deficiency
- Methaemoglobulin reductase deficiency
- Acute intermittent porohydria
- Acetylcholinesterase
For the following HLA associations, identify the affected drug and resulting adverse reactions:
- DR3 DQ2
- B38 DR4 DQ3
- A24 B7, DQ1
- DR3
- DR4
- A29, B12, DR7
what does information on genome and other clinical diagnostic information provide (4 Ps)
Prediction and prevention of disease
Precise diagnosis
Personalised targeted interventions
Participatory role for patients
factors contributing to interindividual variability in drug response
- age
- race
- weight
- gender
- genetics
