L8 - Pharmacogenomics Flashcards
What is pharmacogenetics?
the study of interindividual variations in DNA sequence related to drug response
What is Pharmacogenomics?
The study of the variability of the expression of individual genes relevant to disease susceptibility as well as drug response at cellular, tissue, individual or population level.
Broadly applicable to drug design, discovery and clinical development
What is the fate of a CNS drug and the accompanying genetic variations?
Absorption - different drug transporter genes
Blood, immune response - HLA variations
Effects in the brain - genes of targets e.g the ion channels
Metabolism - e.g Cytochrome P450
Excretion - Drug transporters
What percentage of FDA approved medications are known to be affected pharmacogenes?
7%
18% of total prescriptions
What are the factors to consider in implemetation of diagnostic pharmacogenic testing?
Analytica validity - genotyping accuracy of the test
Clinical validity - Accuracy of test result in identifying clinical status
Clinical utility - risks and benefits of testing
cost-effectiveness - value for money of test
What is the genomics translation highway?
- Population health observations
- Bench
- Bedside
- Evidence-based recommendations
- Healthcare systems and prevention programs
and repeat…
what is the percentage of AED-rash side effects with seizure medication, Carbamazepine?
3.9%
What association predicts AED-rash side effects with seizure medication, Carbamazepine?
HLA-B*1502 - mainly in asia
HLA-A*31:01
What is the protocol now to protect patients from rash with Carbamazepine?
Patients with ancestry from areas in which HLA-B1502 allele is present should be screened for the HLA-B1502 allele before starting treatment with carbamazepine. If they test positive it shouldn’t be started (unless the benefit outweights skin reaction)
What is the testing recommendation for the HLA-A*31:01 allele to prevent rashes?
Moderately strong recommendation in all patients before the initiation of carbamazepine
Is Hla-N*15:02 testing cost-effective?
modelling in singapore and thailand suggest it is, yes.
True or false
HLA-B*`1502 screening has lead to a sharp decline in Carbamazepine prescriptions
true
What is the adherence to HLA-B1502 testing practice?
25%
What is the real world cost -effectiveness of HLA-B1502 testing?
current practice not cost-effective - better physician education, point-of-care testing needed
What are the deficiencies of the current testing workflow?
see slide
expensive delays treatment prolongs hospital stay extra clinic visit clinicians may avoid testing by prescribing more expensive drug
