Pharmacogenomics Flashcards
What are adverse drug reactions?
Negative/undesirable effects of drug treatment.
What contributes towards differential responses to medications?
Pharmacogenomic, demographic factors, clinical factors, dosing factors, other factors.
How does ancestry impart ADR?
Ancestry; genetic factors and environmental factors.
What are two examples of ethnic effects on ADR?
- Black people increased risk of heart failure from hydralazine.
- East asian descent alcohol metabolism.
How do sex differences contribute to ADR?
Women are underrepresented in drug trials, although physiologically different.
How does age impact ADR?
Drug metabolism and elimination is less efficent in extremes, changes in body composition as well as polypharmacy.
Changes in gene expressions for CYPS
What age group is GFR lower in?
Elderly and neonates.
What is a regulatory variation?
Mutation on regulatory site, causes increased for decreased expression.
What is coding variation?
Mutation in coding site: SNP or translocations.
What are splice-site variations?
Mutations at splice sites; create or abolish acceptor/donor sites.
What is expression quantitative loci?
Variations causing changes in downstream (cis) genes or genes elsewhere (trans)
What is the key determinant to a drug response?
Genetics
What is precision health?
Taking genetic and non-genetic factors into account during prescription and administration
What is CYP2D6?
Pharmacogene that is a metabolizing enzyme, has MANY polymorphisms.
What must be done before the administration of codeine to pregnant/nursing women?
Test for CYP2D6 polymorphisms.
What is the result of CYP2D6 duplication?
Ultra fast metabolism
What is the result of CYP2D6 deletion?
Ultra slow metabolism
How many individuals will carry clinically relevant pharmacogenomic variants?
97%
What are important clinical considerations for pharmacogenomic biomarkers and clinical implementation?
Results must be replicated
There must be robust ADR phenotyping when obtaining clinical data
The risk of ADR must be clinically relevant
What are clinical practice guidelines?
CPIC; standardize peer-reviewed consortium that grades evidence and clinical reccommendation
What is the survival rate of childhood cancer?
80%
What is cisplatin-induced hearing loss?
Hearing loss due to treatment of solid tumors, affects language and social development and causes permanent bilateral hearing loss.
What is the risk of cisplatin-induced hearing loss?
40-60%
What was discovered to be a pharmacogene causing cisplatin-induced hearing loss?
TCERG1L
