biomarkers of pharmacogenomics
- these are genetic variants that predict response
- enzymes
- transporters
- receptor proteins
examples of enzymes that could be affected by pharmacogenomics
-select alleles or deletions/duplications in cytochromes
ethnicity and pharmacogenomis
- certain polymorphisms tend to be more prevalent in certain ethnic groups
- this could make people very slow or very rapid metabolizers of drugs which would have very diverse affects depending on the drug
individuals with variants for poor metabolism show…
- increased plasma concentrations of the drug and for longer periods of time
- their AUC is increased
when an inhibitor is given to a genetically poor metabolizer
-there is no change because their metabolism is already reduced due to their genetics
consequences of being a poor metabolizer
- reduced first pass effect
- reduced metabolic clearance
- alternative pathway metabolism
- failure to activate prodrugs
- not affected by inhibitors
what happens when you have a reduced first pass effect
- increased oral bioavailability
- increased plasma levels
what happens when you have reduced metabolic clearance
- increased half life
- increased accumulation with repeated doses
pharmacogenetics in clinical practice
-some drugs such as cetuximab and trastuzumab require genetic testing before use whereas other drugs just recommend it
why dont some physicians use genetic tests before administering certain medications
- resistant to abandon trial and error method
- concern about genetic discrimination
- unfamiliarity with principles of genetics
- lack of outcomes data
- affordability
