Ch 11: Pharmacogenomics Flashcards
genotype
unique genes that determine a specific trait
phenotype
observable trait (outward expression) of the genotype
haplotype
group of genes or DNA variations inherited from a single parent that exist on the same chromosome and are likely inherited together
SNP
single nucleotide polymorphism, most common genetic polymorphism, responsible for majority of individual variability in response to a drug
structural variation
polymorphism involving large portion of DNA
polymorphism
inherited variation in DNA sequence (including SNP and SV)
HLA-B*5701
abacavir (ziagen), abacavir + lamivudine (epzicom), abacavir + duletegravir + lamivudine (Triumeq), abacavir + zidovudine + lamivudine (Trizivir). test all pts before starting, if (+) do not use. fatal hypersensitivity.
HLA-B*5801
allopurinol (zyloprim). If (+) do not use. inc risk of SJS. DC at first sign of allergic rxn, including rash. consider testing high risk pts –> asians.
HLA-B*1502
carbamazepine (tegretol), phenytoin (dilantin), fosphenytoin (cerebyx). if (+) do not use, unless benefit outweighs risk. SJS, TEN risk. test ALL asian pts before starting carbamazepine.
Required or strongly recommeneded pharmacogenomic testing
abacavir and combo meds. azathioprine. carbamazepine. cetuximab and panitumumab. trastuzumab and ado-, lapatinib, and pertuzumab.
CYP450 2C19 genotype
clopidogrel d/t produg needing metab. if *2 or *3 allele then poor metabolizer. consider alt tx.
CYP450 2D6
codeine d/t prodrug to morphine via metab. if 2D6 ultra rapid metabolizer, do not use d/t tox risk. if 2D6 poor metabolizer, do not use d/t lack of efficacy
Warfarin
CYP2C9*2 and *3, VKORC1. inc bleeding risk, start with lower dose.
DPD deficiency
dihydropyrimidine dehydrogenase deficiency. do not use for xeloda and adrucil d/t inc tox
TPMT
thiopurine methyltransferase (TPMT). if low/absent, start at low dose or seek alt tx for azathioprine d/t inc risk of life threatening myelosuppression
