pharmacogenomics
study of genomic influence on drug response
pharmacogenetics
study of individual gene-drug rxns
-usually 1 or 2 genes having dominant effect on drug response
mutation
altering DNA sequence - rare in population
polymorphism
altering DNA sequence - common in population
-affect >1%
single nucleotide polymorphism
most common - marker for pinpointing disease or mapping therapeutic outcome
- coding nonsynonymous - changing base changes protein
- coding synonymous - changing base does NOT change protein
- noncoding
indels
short repeats in the promote that add or subtract amino acids
-insertions/deletions
copy number variation (CNVs)
genomic DNA involved in duplication, deletion, or inversion
haplotype
combination of alleles or SNPs that tend to be inherited together - linkage disequilibrium
-determines the phenotype
Beta2 adrenergic receptor polymorphisms
depending on haplotype of the patient, may not respond to albuterol to help relieve asthma
-may need to take more drug to have effect
pharmacodynamics - simple mutation in drug receptor
can totally change the affect of the drug - change in drug target
-agonist –> partial agonist or vice versa for ex.
pharmacokinetics polymorphisms
change in metabolizer enzyme function determines whether you get the therapeutic effect or side effects of the drug
- Active drug: increase dose with UM and decrease dose with PM
- Pro drug: decrease dose of UM and increase dose of PM
cytochrome P450 enzymes
- CYP2D6 - metabolizes codeine to morphine
- 2C19 - metabolizes clopidogrel
- 2C9 - metabolizes warfarin (anticoagulant) - CYP2C92 and CYP2C93 are polymorphisms decreasing warfarin metabolism; VKORC1 also has polymorphisms
NAT2
phase 2 enzyme who metabolizing effects may lead to a higher susceptibility to cancer
-found in liver - activates and deactivates many chemicals such as cigarettes
