Ch. 11 Pharmacogenomics Flashcards
Purines
Adenine
Guanine
Pyrimidines
Thymine
Cytosine
Haplotype
A group of genes or DNA variations inherited from a single parent that exist on the sam chromosome and are likely to be inherited together
Single nucleotide polymorphism (SNP)
A change in a single nucleotide in a genetic sequence. Most common genetic polymorphism in DNA. Responsible for the majority of individual variability in response to a drug
Mutation associated with Abacavir
HLA-B*5707 (if positive DO NOT USE)
Type of reaction associated with HLA-B*5707
Fatal hypersensitivity
Drugs that contain abacavir
Epzicom
Triumeq
Trizivir
Mutation associated with Allopurinol
HLAB*5801 (if positive DO NOT USE)
Type of reaction associated with HLA-B*5708
Increased risk of SJS
Population to test prior to use of allopurinol
Patients with significant renal impairment or those with Han Chinese or Thai ancestry
Mutation associated with Carbamazepine and phenytoin/fosphenytoin
HLA-B*1502 (if positive DO NOT USE)
Type of reaction associated with HLA-B*1502
SJS, TEN
Population to test prior to starting carbamzepine
All Asian patients
Mutation associated with Clopidogrel
2C192/3 (if pt has the allele, consider alternatives)
Effect of therapy in patients with 2C19 mutation in clopidogrel use
Poor metabolism of clopidogrel (as it is a prodrug) and increased cardiovascular events
CYP450 enzyme associated with Codeine metabolism
2D6
Codeine use in 2D6 ultra-rapid metabolizers
Increase in production of morphine, resulting in toxicity
Codeine use in 2D6 poor metabolizers
Lack of efficacy
CYP450 enzyme associated with use of Warfarin
2C92/3 and VKORC1
Effect of warfarin in patients expressing 2C92/3 and/or VKORC1
Increased bleeding risk, lower dose if variations of alleles are present
Gene expression needed in those to start Trastuzumab therapy
HER2 overexpression
If tumor is HER2 negative, do not use
Cetuxumab and panitumumab gene mutation
KRAS
If a patient is KRAS positive, they cannot use
Cetuximab and panitumumab
Gene associated with AZA use
TPMT
Low/absent TMPT activity in AZA use can cause
Myelosuppression
Enzyme associated with Capecitabine and Fluorouracil use
Dihydropyrimidine dehydrogenase (DPD)
Deficiency in DPD and use of Capecitabine and Fluorouracil can cause
Increased toxicity (diarrhea, neutropenia, neurotoxity) Do not use in patients with DPD deficiency
If a patient produces less VKORC1, they require
A lower dose of warfarin
Which isomer type of warfarin is better metabolized by 2C9?
S-isomer is more potent than the R isomer
