Chapter 79: Pharmacogenomics Flashcards
For a recessive allele to produce a recessive phenotype, the individual must have ___ copies
2
Specific sequence of nucleotides that code for a single protein
gene
What is the most commonly occurring allele
Wild-type
Two identical alleles make up a ____ genotype
homozygous
Two different alleles make up a ____ genotype
heterozygous
The set of unique genes that determine a specific trait in an individual
Genotype
An observable trait of the genotype, such as hair color, or an inherited trait that is not outwardly visible, such as sickle cell disease
Phenotype
A change in a single nucleotide in a genetic sequence
Single nucleotide polymorphism (SNP)
The most common genetic alteration in DNA
SNPs
What is responsible for the majority of individual variability in response to a drug
SNP
Which type of drug metabolizer has fewer functional enzymes to metabolize a drug substrate
Poor metabolizers
Which type of drug metabolizer has more functional enzymes to metabolize a drug substrate
Ultra-rapid metabolizers
Abacavir + abacavir containing combo drugs (Triumeq, Epzicom) requires testing for which HLA gene
HLA-B*5701
Allopurinol (Zyloprim, Aloprim) requires testing for which HLA gene
HLA-B*5801
-Carbamazepine (Tegretol)
-Oxcarbazepine (Trileptal)
-Phenytoin (Dilantin)
-Fosphenytoin (Cerebyx)
require testing for which HLA gene
HLA-B*1502
Patients who test positive for HLA-B*5701 with Abacavir + abacavir containing combo drugs (Triumeq, Epzicom) are at increased risk of
fatal hypersensitivity reaction
Patients who test positive for HLA-B*5801 with allopurinol are at increased risk of
SJS
Patients who test positive for HLA-B*1502 with AEDs are at increased risk of
SJS and TEN
Which ethnic group must be tested prior to starting carbamazepine
Asians
Which CYP enzyme should be tested prior to Plavix therapy
CYP2C19
prodrug
Patients with which star allele(s) are poor metabolizers of Plavix and have increased CV events
*2 and *3
Which CYP enzyme should be tested prior to Codeine therapy
CYP2D6
prodrug
Which patients will be at increased risk of opioid overdose with codeine therapy
Ultra-rapid metabolizers (due to extensive conversion to morphine)
What should be tested prior to warfarin therapy
CYP2C9*2 and *3
VKORC1
Patients on warfarin therapy and have CYP2C9*2 and *3 alleles or VCORC1 G>A variant are at increased risk of
bleeding
What should be done if a patient on warfarin has CYP2C9*2 and *3 alleles or VCORC1 G>A variant
Start with a lower dose
What should be tested prior to trastuzumab (Herceptin) therapy
HER2 gene expression
need HER2 expression for trastuzumab to work
What should be tested prior to Cetuximab (Erbitux) therapy
KRAS mutation
If a patient is positive for the KRAS mutation, what should be done with cetuximab
It should not be used. Only patients who are KRAS-mutation negative (wild-type) should receive the medication
What should be tested prior to azathioprine therapy
TPMT
Low or absent TPMT activity with azathioprine therapy increases the risk of
severe, life threatening myelosuppression
What should be tested for with capecitabine/5-FU?
DPD deficiency
Patients using capecitabine (Xeloda) or fluorouracil and have DPD deficiency are at increased risk of
severe toxicity (diarrhea, neutropenia, neurotoxicity)
Key drugs where testing is required or strongly recommended
- Abacavir and any combination products containing abacavir
- Azathioprine
- Carbamazepine
- Cetuximab and other EGFR inhibitors
- Trastuzumab and other HER2 inhibitors
Avoid the drug when these pharmacogenomic tests are POSITIVE
- HLA-B testing (increased risk of hypersensitivity)
- KRAS mutation (predicts poor response)
