Week 4 Pharmogenomics Module Flashcards Preview

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Flashcards in Week 4 Pharmogenomics Module Deck (45)
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what are three benefits of pharmogentics?

avoid adverse drug reactions, improve efficacy of pharmocologic agents, improve cost-effectiveness of pharmocologic therapy


what is a locus?

a specific position of a gene on a chromosome (the same locus can have different alleles)


what is an allele

a specific gene inherited from one parent. each autosomal locus has two alleles one from mother, one from father)


what is allele frequency?

fraction of the total popn that carries a specific allele


what is a polymorphism?

2 or more alterantive sequences are present in a more than 1% of popn. (SNPs!)


contrast pharmacogenetics and pharmacogenomics

pharmacogenetics: focus on single genes
pharmocogenomics: focus on mulitple genes


polymorphisms impact PF, PD, both?



A pt arrives at the hospital with a rash, the dr give him an oitment. the pt asks if this topical ointment can have systemic effects? what is your reply?

yes, it can be absorbed through the skin and have systemic effects


in order for a drug to impact the CNS, what must occur?

drug must cross blood-brain barrier


other than the kidney, how else can drugs be excreted?

into the bile where they can be reabsorbed in the SI or voided in feces


what occurs in phase 1 drug metabolism? who is the major player

oxidation, reduction, hydrolysis. Cytochrome P450 enzymes


what occurs during phase 2 metabolism?

addition of large polar groups


what does CYP stand for

Cytochrome P450


given: CYP2C19*8, what does "*8" mean? what does *1 refer to?

a different allele of that specific CYP gene. *1 refers to the wt/most abundant allele


which CYP gene metabolizes the most of the commonly used genes? does it have much genetic variability?

CYP3A4/5/7, with little genetic variability


why do we care about preventing ADRs?

they are a leading cause of death in hospitalized pts. hundreds of thousands of deaths annually in US alone


CYP2C9: role, acts on?

hydroxylates (phase I). Acts on warfarin, phenytoin, tolbutamide


warfarin role, indications?

anti-cagulant. Use for pulmonary embolism, heart valve replacement, knee or hip replacement


phenytoin role



tolbutamide role

insulin release stimulator


what protein does Warfarin target? what protein metabolizes warfarin?

Targets: VKORC1
Metabolized by: CYP2C9


Does the FDA require screening for VKORC1 and CYP2C9 alleles prior to prescribing warfarin?

no, although a 28% decrease in hospitalization is seen when this information is used.


individuals who have GG in VKORC1 and *1/*1 are recommended to take 5 to 7 mg of Warfarin, whereas individuals who are AA in VKORC1 and *3/*3 are recommmended to take 0.5 to 2 mg of wararin. what accounts for this?

the GG 1*/1* metabolize warfarin better and are less prone to ADRs and can therefore take a higher dose.


what are 4 drugs metabolized by CYP2D6? which is a pro-drug?

antispychotic, antidepressants, metoprolol (antihypertensive), tamoxifen (anti-cancer, pro-drug)


what drugs inhibit the activity of CYP2D6? 4

cocaine, fluoxetine, paroxetine, protease inhibitors


CYP2D6 has 51 different alleles with varying enzyme activity; what are the four metabolizer categories of CYP2D6?

Poor metabolizer (PM)
intermediate metabolizer (IM)
Efficient metabolizer (EM)
Ultrarapid metabolizer (UM)


a mutation that increased the copy number of the CYP2D6 gene (CYP2D6*2xn) would likely be classified as a...what type of mutation is this?

Ultra metabolizer, GOF


A drug is metabolized and inactivated in the body. If a person is known to be a UM for the drug, how would you augment their dose? what if they were a PM?

increase dose because they are an Ultra metabolizer (will get rid of drug faster)

decrease dose because they are a PM (drug stays longer)


a pro-drug is metabolized and activated in the body. if a person is known to be a UM for the drug, how would you augment their dose?

decrease their dose to prevent too much active drug in the system


what is the active form of Tamoxifen? what is unique about Tamoxifen?

Endoxifen, it is a pro-drug


does the FDA require genetic testing prior to Tamoxifen use?



three patients: a EM, IM, and PM for Tamoxifen. Each are given the same dose. which has the best change of survival?



individuals with G6PD deficiency (a major cause of hemolytic anemia) have an increased risk of hemolytic reaction when taking what drug? does the FDA recommend genetic testing prior to treatment?

Rasburicase. yes


patients with HLA-B*1502 allele have an increased risk of developing life-threatening Steven-Johnson syndrome when taking what? does the FDA recommend prior genetic testing?

Carbamazepine (seizure disorder drug), yes


patients with HLA-B*5701 have an increased risk of developing severe hypersensitivity rxns when taking what? does the FDA recommend prior genetic testing?

abacavir (HIV treament), yes


pts with TPMT-deficiency have an increased risk of myelotoxicicty when taking what? does the FDA recommend prior genetic testing?

Azathioprine, yes


what is the role of TPMT?

phase 2 inactivation of thiopurines


thiopurines are used to treat what?

suppress immune system


low level of TPMT will lead to what if the normal dosage of thiopurine is taken?

leukopenia (decrease plasma WBCs)


In general, when a person is deficient/mutant in a gene, when do ADRs occur?

when they are given a drug that is normally metabolized by the deficient/mutant gene


what is the efficacy of a drug?

the max response achievable from a drug treatment


when does Imatinib have an increased efficacy? is testing done prior to treatment?

when treating C-KIT positive GI tumors. yes


when does Maraviroc have an increased efficacy? is testing done prior to starting treatment?

treating pts with CCR5-tropic HIV-1 infection. Yes


Trastuzumab has increased efficacy when treating what type (genetic) of breast cancer? is testing done prior to treatment?

HER-2 positive. yes


what is the idea behind using genetics to imprice efficacy of drugs?

test for the genetic status prior to determine how likely they are to benefit from the treatment

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