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Foundations 1 > Week 4 Pharmogenomics Module > Flashcards

Week 4 Pharmogenomics Module Flashcards

1
Q

what are three benefits of pharmogentics?

A

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

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2
Q

what is a locus?

A

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

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3
Q

what is an allele

A

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

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4
Q

what is allele frequency?

A

fraction of the total popn that carries a specific allele

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5
Q

what is a polymorphism?

A

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

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6
Q

contrast pharmacogenetics and pharmacogenomics

A

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

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7
Q

polymorphisms impact PF, PD, both?

A

both

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8
Q

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?

A

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

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9
Q

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

A

drug must cross blood-brain barrier

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10
Q

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

A

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

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11
Q

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

A

oxidation, reduction, hydrolysis. Cytochrome P450 enzymes

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12
Q

what occurs during phase 2 metabolism?

A

addition of large polar groups

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13
Q

what does CYP stand for

A

Cytochrome P450

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14
Q

given: CYP2C198, what does “8” mean? what does *1 refer to?

A

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

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15
Q

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

A

CYP3A4/5/7, with little genetic variability

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16
Q

why do we care about preventing ADRs?

A

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

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17
Q

CYP2C9: role, acts on?

A

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

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18
Q

warfarin role, indications?

A

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

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19
Q

phenytoin role

A

anticonvulsant

20
Q

tolbutamide role

A

insulin release stimulator

21
Q

what protein does Warfarin target? what protein metabolizes warfarin?

A

Targets: VKORC1

Metabolized by: CYP2C9

22
Q

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

A

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

23
Q

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?

A

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

24
Q

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

A

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

25
Q

what drugs inhibit the activity of CYP2D6? 4

A

cocaine, fluoxetine, paroxetine, protease inhibitors

26
Q

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

A 
Poor metabolizer (PM)
intermediate metabolizer (IM)
Efficient metabolizer (EM)
Ultrarapid metabolizer (UM)
27
Q

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?

A

Ultra metabolizer, GOF

28
Q

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?

A

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

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

29
Q

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?

A

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

30
Q

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

A

Endoxifen, it is a pro-drug

31
Q

does the FDA require genetic testing prior to Tamoxifen use?

A

no

32
Q

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

A

EM>IM>PM

33
Q

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?

A

Rasburicase. yes

34
Q

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?

A

Carbamazepine (seizure disorder drug), yes

35
Q

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

A

abacavir (HIV treament), yes

36
Q

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

A

Azathioprine, yes

37
Q

what is the role of TPMT?

A

phase 2 inactivation of thiopurines

38
Q

thiopurines are used to treat what?

A

suppress immune system

39
Q

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

A

leukopenia (decrease plasma WBCs)

40
Q

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

A

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

41
Q

what is the efficacy of a drug?

A

the max response achievable from a drug treatment

42
Q

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

A

when treating C-KIT positive GI tumors. yes

43
Q

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

A

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

44
Q

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

A

HER-2 positive. yes

45
Q

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

A

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

Foundations 1 (65 decks)

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