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Flashcards in Pharmacogenetics Deck (97):
1

three things that make us

genetics
environment
epigenetics

2

describes the DNA sequence variation leading to alterations in drug response

pharmacogenomics

3

describes the relationship of protein structure and function

proteomics

4

study of the set of metabolites present within an organism, cell or tissue

metabolomics

5

describes the changes in gene function or expression that occur in the absence of DNA sequence alterations

epigenetics

6

types of drug responses

- full
- partial
- none
- adverse reaction

7

drug response and doses

each specific drug with specific dose is different

8

why is personalized medicine important?

some of our differences translate into how we react to drugs as individuals

9

goal of personalized medicine

- right dose
- right drug
- right indication
- right patient
- right time

10

study of individual gene drug interactions, usually one or two genes that have dominant effect on drug response

pharmacogenetics

11

is pharmacogenetics a simple or complex relationship?

simple

12

is pharmacogenomics a simple or complex relationship?

complex

13

study of genomic influence on drug response, high throughput data

pharmacogenomics

14

What percentage of medication do not work as intended?

10-70%

15

What group of medications have the higher percentage of not working?

B-2 agonists

16

how much money is spent on medication adverse reactions each year?

2 million

17

large single variant event

pharmacogenetics

18

small effect, multiple variants

pharmacogenomics

19

compare genetic polymorphisms in phenotypic groups

pre-genomics

20

compare phenotypes in genotypic groups

post-genomics

21

what does pharmacogenetics involve?

ADME

22

how many genes are associated with pharmacogenetics?

1200

23

how many ADME markers are there in pharmacogenetics?

4800

24

How many markers are clinically actionable?

100

25

What percentage of medications are metabolized to CYP450?

75%

26

which is the most important?

A. CYP3A4
B. CYP2D6
C. CYP2C9 and 2C19

A. CYP3A4 (50%)

27

Which of the following is not inducible?

A. CYP3A4
B. CYP2D6
C. CYP2C9 and 2C19

B. CYP2D6

28

which of the following is inducible?

A. CYP3A4
B. CYP2D6
C. CYP2C9 and 2C19

A and C

29

Which of the following is least important?

A. CYP3A4
B. CYP2D6
C. CYP2C9 and 2C19

C

30

CYPD6 + wildtype (*1XN)

A. ultrarapid
B. extensive
C. intermediate
D. poor

A. ultrarapid

31

CYP2D6 + wildtype (*1)

A. ultrarapid
B. extensive
C. intermediate
D. poor

B. extensive

32

CYP2D6 + wild/mutant (*1/*17)

A. ultrarapid
B. extensive
C. intermediate
D. poor

C. intermediate

33

CYP2D6 + mutant (*17)

A. ultrarapid
B. extensive
C. intermediate
D. poor

D. poor

34

t/f SNP are 1 bp

true

35

If someone has inactive metabolite and ultra rapid, would you need a higher or lower dose?

higher dose because excreted faster

36

Ultrarapid

excrete superfast

37

if someone has an active metabolite and ultra rapid, would you need a higher or lower dose?

lower dose because give high dose or active drug

38

What genes modulate ADME?

TPMP
CYP2D6
UGT1A1

39

What is TPMT a main metabolize of?

chemotherapeutic agents 6MP and azothiopurine

40

TPMT deficiency

leads to severe toxicity associated with treatment (potential mortality)

41

Dose TPMT convert 6MP into an active or inactive metabolite?

active

42

wildtype and TPMT

convert normally to active

43

mutant and TPMT

won't convert to active metabolite

44

If you had a mutant and TPMT would you want a higher or lower dose?

lower dose because the toxicity would be high because still active

45

How many alleles are of CYP2D6 described in this gene?

>70

46

types of CYP2D6 alleles

- extensive metabolizers
- intermediate metabolizes
- poor metabolizers

47

Are extensive metabolizers wild type or mutant?

wild type

48

are intermediate metabolizers wild type or mutant?

both

49

are poor metabolizers wild type or mutant?

mutant

50

what is the standard metabolism allele against which others are compared?

EM CYP2D6

51

how many copies of CYP2D6 in some individuals?

up to 16

52

EM/EM

normal metabolizers

53

IM/IM

intermediate metabolizers

54

IM/PM

intermediate metabolizers

55

PM/PM

poor metabolizers

56

what does CYP2D6 convert codeine tot?

morphine

57

Is codeine inactive or active?

inactive prodrug

58

is morphine inactive or active?

active metabolite

59

CYP2D6 and newborns

codeine can be fatal
Give mom low dose because it rapidly converts to active metabolite

60

what does CYP2D6 convert tamoxifen to?

endoxifen

61

is endoxifen active or inactive?

active

62

is tamoxifen active or inactive?

inactive

63

Do PM have much lower levels of endoxifen than RM?

PM

64

what percentage of european population is deficient in CYP2D6?

6-10%

65

Tamoxifen and CYP2D6 deficiency

efficacy likely low

66

What enzymes does warfarin depend on?

CYP2C9
VKORC1

67

Warfarin and CYP2C9

7 OH warfarin (active)

68

Warfarin and VKORC1

vitamin K reduced

69

What enzyme is inhibited so that warfarin can work?

VKORC1

70

mutant in warfarin that is very sensitive if you give same dose

VKORC1

71

heterozygous or homozygous for CYP2C9 and VKORC1

more sensitive to standard doses of warfarin

72

What drug ranks as the #1 total mentions of deaths for drugs causing adverse events?

warfarin

73

what drug ranks among the top drugs associated with hospital ER visits for bleeding?

warfarin

74

in warfarin what is the overall frequency of major bleeding range from?

2-16%

75

If mutant for warfarin do you want to keep dose or adjust?

adjust

76

if mutant for clopidogrel do you want to keep dose or adjust?

adjust, higher

77

clopidogrel and CYP2C19

makes into active metabolite

78

what drug should be genotyped fro the HLA?

abacavir

79

What do you pre-screen in Abacavir?

HLA-B*5701 (fatal hypersensitivity)

80

Is there a high amount of patients with hypersensitivity to abacavir?

yes

81

change in chromosome without alterations in DNA sequence

epigenetics

82

What are genes turned on or off by in epigenetic?

- DNA methylation
- Histone modifications
- Non coding RNA (miRNA)

83

t/f epigenetic changes cannot be heritable

false

84

study of complete set of epigenetic alterations

epigenomics

85

epigenetic features that maintain different phenotypes in different cells

epigenetic code

86

t/f there are different phenotypes in different cells for epigenetics

true

87

what maintains inactive condensed chromatin state?

cytosine methylation
histone deaceytalaztion

88

What is a big factor in cancer?

hyper methylated

89

catalyzes transfer of methyl group from SAM to SmC

methylation of cytosine

90

where does methylation of cytosine occur?

CpG

91

DNA methylation of the promotor region interferes with binding of transcription factors

suppress gene expression

92

what is essential for gene control, determining both active and repressed states?

chromosomal infrastructure

93

what have a key role in epigenetic?

histones
chromatin

94

how many genes turned off could convert to cancer cell?

3

95

what is a new approach to cancer therapy?

epigenetic silencing

96

medications that target epigenetics

HDAC
DNMT

97

t/f epigenetic changes cannot occur as a result of dietary and other environmental exposure

false