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biochem exam 6 > Pharmacogenetics > Flashcards

Pharmacogenetics Flashcards

1
Q

three things that make us

A

genetics
environment
epigenetics

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2
Q

describes the DNA sequence variation leading to alterations in drug response

A

pharmacogenomics

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3
Q

describes the relationship of protein structure and function

A

proteomics

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4
Q

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

A

metabolomics

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5
Q

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

A

epigenetics

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6
Q

types of drug responses

A
  • full
  • partial
  • none
  • adverse reaction
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7
Q

drug response and doses

A

each specific drug with specific dose is different

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8
Q

why is personalized medicine important?

A

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

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9
Q

goal of personalized medicine

A
  • right dose
  • right drug
  • right indication
  • right patient
  • right time
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10
Q

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

A

pharmacogenetics

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11
Q

is pharmacogenetics a simple or complex relationship?

A

simple

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12
Q

is pharmacogenomics a simple or complex relationship?

A

complex

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13
Q

study of genomic influence on drug response, high throughput data

A

pharmacogenomics

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14
Q

What percentage of medication do not work as intended?

A

10-70%

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15
Q

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

A

B-2 agonists

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16
Q

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

A

2 million

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17
Q

large single variant event

A

pharmacogenetics

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18
Q

small effect, multiple variants

A

pharmacogenomics

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19
Q

compare genetic polymorphisms in phenotypic groups

A

pre-genomics

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20
Q

compare phenotypes in genotypic groups

A

post-genomics

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21
Q

what does pharmacogenetics involve?

A

ADME

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22
Q

how many genes are associated with pharmacogenetics?

A

1200

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23
Q

how many ADME markers are there in pharmacogenetics?

A

4800

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24
Q

How many markers are clinically actionable?

A

100

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25
Q

What percentage of medications are metabolized to CYP450?

A

75%

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26
Q

which is the most important?

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

A

A. CYP3A4 (50%)

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27
Q

Which of the following is not inducible?

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

A

B. CYP2D6

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28
Q

which of the following is inducible?

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

A

A and C

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29
Q

Which of the following is least important?

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

A

C

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30
Q

CYPD6 + wildtype (*1XN)

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

A

A. ultrarapid

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31
Q

CYP2D6 + wildtype (*1)

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

A

B. extensive

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32
Q

CYP2D6 + wild/mutant (1/17)

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

A

C. intermediate

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33
Q

CYP2D6 + mutant (*17)

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

A

D. poor

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34
Q

t/f SNP are 1 bp

A

true

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35
Q

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

A

higher dose because excreted faster

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36
Q

Ultrarapid

A

excrete superfast

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37
Q

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

A

lower dose because give high dose or active drug

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38
Q

What genes modulate ADME?

A

TPMP
CYP2D6
UGT1A1

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39
Q

What is TPMT a main metabolize of?

A

chemotherapeutic agents 6MP and azothiopurine

40
Q

TPMT deficiency

A

leads to severe toxicity associated with treatment (potential mortality)

41
Q

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

A

active

42
Q

wildtype and TPMT

A

convert normally to active

43
Q

mutant and TPMT

A

won’t convert to active metabolite

44
Q

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

A

lower dose because the toxicity would be high because still active

45
Q

How many alleles are of CYP2D6 described in this gene?

A

> 70

46
Q

types of CYP2D6 alleles

A
  • extensive metabolizers
  • intermediate metabolizes
  • poor metabolizers
47
Q

Are extensive metabolizers wild type or mutant?

A

wild type

48
Q

are intermediate metabolizers wild type or mutant?

A

both

49
Q

are poor metabolizers wild type or mutant?

A

mutant

50
Q

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

A

EM CYP2D6

51
Q

how many copies of CYP2D6 in some individuals?

A

up to 16

52
Q

EM/EM

A

normal metabolizers

53
Q

IM/IM

A

intermediate metabolizers

54
Q

IM/PM

A

intermediate metabolizers

55
Q

PM/PM

A

poor metabolizers

56
Q

what does CYP2D6 convert codeine tot?

A

morphine

57
Q

Is codeine inactive or active?

A

inactive prodrug

58
Q

is morphine inactive or active?

A

active metabolite

59
Q

CYP2D6 and newborns

A

codeine can be fatal

Give mom low dose because it rapidly converts to active metabolite

60
Q

what does CYP2D6 convert tamoxifen to?

A

endoxifen

61
Q

is endoxifen active or inactive?

A

active

62
Q

is tamoxifen active or inactive?

A

inactive

63
Q

Do PM have much lower levels of endoxifen than RM?

A

PM

64
Q

what percentage of european population is deficient in CYP2D6?

A

6-10%

65
Q

Tamoxifen and CYP2D6 deficiency

A

efficacy likely low

66
Q

What enzymes does warfarin depend on?

A

CYP2C9

VKORC1

67
Q

Warfarin and CYP2C9

A

7 OH warfarin (active)

68
Q

Warfarin and VKORC1

A

vitamin K reduced

69
Q

What enzyme is inhibited so that warfarin can work?

A

VKORC1

70
Q

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

A

VKORC1

71
Q

heterozygous or homozygous for CYP2C9 and VKORC1

A

more sensitive to standard doses of warfarin

72
Q

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

A

warfarin

73
Q

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

A

warfarin

74
Q

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

A

2-16%

75
Q

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

A

adjust

76
Q

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

A

adjust, higher

77
Q

clopidogrel and CYP2C19

A

makes into active metabolite

78
Q

what drug should be genotyped fro the HLA?

A

abacavir

79
Q

What do you pre-screen in Abacavir?

A

HLA-B*5701 (fatal hypersensitivity)

80
Q

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

A

yes

81
Q

change in chromosome without alterations in DNA sequence

A

epigenetics

82
Q

What are genes turned on or off by in epigenetic?

A
  • DNA methylation
  • Histone modifications
  • Non coding RNA (miRNA)
83
Q

t/f epigenetic changes cannot be heritable

A

false

84
Q

study of complete set of epigenetic alterations

A

epigenomics

85
Q

epigenetic features that maintain different phenotypes in different cells

A

epigenetic code

86
Q

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

A

true

87
Q

what maintains inactive condensed chromatin state?

A

cytosine methylation

histone deaceytalaztion

88
Q

What is a big factor in cancer?

A

hyper methylated

89
Q

catalyzes transfer of methyl group from SAM to SmC

A

methylation of cytosine

90
Q

where does methylation of cytosine occur?

A

CpG

91
Q

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

A

suppress gene expression

92
Q

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

A

chromosomal infrastructure

93
Q

what have a key role in epigenetic?

A

histones

chromatin

94
Q

how many genes turned off could convert to cancer cell?

A

3

95
Q

what is a new approach to cancer therapy?

A

epigenetic silencing

96
Q

medications that target epigenetics

A

HDAC

DNMT

97
Q

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

A

false

biochem exam 6 (3 decks)

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