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Pharmacogenetics > Exam 2 lecture 8 & 10 > Flashcards

Exam 2 lecture 8 & 10 Flashcards

1
Q

variability in patient responses (asthma)

A
  • disease severity/type
  • treatment adherence
  • comorbidities
  • other meds (interaction)
  • environmental triggers
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2
Q

up to ___ of asthma patients treated using current guidelines are not controlled

A

25%

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3
Q

polymorphism affecting asthma patients

A

beta-receptor- target of beta 2 agonist (albuterol salmeterol)

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4
Q

mutations affect receptor susceptibility to

A

down-regulation in response to beta 2 angonists and NOT drug binding

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5
Q

patient response to SABA

A

gly/gly group- improved with albuterol only

arg/arg group did better on placebo

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6
Q

patient response to LABA- salmeterol/placebo

A

ARG/ARG lung function decreased in both trials w/ salmeterol

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7
Q

patient response to LABA while on ICS

A
  • both groups improved with salmeterol compared to palcebo
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8
Q

patient response to LABA (blacks)

A

those with arg/arg mutation did not do better

- says there is clearly genetic factors

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9
Q

summary of impact of beta-receptor polymorphisms

A
  • ARG 16 associated with adverse outcomes with regular use of SABA
  • ARG16 does not appear to adversely affect outcomes with LABAs when used with ICS***
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10
Q

5-10% of asthma patients have reduced responses to

A

glucocorticoids

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11
Q

genetic polymorphisms in glucocorticoid

A

receptors and in regulatory feedback loop

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12
Q

glucocorticoid receptor polymorphisms:

A

some can decrease efficacy and some can increase it

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13
Q

corticotropin releasing hormone receptor 1 role

A

regulation of the endogenous cortisol level

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14
Q

study 1 (ADULT)

A

adults

treated w/ ICS for 8 weeks

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15
Q

study 2 (CAMP)

A

children

ICS, nedocromil or placebo for 8 weeks

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16
Q

GAT mutation

A

patients with GAT did much better then wild type in response to ICS

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17
Q

what is the significance of GCCI1?

A
  • glucocorticoid induced transcript 1
  • expressed in lung and immune cells
  • glucocorticoid therapy may increase expression
  • possible marker of apoptosis
  • mutations that < GLCCI1 expression may decrease response to ICS
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18
Q

what percent of the population has GLCCI1 mutations

A

16%

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19
Q

CRHRI

A

GAT mutation associated with increased efficacy

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20
Q

GLCCI1

A

TT mutation associated with decreased efficacy

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21
Q

inter-individual variability in

A
  • development of diseases
  • drug efficacy
  • drug toxicity
22
Q

overall therapy response

A

50%

23
Q

most common ADRs caused from

A
  • diuretics
  • opioids
  • anticoagulants
24
Q

applications for PG

A
  • identify basis of inter-individual variability
  • enable tailoring of therapy to patient/disease genetics
  • identify novel treatment approached
25
Q

genotyping

A

define a biologic population based on genetics (DNA sequence)

26
Q

phenotyping

A

define a biologic population based on an observable physical or biochemical characteristic (Probe metabolites)

27
Q

genes commonly tested

A
  • invader UGT1A1 (genzyme)
  • HER2
  • HLA B*5701
28
Q

microarrays commonly tested

A
  • ampliChip (Roche diagnostics)- 2 genes (CYP2D6 & 2C19)
  • DMET Plus (Affymetric)- 230 genes including P450’s, drug transporters, etc
  • oncotype Dx (Genomic health)- 16 genes associated with breast cancer
29
Q

microarray genotyping have up to ____ genes on one chip

A

500,000

30
Q

other factors affecting PK & PD

A
  • unidentified genetic factors
  • environmental factors
  • interactions w/ drug, food or disease
31
Q

clopidogrel is metabolized by what enzyme?

A

CYP2C19

32
Q

intermediate metabolizers of clopidogrel have

A

53% increase in risk of death from CV events

33
Q

poor metabolizers of clopidogrel have

A

> 3.5- fold increase in risk for second CV event

34
Q

CYP2C19 polymorphisms are associated with

A

resistance to clopidogrel

  • EM: normal dose
  • IM: higher dose or alternative agent
  • PM: alternative agent
35
Q

alternative agent for PM of clopidogrel

A

prasugrel (Effient)

36
Q

Abacavir is a highly effective NRTI but

A

2-9% iodsyncratic hypersenitivity reaction (HSR)

  • dose dependent
  • not predicted in animal models
  • onset during first 6 weeks: fever, rash, GI and respiratory symptoms
  • potentially fatal
37
Q

decreased HSR risk with albacavir in

A

African americans

38
Q

HSR gene for abacavir reaction

A

HLA-B*5701

39
Q

traditional chemotherapy

A

doxorubicin, cyclophosphamide, paclitaxel, docetaxel

40
Q

targeted chemo

A

trastuzumab

41
Q

hormonal chemo

A

tamoxifen, aromatase inhibitors

42
Q

tumor HER2 over-expression

A
  • 20% breast cancer
  • traditionally associated with poor prognosis
  • not inherited
43
Q

50% of new cases of breast cancer are

A

estrogen receptor (ER) positive, lymph node (LN) negative

44
Q

80% of breast cancer adequately treated with

A

surgery +/- radiation and hormonal therapy

45
Q

chemo can be beneficial for breast cancer

A
  • 25% relative risk reduction for recurrence
46
Q

oncotype Dx

A
  • 21 gene assay: 16 cancer genes & 5 house keeper genes

- predictive of recurrence and survival

47
Q

low risk

A

chemo not beneficial

<18

48
Q

High risk

A

chemo beneficial

>30

49
Q

intermediate risk

A

unclear

18-30

50
Q

HER2 status

A

trastuzumab

51
Q

ER status

A

tamoifen or aromatase inhibitor

52
Q

depending on cancer stage, grade, comorbidities, & clinician experience: oncosype DX

A

traditional chemo

Pharmacogenetics (8 decks)

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