Exam 2 lecture 8 & 10 Flashcards Preview

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Flashcards in Exam 2 lecture 8 & 10 Deck (52):
1

variability in patient responses (asthma)

- disease severity/type
- treatment adherence
-comorbidities
- other meds (interaction)
- environmental triggers

2

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

25%

3

polymorphism affecting asthma patients

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

4

mutations affect receptor susceptibility to

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

5

patient response to SABA

gly/gly group- improved with albuterol only
arg/arg group did better on placebo

6

patient response to LABA- salmeterol/placebo

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

7

patient response to LABA while on ICS

- both groups improved with salmeterol compared to palcebo

8

patient response to LABA (blacks)

those with arg/arg mutation did not do better
- says there is clearly genetic factors

9

summary of impact of beta-receptor polymorphisms

- 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***

10

5-10% of asthma patients have reduced responses to

glucocorticoids

11

genetic polymorphisms in glucocorticoid

receptors and in regulatory feedback loop

12

glucocorticoid receptor polymorphisms:

some can decrease efficacy and some can increase it

13

corticotropin releasing hormone receptor 1 role

regulation of the endogenous cortisol level

14

study 1 (ADULT)

adults
treated w/ ICS for 8 weeks

15

study 2 (CAMP)

children
ICS, nedocromil or placebo for 8 weeks

16

GAT mutation

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

17

what is the significance of GCCI1?

- 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

18

what percent of the population has GLCCI1 mutations

16%

19

CRHRI

GAT mutation associated with increased efficacy

20

GLCCI1

TT mutation associated with decreased efficacy

21

inter-individual variability in

- development of diseases
- drug efficacy
- drug toxicity

22

overall therapy response

50%

23

most common ADRs caused from

- diuretics
- opioids
- anticoagulants

24

applications for PG

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

25

genotyping

define a biologic population based on genetics (DNA sequence)

26

phenotyping

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

27

genes commonly tested

- invader UGT1A1 (genzyme)
- HER2
- HLA B*5701

28

microarrays commonly tested

- 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

microarray genotyping have up to ____ genes on one chip

500,000

30

other factors affecting PK & PD

- unidentified genetic factors
- environmental factors
- interactions w/ drug, food or disease

31

clopidogrel is metabolized by what enzyme?

CYP2C19

32

intermediate metabolizers of clopidogrel have

53% increase in risk of death from CV events

33

poor metabolizers of clopidogrel have

>3.5- fold increase in risk for second CV event

34

CYP2C19 polymorphisms are associated with

resistance to clopidogrel
- EM: normal dose
- IM: higher dose or alternative agent
- PM: alternative agent

35

alternative agent for PM of clopidogrel

prasugrel (Effient)

36

Abacavir is a highly effective NRTI but

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

decreased HSR risk with albacavir in

African americans

38

HSR gene for abacavir reaction

HLA-B*5701

39

traditional chemotherapy

doxorubicin, cyclophosphamide, paclitaxel, docetaxel

40

targeted chemo

trastuzumab

41

hormonal chemo

tamoxifen, aromatase inhibitors

42

tumor HER2 over-expression

- 20% breast cancer
- traditionally associated with poor prognosis
- not inherited

43

50% of new cases of breast cancer are

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

44

80% of breast cancer adequately treated with

surgery +/- radiation and hormonal therapy

45

chemo can be beneficial for breast cancer

- 25% relative risk reduction for recurrence

46

oncotype Dx

- 21 gene assay: 16 cancer genes & 5 house keeper genes
- predictive of recurrence and survival

47

low risk

chemo not beneficial
<18

48

High risk

chemo beneficial
>30

49

intermediate risk

unclear
18-30

50

HER2 status

trastuzumab

51

ER status

tamoifen or aromatase inhibitor

52

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

traditional chemo