Exam 2 lecture 8 & 10

Question 1

variability in patient responses (asthma)

Answer 1

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

Question 2

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

Answer 2

25%

Question 3

polymorphism affecting asthma patients

Answer 3

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

Question 4

mutations affect receptor susceptibility to

Answer 4

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

Question 5

patient response to SABA

Answer 5

gly/gly group- improved with albuterol only

arg/arg group did better on placebo

Question 6

patient response to LABA- salmeterol/placebo

Answer 6

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

Question 7

patient response to LABA while on ICS

Answer 7

• both groups improved with salmeterol compared to palcebo

Question 8

patient response to LABA (blacks)

Answer 8

those with arg/arg mutation did not do better

- says there is clearly genetic factors

Question 9

summary of impact of beta-receptor polymorphisms

Answer 9

• 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***

Question 10

5-10% of asthma patients have reduced responses to

Answer 10

glucocorticoids

Question 11

genetic polymorphisms in glucocorticoid

Answer 11

receptors and in regulatory feedback loop

Question 12

glucocorticoid receptor polymorphisms:

Answer 12

some can decrease efficacy and some can increase it

Question 13

corticotropin releasing hormone receptor 1 role

Answer 13

regulation of the endogenous cortisol level

Question 14

study 1 (ADULT)

Answer 14

adults

treated w/ ICS for 8 weeks

Question 15

study 2 (CAMP)

Answer 15

children

ICS, nedocromil or placebo for 8 weeks

Question 16

GAT mutation

Answer 16

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

Question 17

what is the significance of GCCI1?

Answer 17

• 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

Question 18

what percent of the population has GLCCI1 mutations

Answer 18

16%

Question 19

CRHRI

Answer 19

GAT mutation associated with increased efficacy

Question 20

GLCCI1

Answer 20

TT mutation associated with decreased efficacy

Question 21

inter-individual variability in

Answer 21

• development of diseases
• drug efficacy
• drug toxicity

Question 22

overall therapy response

Answer 22

50%

Question 23

most common ADRs caused from

Answer 23

• diuretics
• opioids
• anticoagulants

Question 24

applications for PG

Answer 24

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

Question 25

genotyping

Answer 25

define a biologic population based on genetics (DNA sequence)

Question 26

phenotyping

Answer 26

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

Question 27

genes commonly tested

Answer 27

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

Question 28

microarrays commonly tested

Answer 28

- 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

Question 29

microarray genotyping have up to ____ genes on one chip

Answer 29

500,000

Question 30

other factors affecting PK & PD

Answer 30

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

Question 31

clopidogrel is metabolized by what enzyme?

Answer 31

CYP2C19

Question 32

intermediate metabolizers of clopidogrel have

Answer 32

53% increase in risk of death from CV events

Question 33

poor metabolizers of clopidogrel have

Answer 33

>3.5- fold increase in risk for second CV event

Question 34

CYP2C19 polymorphisms are associated with

Answer 34

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

Question 35

alternative agent for PM of clopidogrel

Answer 35

prasugrel (Effient)

Question 36

Abacavir is a highly effective NRTI but

Answer 36

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

Question 37

decreased HSR risk with albacavir in

Answer 37

African americans

Question 38

HSR gene for abacavir reaction

Answer 38

HLA-B*5701

Question 39

traditional chemotherapy

Answer 39

doxorubicin, cyclophosphamide, paclitaxel, docetaxel

Question 40

targeted chemo

Answer 40

trastuzumab

Question 41

hormonal chemo

Answer 41

tamoxifen, aromatase inhibitors

Question 42

tumor HER2 over-expression

Answer 42

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

Question 43

50% of new cases of breast cancer are

Answer 43

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

Question 44

80% of breast cancer adequately treated with

Answer 44

surgery +/- radiation and hormonal therapy

Question 45

chemo can be beneficial for breast cancer

Answer 45

- 25% relative risk reduction for recurrence

Question 46

oncotype Dx

Answer 46

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

Question 47

low risk

Answer 47

chemo not beneficial | <18

Question 48

High risk

Answer 48

chemo beneficial | >30

Question 49

intermediate risk

Answer 49

unclear | 18-30

Question 50

HER2 status

Answer 50

trastuzumab

Question 51

ER status

Answer 51

tamoifen or aromatase inhibitor

Question 52

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

Answer 52

traditional chemo