Exam 2 lectures 14 & 15 Flashcards Preview

Pharmacogenetics > Exam 2 lectures 14 & 15 > Flashcards

Flashcards in Exam 2 lectures 14 & 15 Deck (39):
1

targeted therapies are treatments that

target specific characteristics of diseased cells

2

targeted therapies are generally less

harmful to normal, healthy cells

3

targeted therapies can be various forms:

small molecules, RNA/DNA-based oligonucleotides, antibodies, & peptides/proteins

4

key factors in the discovery & development of targeted therapy

- new technology
- new targets
-target validation in early development phase
- predictive models

5

molecular targeted drug may target at various levels:

molecular, cellular, tissue/organ, system, whole body, population

6

effects of targeted therapy can be

physiological
biochemical
functional

7

criteria for target validation

- causal relation between target & disease
- correlation with disease status
- specificity
- affinity
- mode of action (onset)
- regulation of effects

8

methods of target validation

- molecular/ genetic/ genomic
- biochemical/proteomic
- physiological/functional
- pharmacological/ tocicological
- population-based

9

testing system in target validation

- cell-free in vitro
- cell
-organ (in vitro & in vivo)
- small animals
- non-human primates
- humans
- computational biology/bioinformatics

10

evaluation of target validation

-qualitative (yes/no, withdrawal effect)
- quantitative ( dose-effect& dose-response relationships)
- biological effects vs. statistical signnificance

11

dose-effect

individual level

12

dose-response

group level
- most drugs are approved based on the population level

13

interpretation of target validation

- geno vs pheno
- in vitro vs in vivo
- animals vs humans
- healthy subjects vs patients
- other host factors (age,, sex, race)
-other limitations (dose-range)
- research tools vs drug class/entiiy

14

biomarkers for selection of cancer therapy: EGFR

- erlotinib (lung cancer)
- cetuximab (colon cancer)

15

biomarkers for selection of cancer therapy: HER2

- trastuzumab (breast cancer)
- lapatinib (breast cancer)

16

biomarkers for selection of cancer therapy: KRAS

cetuximab (colon cancer)

17

oncotype DX scoring

- for breast cancer therapy with tamoxifen
- recurrence score
- 31 high risk (benefit from chemo)

18

MammaPrint

- breast cancer therapy
- predict risk of metastasis
- aggressive therapy can be considered for those with poor prognosis
- for pts <61, early stage I & II

19

DPD (Dihydroprimidine dehydrogenase)

- drug disposition in cancer therapy
- DPD responsible for >85% 5-FU breakdown

20

thymidylate synthase (TS)

- drug disposition in cancer therapy
- molecular target for 5-FU
- over expression linked to drug resistance

21

PGX factors in targeted therapy

genetic variations in pathogens, targeted genes, in genes associated with drug metabolism/dispoition, & in signalling pathways involved in drug response & toxicity
other factors (interactions & physiology/disease status)

22

purpose of PG testing

- provide evidence for PG variations
-improve healthcare outcome by enhancing selection & dosing of therapy
-provide rationale for stratification of subjects in clinical studies
- facilitate PG research & developing novel drugs

23

CYP2D6/PM

- poor response to tamoxifen
-for postmenpausal women with breast cancer can be treated with aromatoase inhibitor
- in pre-&perimenopausal women, no alternative therapy
- test can be used for monitoring response & prognosis

24

nocebo

negative response to treatment
- can be an effect of PG testing

25

selection of target patient population: conventional approaches

- age. sex, race, etc
- disease status, pathology, stage
- co-morbidity
- physiology/ pathology,: prego, liver & kidney function

26

PG approaches add on

PK characteristics (ADME: disease-independent)-differentiating people
- PD characteristics (disease subtype)- differentiating disease

27

approval of race-targeted drug BiDil

- fixed dose of isosorbide dinitrate & hydralazine hcl
- indication: HF; adjunct to standard therapy; black people
- commercial failure; negative publicity; high cost compared to the 2 separate drugs alone
- no comparison to other racial groups

28

about --- drugs prescribed to children were not tested in children; they are not labeled for pediatric use

2/3

29

policies developed to encourage testing drugs in children

- pediatric research equity act
- best pharmaceuticals for children act
- marking incentive: 6-month exclusivity

30

PG considerations in children

- developmental changes in gene expression in children
-metabolizing enzymes-age related
- pediatric diseases vs adult diseases
- clinical trials in children- minimal risk
- including children in clinical trials
- including children in PG testing

31

lawsuit of lyme vaccine

- LYMeric
- OspA triggers development of autoimmune arthritis in individuals with HLA-DR4 gene
- withdrawn from market

32

OBRA90

pharmacist has to inform patient of risk of ADE if known genetic variant in patient or it will be a breach of duty

33

if PGX testing is considered different for traditional genetic testing

a detailed consent form is probably NOT needed

34

formal consent form needed if:

familial implication
ancillary info needed
risk of discrimination
laws

35

under federal law & laws of many states

individuals DO NOT own their health data or stored specimens (at least in the sense of medical research)

36

HIPAA pricacy rule distinguishes

individually identifiable health info (IIHI) from de-identified health info

37

in general, disclosure or research use of IIHI needs

informed consent

38

de-identified health info can be used

without authorization

39

major goal of PG in clinical trials

stratify patients- improve response & reduce side effects