Exam 2 lecture 11 Flashcards Preview

Pharmacogenetics > Exam 2 lecture 11 > Flashcards

Flashcards in Exam 2 lecture 11 Deck (35):
1

genetic info can help:

- develop gene therapy
- predict disease risk
- guide therapy
- guide drug development

2

stake holders involved

patients, healthcare providers, industry, insurers, government, society

3

patient perspective

using it to guide therapy was more widely accepted that predict disease risk

4

provider perspective

using to guide therapy was more widely accepted

5

pharmaceutical industry perspective

mixed incentives

6

positives for pharmaceutical industries

new drug targets
drugs with better side effects
more efficient drug developments
salvage drugs

7

negatives for pharmaceutical industry

decreased market share
fewer blockbuster drugs
orphan popilations

8

diagnostic industry perspective

positive incentive: increased market share

9

insurer perspective

- predicting disease not widely accepted
- guide therapy more accepted (HER2)

10

government perspective

safety and efficacy
medicare/medicaid reimbursement
regulations

11

society perspective

maximize benefits for all stakeholders
minimize risks and costs

12

cost

genetic testing
subsequent intervention
genetic counseling

13

benefits

improved therapeutic response
avoid adverse effects
avoid unnecessary treatments
improved quality of life

14

clinical validity

how consistently and accurately the test detects or predicts the outcomes of interest
how true something is

15

clinical utility

how likely the test is to significantly improve patient outcomes

16

dose limiting toxicity for TMPT polymorphism

myelosuppression (neutropenia)

17

as prevalence goes up

cost effectiveness goes up

18

genotyping prevalence has to be

at least 1% to be cost effective
(homozygous TMPT)

19

cost effectiveness

<$50.000 per QALY

20

if frequency is 0.5% or less, the cost of the genetic test becomes important & cost effectiveness is retained if

the cost of the genetic test is <$100

21

warfarin

oral anticoagulant for treatment/prevention of thromboembolism

22

dosing algorithm of warfarin

-start at 5 or 10 mg
- check INR day 3
- adjust dose
- check INR day 5
- adjust dose
etc

23

current warfarin challenges

- narrow therapeutic range (INR)
- patients are in therapeutic range only about 66% of the time
- up to 20-fold variability in dose requirements

24

INR too low

ineffective anticoagulation->thromboembolism

25

INR too high

too much anticoagulation->hemorrhage

26

higher dose of warfarin required

- low age, high weight, high Vitamin K intake, smoking, hypothyroidism, CYP2C9 inducers, blacks

27

lower dose of warfarin required

- high age, low weigh, low vitamin K intake, cancer, liver disease heart disease, hyperthyroidism, factor VII or X mutation, female, drugs (amiodarone, statins, azoles, sulfa)

28

genetic factors affecting warfarin

- CYP2C9 polymorphism
- VKORC1 polymorpism
- others (gamma glutamyl carboxylase, CYP4F2

29

CYP2c9 polymorphism with warfarin

- can be impaired a little or a lot
- variants more likely to require lower doses

30

CYP2C9 study results

study group using pharmacogenetic algorithm reached therapeutic & stable INRs sooner than control group

31

VKORC1 polymorphisms

- can cause less warfarin sensitivity, intermediate or more sensitivity
-

32

VKORC1 study results

- Primary endpoint not significantly different
- PG algorithm predicted dose better w/ fewer & smaller adjustments but no different in adverse effects

33

precision medicine

an emerging approach for disease prevention & treatment that takes into account people's individual variations in genes, environment & lifestyle

34

the precision medicine initiative

will generate the scientific evidence needed to move the concept into clinical practice

35

research based upon the cohort data will"

- advance PG, the right drug for the right patient at the right dose
- ID new targets for treatment & prevention
- test whether mobile devices can encourage healthy behavior
- lay scientific foundation for precision medicine for many diseases