pharm: pharmacogenomics

Question 1

What terms refer to the study of ways in which DNA sequence variation affects the response of individual patients to medications?

Answer 1

Pharmacogenetics and Pharmacogenomics

Question 2

Individual variation to the response can be affected genetically in what 3 ways?

Answer 2

1. Concentration of drug reaching its target
2. Genetic variation at the drug site of action
3. Pharmacogenetic variation related to unpredicted adverse effects

Question 3

The most common factor responsible for genetic variation in pharmacology is in the inherited variation in what?

Answer 3

Enzymes that catalyze drug metabolism

Question 4

Phase II enzymatic acetylation of the anti-tuberculosis drug isoniazid: patients treated with isoniazid can be classified as either ________ or ________ acetylators.

Answer 4

Slow or fast

Question 5

How do slow acetylators metabolize isoniazid and what does this cause?

Answer 5

Metabolize slowly and have high blood drug levels

Question 6

How do fast acetylators metabolize isoniazid and what does this cause?

Answer 6

Metabolize rapidly and have low blood drug levels

Question 7

Tamoxifen is a drug used to treat what?

Answer 7

Breast-cancer

Question 8

What type of drug is Tamoxifen and how does this impact its metabolism?

Answer 8

Tamoxifen is a prodrug that needs to be metabolized in order to be bio-transformed to its much more active metabolite

Question 9

What enzyme metabolizes Tamoxifen?

Answer 9

CYP2D6

Question 10

Poor CYP2D6 metabolizers have _________ outcomes with respect to Breast Cancer recurrence.

Answer 10

Poorer

Question 11

Extensive CYP2D6 show much better outcomes when using Tamoxifen, why?

Answer 11

Because Tamoxifen is a prodrug that needs be metabolized to become active. Therefore, better metabolizers work in a quicker and more efficient manner

Question 12

Codeine is a _______ drug.

Answer 12

Prodrug

Question 13

Codeine active metabolite?

Answer 13

morphine

Question 14

For codeine to be metabolized into morphine, it is metabolized by __________.

Answer 14

CYP2D6

Question 15

Warfarin is predominantly metabolized by what enzyme?

Answer 15

CYP2C9

Question 16

Some patients carry variant alleles of Warfarin which means what in terms of required dosage?

Answer 16

Require decreased doses of Warfarin to achieve therapeutic anticoagulant effect

Question 17

Without dose adjustments in warfarin, patients with variant alleles have an increased risk of ______________ during warfarin therapy.

Answer 17

Hemorrhaging due to over-anticoagulation effect

Question 18

What is Simvastatin used for?

Answer 18

Lowering cholesterol

Question 19

What are the 4 big stages of Drug evaluation?

Answer 19

In vitro studies
Animal testing
Clinical Testing
Marketing

Question 20

What does in vitro pharmacology mean?

Answer 20

Research of effects of drugs conducted outside of living organisms

Question 21

Animal testing during drug evaluation is a process used to investigate what 5 things?

Answer 21

Acute testing
Subacute and chronic toxicity
Carcinogenicity
Pharmacologic effect of drug
Reproductive toxicity

Question 22

What is the Investigational New Drug Application (IND)?

Answer 22

An application that must be submitted with the FDA before it can be studied in humans

Question 23

How many drug evaluation phases of clinical trials are there?

Answer 23

4

Question 24

Phase 1 of Clinical trials is an evaluation of what?

Answer 24

Evaluation of dose-response relationship and the PK

Question 25

What does Phase 1 of Clinical trials determine?

Answer 25

Safety and PK of drug

Question 26

How many people are involved in Phase 1 of clinical trials?

Answer 26

Small number (20-100) normal/healthy volunteers

Question 27

Is Phase 1 of clinical trials blind or open?

Answer 27

Non-blind/open

Question 28

Phase II of clinical trials determines what?

Answer 28

Disease-effectiveness of drug

Question 29

How many people are involved during Phase II clinical trial testing?

Answer 29

100-200 moderate patients (sick volunteers)

Question 30

Is Phase II of clinical trials blind or open?

Answer 30

Single blind-placebo or positive control drug

Question 31

Phase III of clinical trials focuses on what two things?

Answer 31

Safety and toxicity

Question 32

How many people are involved during Phase III clinical trials?

Answer 32

Many patients (hundreds-thousands)

Question 33

Is Phase III of clinical trials blind or open?

Answer 33

Double-blind cross-over design

Question 34

During Phase III clinical trials, the new drug being tested is compared with what two things?

Answer 34

Placebo or old therapy

Question 35

If a drug makes it through Phase III of clinical trials, what must be submitted to the FDA?

Answer 35

New drugs approval (NDA)

Question 36

What is often noted/watched for during Phase IV of clinical trials?

Answer 36

Toxicities that have never been seen before.