Pharmacogenetics

Question 1

What are the general steps of drug development

Answer 1

1. Discovery
2. Effective dosings
3. Animal testing
4. Clinical trials
5. Gather additional info
6. New drug application with FDA

Question 2

Why are drug tests done on animals?

Answer 2

They give us a prediction of how a drug will work in humans

Question 3

What are we looking for in animal testing

Answer 3

Subacute Toxicity

Question 4

When do you see chronic toxicitiy

Answer 4

When you’ve been on the drug for a long time

Question 5

There are thousands of drugs discovered each year. Of those thousands how many make it to clinical trials?
How many make it to application?

Answer 5

Trials: 5
Application: 1

Question 6

What are some important limitations in pre-clinical testing

Answer 6

1. It is time consuming and expensive
2. You have to test a large number of animals
3. It is not completely reliable (animals aren’t people)

Question 7

What do you file around the time of animal testing?

Answer 7

Patent

Question 8

How long do patents last for?

What happens after that?

Answer 8

10-14 years

After that generics can come out

Question 9

What does phase 1 look at?

Answer 9

Is the drug safe

Question 10

What does phase 2 look at

Answer 10

Does it work, efficacy

Question 11

What is phase 3 looking at?

Answer 11

Does it work and is it safe? Use double blind testing. You will see the common side effects here

Question 12

What patients do you use in phase1 ? How many do you use?

Answer 12

You are using healthy people, EXCEPT for sometimes in cancer and HIV drugs)

Low number of people (20-100)

Question 13

What patients are used in phase 2?

How many pts are used?

Answer 13

People who have the disease

100-200 people

Question 14

How many people are tested in phase 3?

Answer 14

Thousands

Question 15

Less than _____ of the drugs tested in clinical trials reach the marketplace

Answer 15

1/3

Question 16

What are the. Confounding factors in clinical trials

Answer 16

1. Variable drug history
2. Presence of other diseases and risk factors
3. Subject observer bias

Question 17

You MUST use a large enough population of subjects

Answer 17

Yes

Question 18

What can influence patients

Answer 18

The placebo effect

Question 19

How do you overcome subject and observer bias

Answer 19

Double blind design

Question 20

30-50% is the results of a drug are due to this this

Answer 20

Placebo effect

Question 21

What kind of design is used for clinical trials

Answer 21

Crossover

See slide 23 fro an example

Question 22

What does the FDA do?

Answer 22

Oversees the drug evaluation process

Makes sure drug is safe and effective

Question 23

Pure food and drug act of 1906

Answer 23

In response to unsanitary and unethical practices in meat pacing industry

Question 24

Federal food, drug, ad cosmetic act of 1938

Answer 24

Due to series of deaths associated with sulfanilamide

Question 25

What what's the thalidomide tragedy of 1957?

Answer 25

Drug that when taken in pregnancy causes severe birth defects (no arms)

Question 26

How do you evaluate a clinical drug study

Answer 26

``` You look at the objectives The experiment methods The ethics The stats Does the drug fifer significant advantages of cost, efficacy, or safety over existing agents? ```

Question 27

What are orphan drugs

Answer 27

Drugs for rare diseases

Question 28

What is considered a rare disease in the US

Answer 28

Disease that affect fewer than 200,000 people in the US

Question 29

What is pharmacogenetics?

Answer 29

The study of the genetic basis of variation in drug response. Looks at the effects a single gene has on a drug

Question 30

What is pharmacogenomics

Answer 30

The study of the whole genomes effect on a drug

Question 31

What is the most common basis for genetic variation

Answer 31

Single nucleotide polymorphism (SNP)

Question 32

What is a SNP

Answer 32

A single nucleotide is exchanged for another

Question 33

The human genome consists of how many nucleotides

Answer 33

3 billion

Question 34

How do SNPs affect the genome

Answer 34

They can influence protein expression by altering amino acid sequence

Question 35

What is the central dogma

Answer 35

DNA>RNA>Protein

Question 36

How many amino acids are there? | How are they grouped?

Answer 36

20 | Grouped based on similarities in structures

Question 37

What is a missense SNP

Answer 37

Changes the identity of an amino acid

Question 38

What is a conservative missense SNP

Answer 38

A.A replaced with another A.A with similar properties

Question 39

Wha is a non-conservative missense SNP

Answer 39

A.A is changed to an A.A that is not similar

Question 40

What is a nonsense SNP

Answer 40

Leads to a stop codon

Question 41

What is a synonymous (silent) SNP

Answer 41

Does not change the amino acid

Question 42

Poor metabolizers and standard drugs

Answer 42

Reduced elimination Increased toxicity Drug will buildup in body

Question 43

Intermediate metabolizers and standard drugs

Answer 43

Possibility increased toxicity risk

Question 44

Rapid metabolizer and standard drugs

Answer 44

Reduced effectiveness | Increased elimination

Question 45

Poor metabolizer and prodrug

Answer 45

Decreased effectiveness and decreased activation

Question 46

Intermediate metabolizer and prodrugs

Answer 46

Possible reduced effectiveness

Question 47

Rapid metabolizer and prodrugs

Answer 47

Increased activation Increased toxicity risk Very dangerous

Question 48

CYP2C9 affects this drug________ How does it affect it?

Answer 48

Warfarin Increased bleeding risk for patients with CYP2C9*2 and CYP2C9*3

Question 49

CYP2C19 affects what drugs? What affect does it have?

Answer 49

Metabolism of proton pump inhibitors Advantage is Helicobacter pylori eradication

Question 50

CYP2D6 affects what drugs What is the affect seen?

Answer 50

Codeine CYP2D6*2 Rapid metabolizers: increased option effect (avoid use), increased CYP function Poor: little or no CYP2D6 function

Question 51

CYP3A4 metabolizers what drugs?

Answer 51

Most drugs

Question 52

What is personalized medicine?

Answer 52

Use of an individuals genetic information to guide decisions of prevention, diagnosis, and treatment of a disease