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Flashcards in Pharmacogenetics Deck (52):
1

What are the general steps of drug development

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

2

Why are drug tests done on animals?

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

3

What are we looking for in animal testing

Subacute Toxicity

4

When do you see chronic toxicitiy

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

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?

Trials: 5
Application: 1

6

What are some important limitations in pre-clinical testing

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)

7

What do you file around the time of animal testing?

Patent

8

How long do patents last for?
What happens after that?

10-14 years

After that generics can come out

9

What does phase 1 look at?

Is the drug safe

10

What does phase 2 look at

Does it work, efficacy

11

What is phase 3 looking at?

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

12

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

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

Low number of people (20-100)

13

What patients are used in phase 2?

How many pts are used?

People who have the disease

100-200 people

14

How many people are tested in phase 3?

Thousands

15

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

1/3

16

What are the. Confounding factors in clinical trials

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

17

You MUST use a large enough population of subjects

Yes

18

What can influence patients

The placebo effect

19

How do you overcome subject and observer bias

Double blind design

20

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

Placebo effect

21

What kind of design is used for clinical trials

Crossover
See slide 23 fro an example

22

What does the FDA do?

Oversees the drug evaluation process

Makes sure drug is safe and effective

23

Pure food and drug act of 1906

In response to unsanitary and unethical practices in meat pacing industry

24

Federal food, drug, ad cosmetic act of 1938

Due to series of deaths associated with sulfanilamide

25

What what's the thalidomide tragedy of 1957?

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

26

How do you evaluate a clinical drug study

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?

27

What are orphan drugs

Drugs for rare diseases

28

What is considered a rare disease in the US

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

29

What is pharmacogenetics?

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

30

What is pharmacogenomics

The study of the whole genomes effect on a drug

31

What is the most common basis for genetic variation

Single nucleotide polymorphism (SNP)

32

What is a SNP

A single nucleotide is exchanged for another

33

The human genome consists of how many nucleotides

3 billion

34

How do SNPs affect the genome

They can influence protein expression by altering amino acid sequence

35

What is the central dogma

DNA>RNA>Protein

36

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

20
Grouped based on similarities in structures

37

What is a missense SNP

Changes the identity of an amino acid

38

What is a conservative missense SNP

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

39

Wha is a non-conservative missense SNP

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

40

What is a nonsense SNP

Leads to a stop codon

41

What is a synonymous (silent) SNP

Does not change the amino acid

42

Poor metabolizers and standard drugs

Reduced elimination
Increased toxicity
Drug will buildup in body

43

Intermediate metabolizers and standard drugs

Possibility increased toxicity risk

44

Rapid metabolizer and standard drugs

Reduced effectiveness
Increased elimination

45

Poor metabolizer and prodrug

Decreased effectiveness and decreased activation

46

Intermediate metabolizer and prodrugs

Possible reduced effectiveness

47

Rapid metabolizer and prodrugs

Increased activation
Increased toxicity risk
Very dangerous

48

CYP2C9 affects this drug________

How does it affect it?

Warfarin

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

49

CYP2C19 affects what drugs?

What affect does it have?

Metabolism of proton pump inhibitors

Advantage is Helicobacter pylori eradication

50

CYP2D6 affects what drugs

What is the affect seen?

Codeine
CYP2D6*2

Rapid metabolizers: increased option effect (avoid use), increased CYP function

Poor: little or no CYP2D6 function

51

CYP3A4 metabolizers what drugs?

Most drugs

52

What is personalized medicine?

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