Flashcards in Pharmacogenetics Deck (52):
What are the general steps of drug development
2. Effective dosings
3. Animal testing
4. Clinical trials
5. Gather additional info
6. New drug application with FDA
Why are drug tests done on animals?
They give us a prediction of how a drug will work in humans
What are we looking for in animal testing
When do you see chronic toxicitiy
When you've been on the drug for a long time
There are thousands of drugs discovered each year. Of those thousands how many make it to clinical trials?
How many make it to application?
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)
What do you file around the time of animal testing?
How long do patents last for?
What happens after that?
After that generics can come out
What does phase 1 look at?
Is the drug safe
What does phase 2 look at
Does it work, efficacy
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
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)
What patients are used in phase 2?
How many pts are used?
People who have the disease
How many people are tested in phase 3?
Less than _____ of the drugs tested in clinical trials reach the marketplace
What are the. Confounding factors in clinical trials
1. Variable drug history
2. Presence of other diseases and risk factors
3. Subject observer bias
You MUST use a large enough population of subjects
What can influence patients
The placebo effect
How do you overcome subject and observer bias
Double blind design
30-50% is the results of a drug are due to this this
What kind of design is used for clinical trials
See slide 23 fro an example
What does the FDA do?
Oversees the drug evaluation process
Makes sure drug is safe and effective
Pure food and drug act of 1906
In response to unsanitary and unethical practices in meat pacing industry
Federal food, drug, ad cosmetic act of 1938
Due to series of deaths associated with sulfanilamide
What what's the thalidomide tragedy of 1957?
Drug that when taken in pregnancy causes severe birth defects (no arms)
How do you evaluate a clinical drug study
You look at the objectives
The experiment methods
Does the drug fifer significant advantages of cost, efficacy, or safety over existing agents?
What are orphan drugs
Drugs for rare diseases
What is considered a rare disease in the US
Disease that affect fewer than 200,000 people in the US
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
What is pharmacogenomics
The study of the whole genomes effect on a drug
What is the most common basis for genetic variation
Single nucleotide polymorphism (SNP)
What is a SNP
A single nucleotide is exchanged for another
The human genome consists of how many nucleotides
How do SNPs affect the genome
They can influence protein expression by altering amino acid sequence
What is the central dogma
How many amino acids are there?
How are they grouped?
Grouped based on similarities in structures
What is a missense SNP
Changes the identity of an amino acid
What is a conservative missense SNP
A.A replaced with another A.A with similar properties
Wha is a non-conservative missense SNP
A.A is changed to an A.A that is not similar
What is a nonsense SNP
Leads to a stop codon
What is a synonymous (silent) SNP
Does not change the amino acid
Poor metabolizers and standard drugs
Drug will buildup in body
Intermediate metabolizers and standard drugs
Possibility increased toxicity risk
Rapid metabolizer and standard drugs
Poor metabolizer and prodrug
Decreased effectiveness and decreased activation
Intermediate metabolizer and prodrugs
Possible reduced effectiveness
Rapid metabolizer and prodrugs
Increased toxicity risk
CYP2C9 affects this drug________
How does it affect it?
Increased bleeding risk for patients with CYP2C9*2 and CYP2C9*3
CYP2C19 affects what drugs?
What affect does it have?
Metabolism of proton pump inhibitors
Advantage is Helicobacter pylori eradication
CYP2D6 affects what drugs
What is the affect seen?
Rapid metabolizers: increased option effect (avoid use), increased CYP function
Poor: little or no CYP2D6 function
CYP3A4 metabolizers what drugs?