Lecture 8- Pharmacogenetics part I Flashcards
1
Q
pharmacogenetics and pharmacogenomics
A
- also called precision medicine
- using genetic and genomic info to more accurately predict drug responses
2
Q
goals for personalized medicine
A
- identify genetic differences between people that affect drug response
- develop genetic tests that predict an individual’s response
- tailor medical treatments to the individual
- increase effectiveness
- minimize adverse side effects
3
Q
pharmacogenetics
A
- evaluates how an individual’s genetic makeup corresponds to their response to a particular medication
4
Q
pharmacogenomics
A
- combines pharmacogenetics with genomic studies
- uses large groups of patients to evaluate how candidate drugs interact with a range of genes and their protein products
5
Q
personalized medicine
A
- = population stratification
- looking at their genome
- actual base changes that vary throughout a population
- associated with drug being toxic and effective
6
Q
pharmacogenetics
A
- focused on known “major” drug metabolizing enzymes
7
Q
pharmacogenetics and drugs
A
ultra-drug metabolizer
- inactivation of the drug rapidly so it is ineffective
poor drug metabolizer
- end up with toxic doses of the drug
8
Q
pharmacogenetics and pro-drugs
A
ultra drug metabolizer
- pro-drug is metabolized to active form of drug to end up with toxic doses off the drug
- mutation in this gene required to activate the drug
- metabolizes too much of the drug, end up with too much active drug
poor drug metabolizer
- very little conversion of the pro-drug to the active form of the drug
- drug is ineffective
9
Q
main consequences of genetic polymorphisms
A
None
- outside of coding and regulatory regions
- synonymous substitution
- no impact on function of protein
Decrease or loss of function of the encoded protein
Increase in function of the encoded protein
10
Q
Decreased function
A
- less enzyme may be produced (decreased regulation)
- enzyme may not be complete (stop codon insertion)
- enzyme may not be as stable
- less binding affinity to substrate
11
Q
Increased in function
A
- more production (regulation or genomic copies)
- more stable
- more binding affinity
12
Q
Tuberculosis (TB)
A
- infectious disease caused by mycobacterium tuberculosis
- attacks the lungs, can affect other parts of the body
- airborne disease
13
Q
Isoniazid
A
- anti-biotic
- first used to treat tuberculosis
- metabolized in the liver via acetylation and then cleared from the body
- high incidence of peripheral neuropathy caused by the drug reaching toxic levels
14
Q
Looked at serum levels of isoniazid
A
- Look at serum levels of active drug
- Hoping for: bell curve with a normal distribution
- everyone gets to the same serum concentration at the same time
- Bimodal/trimodal graph
- some difference in the population that is driving why they don’t reach same conc
- Slower rate of acetylation: not cleared from the body
- mutations within NAT2 that result in slower acetylation
15
Q
NAT-1
A
- N-acetyltransferase gene
- little variation in the population
18
Q
thiopuring methyltransferase (TPMT)
A
- enzyme that provides methylation of thiopurines
- thiopurines are converted into thioguanine nucleotides (TGNs)
- TGNs get inserted into DNA, inhibit DNA replication and can have toxic effects within the cell at high levels
- reduced TPMT activity can lead to fatal toxicity
20
Q
normal alcohol metabolism
A
- Certain people don’t have a functioning ALDH2, get a build up of acetaldehyde à feeling not well
