Pharm Genomics Flashcards
(40 cards)
What is PharmacoGENETICS?
Study of how variation in a single gene can affect response to a single drug.
What are the 4 applications for pharmacogenetics?
- Appropriate Pt Selection
- Optomization of drug dosing
- ID Pt risk for adverse events
- Increase efficiency of drug devt of clinical trials
What are the struggles of testing your drug on a diverse population?
Need to test a lot more people to see statistical significance
May be very effective in a select population but drug will never get to market.
What is a mutation?
A difference in the DNA code that occurs in less thn 1% of the population
What is a polymorphism?
Difference in DNA code that occurs in greater than 1% of the population
What is a SNP?
Single nucleotide polymorphism
What is the difference between a synonymous AA and a non-synonymous AA?
Syn- BP change does not cause AA subs
-Decreased transcript stability or aleter splicing
Non syn- Leads to AA substitution
-Change in protein structure, stability, substrate affinity, intro of a stop codon
What is a Copy Number Variation?
A copy number variation. complete deletion or duplication of a particular gene.
What is a Cosmopolitan Polymorphism?
Poly common across all ethnic groups
What is a population polymorhism?
Poly that differ between groups
What is the phenotype to genotype approach?
Directly measure pharmacogenetic trait (warfarin effects on blood coagulation)
What is a Pharmacogenetic trait?
Measurable trait associated with a drug: Enzyme activity Drug levels in bodily fluids Drug metabolites in bodily fluids Physiological Response
What is the Candidate gene approach?
Genotyping a specific gene that is predicted to cause differences
Requires knowledge of cellular mechanism
What is the Genome wide approach?
Doesn’t require knowledge of cellular mechanisms resp. for trait
Unbiased survey of all differences in entire genome bet 2 groups
What are the techniqes used in Genome wide apporach?
Sanger sequencing (gold standard, expensive and time consuming)
SNP Microarrays
Next generation sequencing
What is the SNP Microarray Technique?
Simgle Stranded small fragments of genomic DNA where there are known to be SNPs, fixed to a slide
Ea spot on slide repesents either A or B allele
What is next Generation Sequencing
Allows us to sequence 25 GBases/day or 8 complete genome
Lots of computaional power needed
What are the gene polymorphisms effecting pharm-Kinetics?
Metabolic Ez- CYP2D6 CYP2C19 CYP2C9 DPD (Dohydropyrimidine dehydrogenase) TPMT(Thiopurine methyltransferase) Drug Transporters- Solute Carrier Organic Anion Transporter 1B1(SLCO1B1)
What drugs does CYP2D6 Metabolize?
Tamoxifen
Codeine
Paroxetine
How does CYP 2D6 effect Tamoxifen?
IT metabolizes and ACTIVATES IT! If they are poor metabolizers, they have a higher chance of relapse(best to use another drug(aromatase inhibitor))
How does CYP 2D6 effect Codeine?
it ACTIVATES Codeine by converting it to Morphine. Pt can have either excessive SA or inadequate analgesia.
How does CYP 2D6 effect Paroxetine?
Is INACTIVATED by metabolism.
Poor metabolizers have more SA.
What drug does CYP 2C19 affect?
Clopidogrel
Omeprazole, Lansoprazole
How does CYP 2C19 effect Clopidogrel?
It ACTIVATES Clopidogrel
Poor metabolizers will need to use a different drug
