Pharmacogenomics Flashcards
What is pharmacogenetics?
Study of genes and their alleles in relationship to drug response in a given patient
What is pharmacogenomics?
Study of genes related to drug metabolism and the use of this knowledge to develop new, targeted drugs
Major system to metabolize drugs?
Cytochrome P450….CYP
What percentage of ADRs are related to genetic anomalies?
About 50%
Major benefits of pharmacogenomics?
Each patient gets exactly the right medication for his or her situation
What are ADME core markers?
Known genes involved in drug metabolism
Functional alleles for poor metabolizers?
None….so there is an accumulation of drug that may be toxic
Need a lower dose of the medication
Number of functional alleles for an extensive metaboizer?
2…this is a “normal” individual.
Number of functional alleles for an ultra metabolizer?
More than 2. Might need higher doses of the drug
Number of functional alleles for an intermediate metabolizer?
1 functional allele
Need a lower than normal dose.
What is TMPT?
Thiopurine methyl transferase
It catalyze a the methylation of 6-MP and 6-T
What occurs in individuals with 2 mutations in TPMT? What happens in heterozygotes?
2 mutated alleles= bone marrow toxicity because accumulation of 6-MP
heterozygotes= mild toxicity, require a lower dose
Function of G6PD?
Relieves oxidative stress in cells by regenerating reduced glutathione and prevents induction of hemolysis
Who is G6 PD deficiency usually seen in?
African American males and people from the Mediterranean area
malignant hypothermia is due to mutations in….
RYR1 and CACNL1A3 and 4 other loci
T/F: malignant hypothermia is a recessive trait.
False…autosomal dominant
Functions/ mechanisms of warfarin?
Inhibits the enzyme epoxied reducatse (which inhibits vit k metabolism).
Inhibits vit k reducatse to prevent reduction of vit k
2 genes involved in warfarin metabolism:
VKORC1 and CYP2C9
Who requires a larger dose of warfain with a VKORC1 mutation? Who requires a smaller one?
Asian= low dose
African Americans= high dose
Who is a CYP2C9 mutation common in?
Caucasians
What reactions with warfarin to increase or decrease risk of bleeding?
Medications increase the risk of bleeding (aspirin, ibuprofen, acetaminophen)
Foods high in vit K decrease the function of warfarin
