Pharmacogenetics

Question 1

• Pharmacogenetics?
• Pharmacogenomics?
• Codeine to Morphine mechanism?
• Pathway once drug is taken? (3)
• Pharmacokinetics?
• Pharmacodynamics?
• Phase 1? Ex?
• Phase 2? Ex?
• % of people drugs are effective in?
• CYP450 active where? (2) Families?
• Acts on about 40% of drugs?
• CYP that actually activates drugs?
• CYP’s genotype vs. phenotype effect?

Answer 1

• Variable drug response due to individual genes
• Variable drug response due to multiple loci
• 80% inactivated by CYP3A4; 10% Activated by CYP2D6; More CYP2D6 = More morphine
• Reach target –> exert effect –> eliminated
• ADME (Absorption, metabolism, distribution; excretion
• Relationship b/n drug conc. at site and effect
• Drug made active (OH added)
• Drug prepared for excretion (Conj. reaction)
• 25-60%
• Liver, and intestinal epithelium; 3 families
• CYP3A4
• CYP2D6
• Mutations to CYP can effect how we metabolize drugs

Question 2

Common Genes/Drugs:
1? Mutations? Drugs related? (2) Inducers? Inhibitors? (2)

2? Drugs related? (2) Inhibitors? (3)

3.? Relationship to vit k? Drugs related? Who can’t metabolize?

Answer 2

1. ) CYP3A; least; felodipine, cyclosporin; Rifampicin; grapefruit juice and ketoconozide
2. ) CYP2D6; antidepressants, codeine; quinidine, flouxetine, paroxetine
3. ) CYP2C9; Decreased; warfarin; 20% whites can’t metabolize it

Question 3

Common Genes/ Drugs part 2:
4? Related drugs? Who are slow metabolizers? (2)

5? Drugs related? (2) Kills who? Ex?

6? Inheritance pattern? Drugs related? (2) Suseptible to? Avoid?

Answer 3

4. ) NAT (N-acetyl trans. for phase 2); Isonaizid for TB; 50% whites and 90% Japanese
5. ) TPMT (methyl transferase); 6-mecarpopurine, 6-thioguanine; kid with full immunosurpression; Lymphoblastic Leukemia with this need lower dose (acts on Aziathropine)
6. ) G6PD; X linked; sulframide; dapsone; hemolytic anemia; anti malerials