Nanda - Pharmacogenomics

Question 1

Pharmacokinetics

Answer 1

How the body processes the drug - clearance/excretion, metabolism, transportation, absorption

Question 2

Pharmacodynamics

Answer 2

Drug activity, site at downstream targets

• site of action, medical activity
• dynamic, exciting!!!

Question 3

Pharmacogenomics

Answer 3

-omic approach to pharmacogenetics, use GWAS (genome-wide association studies) to assess SNP variation driving differential drug effects in population

Question 4

Cytochrome p450’s

Answer 4

family of heme-containing enzymes mainly expressed in liver. Responsible for detoxification, exporting foreign compounds. Can also activate drugs (i.e. codeine–>morphine).

• Do redox reactions, like adding O2 to molecules, increasing solubilities by hydroxylation, epoxidation… key for drug metabolism/excretion
• “promiscuous” enzymes, react with multiple molecules, not lock and key

Question 5

CYP2C9

Answer 5

Metabolizes warfarin. Important to know since other drugs might also be involved with CYP2C9, causing contraindication

• Hydroxylates warfarin to make it more soluble toward excretion. Rate of hydroxylation determines “sensitivity” or “tolerance” toward drug
• So affects pharmacokinetics
• Mutations in CYP2C9 can +/- warfarin sensitivity

Question 6

Warfarin

Answer 6

Coumadin, blood thinner. Prevents inappropriate clotting (embolisms, thrombosis).

• Impairs synthesis of Vitamin K-dependent clotting factors
• Competitive inhibitor of vitamin K epoxide reductase (VKORC1, recycles vitamin K). But influx of vitamin K can outcompete
• Target INR is 2-3

Question 7

Drug Sensitivity & Tolerance

Answer 7

Sensitivity: underactive drug-metabolizing enzyme causes stronger drug effects in patient despite normal dosage (i.e. lasting 8 hours instead of 6, or thinning blood too much).
Tolerance: overactive drug-metabolizing enzyme causes weaker drug effects in patient at usual dosage, making them more “tolerant” of drug

Question 8

VKORC1 (Vitamin K Epoxide Reductase)

Answer 8

Inhibited by warfarin, preventing regeneration of reduced vitamin K

• SNPs in VKORC1 correlate with warfarin sensitivity
• determined by GWAS

Question 9

Pharmacogenomics

Answer 9

Study of inherited differences in drug metabolism and response. Can affect pharmacokinetics and pharmacodynamics