lecture 9 - genetic variability *

Question 1

pharmacogenomics (PGx)

Answer 1

investigation of variations of DNA and RNA characteristics as related to drug response (genome science)

Question 2

pharmacogenetics (PGt)

Answer 2

is a subset of PGx and is defined as the influence of variations in DNA sequence on drug response (clinical relevance)

Question 3

predictable variability - pharmacokinetics (CL)

Answer 3

• cytochrome P450

• non-cytochrome metabolism (acetylation, glucuronidation, purine breakdown, alcohol
dehydrogenase)

• transporters (PGP, organic anion)

Question 4

predictable variability - pharmacodynamics (C50)

Answer 4

• Vitamin K epoxide reductase (VKORC1)

* Vitamin K1 oxidase (CYP4F2)

Question 5

Significance of genetic variance

Answer 5

• body size, renal function, post-menstrual age are most important determinants of drug dose
• in clinical situations, most genetic variances only 20-30% difference in dose (not that significant)

Question 6

what pharmacokinetic parameter is mostly to account for inter-individual variability in due to genetic differences

Answer 6

metabolism

Question 7

why is it important to predict drug responsiveness as accurately as possible

Answer 7

maximise therapeutic effect

minimise off-target effects

minimise toxic effects