Pharmacogenetics

Question 1

What is genetic polymorphism?

Answer 1

Presence of 2 or more alleles in a population for a given locus

The more alleles in the population, the higher the polymorphism

Question 2

What are cytochrome P450 enzymes?

Answer 2

Drug metabolizing enzymes and enzymes responsible for cholesterol , steroids, prostacyclins, and thromboxane A2

Question 3

What are possible variations for CYP2D6 (codeine metabolizing enzyme) in humans?

Answer 3

Deletion - poor metabolizers

Duplications - ultra metabolizers

Question 4

What is the danger of being an ultra metabolizer for codeine?

Answer 4

Can quickly increase morphine concentration and lead to impaired respiration and sedation

Question 5

What are the three classes of pharmacogenes?

Answer 5

Drug metabolizing enzymes

Drug transporters

Drug target

Question 6

What is the significance of a drug being a prodrug or active agent in the case of drug metabolizing enzymes?

Answer 6

Prodrug - LoF mutation for the enzymes results in little or no efficacy

Active agent - LoF mutation for the enzyme results in toxicity or increased exposure

Question 7

What results from polymorphisms in genes encoding drug transporters?

Answer 7

Generally result in changes in the drug’s pharmacokinetics

Patient outcomes vary depending upon where the transporter is expressed

Question 8

What results from polymorphisms in genes encoding drug targets?

Answer 8

Results in changes in the drug’s pharmacodynamics or efficacy