Introduction to pharmacogenetics

Question 1

What is the main cyotochrome P450 enzyme in drug metabolism?

Answer 1

CYP3A4/5

Question 2

CYP activity

Answer 2

• influences the risk for ADEs or for therapy non-response
• cannot be precisely predicted

Question 3

Which drug should be given dependent on OATP1B1 genotype?

Answer 3

Simvastatin

Question 4

Hepatic drug metabolism

Answer 4

• Uptake transporters (OATPs) transfer the drug from the blood into the hepatocyte
• Phase I and Phase II enzymes metabolise the drug
• Efflux transporters (MPR2) transport the water soluble end product of hepatic metabolism out of the hepatocyte

Question 5

What does pharmacogenetics/genomis try to explain?

Answer 5

• the individual reactions to therapeutics
• the individual risk for side effects
• the non-response to therapeutics

Question 5

Interpreting Manhattan plots

Answer 5

The higher the dot, the higher the significance of association of the gene with the disease

Question 6

What determines the efficacy and safety of drug metabolism at the end?

Answer 6

• epidemiology
• genetics
• regulation of transcription and translation

Question 8

Pharmacogenetics/genomics try to explain stuff on the basis of what?

Answer 8

• drug metabolising enzymes
• drug transporters
• drug targets (e.g. receptors)

Question 9

How do CYP2C19 poor metabolisers react to the following therapeutics?

• diazepam
• sertraline
• PPIs

Answer 9

• Diazepam: Prolonged sedation
• Sertraline: nausea/vomitus increased
• PPIs: better therapy efficacy in H. pylori therapy