Pharmacogenetics

Question 1

Define pharmacokinetics and pharmacodynamics

Answer 1

Pk= What the body does to the drug
Pd= What the drug does to the body

Question 2

How can genetic variation effect drug?

Answer 2

• Absorption
• Activation
• Altered target
• Catabolism
• Excretion

Question 3

How is Thiopurine methyltransferase be a problem with drug metabolism?

Answer 3

• Inactivates certain drugs
• Includes Azathioprine (immunosuppressant), 6-mercaptopurine & 6-thioguanine (chemo)
• Gene polymorphisms reduce enzyme protein activity
• Severe toxicity if both copies of the gene have the variant

Question 4

How can N-Acetyltransferase activity be a problem in drug metabolism?

Answer 4

• Liver enzymes inactivating drugs by acetylation
• Fast & slow acetylators
• Slow acetylators inc risk of side effects

Question 5

How is Succinylcholine a problem in drug metabolism?

Answer 5

• Related to poison curare
• Muscle relaxant
• Rare gene variant homozygotes have reduced butyrylcholinesterase activity
• Effects may last hours can cause death without ventilation

Question 6

How is warfarin a problem in drug metabolism?

Answer 6

• Oral anticoagulant to reduce embolism/thrombosis
• Decreases availability of it K
• Dose too low= patient remains at risk
• Dose too high= risk of haemorrhage

Question 7

What is Trastuzumab (Herceptin) and what patients is it used in?

Answer 7

• Monoclonal antibody for HER2 receptor

- Used in the 20% of breast cancers which have over-expression of HER2

Question 8

Why are BRAF inhibitors used for treating melanomas?

Answer 8

• Melanoma resistant to chemo

- 50% melanomas have somatic mutation in BRAF gene

Question 9

Name some new genetic testing technologies and what they can potentially idenntify

Answer 9

• SNP chips
• Next generation sequencing
• Genetic variations for multiple genes/ polymorphisms or whole genome