Pharmacogenetics

Question 1

What is pharmacogenetics?

Answer 1

The study of genetic variation in relation to drug response.

Question 2

What is pharmacodynamics?

Answer 2

What the drug does to your body.

Question 3

What is pharmacokinetics?

Answer 3

What your body does to the drug.

-i.e. metabolism

Question 4

What is personalised medicine?

Answer 4

Therapies tailored to the individual.

Question 5

What is stratified medicine?

Answer 5

Selecting therapies for groups of patients with shared biological characteristics.

Question 6

NB what is the difference between germline and somatic mutations?

Answer 6

Germline are hereditary, somatic are acquired.

Question 7

What proportion of UK hospital admissions are related to adverse drug reactions?

Answer 7

6.5%.

Question 8

What effect does thiopurine have on drug metabolism?

Answer 8

Inactivates certain drugs, causing toxicity.

-e.g. azathioprine (immunosuppressant)

Question 9

What are N-acetlytransferase?

Answer 9

Liver enzymes that inactivate drugs by acetylation.

• SNP variation alters speed
• e.g. isonazid (TB drug)

Question 10

What is succinylcholine?

Answer 10

Muscle relaxant used in anaesthesia.

-related to curare (poison)

Question 11

What gene mutations alter succinylcholine activity?

Answer 11

BCHE gene variants.

• reduced butyrylcholinesterase activity
• effects last hours instead of minutes

Question 12

What causes aminoglycoside induced hearing loss?

Answer 12

G>A mutation in mitochondrial MT-RNR1 gene.

• aminoglycosides more likely to bind
• maternal inheritance

Question 13

Optimum warfarin dose varies 20x between individuals. What genes explain 50% of this variability? (2)

Answer 13

• Cytochrome P450 (CYP2C9)

- Vitamin K oxidoreductase complex 1 (VKORC1)

Question 14

Why might it be helpful to test for polymorphisms before treatment?

Answer 14

May reduce adverse effects and hospital admissions.

-personalised therapy

Question 15

What effect does Trastuzumab have on breast cancer?

Answer 15

Antibody against HER2 receptor.

• effective in patients with HER2 overexpression (20%)
• can be detected using FISH

Question 16

What somatic mutation is present in ~50% of melanomas?

Answer 16

BRAF gene mutation.

-Vemurafenib is effective against it