Pharmacogenomics

Question 1

NAT 2

Answer 1

Slow inactivation of isoniazid. There are two forms of the enzyme.

Question 2

Serum pseudocholinesterase

Answer 2

Prolonged respiratory paralysis on exposure to suxamethonium. There is deficiency of the enzyme.

Question 3

G6PD meaning

Answer 3

Glucose-6-phosphate dehydrogenase

Question 4

G6PD

Answer 4

Absence causes haemolysis after antimalarial medication

Question 5

TMPT meaning

Answer 5

Thiopurine methyl transferase

Question 6

TMPT and pharmacogenetics

Answer 6

It is absent in some people, causing them to use other metabolic pathways for the metabolism of thiopurine and 6-mercaptopurine, leading to bone marrow toxicity.

Question 7

How does pharmacogenomics cause challenges in clinical practice?

Answer 7

There is individual variability in drug response, affecting efficacy and the possibility of ADR which has caused death in some cases.

The drug development process may take longer

Question 8

Genetic polymorphisms influencing drug disposition

Answer 8

Not everyone expresses functional CYP450 enzymes. For instance, not everyone expresses CYP3A5, but it is not clear because the drugs metabolized by this are also metabolized by CYP3A4. If both are present, there is a net effect.

Question 9

CYP1A1

Answer 9

Caffeine, Testosterone, R-Warfarin

Question 10

1A2

Answer 10

Acetaminophen, Caffeine, Phenacetin, R-Warfarin

Question 11

2A6

Answer 11

17 beta-Estradiol, Testosterone

Question 12

2B6

Answer 12

Cyclophosphamide, Erythromycin, Testosterone

Question 13

2C-family

Answer 13

Acetaminophen, Hexobarbital,
Phenytoin, Testosterone, R- Warfarin

Question 14

2E1

Answer 14

Acetaminophen, Caffeine, Chlorzoxazone, Halothane

Question 15

2D6

Answer 15

Acetaminophen, Codeine, Debrisoquine

Question 16

3A4

Answer 16

Acetaminophen
Caffeine
Carbamazepine
Codeine
Cortisol
Erythromycin
Phenytoin
Testosterone
Halothane
Zidovudine

Question 17

Risks associated with CYP enzyme inhibition or induction cover…

Answer 17

• Degradation of co-medicated drugs
• Drug plasma concentration
• Adverse/therapeutic failure

Question 18

1A2 inhibitor and inducer

Answer 18

Cimetidine & Tobacco smoke

Question 19

2B6 inhibitor and inducer

Answer 19

Thiotepa & Phenobarbital

Question 20

2C19

Answer 20

Fluoxetine & Prednisone

Question 21

2C9

Answer 21

Paroxetine & Secobarbital

Question 22

2D6

Answer 22

CPZ, ranitidine & Dexamethasone

Question 23

2E1

Answer 23

Disulfiram & Ethanol

Question 24

3A4,5,7

Answer 24

Grapefruit juice & Glucocorticoid

Question 25

Genetic Polymorphism of Drug Targets

Answer 25

1. Patients with the β2-ADR receptor arginine genotype experience poor asthma control, compared with patients who have the glycine genotype
2. Polymorphisms in the vitamin K epoxide reductase complex subunit 1 (VKORC1) gene contribute to the variability in response to warfarin therapy
3. Patients expressing HER2 receptor are more likely to benefit from the monoclonal antibody trastuzumab

Question 26

Codeine metabolism

Answer 26

• Codeine is a commonly used opioid
• Prodrug
• Must be metabolized into morphine for activity
• CYP2D6 is the metabolizing enzyme
• 7% of Caucasians are defficient in gene
• Codeine does not work effectively in these individuals

Question 27

Tamoxifen metabolism

Answer 27

• Tamoxifen is used to treat breast cancer and infertility
• Needs to be converted to endoxifen to be active
• Catalyzed by CYP2D6
• 6-10% European population are deficient
• Efficacy of tamoxifen is low in this population
• Suggests alterative treatments

Question 28

Limitations of pharmacogenomics

Answer 28

• Cost
• Access to adequate technology
• Confidentiality of info

Question 29

Expected outcomes of pharmacogenomics

Answer 29

Right dose
Right drug
Right indication
Right patient