E02_02 Pharmacogenomics of ADRs

Question 1

2017, 2018_Pharmacogenomics

A patient is taking amlodipine (CYP 3A substrate) for hypertension and has been having good BP control. He decides to drink grapefruit (CYP 3A inhibitor) on a regular basis. What would happen to his blood pressure?

A. Increase
B. Decrease
C. No change

Answer 1

B. Decrease

Type A ADR
✓ Dose-related effect on BP
✓ Predictable

Question 2

2017, 2018_Pharmacogenomics

The active drug nortriptyline is metabolized by CYP2D6 into its inactive metabolite. What would happen to an ultrarapid metabolizer of CYP2D6?

A. Increase in nortriptyline and increase metabolite concentrations
B. Increase in nortriptyline and decrease metabolite concentrations
C. Decrease in nortriptyline and increase metabolite concentrations
D. Decrease in nortriptyline and decrease in metabolite concentrations

Answer 2

C. Decrease in nortriptyline and increase metabolite concentrations

With an ultrarapid metabolizer, you get a greater amount of CYP2D6 (thus amplifying its action; i.e. More nortriptyline metabolized, producing more inactive metabolite).

Question 3

2017, 2018_Pharmacogenomics

True or False. Phenytoin is metabolized by both CYP2C9 and CYP2C19. Assuming that it is unlikely for a person to be a poor metabolizer of both enzymes, it follows that it is also unlikely to develop phenytoin toxicity.

Answer 3

False

Phenytoin has a narrow therapeutic range, toxicity can arise from other causes.

Question 4

2017, 2018_Pharmacogenomics

True or False. Amitryptyline is a prodrug and is metabolized by CYP2C19 into the active form nortriptyline. You can give either drug in a CYP2C19 poor metabolizer.

Answer 4

False

“Poor metabolizer” = poor producer of enzyme; You need 2C19 to activate Amitryptiline.

Question 5

2017, 2018_Pharmacogenomics

True or False. The bioavailability of drugs metabolized by the CYP3A family is more affected than those metabolized by the CYP2D6.

Answer 5

True

The bioavailability of drugs metabolized by the CYP3A family is more affected than those metabolized by the CYP2D6. – CYP3A > 2D6 > 2C > 2A > 1A

Question 6

2017, 2018_Pharmacogenomics

True or False. Idiosyncratic reactions are the most common adverse drug reaction

Answer 6

False

Augmented (Type A) reactions are the most common ADRs – not Idiosyncratic (B)

Question 7

2014_Pharmacogenomics

True or False. CYP3A4 is the most important cytochrome p450 enzyme because it metabolizes 33% of all drugs that are metabolized

Answer 7

True

CYP3A - 33%
CYP2D6 - 26%
CYP2C - 25%

Question 8

2014, 2016 (Finals)_Pharmacogenomics

True or False. Pharmacogenetics is important only for the genes of the cytochrome p450 enzymes.

Answer 8

False

There are other enzymes which are being used in studying pharmacogenetics

Question 9

2014, 2016 (Finals)_Pharmacogenomics

True or False. In tamoxifen metabolism, CYP2D6 is more important than CYP3A4.

Answer 9

True

It is through the metabolism of CYP2D6 enzymes that the active drug of tamoxifen is formed.

Question 10

2014_Pharmacogenomics

True or False. Individualized medicine started only when pharmacogenetics started to mature as a medicine.

Answer 10

False

Question 11

2014_Pharmacogenomics

Tamoxifen is anti-estrogen in all the tissues that it affects.

Answer 11

False

Anti-estrogenic in the breast, but estrogenic in the bone and uterus.

Question 12

2014_Pharmacogenomics

If we start a patient on rifamipicin, an inducer of CYP3A4, we need to immediately increase the dose of any CYP3A4 substrate (such as simvastatin) that is concomitantly taken by the patient in order to prevent toxicity.

Answer 12

False

Do it so that the drug (simvastatin), will still work (?)

Question 13

2014_Pharmacogenomics

The patient has one allele of PM for CYP2D6 and one allele of EM. His phenotype is:

A. EM
B. IM
C. PM
D. UM

Answer 13

A. EM

CYP2D6 follows an autosomal dominant pattern.

Dominance: UM > EM > IM > PM
*ultra, extensive, intermediate, poor

CYP2C9 and CYP2C19 are co-dominant (e.g. EM/PM –> IM)

Question 14

2014_Pharmacogenomics

Patient is a poor metabolizer of CYP2D6. If he is taking codeine, you expect the analgesic effect to be ____ when compared with extensive metabolizers.

A. increased
B. decreased
C. the same

*Clue: Codeine is a prodrug for Morphine

Answer 14

B. decreased

You need CYP2D6 to activate codeine into its active form –> morphine

Question 15

2014_Pharmacogenomics

A patient is taking amlodipine (a CYP3A substrate) for HTN and has been giving good BP control. He decides to drink grapefruit juice (a CYP3A inhibitor) on a regular basis. What would he do with his amlodipine dose?

A. increase
B. decrease
C. no need to change

Answer 15

B. decrease

To prevent amlodipine toxicity (–> hypotension)

Question 16

2014_Pharmacogenomics

If a person is a poor metabolizer of an active drug, we would expect the following when this drug is given at the usual doses.

A. Increased toxicity, increased efficacy
B. Increased toxicity, decreased efficacy
C. Decreased toxicity, increased efficacy
D. Decreased toxicity, decreased efficacy

Answer 16

A. Increased toxicity, increased efficacy