Exam II Polymorphisms

Question 1

Define phenotype relationship to polymorphism specific to drugs

Answer 1

A genetic variation in a gene changing expression of drug metabolism which can effect drug clearance

Question 2

What percentage of drugs are eliminated by metabolism?

Answer 2

Over 75%

Question 3

A common genetic variation in DNA is defined as occurring in what percentage of the population?

Answer 3

At least 1%

Question 4

Common oxidation enzymes effected by polymorphism:

Answer 4

Cytochromes P450
Alcohol dehydrogenase 
Aldehyde dehydrogenase
Glucose-6-phosphate dehydrogenase
Flavin monooxygenases: FMO2, FMO3

Question 5

Common reduction enzymes effected by polymorphism:

Answer 5

Dihydropyrimidine dehydrogenase (DPD)

Question 6

Common hydrolysis enzymes effected by polymorphism:

Answer 6

Butyryl cholinesterase

Arylesterase/paraoxanase

Question 7

Common acetylation enzymes effected by polymorphism:

Answer 7

N-acetyl-transferase 2 (NAT2)

Question 8

Common glucuronidation enzymes effected by polymorphism:

Answer 8

UDP

UGTs

Question 9

Common methylation enzymes effected by polymorphism:

Answer 9

TMT
COMT
TPMT

Question 10

Common sulfation enzymes effected by polymorphism:

Answer 10

Sulfotransferases

Question 11

Common glutathione conjugation enzymes effected by polymorphism:

Answer 11

Glutathione-S-transferase M1 (GSTM1)

Question 12

How does polymorphism effect N-acetylation?

Answer 12

People can be either fast or slow acetylators, slow acetylators are at higher risks of adverse effects

Question 13

Class examples of drugs metabolized by N-acetyltransferases

Answer 13

Isoniazid
Sulfamethoxazole
Procainamide
Dapsone
Acebutolol
Hydralazine

Question 14

Inability to metabolize isoniazid results in formation of _______ which can convert to _____________

Answer 14

Hydrazine, reaction intermediates

Question 15

What enzyme metabolizes isoniazid?

Answer 15

NAT2

Question 16

50% of what race(s) are slow acetylators?

Answer 16

Caucasians and Africans

Question 17

92% of what race(s) are slow acetylators of NAT2?

Answer 17

Middle Easterners

Question 18

Which race(s) is/are fast acetylators?

Answer 18

Asian and Native Americans

Question 19

DPD deficiency occurs in what percentage of population?

Answer 19

8%

Question 20

What drug does DPD metabolize?

Answer 20

5-fluorouracil

Question 21

TPMT polymorphism effects toxicity and efficacy of what type of drugs?

Answer 21

Thiopurine

Question 22

What are the 3 categories of CYP2D6 polymorphisms? (Type of metabolizers)

Answer 22

Poor metabolizers, extensive metabolizers, ultra rapid metabolizers

Question 23

T/F Poor CYP2D6 metabolizers show greater AUC and therefore require lower doses?

Answer 23

True

Question 24

Which pain drug can result in overdose due to hyper metabolism of CYP2D6?

Answer 24

Tramadol

Question 25

Example of drug class for CYP2C19

Answer 25

Benzodiazepines

Question 26

T/F most FMO polymorphisms occur in FMO3

Answer 26

True

Question 27

Polymorphism of FMO3 effects what drugs?

Answer 27

Methimazole, sulindac, ranitidine

Question 28

Which enzyme is responsible for metabolism of bilirubin?

Answer 28

UGT1A1

Question 29

People with low UGT1A7 are at greater risk of?

Answer 29

Lung damage, cancer