Principles of Pharmacogenomics 1

Question 1

In the 1950s, what did Succinylcholine show?

Answer 1

Discovered poor and ultraextensive metabolizers, which were heritable traits

Question 2

In the 1970s, what did Debrisoquine show?

Answer 2

Discovered poor and extensive metabolizers that had the abnormal and normal phenotypes respectively

Question 3

Poor metabolizers have (increased/decreased) parent drug concentration

Answer 3

increased

Question 4

Poor metabolizers have (increased/decreased) synthesis of CYP

Answer 4

decreased

Question 5

Carriers of one functional and defective allele is known as _______ metabolizers

Answer 5

Intermediate

Question 6

Carriers of two defective alleles is known as ________ metabolizers

Answer 6

Intermediate

Question 7

Carriers of tow functional alleles is known as __________ metabolizers

Answer 7

Extensive

Question 8

What kind of metabolizer is at higher risk for adverse effects?

Answer 8

Poor metabolizers

Question 9

What kind of metabolizer is more likely to have less of a therapeutic effect?

Answer 9

Ultra-rapid metabolizers

Question 10

Duplication of CYP___ is responsible for ultra-rapid metabolism

Answer 10

CYP2D6

Question 11

What are the variants of CYP2D6 that are made up in poor metabolism?

Answer 11

CYP2D63 thru CYP2D66

Question 12

Poor metabolizer + CYP2D6

If given codeine or tramadol, what happens?

Answer 12

Less analgesic relief from codeine or tramadol

Converts codeine to morphine + tramadol to an active metabolite

Question 13

Ultrarapid metabolizer + CYP2D6

If given codeine or tramadol, what happens?

Answer 13

Potential for much greater than average efficacy and AE

Question 14

What is the purpose of CYP2D6?

Answer 14

Metabolize 25-30% of all clinically used drugs

Question 15

What is the purpose of CYP2C19?

Answer 15

Metabolize benzos, some tricyclic antidepressants, and PPIs

Question 16

Do Tricyclic antidepressants have broad or narrow therapeutic window?

Answer 16

Narrow

Question 17

Do PPIs have broad or narrow therapeutic window?

Answer 17

Broad

Question 18

Poor metabolizers + CYP2C19

What happens if given a PPI?

Answer 18

Higher cure rates, correlates w/ higher plasma

Question 19

CYP___ metabolizes Clopidogrel to active metabolites

Answer 19

CYP2C19

Question 20

CYP2C19*2 + Clopidogrel

What happens?

Answer 20

Correlates w/ poor anti-platelet aggregating activity of Clopidogrel

Question 21

Which CYP is the most abundant and responsible for about 50% of marketed drug metabolism?

Answer 21

CYP3A

Question 22

Where is CYP3A commonly found?

Answer 22

Liver + Intestines

Question 23

Which CYP is responsible for fetal metabolism?

Answer 23

CYP3A4, CYP3A5, and CYP3A7

Question 24

What variant of CYP3A has splicing defects and are not expressed?

Answer 24

CYP3A53 and CYP3A56

Question 25

What is the purpose of CYP3A5*1?

Answer 25

Enzyme expression, just need 1 copy