Pharmacogenetics

Question 1

Factors affecting response to medicine? (2)

Answer 1

Genes

Interactions w/ other drugs

Question 2

Pharmacogenetics?

Answer 2

How do genes affect drug response?

Question 3

How did concept of pharmacogenomics change?

Answer 3

Initially pharmacogenetics: generalized, small number of genes based

Pharmacogenomics:
Includes complex pathways and whole genome based

Question 4

What are the flavors of pharmacogenomics? (2)

Answer 4

Variation in Drug response - pharmacodynamics

Variation in Drug deposition - pharmacokinetics

Question 5

G6PD deficiency?

Answer 5

Was initially caused by primaquine (anti malarial drug)

Led to hemolytic anemia

Can have genetic basis as well

Question 6

What are two important transporters in PK?

Answer 6

ABC transporters

And SLC transporters

Question 7

What are the 2 important enzyme classes in PK?

Answer 7

Bioactivation...
Oxidation
CYP
Polar species
Phase 1
Renal elimination

Clearance...
Conjugation
Glucoronidation
Non polar species
Phase 2
Biliary elimination (stool)

Question 8

Important example for phase 2?

Answer 8

UGT

Question 9

Important example for phase 1?

Answer 9

CYP

Question 10

2C19 poor metabolism in which populations?

Answer 10

Mostly in China and japan

Less in caucasians

Question 11

UGT poor metabolims in which population?

Answer 11

Mostly in caucasians

Less so in china and japan

Question 12

CYP 2D6?

Answer 12

Highly polymorphic

Responsible for metabolism of antidepressants, antipsychotics, analgesics, CV drugs

Question 13

Different metabolizers

Answer 13

Ultrarapid metabolizers
Extensive metabolizers
Poor metabolizers

Question 14

Poor 2D6 metabolizers in which population?

Answer 14

Caucasian

Question 15

Which population is not responsive to codeine?

Answer 15

10 percent of patients (caucasians) not responsive to codeine

Question 16

Tamoxifen

Answer 16

Breast cancer drug

Needs to be metabolized by 2D4

To endoxifen (100 times more potent)

Tends to be ineffective in caucasians

Question 17

Ultrarapid, extensive and poor metabolizers of 2D6 in middle east?

Answer 17

UM - emirates, syria and jordan

EM - significant in most

PM - mostly egypt

Question 18

First FDA cleared test for analysis of 2D6 and 2C19?

Answer 18

AmpliChip CYP450 test

Indicates responders (good metabolizers)
vs non responders (poor metabolizers)

Question 19

To be continued!!

Answer 19

Ahahahahaha