Pharmacogenics

Question 1

Pharmacogenetics

Answer 1

the study of differences in drug response due to allelic variation in genes affecting drug metabolism, efficacy, and toxicity
variable response to individual gene

Question 2

Pharamacogenomics

Answer 2

the genomic approach to the pharmacogenetics, is concerned with the assessment of common genetic variants in the aggregate for their impact on the outcome of drug therapy.
Variable response due to multiple loci across the genome

Question 3

pharamcogenetics is the study or

Answer 3

clinical testing of genetic variation that gives rise to differing response to drugs

Question 4

codeine metabolism

Answer 4

require CYP2D6 gene to activate.

More copies makes you metabolize more

Question 5

normally metabolize ____% of codeine to morphine

Answer 5

10%

Question 6

once a drug is taken, the drug must:

Answer 6

1. reach its target
2. exert its effect
3. do the above before being inactivated/eliminated

Question 7

pharmacokinestics

Answer 7

describes absorption, distribution, metabolism and excretion of drugs (commonly referred to as ADME)
cytochrom p450, glyconyltransferase, thiopureine methyltransferase

Question 8

pharmacodynamics

Answer 8

describes the relationship between the concentration of a drug at its site of action and observed biological effects

Question 9

most major drugs are only effective in ___% of patients

Answer 9

25-60

Question 10

the CYP450 complex is

Answer 10

1. the gene products active in liver and intestinal epithelium
2. 3 main families: (CYP1, CYP2, CYP3)
3. CYP3A4

Question 11

the CYP1, CYP2, CYP3 have 6 main genes:

and phase I for ___% of common drugs

Answer 11

CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4

90%

Question 12

what gene accounts for 40% of all common drugs

Answer 12

CYP3A4

There is less genetic variation on CYP3A4 than other CYPs

Question 13

Most CYP’s function to _____ drugs

Answer 13

inactivate.

But rarely they are needed to activate

Question 14

example of gene needed to activate a drug

Answer 14

CYP2D6

which converts codeine to morphine

Question 15

gene: CYP3A:

Answer 15

1. cyclosporine
2. ketoconanazole
3. rifampin
4. grapefruit juice

Question 16

CYP2D6 gene

Answer 16

codeine, this is needed to activate

Question 17

CYP2c9 + VKORC1

Answer 17

warfarin

Question 18

NAT

Answer 18

isoniazid

Question 19

TPMT

Answer 19

6-mercaptopurine/6-thiguanine and childhood

Question 20

G6PD

Answer 20

hemolytic anemia after sulfa drugs

Question 21

Pharmacokinetics:

• Genetic Examples:

Answer 21

Cytochrome P450, glucuronyltransferase, thiopurine methyltransferase

Question 22

Pharmacodynamics:

• Genetic Examples:

Answer 22

Glucose-6-phosphate dehydrogenase, vitamin K epoxide complex

Question 23

Pharmacokinestics is broken down farther into

Answer 23

two basic ways that drugs are metabolized through biotransformers

Question 24

pharmacokinestics phases

Answer 24

phase 1

phase 2

Question 25

phase 1 metabolism

Answer 25

attach a polar group onto the compound to make it more soluble; usually a hydroxylation step

Question 26

phase 2 metabolism

Answer 26

attach a sugar/acetyl group to detoxify the drug and make it easier to excrete

Question 27

Frameshift -->

Answer 27

alter reading frame --> NO ACTIVITY

Question 28

splicing-->

Answer 28

skip exons and/or alter reading frame--> no activity

Question 29

missense -->

Answer 29

alter protein function--> usually REDUCED ACTIVITY

Question 30

copy number alleles -->

Answer 30

increased gene copy alleles --> INCREASED (ULTRAFAST)

Question 31

based on the combinations (since individuals have 2 alleles in their genotypes), have 3 major phenotypes

Answer 31

1. normal 2. poor (includes null alleles) 3. ultrarapid/ultrafast

Question 32

A single 8 oz glass of grapefruit juice can inhibit _______ activity for 24-48 hours.

Answer 32

CYP3A (largely through intestinal inhibition of CYP3A).

Question 33

drinking grapefruit juice while taking felodipine for hypertension can lead to ________

Answer 33

significant hypotension due to potentiation of the felodipine effect since CYP3A activity is reduced and metabolism/elimination of felodipine is similarly slowed.

Question 34

Dosage of the immunosuppressive drug _______ (used in kidney transplants for instance) must be reduced by _____% to avoid toxicity when the _________ is added to treat a fungal infection.

Answer 34

cyclosporine 75% antifungal ketoconazole

Question 35

Mechanism- ketoconazole temporarily inhibits _____ metabolism which leads to raised levels of _______ which can be neprotoxic.

Answer 35

CYP3A cyclosporine

Question 36

Renal transplant patient who is exposed to tuberculosis and requires________:

Answer 36

rifampin prophylaxis:

Question 37

the dose of cyclosporine must be ______ since rifampin is a _____ inducer and leads to more ______.

Answer 37

increased CYP3 rapid metabolism and elimination of cyclosporine. If you fail to take this into account, the cyclosporine levels will decrease and organ rejection will become a problem.

Question 38

gene: CYP3A drugs:

Answer 38

cyclocsporin

Question 39

CYP3A inhibitors

Answer 39

1. ketocoazole | 2. grapefruit juice

Question 40

CYP3A inducer

Answer 40

rifampin

Question 41

what gene effects cyclosporin?

Answer 41

CYP3A

Question 42

gene: CYP2D6 drugs:

Answer 42

1. tricyclic antidepressants | 2. codeine

Question 43

CYP2D6 inhibitors

Answer 43

1. qinidine 2. fluoxetine 3. paroxetine

Question 44

what gene is involved with tricyclic antidepressants?

Answer 44

CYP2D6

Question 45

gene: NAT drug:

Answer 45

isoniazid for tuberculosis

Question 46

isoniazid for tuberculosis gene involved is?

Answer 46

NAT

Question 47

gene: TMPT drugs:

Answer 47

1. 6-mercaptopurine 2. 6-thioguanine leukemia -Often presented as the classic example of a pharmacogenetic mechanism that can be fatal if ignored

Question 48

what gene is involved in 6-mercaptopurine?

Answer 48

TMPT

Question 49

G6PD | drug?

Answer 49

1. sulfonamide | 2. dapsone

Question 50

mechanism of G6PD drugs

Answer 50

X-linked enzymes

Question 51

G6PD deficient individuals are susceptible ______

Answer 51

to hemolytic anemia after drug exposures

Question 52

gene affected by sulfonamide

Answer 52

G6PD

Question 53

gene for dapsone?

Answer 53

G6PD

Question 54

gene for warfarin

Answer 54

VKORC1

Question 55

Warfarin is a

Answer 55

blood thinner that is most commonly prescribed medicines, given to >200,000 patients/yr

Question 56

one of the most commonly prescribed drugs

Answer 56

warfarin

Question 57

drug for VKORC1

Answer 57

Warfarin