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Flashcards in Pharmacogenics Deck (57)
1

Pharmacogenetics

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

2

Pharamacogenomics

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

3

pharamcogenetics is the study or

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

4

codeine metabolism

require CYP2D6 gene to activate.
More copies makes you metabolize more

5

normally metabolize ____% of codeine to morphine

10%

6

once a drug is taken, the drug must:

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

7

pharmacokinestics

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

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pharmacodynamics

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

9

most major drugs are only effective in ___% of patients

25-60

10

the CYP450 complex is

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

11

the CYP1, CYP2, CYP3 have 6 main genes:
and phase I for ___% of common drugs

CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4

90%

12

what gene accounts for 40% of all common drugs

CYP3A4

There is less genetic variation on CYP3A4 than other CYPs

13

Most CYP's function to _____ drugs

inactivate.

But rarely they are needed to activate

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example of gene needed to activate a drug

CYP2D6

which converts codeine to morphine

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gene: CYP3A:

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

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CYP2D6 gene

codeine, this is needed to activate

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CYP2c9 + VKORC1

warfarin

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NAT

isoniazid

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TPMT

6-mercaptopurine/6-thiguanine and childhood

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G6PD

hemolytic anemia after sulfa drugs

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Pharmacokinetics:
• Genetic Examples:

Cytochrome P450, glucuronyltransferase, thiopurine methyltransferase

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Pharmacodynamics:
• Genetic Examples:

Glucose-6-phosphate dehydrogenase, vitamin K epoxide complex

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Pharmacokinestics is broken down farther into

two basic ways that drugs are metabolized through biotransformers

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pharmacokinestics phases

phase 1
phase 2

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phase 1 metabolism

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

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phase 2 metabolism

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

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Frameshift -->

alter reading frame --> NO ACTIVITY

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splicing-->

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

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missense -->

alter protein function--> usually REDUCED ACTIVITY

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copy number alleles -->

increased gene copy alleles --> INCREASED (ULTRAFAST)

31

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

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

32

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

CYP3A


(largely through intestinal inhibition of CYP3A).

33

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

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

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.

cyclosporine

75%

antifungal ketoconazole

35

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

CYP3A

cyclosporine

36

Renal transplant patient who is exposed to tuberculosis and requires________:

rifampin prophylaxis:

37

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

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.

38

gene: CYP3A
drugs:

cyclocsporin

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CYP3A inhibitors

1. ketocoazole
2. grapefruit juice

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CYP3A inducer

rifampin

41

what gene effects cyclosporin?

CYP3A

42

gene: CYP2D6
drugs:

1. tricyclic antidepressants
2. codeine

43

CYP2D6 inhibitors

1. qinidine
2. fluoxetine
3. paroxetine

44

what gene is involved with tricyclic antidepressants?

CYP2D6

45

gene: NAT
drug:

isoniazid for tuberculosis

46

isoniazid for tuberculosis gene involved is?

NAT

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gene: TMPT
drugs:

1. 6-mercaptopurine
2. 6-thioguanine

leukemia
-Often presented as the classic example of a pharmacogenetic mechanism that can be fatal if ignored

48

what gene is involved in 6-mercaptopurine?

TMPT

49

G6PD
drug?

1. sulfonamide
2. dapsone

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mechanism of G6PD drugs

X-linked enzymes

51

G6PD deficient individuals are susceptible ______

to hemolytic anemia after drug exposures

52

gene affected by sulfonamide

G6PD

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gene for dapsone?

G6PD

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gene for warfarin

VKORC1

55

Warfarin is a

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

56

one of the most commonly prescribed drugs

warfarin

57

drug for VKORC1

Warfarin