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M2M exam 2 > Pharmacogenics > Flashcards

Pharmacogenics Flashcards

1
Q

Pharmacogenetics

A

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

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2
Q

Pharamacogenomics

A

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

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3
Q

pharamcogenetics is the study or

A

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

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4
Q

codeine metabolism

A

require CYP2D6 gene to activate.

More copies makes you metabolize more

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5
Q

normally metabolize ____% of codeine to morphine

A

10%

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6
Q

once a drug is taken, the drug must:

A
  1. reach its target
  2. exert its effect
  3. do the above before being inactivated/eliminated
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7
Q

pharmacokinestics

A

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

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8
Q

pharmacodynamics

A

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

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9
Q

most major drugs are only effective in ___% of patients

A

25-60

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10
Q

the CYP450 complex is

A
  1. the gene products active in liver and intestinal epithelium
  2. 3 main families: (CYP1, CYP2, CYP3)
  3. CYP3A4
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11
Q

the CYP1, CYP2, CYP3 have 6 main genes:

and phase I for ___% of common drugs

A

CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4

90%

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12
Q

what gene accounts for 40% of all common drugs

A

CYP3A4

There is less genetic variation on CYP3A4 than other CYPs

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13
Q

Most CYP’s function to _____ drugs

A

inactivate.

But rarely they are needed to activate

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14
Q

example of gene needed to activate a drug

A

CYP2D6

which converts codeine to morphine

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15
Q

gene: CYP3A:

A
  1. cyclosporine
  2. ketoconanazole
  3. rifampin
  4. grapefruit juice
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16
Q

CYP2D6 gene

A

codeine, this is needed to activate

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17
Q

CYP2c9 + VKORC1

A

warfarin

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18
Q

NAT

A

isoniazid

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19
Q

TPMT

A

6-mercaptopurine/6-thiguanine and childhood

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20
Q

G6PD

A

hemolytic anemia after sulfa drugs

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21
Q

Pharmacokinetics:

• Genetic Examples:

A

Cytochrome P450, glucuronyltransferase, thiopurine methyltransferase

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22
Q

Pharmacodynamics:

• Genetic Examples:

A

Glucose-6-phosphate dehydrogenase, vitamin K epoxide complex

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23
Q

Pharmacokinestics is broken down farther into

A

two basic ways that drugs are metabolized through biotransformers

24
Q

pharmacokinestics phases

A

phase 1

phase 2

25
Q

phase 1 metabolism

A

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

26
Q

phase 2 metabolism

A

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

27
Q

Frameshift –>

A

alter reading frame –> NO ACTIVITY

28
Q

splicing–>

A

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

29
Q

missense –>

A

alter protein function–> usually REDUCED ACTIVITY

30
Q

copy number alleles –>

A

increased gene copy alleles –> INCREASED (ULTRAFAST)

31
Q

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

A
  1. normal
  2. poor (includes null alleles)
  3. ultrarapid/ultrafast
32
Q

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

A

CYP3A

(largely through intestinal inhibition of CYP3A).

33
Q

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

A

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

34
Q

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.

A

cyclosporine

75%

antifungal ketoconazole

35
Q

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

A

CYP3A

cyclosporine

36
Q

Renal transplant patient who is exposed to tuberculosis and requires________:

A

rifampin prophylaxis:

37
Q

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

A

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
Q

gene: CYP3A
drugs:

A

cyclocsporin

39
Q

CYP3A inhibitors

A
  1. ketocoazole

2. grapefruit juice

40
Q

CYP3A inducer

41
Q

what gene effects cyclosporin?

42
Q

gene: CYP2D6
drugs:

A
  1. tricyclic antidepressants

2. codeine

43
Q

CYP2D6 inhibitors

A
  1. qinidine
  2. fluoxetine
  3. paroxetine
44
Q

what gene is involved with tricyclic antidepressants?

45
Q

gene: NAT
drug:

A

isoniazid for tuberculosis

46
Q

isoniazid for tuberculosis gene involved is?

47
Q

gene: TMPT
drugs:

A
  1. 6-mercaptopurine
  2. 6-thioguanine

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

48
Q

what gene is involved in 6-mercaptopurine?

49
Q

G6PD

drug?

A
  1. sulfonamide

2. dapsone

50
Q

mechanism of G6PD drugs

A

X-linked enzymes

51
Q

G6PD deficient individuals are susceptible ______

A

to hemolytic anemia after drug exposures

52
Q

gene affected by sulfonamide

53
Q

gene for dapsone?

54
Q

gene for warfarin

55
Q

Warfarin is a

A

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

56
Q

one of the most commonly prescribed drugs

57
Q

drug for VKORC1

M2M exam 2 (23 decks)

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