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Pharm > Pharmacogenomics 2 > Flashcards

Pharmacogenomics 2 Flashcards

1
Q

What are the pharmacogenetic phenotypes that affect the pharmacokinetics?

A

Polymorphisms in enzymes or drug transporters

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2
Q

What are the pharmacogenetic phenotypes that affect the pharmacodynamics?

A

Polymorphisms that affect receptors or enzymes..

Alters drug response.

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3
Q

What are the major gene polymorphisms that affect pharmacokinetics?

A

CYPs

Drug transporters

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4
Q

CYP2D6 affect which three major drugs?

A

Tamoxifen
Codeine
Paroxetine

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5
Q

How many different polymorphisms occur in CYP2D6? What do these cause?

A

12–non-functional alleles

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6
Q

What is the genetic makeup of ultra metabolizers with CYP2D6?

A

Three copies of the CYP gene

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7
Q

What is the genetic makeup of poor metabolizers with CYP2D6?

A

Two non-functioning copies of the CYP genes

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8
Q

What is the genetic makeup of intermediate metabolizers?

A

Single active gene. Other is inactive.

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9
Q

What is the genetic makeup of Enhanced metabolizers?

A

Two copies of the CYP gene

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10
Q

What enzyme metabolizes tamoxifen?

A

CYP2D6

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11
Q

What are the active metabolites of tamoxifen?

A

4OH Tamoxifen

Endoxifen

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12
Q

What is the effect of poor metabolizers of CYP2D6 with tamoxifen?

A

Cannot convert tamoxifen into active forms well.

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13
Q

What is the MOA of tamoxifen?

A

Binds to ER for breast CA

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14
Q

What is the clinical significance of poor CYP2D6 metabolizers on Tamoxifen?

A

if poor, then consider different drug

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15
Q

What is the relationship between CYP2D6 and codeine?

A

Codeine is a prodrug that needs to be activated by codeine.

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16
Q

What are the three possible metabolites of codeine? Which are active/inactive?

A

Norcodeine or codeine-6-glucuronide

Morphine

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17
Q

What is the clinical significance of CYP2D6 and codeine?

A

Poor metabolizers will not get effect/inadequate analgesia

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18
Q

What is the relationship of Paroxetine and CYP2D6?

A

Poor metabolizers will have increased plasma levels, and more side effects.

Ultra Metabolizers will have no effect

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19
Q

What are the two drugs that are metabolized by CYP2C19?

A

Clopidogrel

Omeprazole/Lansoprazole

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20
Q

What is the MOA of clopidogrel?

A

Inhibits ADP on platelets

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21
Q

What is the relationship between clopidogrel and CYP2C19?

A

poor metabolizers will need higher dose d/t lower generation of active metabolites

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22
Q

What is the enzyme that metabolizes Clopidogrel?

A

CYP2C19

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23
Q

What is the enzyme that metabolizes Omeprazole?

A

CYP2C19

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24
Q

What is the enzyme that metabolizes Lansoprazole?

A

CYP2C19

25
Q

What is the enzyme that metabolizes Codeine?

A

CYP2D6

26
Q

What is the relationship between CYP2C19 and omeprazole/lansoprazole?

A

Poor metabolizers have higher cure rates–do not clear drugs as fast

27
Q

What is the drug that CYP2C9 metabolizes?

A

Warfarin

28
Q

What enzyme clears warfarin? What does it turn it into?

A

CYP2C9

Hydroxywarfarin

29
Q

What is the MOA of warfarin?

A

inhibits Vitamin K epoxidase (VKORC1)

30
Q

What is the relationship between CYP2C9 and warfarin?

A

Slow metabolizers need a lower dose, o/w risk of bleeding

31
Q

What are the two enzymes that can change the efficacy of warfarin? How does each do this?

A

CYP2C9 = pharmacokinetics

VKORC1 = pharmacodynamics

32
Q

What is the least active polymorphisms of VKORC1?

A

VKOR1AA has the lowest activity

33
Q

What is the use of dasatinib? Target?

A

CML– phili chromosome

34
Q

What is the use or imatinib? Target?

A

CML – phili chromosome

35
Q

What is the use of erlotinib? Target?

A

Metastatic non-small cell lung CA– EGFR

36
Q

What is the use of Trastuzumab? Target?

A

HER2

Breast Ca

37
Q

What is the use of cetuxiamb? Target?

A

EGFR

Metastatic colorectal CA

38
Q

What are the enzymes that metabolize 5FU?

A

DPD (dihydropyrimidine dehydrogenase)

TYMS (thymidylate synthetase)

39
Q

What is the enzyme that metabolizes 6MP?

A

TPMT (thiopurine methyltransferase)

40
Q

What is the adverse effect of not screening for DPD or TYMS prior to giving 5FU? MOA?

A

Severe myelosuppression

Causes DNA damage by decreasing dTTP levels

41
Q

What is the use of 5FU?

A

Breast CA, neck CA

42
Q

What is capecitabine?

A

Prodrug of 5FU

43
Q

What is the function of DPD in 5-FU metabolism? How can polymorphisms affect this?

A

Inactivates it

Changes pharmacokinetics

44
Q

What is the relationship between 5-FU and TYMS? How can polymorphisms affect this?

A

TYMS is what 5FU inhibits

Changes pharmacodynamics of 5FU

45
Q

What is the relationship between 6-MP and TPMT? Changes in TMPT cause what?

A

TMPT inactivates 6-MP

Pharmacokinetics change

46
Q

What is 6MT used to treat?

A

Lymphoblastic leukemia

47
Q

What is the adverse effect of not screening TPMT with 6-MP use?

A

Severe myelosuppression and secondary CA

48
Q

What is the transporter of simvastatin? What is the effect of polymorphisms in this?

A

Solute carrier organic anion transporter 1B1 (SLCO1B1)

Changes pharmacokinetics

49
Q

What are the three different genotypes of SLCO1B1?

A 
T/T = normal
T/C = Decreased transport
C/C = low transport
50
Q

Polymorphisms in what part of the estrogen receptor leads to varying effects? What effects are seen?

A

Between the 1st and 2nd exons of the ER-alpha gene

This causes a greater increase in HDL level following HRT

51
Q

What is the gene that changes albuterol use? What does this change?

A

ADRB2

Will decrease response to albuterol due to changes in responsiveness of B2 receptor

52
Q

Passive smoking has what effect on ADRB2?

A

Appears to augment the down regulate the effect of metabolism in the weak metabolizers

53
Q

What are the two common genetic changes in the coagulation cascade that can increase thromboembolisms?

A

Factor V and prothrombin

54
Q

What allele causes a hypersensitivity reaction against abacavir? Does this affect the pharmacokinetics/dynamics?

A

HLA-B 57:01

No effect

55
Q

Pts with the HLA-B 57:01 polymorphism should not receive what drug? Why?

A

Abacavir

Hypersensitivity–steven johnson syndrome

56
Q

Absence of certain alleles in what gene correlate with better therapeutic success for alzheimer’s disease with tacrine?

A

APOE

57
Q

Absence of certain APOE alleles improves what part of Alzheimers treatment?

A

Better success with Tacrine

58
Q

What is the common treatment for HBC and HBV? What is the genome that has a highly predictive response to treatment?

A

IFN-alpha

IL-28

59
Q

What are the two genotypes of Il-28 that affect the response of IFN-alpha treatment?

A

CC = favorable

CT or TT = unfavorable

Pharm (73 decks)

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