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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?

25
What is the enzyme that metabolizes Codeine?
CYP2D6
26
What is the relationship between CYP2C19 and omeprazole/lansoprazole?
Poor metabolizers have higher cure rates--do not clear drugs as fast
27
What is the drug that CYP2C9 metabolizes?
Warfarin
28
What enzyme clears warfarin? What does it turn it into?
CYP2C9 Hydroxywarfarin
29
What is the MOA of warfarin?
inhibits Vitamin K epoxidase (VKORC1)
30
What is the relationship between CYP2C9 and warfarin?
Slow metabolizers need a lower dose, o/w risk of bleeding
31
What are the two enzymes that can change the efficacy of warfarin? How does each do this?
CYP2C9 = pharmacokinetics VKORC1 = pharmacodynamics
32
What is the least active polymorphisms of VKORC1?
VKOR1AA has the lowest activity
33
What is the use of dasatinib? Target?
CML-- phili chromosome
34
What is the use or imatinib? Target?
CML -- phili chromosome
35
What is the use of erlotinib? Target?
Metastatic non-small cell lung CA-- EGFR
36
What is the use of Trastuzumab? Target?
HER2 | Breast Ca
37
What is the use of cetuxiamb? Target?
EGFR | Metastatic colorectal CA
38
What are the enzymes that metabolize 5FU?
DPD (dihydropyrimidine dehydrogenase) TYMS (thymidylate synthetase)
39
What is the enzyme that metabolizes 6MP?
TPMT (thiopurine methyltransferase)
40
What is the adverse effect of not screening for DPD or TYMS prior to giving 5FU? MOA?
Severe myelosuppression Causes DNA damage by decreasing dTTP levels
41
What is the use of 5FU?
Breast CA, neck CA
42
What is capecitabine?
Prodrug of 5FU
43
What is the function of DPD in 5-FU metabolism? How can polymorphisms affect this?
Inactivates it *Changes pharmacokinetics*
44
What is the relationship between 5-FU and TYMS? How can polymorphisms affect this?
TYMS is what 5FU inhibits Changes *pharmacodynamics* of 5FU
45
What is the relationship between 6-MP and TPMT? Changes in TMPT cause what?
TMPT inactivates 6-MP Pharmacokinetics change
46
What is 6MT used to treat?
Lymphoblastic leukemia
47
What is the adverse effect of not screening TPMT with 6-MP use?
Severe myelosuppression and secondary CA
48
What is the transporter of simvastatin? What is the effect of polymorphisms in this?
Solute carrier organic anion transporter 1B1 (SLCO1B1) Changes pharmacokinetics
49
What are the three different genotypes of SLCO1B1?
``` T/T = normal T/C = Decreased transport C/C = low transport ```
50
Polymorphisms in what part of the estrogen receptor leads to varying effects? What effects are seen?
Between the 1st and 2nd exons of the ER-alpha gene This causes a greater increase in HDL level following HRT
51
What is the gene that changes albuterol use? What does this change?
ADRB2 Will decrease response to albuterol due to changes in responsiveness of B2 receptor
52
Passive smoking has what effect on ADRB2?
Appears to augment the down regulate the effect of metabolism in the weak metabolizers
53
What are the two common genetic changes in the coagulation cascade that can increase thromboembolisms?
Factor V and prothrombin
54
What allele causes a hypersensitivity reaction against abacavir? Does this affect the pharmacokinetics/dynamics?
HLA-B 57:01 No effect
55
Pts with the HLA-B 57:01 polymorphism should not receive what drug? Why?
Abacavir | Hypersensitivity--steven johnson syndrome
56
Absence of certain alleles in what gene correlate with better therapeutic success for alzheimer's disease with tacrine?
APOE
57
Absence of certain APOE alleles improves what part of Alzheimers treatment?
Better success with Tacrine
58
What is the common treatment for HBC and HBV? What is the genome that has a highly predictive response to treatment?
IFN-alpha IL-28
59
What are the two genotypes of Il-28 that affect the response of IFN-alpha treatment?
CC = favorable CT or TT = unfavorable

Pharm (73 decks)

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