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Spring 2024 (All Classes Except Therapeutics+ Lab) > Pharmacogenomics Final > Flashcards

Pharmacogenomics Final Flashcards

1
Q

What are the indications for clopidogrel?

A

STEMI
Unstable Angina
PCI

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2
Q

What is the MOA of Clopidogrel?

A

Prodrug

-Active metabolite: R-130964

-Irreversible binds to the P2Y12 receptor on platelets

-Inhibits ADP-mediated platelet aggregation

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3
Q

After giving clopidogrel, what % is hydrolyzed to inactive metabolites?

A

85%

(only 15% is active)

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4
Q

Which enzyme is important in clopidogrel metabolism?

A

CYP2C19

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5
Q

What are the barriers to implementing CYP2C19 genetic testing prior to a PCI?

A

Turn-around-time of test
Strength of association has been questioned

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6
Q

What is warfarin used for?

A

Afib
Prevention and treatment of thromboembolic disease (DVT), (PE)

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7
Q

What is the MOA of warfarin?

A

Inhibits vitamin K epoxide reductase 1 (VKORC1)

-decreases formation of vitamin K dependent clotting factors

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8
Q

CYP2C9 eliminates which enantiomer of warfarin?

A

S-enantiomer

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9
Q

What is the surrogate marker used in clinical practice to decide if warfarin treatment is working?

A

INR

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10
Q

What are the 2 most studied alleles of CYP2C9?

A

*2 and *3

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11
Q

By how much does the loss of function CYP2C9*2 reduce warfarin clearance?

A

30-40%

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12
Q

What dose reduction is needed with CYP2C9*2 and warfarin?

A

19% dose reduction per allele

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13
Q

The loss of function CYP2C983 reduces warfarin clearance by what?

A

75-90%

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14
Q

What dose reduction is needed with CYP2C9*3?

A

33% dose reduction per allele

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15
Q

What are the two SNP locations in VKORC1 with warfarin?

A

1639G>A

1173C>T

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16
Q

Which VKORC1 SNP has the greatest sensitivity?

A

AA/TT

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17
Q

Which VKORC1 SNP has the greatest tolerance?

A

GG/CC

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18
Q

What is the function of CYP4F2?

A

Metabolizes vitamin K to hydroxyl metabolite

-results in less vitamin K for clotting factors

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19
Q

What is the CYP4F2 SNP?

A

rs2108622

1297G>A
*reduced function allele
*greater vitamin K availability

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20
Q

How much variability is contributed to warfarin dosing by CYP4F2?

A

1-3%

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21
Q

What is the MOA of statins?

A

Inhibit rate-limiting step in cholesterol biosynthesis

-Up-regulate LDL receptors
-Decrease serum LDL concentrations

HMG Co-A Reductase Inhibitors

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22
Q

Which statin is not affected by the SLCO1B1 genotype?

A

Fluvastatin

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23
Q

What drugs are affected by the Human Leukocyte Antigen Complex (HLA)?

A

Carbamazepine
Abacavir
Allopurinol

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24
Q

What role does HLA play?

A

Critical in the immune system

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25
Q

Carbamazepine HLA-B*1502 and SJS-TEN is associated with what adverse reaction?

A

Steven’s Johnson Syndrome

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26
Q

Why is the association between HLA-B*1502 and Steven’s Johnson Syndrome weaker in other Asian populations and not established in Caucasians?

A

These populations have less of the variant present

27
Q

Who has the highest risk of Steven’s Johnson Syndrome as a result of having HLA-B*1502 and taking carbamazepine?

A

Chinese

28
Q

Which drug has a non-linear pharmacokinetic disposition?

A

Phenytoin

(when you double the drug, the exposure will more than double)

29
Q

For which group of drugs does hereditary involvement suggest a role in pharmacogenomics?

A

Psychosis and Depression

30
Q

what are the goals of pharmacogenomics in psychiatry?

A

Focus on drug-metabolizing enzymes
Minimize side effects
Identify patients unlikely to respond

31
Q

What are the future goals of pharmacogenomics in psychiatry?

A

Predict positive drug response

32
Q

Which enzyme is upregulated by smoking?

A

CYP1A2

33
Q

Which enzyme may be active in the brain and metabolize serotonin?

A

CYP2D6

34
Q

What is personalized medicine?

A

*Does not just apply to genetics

-It is how every pharmacist and clinician practices: right dose, right drug, to right patient

Revisited definition: A form of medicine that uses information about a person’s genes, lifestyle, and environment to prevent, diagnose, and treat disease

35
Q

How many drugs have pharmacogenomic information in their labeling?

A

> 300

36
Q

When is pharmacogenomics most informative?

A

When we are considering drug and event characteristics

Event characteristics:
Serious (fatal, irreversible)
Difficult to predict
Alternative therapy available

37
Q

What is the goal for pharmacogenomics in the future?

A

Take a patient’s full genetic profile and apply the best therapy to that patient

(overall goal is to know more than just SNPs)

38
Q

Where are we currently in clinical pharmacogenomic practice?

A

Identify a known SNP with a large clinical effect and adjust drug therapy or dosage accordingly

(Identify SNPs that change clinical outcome)

39
Q

Where are we going in clinical pharmacogenomics practice?

A

Genome wide screening (including variants of unknown significance) with bioinformatic prediction to adjust drug therapy or dosage

(sequencing the entire human genome and using it to adjust drug therapy or dosage)

40
Q

What is the difference between pharmacogenetics and pharmacogenomics?

A

NONE

-used synonymously

Pharmacogenetics=Pharmacogenomics=PGx

41
Q

What type of drug is voriconazole?

A

Triazole antifungal

-used for invasive fungal infections including aspergillosis and candidiasis

42
Q

What is the greatest risk with voriconazole dosing?

A

Therapeutic failure

43
Q

What are 2 important things to remember about Voriconazole’s pharmacokinetics?

A

Narrow therapeutic index
Nonlinear pharmacokinetics

44
Q

Management of cancer genetics has shifted from what to what?

A

From cytotoxic agents (chemotherapy, kills all quick growing cells)
**typical gold standard

To chemical and biological agents (target critical genes or pathways, not as narrow of a therapeutic index, gene expression determines proper agent)
**less adverse effects, where treatment is heading

45
Q

What are somatic mutations in the context of oncology?

A

Variations found within the tumor
(non-inheritable)

-Include oncogenes that drive the cancer and can be targeted

46
Q

What are germline mutations?

A

Heritable variations found within the individual

47
Q

What are predictive markers in oncology used for?

A

Used to identify subpopulations of patients most likely to respond to a therapy

48
Q

What is Acute Lymphoblastic Leukemia (ALL)?

A

-Cancer of the blood and bone marrow
*Most common childhood malignancy
-90% survival rate

49
Q

What is the treatment for Acute Lymphoblastic Leukemia (ALL)?

A

Maintenance chemotherapy (up to 2y)

Oral 6-mercaptopurine 50mg***

50
Q

When there is a mutation in a cancer-associated gene what normally happens to its function?

A

Typically leads to overactivity of the receptor
-bad, enhances cancer’s survival ability
-can increase angiogenesis (increased blood vessels help the tumor grow)

51
Q

What are the 2 types of lung cancer?

A

Non-Small Cell Lung Cancer (NSCLC)

Small Cell Lung Cancer (SCLC)

52
Q

What is the most common type of lung cancer?

A

Non-Small Cell Lung Cancer (NSCLC)

53
Q

What is the first-line drug treatment for lung cancer (NSCLC)?

A

Chemotherapy

*targeted therapy linked to biomarkers may help overcome drug resistance

54
Q

Which receptor do Tyrosine Kinase Inhibitors target (TKIs)?

A

EGFR

-because it has a tyrosine kinase domain in it

55
Q

How does the EGFR protein tyrosine kinase family contribute to cancer formation?

A

-Overexpression implicated in numerous cancers
-Dysregulated and active

56
Q

What drug might we use to treat Non-small cell lung cancer (NSCLC) instead of chemotherapy?

A

TKI inhibitors

57
Q

When would we choose to use TKI inhibitors to treat NSCLC rather than chemotherapy?

A

If mutations in EGFR (HER1/ErbB1) are present: Use TKI inhibitors

If mutations are not present: Chemotherapy may be more effective

58
Q

When would we use erlotinib and afatinib?

A

In treatment of patients with NSCLC who have:

Exon 19 deletions

Exon 21 (L858R) substitution mutations

-in EGFR

59
Q

What is a clinical barrier to genotype guided dosing with the use of such drugs as erlotinib and afatinib?

A

In many cases, it is desired to begin therapy before the genotype results are available

60
Q

What is the function of Cetuximab/Panitumumab?

A

MABs that inhibit the growth and survival of tumor ells with overexpressed EGFR

61
Q

What cancer types are Cetuximab/Panitumumab indicated in?

A

Colon
Head and Neck
NSCLC

62
Q

Resistance to cetuximab and panitumumab has an association with mutations in what?

A

KRAS

63
Q

What kind of receptor is ALK?

A

Tyrosine Kinase receptor

64
Q

Phase II reactions are primarily what?

A

Conjugation Reactions

-add a conjugate to deactivate drug/metabolite

Spring 2024 (All Classes Except Therapeutics+ Lab) (9 decks)

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