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Pharmacology Test 4 > Pharmacogenomics 3 & 4 > Flashcards

Pharmacogenomics 3 & 4 Flashcards

1
Q

The patients with the greatest area under the plasma concentration-time curve are those with which CYP2C19 phenotype?
A. Poor Metabolizer
B. Intermediate metabolizer
C. Extensive metabolizer

A

A. Poor Metabolizer

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2
Q

The same cure rates would probably be obtained doing this same study in a Caucasian population. T/F

A

False

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3
Q

Adverse effects of amoxicillin are increased in the subjects with the low activity variants of CYP2C19. T/F

A

False

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4
Q

Which of the following statements are rationale(s) given by the author for why subjects with the double mutant CYP2C19 genotype were more successfully treated than subjects with the other genotypes?

A. Omeprazole decreases gastric acid pH, increasing the stability of amoxicillin the stomach.
B. Omeprazole raises gastric acid pH, increasing the stability of amoxicillin the stomach.
C. The competition for omeprazole and amoxicillin CYP2C19 metabolism is decreased in subjects that are poor metabolizers.
D. The systemic availability of omeprazole is increased in persons with the poor
E. Omeprazole increases amoxicillin concentrations in gastric juices.

A

B. Omeprazole raises gastric acid pH, increasing the stability of amoxicillin the stomach.
D. The systemic availability of omeprazole is increased in persons with the poor
E. Omeprazole increases amoxicillin concentrations in gastric juices.

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5
Q

These authors were looking for an association between:
A. CYP2C19 genotype and incidence of gastric ulcer disease
B. CYP2C19 genotype and omeprazole AUC
C. CYP2C19 genotype and cure rate of H. pylori infection
D. CYP2C19 genotype and amoxicillin dose

A

C. CYP2C19 genotype and cure rate of H. pylori infection

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6
Q 
What is S-mephenytoin 4’-hydroxylase?
A.  CYP2D6
B.  CYP1A1
C.  CYP2C19
D.  CYP3A5
A

C. CYP2C19

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7
Q

Trastuzumab

What gene is being evaluated?

A

HER2 receptor not a gene

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8
Q

Trastuzumab

For which variant of that gene?

A

HER2 Receptor (Protein)(Overexpression of subclass of receptor than seen in non-tumor tissues).

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9
Q

Trastuzumab

How does the variant affect patient response to the drug?

A

a. You have to have HER2 receptors being highly expressed in order for Herceptin therapy to work.
i. If the protein is there and the receptor is present, the drug should work.
ii. Not overexpressed or not expressed at all - do not use this drug.

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10
Q

Trastuzumab

Are we genotyping the tumor or the patient?

A

. We are genotyping the tumor to see if the tumor expresses the HER2

a. NOT genotyping the patient
b. We are trying to get this drug to interact with the TUMOR based on receptors present

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11
Q

Trastuzumab

Are we doing this genotyping to ensure efficacy or prevent toxicity?

A

to ensure efficacy of Herceptin therapy

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12
Q

Trastuzumab
Are we genotyping or doing cytology studies (looking at the presence of cell surface receptors using immunohistochemistry for example?

A

We are doing cytology studies (looking for the presence of cell receptors, specifically the HER2 receptors to see if there is overexpression.) Not looking at DNA sequence

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13
Q

Trastuzumab

Does the FDA say what genotyping test to use?

A

HER2 Testing, FDA approved. Use different tests depending on whether it is breast cancer or gastric cancer.
Not a specific company, just use a product that is FDA approved.

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14
Q

Trastuzumab

Is there a particular patient population or tumor type that should be genotyped?

A

breast or gastric/gastroesophageal adenocarcinoma

Nursing mothers.

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15
Q

Trastuzumab

How do genotyping results affect clinical use of the drug or clinical care of the patient?

A

If there is an overexpression of the HER2 receptor, then use the drug.
Not overexpressed or not expressed at all - do not use this drug.

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16
Q

Abacavir

What gene is being evaluated?

A

HLA-B

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17
Q

Abacavir

For which variant of that gene?

A

HLA-B*5701

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18
Q

Abacavir

How does the variant affect patient response to the drug?

A

Potential hypersensitivity reaction- fatal

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19
Q

Abacavir

Are we genotyping the tumor or the patient?

A

Patient

20
Q

Abacavir

Are we doing this genotyping to ensure efficacy or prevent toxicity?

A

Prevent toxicity - more specifically hypersensitivity adverse reaction

21
Q

Abacavir
Are we genotyping or doing cytology studies (looking at the presence of cell surface receptors using immunohistochemistry for example?

A

Genotyping (genetic sequencing)

22
Q

Abacavir

Does the FDA say what genotyping test to use?

A

PCR sequencing is ideal

23
Q

Abacavir

How do genotyping results affect clinical use of the drug or clinical care of the patient?

A

Variant present – DO NOT GIVE THIS DRUG. If they have a hypersensitivity reaction but previously tested negative for variant, the hypersensitivity reaction is NOT due to that variant (it is due to another variant or other factor).

24
Q

Abacavir

Is there a particular patient population or tumor type that should be genotyped?

A

Caucasians mostly (5-8%), Asians (less frequent) African American (less)

25
Q

Carbamazepine

What gene is being evaluated?

A

HLA-B

26
Q

Carbamazepine

For which variant of that gene?

A

HLA-B1502 allele carriers
There is a strong association between the risk of developing SJS/TEN with carbamazepine treatment and the presence of an inherited variant of the HLA-B gene, HLA-B1502 (Dermal Response)

27
Q

Carbamazepine

Are we genotyping the tumor or the patient?

A

patient

28
Q

Carbamazepine

Are we doing this genotyping to ensure efficacy or prevent toxicity?

A

preventing toxicity SJS/TEN or other hypersensitivity reactions

29
Q

Carbamazepine
Are we genotyping or doing cytology studies (looking at the presence of cell surface receptors using immunohistochemistry for example?

A

Genotyping

30
Q

Carbamazepine

Does the FDA say what genotyping test to use?

A

high-resolution ‘HLA-B1502 typing’ is recommended. The test is positive if either one or two HLA-B1502 alleles are detected and negative if no HLA-B*1502 alleles are detected.

31
Q

Carbamazepine

How do genotyping results affect clinical use of the drug or clinical care of the patient?

A

Tegretol should not be used in patients positive for HLA-B*1502 unless the benefits clearly outweigh the risks. Tested patients who are found to be negative for the allele are thought to have a low risk of SJS/TEN.

32
Q

Carbamazepine

Is there a particular patient population or tumor type that should be genotyped?

A

Prior to initiating Tegretol therapy, testing for HLA-B1502 should be performed in patients with ancestry in populations in which HLA-B1502 may be present. Across Asian populations, notable variation exists in the prevalence of HLA-B1502. (Not limited to HAN (sp?) descent anymore) HLA-B1502 is largely absent in individuals not of Asian origin (e.g., Caucasians, African-Americans, Hispanics, and Native Americans).

33
Q

Where can you find information about pharmacogenomic testing?

A

Table of Pharmacogenomic Biomarkers in Drug Labels on the FDA science research website

34
Q

What is pharmGkb?

A

pharmacogenetics knowledge base

Wrote this because people have data about pharmacogenomics but don’t know how to use it.

35
Q

What gene are we worried about with warfarin?

A

CYP2C9 and VKORC1

36
Q

What dose does a homozygous CYP2C93 and VKORC1 AA for warfarin vs. a homozygous CYP2C91 and VKORC1 wildtype?

A

CYP2C9*3 and VKORC1 AA dose should be 0.5-2

CYP2C9*1 and VKORC1 wildtype dose should be 5-7

37
Q

Or how much do you need to knock down a dose of a thiopurine medication if a person has a TPMT variant homozygote?

A

Reduce by 10 fold and three times weekly instead of daily. Allow 4-6 weeks to reach steady state and then adjust dose accordingly. Ex: 10 mg/m2/d three times a week.

38
Q

What is the risk of overdosing a patient on warfarin?

A

bleeding

39
Q

What is the risk of overdosing a patient on thiopurine?

A

potentially lethal bone marrow suppression

40
Q

What does the EGAPP guidelines do?

A

evaluation of genomic application in practice and prevention. Provides people with information about genetics related to disease states.

41
Q

What are the questions that should be asked when trying to understand polymorphisms?

A

Is there relevant polymorphism and what are its affects?
Who is likely to be impacted?
Relevant to a drug? (affects PK or PD, may have no affect on drug)
Relevant to a disease (not really our focus)

42
Q

What is the primary enzyme responsible for omeprazole metabolism?

A

CYP2C19

variants might increase efficacy of omeprazole

43
Q

Does a polymorphism exist for the CYP2C19?

A

Yes
CYP2C192
CYP2C193

44
Q

What variant could cause a hypersensitivity rash when abacavir is given?

A

HLA-B*5701

45
Q

What studies were done on abacavir hypersensitivity in the HLA-B*5701 gene?

A

PREDICT-1 showed that screeing can accurately predict patients who might be hypersensitive. 2.7% vs 0%.
SHAPE showed similar trend in whites and blacks.
ARIES investigated negative patients and less than 1% had clinically suspected HSR

Pharmacology Test 4 (5 decks)

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