Pharmacogenomics: exam 1

Question 1

What type of patient responders should you remove during a patient diagnosis?

Answer 1

remove non-responders and toxic responders

Question 2

What type of patient responders should you treat during a patient diagnosis?

Answer 2

treat responders and patients not predisposed to toxicity

Question 3

different version of the same gene

Answer 3

alleles

Question 4

gene spellings found on both copies of your gene

Answer 4

genotype

Question 5

a set of DNA variants along a single chromosome that tend to be inherited together

Answer 5

haplotype

Question 6

the specific combination of two haplotypes, or sets of genes, inherited from both parents for a particular gene or region of DNA

Answer 6

diplotype

Question 7

biologic or measurable expression of the genetic trait that is dependent upon the level of penetrance of the gene, the accuracy and selectivity of the method used to measure it, and the influence of environmental factors in the expression of the trait.

Answer 7

phenotype

Question 8

testing ____ is as easy as performing a cheek swab

Answer 8

genotype

Question 9

what methods do genotypes rely on?

Answer 9

Many methods to determine the genotype rely on DNA amplification techniques based on the polymerase chain reaction that yields millions of copies of the specific target gene

Question 10

The ____ has a comprehensive list of approved drugs with their pharmocogenomic information

Answer 10

FDA

Question 11

-receptors and drug targets
- usually substitute the drug

Answer 11

pharmacodynamics

Question 12

• enzymes and transporters
• adjust dose/drug

Answer 12

pharmacokinetic

Question 13

Genetic polymorphisms of drug exposure has graphs for ____

Answer 13

metabolism genotypes

Question 14

catalyzes the N-acetylation of numerous aromatic amine and hydrazine drugs

Answer 14

N-acetyltransferase 2

Question 15

isoniazid, sulfonamides, procainamide, hydralazine, amifampridine are examples of what?

Answer 15

N-acetyltransferase 2

Question 16

Describe how SNPS are related to acetylation:

Answer 16

-SNPs in coding region cause unstable N-acetyltransferase proteins with increased degradation resulting in slow acetylator phenotype.
-The frequency of these SNPs and slow acetylator phenotype varies with ethnicity

Question 17

Describe slow acetylators and what they are predisposed to:

Answer 17

Peripheral neuropathy from isoniazid
-Drug induced SLE from procainamide and hydralazine
-Urinary bladder cancer from tobacco use

Question 18

Describe rapid acetylators and what they are predisposed to

Answer 18

-Myelosuppression from amonafide
-Colorectal cancer from dietary carcinogens

Question 19

Mary is a 50 year old female who experiences peripheral neuropathy following isoniazid therapy for tuberculosis. This is most likely due to a genetic polymorphism in:

Answer 19

N-acetyltransferase 2

Question 20

catalyzes the deactivation of anticancer and anti-inflammatory drugs

Answer 20

TPMT

Question 21

mercaptopurine, 6-thioguanine and azathioprine are examples of what?

Answer 21

TPMT

Question 22

A defect in TPMT causes severe ____ _____ following standard doses of these drugs

Answer 22

hematapoietic toxicity

Question 23

_____ TPMT enzymes with reduced stability and or catalytic activity

Answer 23

variant

Question 24

Brett is a five year old male who experiences severe hematopoietic toxicity from mercaptopurine as part of multiagent chemotherapy for treatment of acute lymphoblastic leukemia. This is most likely due to a genetic polymorphism in:

Answer 24

Thiopurine-S-methyltransferase

Question 25

catalyzes the glucuronidation of bilirubin

Answer 25

UGT

Question 26

xenobiotics is an example of what?

Answer 26

UGT

Question 27

Transcriptional regulation of UGT is mediated by series of ____ ____ in the proximal promoter.

Answer 27

TA repeats

Question 28

Deficiency in UGT1A1-catalyzed bilirubin glucuronidation is associated with 7 TA repeats in the promoter (UGT1A1*28) resulting in _____ _____

Answer 28

Gilbert's syndrome

Question 29

what is UGT polymorphism associated with?

Answer 29

increased toxicity (myelosuppression and diarrhea) following use of irinotecan, a topoisomerase I inhibitor used in the treatment of several cancers.

Question 30

what is irinotecan?

Answer 30

a topoisomerase I inhibitor

Question 31

_____is important in the oxidation of a wide diversity of drugs.

Answer 31

CYP2D6

Question 32

the poor metabolizer phenotype for CYP2D6 yields accumulation of parent drugs for a variety of drugs such as:

Answer 32

beta blockers, anti-arrhthmics, antidepressants, and neuroleptics

Question 33

what transforms codeine into morphine?

Answer 33

CYP2D6

Question 34

what transforms tamoxifen into endoxifen?

Answer 34

CYP2D6

Question 35

the ultra-rapid metabolizer phenotype results from CYP2D6 duplication and may be more sensitive to what?

Answer 35

the toxic effects of metabolites ex: codeine ---> morphine

Question 36

what catalyzes the oxidation of the anticoagulant warfarin, as well as other drugs including phenytoin, tolbutamide, and losartan?

Answer 36

CYP2C9

Question 37

what is prescribed to prevent blood clots?

Answer 37

warfarin

Question 38

why is warafin a difficult drug to use?

Answer 38

the optimal dose varies widely and depends on many factors such as polymorphisms in CYP2C9 and VKORC1

Question 39

CYP2C9 alleles may exhibit up to a ____ reduction in warfarin clearance, resulting in _____ _____ during warfarin therapy.

Answer 39

90%, bleeding complications

Question 40

what is used to catalyzes the oxidation of many clinically useful drugs including clopidogrel, proton pump inhibitors, and selective serotonin reuptake inhibitors?

Answer 40

CYP2C19

Question 41

Poor CYP2C19 metabolizers are at high risk of treatment failure due to insufficient levels of active metabolite. These patients are at increased risk for :

Answer 41

heart attack, stroke, stent thrombosis and death due to inadequate therapeutic effects from clopidogrel treatment.

Question 42

Patients that are CYP2C19 poor metabolizers may have sub-therapeutic levels of active metabolite following standard dosing of:

Answer 42

Clopidogrel

Question 43

A common name for clopidogrel is?

Answer 43

Plavix

Question 44

__ - _____ ____ mediate critical sympathetic responses in the cardiovascular, pulmonary, metabolic, and central nervous systems.

Answer 44

β-adrenergic receptors

Question 45

example of β-adrenergic receptor

Answer 45

albuterol

Question 46

Polymorphisms in ___ ____ may alter agonist or antagonist efficacy because of a variant β1 or β2 receptor and provide a basis for failure of β2 receptor antagonist therapy in numerous patients with heart failure.

Answer 46

β receptors

Question 47

drug transporter polymorphisms do what?

Answer 47

Transport proteins influence drug absorption, distribution, and excretion across cellular membranes

Question 48

Hepatic uptake and elimination of statin drugs are facilitated by the solute carrier transporter family 1B1 is an example of what?

Answer 48

drug transporter polymorphism

Question 49

a single coding nucleotide polymorphisms increases system exposure to simvastatin and risks _____?

Answer 49

muscle toxicity

Question 50

Effective drugs previously discarded because of toxicity in some patients will be useful when targeted to patients of appropriate genetic profile will ultimately do what?

Answer 50

lower cost of drugs

Question 51

The "idiosyncratic" drug response will increasingly be ____, _____, and _____

Answer 51

predictable, preventable, and unacceptable (i.e., considered malpractice).

Question 52

what is the purpose of pharmcogenomics?

Answer 52

the branch of precision medicine that predicts the therapeutic and toxic effects of drug therapy based on genetic variation in drug concentration (pharmacokinetics) or response (pharmacodynamics).

Question 53

_____ enables prescription of the optimal drug at the optimal dosing regimen to each individual patient, as opposed to the one size fits all approach to drug treatment.

Answer 53

pharmcogenomics

Question 54

The Clinical Pharmacogenetics Implementation Consortium (CPIC) formulates and distributes practice guidelines to enable translation of pharmacogenetic information into:

Answer 54

actionable prescribing decisions

Question 55

genetic polymorphism of drug sensitivity measures

Answer 55

drug receptor genotypes