Question 1

A combination of alleles that are located closely together on the same chromosome and are inherited together is the definition of:&#10;A) haplotype.&#10;B) pseudogene.&#10;C) allelic diversity.&#10;D) genotype.

Accepted Answer

A haplotype refers to a group of alleles that are inherited together because they are located closely together on the same chromosome. The term is often used in the context of discussing genetic variation and disease susceptibility.

Question 2

Regarding pharmacogenetics,a phase 1 enzyme metabolizes drugs by:&#10;A) conjugating an acetyl group to a drug compound.&#10;B) transferring a methyl group to a drug substrate.&#10;C) conjugating an amine group to a drug substrate.&#10;D) oxidizing a drug substrate.

Accepted Answer

Phase 1 enzymes, also known as oxidizing enzymes, metabolize drugs by adding or exposing functional groups such as –OH, –NH2, or –SH. These functional groups then promote the conjugation of phase 2 enzymes to further modify the drug molecule to make it more polar, water-soluble, and easily eliminated from the body. Oxidation is one of the most common reactions catalyzed by phase 1 enzymes. Thus, choice D, oxidizing a drug substrate, is the best answer for this question.

Question 3

A drug substrate for the metabolizing enzyme UGT1A1 is:&#10;A) tamoxifen.&#10;B) codeine.&#10;C) diazepam&#10;D) irinotecan.

Accepted Answer

Irinotecan is a drug substrate for the metabolizing enzyme UGT1A1. UGT1A1 converts irinotecan to its active metabolite, SN-38. The activity of UGT1A1 is highly variable among individuals, which can lead to differences in the response and toxicity of irinotecan treatment. The other choices are not drug substrates for UGT1A1. Tamoxifen is metabolized by CYP2D6 and 3A4, codeine is primarily metabolized by CYP2D6, and diazepam is metabolized by CYP2C19 and 3A4.

Question 4

The metabolizing enzyme that catalyzes the transfer of an acetyl moiety from acetyl-CoA to homocyclic and heterocyclic arylamines and hydrazines in,for example,substrates related to cigarette smoke is:

A) CYP2C6.
B) CYP2D9.
C) NAT1.
D) UGT1A1.

Accepted Answer

NAT1 (N-acetyltransferase 1) is the metabolizing enzyme that catalyzes the transfer of an acetyl moiety from acetyl-CoA to homocyclic and heterocyclic arylamines and hydrazines in substrates related to cigarette smoke. It is primarily expressed in the liver and has implications in drug metabolism and carcinogenesis. CYP2C6, CYP2D9, and UGT1A1 are not known to play a significant role in the metabolism of these substrates.

Question 5

You are appointed director of the county hospital cardiac laboratory and have been asked to identify individuals that might not respond well to platelet-inhibiting,clot-destroying drugs.Which of the following polymorphic genes would you be most interested in having genotyped to discover these individuals?

A) TPMT
B) UGT1A1
C) CYP2C19
D) CYP2D6

Accepted Answer

CYP2C19 is the gene responsible for encoding an enzyme that metabolizes many drugs, including clopidogrel, a platelet-inhibiting, clot-destroying drug. Variants in this gene can lead to reduced function of the enzyme, resulting in decreased drug efficacy and increased risk of adverse cardiovascular events in patients treated with clopidogrel.

Question 6

The HLA gene and its variants that have been associated most closely with drug hypersensitivity and that can be assessed in a laboratory is HLA-:&#10;A) A.&#10;B) B.&#10;C) C.&#10;D) D.

Accepted Answer

The HLA-B gene and its variants are most closely associated with drug hypersensitivity reactions and can be assessed in a laboratory through genetic testing. HLA-A and HLA-C genes are also involved in immune responses to drugs, but their association with hypersensitivity reactions is not as strong as that of HLA-B. HLA-D is related to antigen presentation and is not directly involved in drug hypersensitivity reactions.

Question 7

Which two of the following metabolizing enzymes are involved in metabolism of warfarin?&#10;A) TPMT and CYP2D9&#10;B) CYP2D9 and CYP2D19&#10;C) VKORC1 and CYP2C9&#10;D) NAT1 and VKORC1

Accepted Answer

The metabolizing enzymes involved in the metabolism of warfarin are VKORC1 and CYP2C9. These enzymes play a role in the metabolism of vitamin K and synthesis of clotting factors in the liver, which is inhibited by warfarin. Other options such as A, B, and D are not involved in the metabolism of warfarin.

Question 8

A drug substrate for the metabolizing enzyme CYP2D6 is:&#10;A) tamoxifen.&#10;B) codeine.&#10;C) diazepam.&#10;D) irinotecan.

Accepted Answer

The answer of A drug substrate for the metabolizing enzyme...

Question 9

Which one of the following metabolizing enzymes is considered a phase 1 enzyme?&#10;A) CYP2C6&#10;B) VKORC1&#10;C) NAT1&#10;D) UGT1A1

Accepted Answer

Phase 1 enzymes are responsible for biotransformation reactions such as oxidation, reduction, and hydrolysis. CYP2C6 is a member of the cytochrome P450 family, which is involved in oxidation reactions, making it a phase 1 enzyme. VKORC1, NAT1, and UGT1A1 are all phase 2 enzymes involved in conjugation reactions.

Question 10

The enzyme that metabolizes 5-fluorouracil is:&#10;A) DPD.&#10;B) TMPT.&#10;C) CYP2D6.&#10;D) NAT1.

Accepted Answer

The enzyme that metabolizes 5-fluorouracil is DPD (dihydropyrimidine dehydrogenase). This enzyme plays a crucial role in the breakdown of 5-fluorouracil, converting it to the inactive metabolite dihydrofluorouracil. Deficiency or reduced activity of DPD can cause toxicities associated with 5-fluorouracil treatment, such as severe and potentially fatal diarrhea, mucositis, and myelosuppression. TMPT (thiopurine methyltransferase) is an enzyme that metabolizes thiopurine drugs, CYP2D6 (cytochrome P450 2D6) is involved in the metabolism of many drugs, and NAT1 (N-acetyltransferase 1) is involved in the metabolism of certain drugs, but none of these enzymes are directly involved in the metabolism of 5-fluorouracil.

Question 11

Tamoxifen is a drug that is used to prevent or treat some forms of breast cancer.Before it can have a physiological effect,tamoxifen must be metabolized to an active metabolite called endoxifen.Tamoxifen is therefore considered to be a:

A) metabolizer.
B) prodrug.
C) transferase.
D) cytochrome.

Accepted Answer

The answer of Tamoxifen is a drug that is used...

Question 12

You have been asked to direct a pharmacogenetics testing laboratory in a hospital with many transplant patients who receive mercaptopurine derivatives to control transplant rejection.Which of the following enzyme phenotyping or genotyping services would be the highest priority to establish initially?

A) N-acetyltransferase genotyping
B) Thiopurine methyltransferase (TPMT)genotyping
C) CYP1A1 genotyping
D) CYP2D6 phenotyping

Accepted Answer

The answer of You have been asked to direct a...

Question 13

A pharmacogenetic drug-gene target would be most successful when clinically implemented when it:&#10;A) is associated with a clinically significant effect on the relationship between drug dose and plasma concentration.&#10;B) does not involve a major metabolic pathway but instead is involved in alternate pathways.&#10;C) indicates alternative drugs that are much more efficient than conventional drugs in producing a dose-response.&#10;D) allows for an extended period of time for changes to be made in drug dosing.

Accepted Answer

The answer of A pharmacogenetic drug-gene target would be most...

Question 14

Bilirubin is an important endogenous substrate of which one of the following enzymes?&#10;A) N-acetyltransferase&#10;B) Thiopurine methyltransferase&#10;C) UGT1A1&#10;D) CYP3A4

Accepted Answer

The answer of Bilirubin is an important endogenous substrate of...

Question 15

A limitation of using genotyping in pharmacogenetic testing would be:&#10;A) the lack of gene variants to actually test for.&#10;B) interindividual variation in gene expression.&#10;C) a strong genotype-phenotype correlation.&#10;D) the lack of good positive controls.

Accepted Answer

The answer of A limitation of using genotyping in pharmacogenetic...

Deck 46: Pharmacogenetics