Question 1

Carbamazepine has a Black Box Warning recommending testing for the HLA-B*1502 allele in patients with Asian ancestry prior to starting therapy due to:&#10;A) Decreased effectiveness of carbamazepine in treating seizures in Asian patients with the HLA-B*1502 allele&#10;B) Increased risk for drug interactions in Asian patients with the HLA-B*1502 allele&#10;C) Increased risk for Stevens-Johnson syndrome in Asian patients with HLA-B*1502 allele&#10;D) Patients who have the HLA-B*1502 allele being more likely to have a resistance to carbamazepine&#10;

Accepted Answer

The Black Box Warning for carbamazepine recommends testing for the HLA-B*1502 allele in patients with Asian ancestry prior to starting therapy due to an increased risk for Stevens-Johnson syndrome in these patients.

Question 2

Inhibition of P-glycoprotein by a drug such as quinidine may lead to:&#10;A) Decreased therapeutic levels of quinidine&#10;B) Increased therapeutic levels of quinidine&#10;C) Decreased levels of a coadministered drug, such as digoxin, that requires P-glycoprotein for absorption and elimination&#10;D) Increased levels of a coadministered drug, such as digoxin, that requires P-glycoprotein for absorption and elimination&#10;

Accepted Answer

Inhibition of P-glycoprotein by quinidine will prevent the elimination of coadministered drugs like digoxin that require P-glycoprotein for elimination, leading to increased levels of these drugs in the body. Therefore, D is the correct answer. A is incorrect because inhibition of P-glycoprotein by quinidine will lead to increased levels of quinidine. B is incorrect because the therapeutic levels of quinidine will not be affected by its own inhibition of P-glycoprotein. C is incorrect because inhibition of P-glycoprotein by quinidine will lead to increased, not decreased, levels of coadministered drugs like digoxin that require P-glycoprotein for absorption and elimination.

Question 3

Patients who have a poor metabolism phenotype will have:&#10;A) Slowed metabolism of a prodrug into an active drug, leading to accumulation of prodrug&#10;B) Accumulation of inactive metabolites of drugs&#10;C) A need for increased dosages of medications&#10;D) Increased elimination of an active drug&#10;

Accepted Answer

Patients with a poor metabolism phenotype will have reduced activity of drug-metabolizing enzymes, especially in the liver. This will lead to slow metabolism of prodrugs into active drugs, resulting in accumulation of the prodrug in the body.

Question 4

Warfarin resistance may be seen in patients with VCORC1 mutation, leading to:&#10;A) Toxic levels of warfarin building up&#10;B) Decreased response to warfarin&#10;C) Increased risk for significant drug interactions with warfarin&#10;D) Less risk of drug interactions with warfarin&#10;

Accepted Answer

A mutation in VCORC1 can lead to a decreased response to warfarin, making it less effective in treating thrombosis. It does not necessarily lead to toxic levels of warfarin building up, and the risk for drug interactions is not affected by this mutation.

Question 5

Pharmacogenetic testing is required by the U.S. Food and Drug Administration prior to prescribing:&#10;A) Erythromycin&#10;B) Digoxin&#10;C) Cetuximab&#10;D) Rifampin&#10;

Accepted Answer

Pharmacogenetic testing is required by the FDA prior to prescribing Cetuximab due to its association with genetic variations that affect drug metabolism and efficacy. Testing can help identify which patients are likely to experience adverse reactions or benefit most from the drug. Testing is not required for the other options.

Question 6

A provider may consider testing for CYP2D6 variants prior to starting tamoxifen for breast cancer to:&#10;A) Ensure the patient will not have increased adverse drug reactions to the tamoxifen&#10;B) Identify potential drug-drug interactions that may occur with tamoxifen&#10;C) Reduce the likelihood of therapeutic failure with tamoxifen treatment&#10;D) Identify poor metabolizers of tamoxifen&#10;

Accepted Answer

CYP2D6 variants can affect the metabolism and efficacy of tamoxifen. Poor metabolizers may have reduced conversion of tamoxifen to its active form, reducing the drug's effectiveness. Testing for these variants prior to starting tamoxifen can help identify patients who may benefit from alternative therapies.

Question 7

Ultra-rapid metabolizers of drugs may have:&#10;A) To have dosages of drugs adjusted downward to prevent drug accumulation&#10;B) Active drug rapidly metabolized into inactive metabolites, leading to potential therapeutic failure&#10;C) Increased elimination of active, nonmetabolized drug&#10;D) Slowed metabolism of a prodrug into an active drug, leading to an accumulation of prodrug&#10;

Accepted Answer

Ultra-rapid metabolizers metabolize drugs so quickly that the active drug is rapidly metabolized into inactive metabolites. This can lead to potential therapeutic failure.

Question 8

Up to 21% of Asians are ultra-rapid 2D6 metabolizers, leading to:&#10;A) A need to monitor drugs metabolized by 2D6 for toxicity&#10;B) Increased dosages needed of drugs metabolized by 2D6, such as the selective serotonin reuptake inhibitors&#10;C) Decreased conversion of codeine to morphine by CYP 2D6&#10;D) The need for lowered dosages of drugs, such as beta blockers&#10;

Accepted Answer

The answer of Up to 21% of Asians are ultra-rapid...

Question 9

Genetic testing for VCORC1 mutation to assess potential warfarin resistance is required prior to prescribing warfarin.

Accepted Answer

Genetic testing for VKORC1 (not VCORC1) mutation is not universally required before prescribing warfarin, but it can help tailor the dose for individual patients. The decision to perform genetic testing is based on clinical judgment and patient-specific factors.

Question 10

Genetic polymorphisms account for differences in metabolism, including:&#10;A) Poor metabolizers, who lack a working enzyme&#10;B) Intermediate metabolizers, who have one working, wild-type allele and one mutant allele&#10;C) Extensive metabolizers, with two normally functioning alleles&#10;D) All of the above&#10;

Accepted Answer

Genetic polymorphisms account for all three types of metabolizers: poor metabolizers (lack of working enzyme), intermediate metabolizers (one working and one mutant allele), and extensive metabolizers (two normally functioning alleles).

Question 11

A genetic variation in how the metabolite of the cancer drug irinotecan SN-38 is inactivated by the body may lead to:&#10;A) Decreased effectiveness of irinotecan in the treatment of cancer&#10;B) Increased adverse drug reactions, such as neutropenia&#10;C) Delayed metabolism of the prodrug irinotecan into the active metabolite SN-38&#10;D) Increased concerns for irinotecan being carcinogenic&#10;

Accepted Answer

The answer of A genetic variation in how the metabolite...

Question 12

Rifampin is a nonspecific CYP450 inducer that may:&#10;A) Lead to toxic levels of rifampin and must be monitored closely&#10;B) Cause toxic levels of drugs, such as oral contraceptives, when coadministered&#10;C) Induce the metabolism of drugs, such as oral contraceptives, leading to therapeutic failure&#10;D) Cause nonspecific changes in drug metabolism&#10;

Accepted Answer

The answer of Rifampin is a nonspecific CYP450 inducer that...

Deck 8: An Introduction to Pharmacogenomics