Pharmacogenetics and Pharmacogenomics
1. Which of the following is not true about pharmacogenetics?
a. It is the branch of pharmacology that seeks to understand the genetic basis for differences in drug responsiveness among humans.
b. Pharmacogenetics is defined as the investigation of variations in DNA and RNA characteristics as related to drug response.
c. Pharmacogenetics is defined by the US Food and Drug Administration (FDA) as the investigation of the role of variations in DNA sequence on drug response.
d. Pharmacogenetics and pharmacogenomics are areas of intense interest and development within the biotechnology and pharmaceutical industries.
2. Which of the following is not true about codeine?
a. Codeine, one of the commonly prescribed opioid analgesics for pain in dentistry.
b. Codeine is a prodrug and its activation to morphine depends on CYP2D6 enzyme.
c. If a patient inherits a deficiency in CYP2D6 or the m-opioid response system, it is unlikely that standard doses of codeine will be of therapeutic benefit.
d. Codeine is an effective analgesic in all genetic subset of the population.
3. Which of the following is not true about genotype?
a. A biological or measurable expression of the genetic trait.
b. An individual’s genotype is a genetic trait defined by the DNA sequences (i.e., alleles) inherited from the mother and the father.
c. An individual can inherit two copies of the same allele (homozygous genotype) or a
different allele from each of the parents (heterozygous genotype).
d. Many methods to determine the genotype have been developed in the past two decades, including restriction fragment length polymorphism analysis, allele-specific amplification, and DNA sequencing.
4. What are monogenic phenotypes?
a. Phenotypes that derive from some combination of variations in multiple genes.
b. Phenotypes that derive from genetic variations in a single gene.
c. Phenotypes that derive from genetic variations in all the genes.
d. Phenotypes that do not have any variation in gene.
5. The frequency of specific alleles, genotypes, and phenotypes for drug-metabolizing enzymes varies widely with ethnic origin.
a. True.
b. False.
c. The statement is partially true.
d. The statement is true but not for drug-metabolizing enzymes.
6. Which of the following is not true about genetic polymorphism?
a. It is anticipated that genetic polymorphism is present in all the drug-metabolizing enzymes.
b. It has been proved that genetic polymorphism is present in all the drug-metabolizing enzymes.
c. Many of the genetic polymorphisms are already known to be important in therapeutics.
d. CYP2D6 shows genetic polymorphism.
7. N-acetylation is an important phase II conjugation reaction for many drugs, EXCEPT
a. procainamide.
b. dapsone.
c. hydralazine.
d. metoclopramide.
8. The acetylation polymorphism was originally discovered by studying the development of peripheral neuropathy in patients administered
a. rifampicin.
b. isoniazid.
c. dapsone.
d. sulfonamides.
9. Which of the following statements is wrong?
a. N-acetylation of aromatic amine-containing and hydrazine-containing drugs are catalyzed by N-acetyltransferase isozymes.
b. Genetic polymorphisms have been identified only in NAT1.
c. Acetylator genotypes derived from more than 25 different NAT2 alleles have been identified in humans.
d. Eleven identified SNPs in the NAT2 gene affect protein expression or stability or both.
10. What is the cytochrome P450 (CYP) system?
a. It is a family of microsomal enzymes with nonselective but frequently overlapping substrate specificities.
b. It is a family of microsomal enzymes with selective but frequently nonoverlapping substrate specificities.
c. It is a family of microsomal enzymes with selective but frequently overlapping substrate specificities.
d. It is a family of microsomal enzymes with nonselective but frequently nonoverlapping substrate specificities.
11. Which are the three drug oxidation polymorphisms that have received the most clinical attention?
a. CYP2D6, CYP2C9, and CYP2C19.
b. CYP2D6, CYP2C9, and CYP27A1.
c. CYP2D6, CYP2C9, and CYP4V2.
d. CYP2D6, CYP2C9, and CYP11B2.
12. Which of the following enzymes is required for tamoxifen to be biotransformed to the potent antiestrogen endoxifen?
a. CYP2C9.
b. CYP2D6.
c. CYP2C19.
d. CYP1B1.
13. Enzyme CYP2C9 does not catalyze the oxidation of
a. warfarin.
b. codeine.
c. phenytoin.
d. losartan.
14. Warfarin is a difficult drug to use because of many factors. Which of the following factors does not contribute to warfarin metabolism?
a. Genetic polymorphisms in CYP2C9.
b. Genetic polymorphisms in CYP4F2 (which oxidizes vitamin K).
c. Vitamin K epoxide reductase (VKORC1, the target of warfarin inhibition).
d. Homocysteine levels.
15. Which of the following is not true about CYP2C19?
a. CYP2C19 catalyzes the oxidation of mephenytoin.
b. CYP2C19 catalyzes the oxidation of omeprazole.
c. Individuals with genetic deficiencies may experience increased sedation and ataxia with the anticonvulsant mephenytoin.
d. Individuals with genetic deficiencies may experience decreased therapeutic efficacy with omeprazole used for the treatment of peptic ulcer.
16. Which of the following is not true about plasma cholinesterase?
a. Plasma cholinesterase catalyzes the hydrolysis of choline esters.
b. Individuals with genetic deficiency in plasma cholinesterase experience prolonged apnea when treated with succinylcholine.
c. The primary atypical form of plasma cholinesterase possesses an SNP that changes an amino acid (aspartic acid to glycine) in the anionic site of the esterase, reducing its affinity for succinylcholine.
d. Succinylcholine is frequently used to produce muscular relaxation for endotracheal intubation.
17. Thiopurine S-methyltransferase (TPMT) catalyzes the deactivating S-methylation of the following drugs, EXCEPT
a. 6-mercaptopurine.
b. 6-thioguanine.
c. omeprazole.
d. azathioprine.
18. Genetic variants of the multidrug resistance transporter P-glycoprotein, the product of the MDR1 gene, have been associated with altered transport, efficacy, and toxicity of all the following, EXCEPT
a. digoxin.
b. tacrolimus.
c. irinotecan.
d. azathioprine.
19. Malignant hyperthermia (MH) can present with all of the following manifestations, EXCEPT
a. bradycardia.
b. hypercarbia.
c. hypoxia.
d. tachycardia.
20. Which of the following drugs is given in acute attack of malignant hyperthermia?
a. Atropine.
b. Adrenaline.
c. Diazepam.
d. Dantrolene.
21. Which of the following is not true about uridine diphosphate glucuronosyltransferase (UGT)?
a. UGT catalyzes the glucuronidation of bilirubin and various drugs and xenobiotics.
b. The UGT1A family of enzymes is represented in the genome by a series of six invariant exons.
c. UGT enzyme levels are regulated primarily through transcriptional control and genetic variation in promoter structure influences transcription rate.
d. Individuals with genetic polymorphism in UGT1A1 have been shown to experience
increased toxicity (myelosuppression and diarrhea) with the use of irinotecan.
22. Which of the following is used extensively during chemotherapy of solid tumors?
a. 5-Fluorouracil.
b. Azathioprine.
c. Dantrolene.
d. Efavirenz.
23. Patients with genetic deficiency of dihydropyrimidine dehydrogenase have
a. a 70% lower clearance of 5-fluorouracil and may experience severe toxicity from modest doses.
b. an 80% lower clearance of 5-fluorouracil and may experience severe toxicity from modest doses.
c. a 90% lower clearance of 5-fluorouracil and may experience severe toxicity from modest doses.
d. a 60% lower clearance of 5-fluorouracil and may experience severe toxicity from modest doses.
24. The individuals who are homozygous for the UGT1A1*28 allele are at increased risk for which of the following conditions after initiation of irinotecan treatment?
a. Lymphocytopenia.
b. Anemia.
c. Neutropenia.
d. Thrombocytopenia.
25. Which of the following is not true about b2-adrenergic receptor?
a. b2-Adrenergic receptor genotype variation has been shown to affect therapeutic response to b2-selective agonists such as albuterol.
b. Polymorphisms in b receptors potentially influence drug treatment of cardiovascular diseases.
c. b2 receptor variant is associated with lower systemic vascular resistance and a greater vasodilatory response.
d. Individuals with this b2 receptor variant might not be sensitive to a vasodilator (e.g., captopril) acting via another mechanism, secondary to the altered systemic vascular tone.
