Pharmacology/Medicinal Chemistry II Test 2 November 30, 2004

1. The administration of acyclovir would result in which of the following:

a) Much greater accumulation of acyclovir triphosphate in uninfected cells than in virally infected
cells.
b) Inhibition of viral DNA polymerase without chain termination.
c) Phosphorylation of acyclovir to acyclovir monophosphate by host cell kinases.
d) Competition of acyclovir triphosphate with dGTP for interaction with the viral DNA polymerase.
e) Inhibition of IMP dehydrogenase only in virally infected cells.

2. Zidovudine will decrease the magnitude of effect of ________ when the two are given together.
a) didanosine
b) stavudine
c) zalcitabine
d) abacavir
e) indinavir

3. Which of the following is true for non-nucleoside reverse transcriptase inhibitors (NNRTI)?
a) They are not incorporated into DNA.
b) They compete with dNTP for binding to reverse transcriptase.
c) They undergo phosphorylation by host cell kinases.
d) There is no cross-resistance among the different NNRTI.

4. Resistance to Ara-C could occur as a result of:

a) a high level of deoxycytidine kinase expression in tumor cells
b) an increased expression of dihydrofolate reductase in tumor cells
c) a decreased level of expression of cytidine deaminase in tumor cells
d) an increased production of scavenger molecules, such as glutathione
e) a high level of expression of deoxycytidine deaminase in tumor cells

5. The site of initial proliferation of mycobacerital responsible for tuberculosis is in the macrophage.
Which of the following drugs is least efficacious against mycobacteria inside macrophages?
a) pyrazinamide
b) ethambutol
c) isoniazid
d) rifampin

6. Treatment with interferon α induces the synthesis of proteins which:

a) block glycosylation of proteins
b) inhibit initiation of protein synthesis
c) cleave viral mRNA
d) prevent 5’ mRNA capping
e) all of the above

7. Which of the following is most likely to cause a significant elevation of uric acid in the blood
(hyperuricemia)?
a) isoniazid
b) rifampin
c) busulfan
d) 5-fluorouracil
e) pyrazinamide
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8. The incidence of opportunistic infections associated with AIDS patients:
a) increase as the number of helper T cells increases
b) decreases as the HIV titer increases
c) is the greatest during the first 3-12 weeks following the initial HIV infection
d) is highest prior to the emergence of the flu-like syndrome associated with an HIV infection
e) none of the above are true

9. Patient X has been taking a three drug combination for the treatment of tuberculosis. Patient X notices
since that since drug treatment was initiated, whenever she goes to the gym for her workout, her sweat
has an orange color to it. Her doctor tells her that one of the drugs she is taking is most likely
responsible for this. Which drug is the doctor referring to?
a) pyrazinamide
b) rifampin
c) streptomycin
d) ciprofloxacin
e) ethambutol

10. Treatment with ______________ can cause significant bone marrow toxicity?
a) 6-mercaptopurine
b) 5-Fu
c) lomustine (CCNU)
d) mechlorethamine
e) all of the above

11. Influenza is a type of _________.

a) retrovirus
b) DNA virus
c) RNA virus

12. Sylvia has been undergoing treatment for active tuberculosis. Although she has faithfully used oral
contraceptives, a recent visit to her gynecologist confirms that Sylvia is not pregnant. Furthermore, the
gynecologist explains that failure of the oral contraceptive was most likely due to the presence of
rifampin (one of the drugs she was taking). What is the most likely explanation for this effect?
a) Rifampin caused a significant increase in the metabolism of the oral contraceptive so it was not
effective.
b) Rifampin decreased the absorption of the oral contraceptive so it was not effective.
c) Rifampin inhibited the enzyme that activates the oral contraceptive, so it was not effective.

13. Which of the following has been shown to be effective at decreasing the incidence of transmission of
HIV from mother to newborn?
a) nevirapine
b) nelfinavir
c) abacavir
d) delavirdine
e) ribavirin

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14. A baseline vision test is recommended prior to initiation of therapy with _________.
a) flerofloxacin
b) nitrofurantoin
c) interferon α
d) cidofovir
e) ethambutol

15. Which of the flowing drugs will slow progression of cells into S phase?
a) Ara-C
b) 6-mercaptopurine
c) cisplatin
d) methotrexate
e) all of the above

16. Which of the following drugs can potentially cause significant liver toxicity?
a) rifampin
b) isoniazid and pyrazinamide
c) isoniazid, ethambutol, and rifampin
d) isoniazide but not pyrazinamide
e) pyrazinamide and ethambutol

17. The mechanism of action of ciprofloxacin includes:

a) inhibition of DNA gyrase activity
b) inhibition of ligation of Okazaki fragments that are generated during DNA replication
c) blockage of DNA polymerase progression along the DNA template
d) generation of oxygen radicals which cause DNA damage
e) none of the above

18. Which of the following drugs does not require phosphorylation in order to act?
a) ganciclovir
b) foscarnet
c) zalcitabine
d) cidofovir
e) ribavirin

19. Which of the following drugs would be safe for use in a pregnant woman?
a) ribavirin
b) ganciclovir
c) cidoflovir
d) none of the above would be safe for use during pregnancy

20. What is the basis of the specificity of amphotericin B for fungal cells?
a) The fungal enzyme that is inhibited by amphotericin B is not present in mammalian cells.
b) The target molecule that amphotericin B binds to is present in much higher concentration in
fungal cells than in mammalian cells.
c) Amphotericin B is metabolized to an inactive metabolite in mammalian cells.
d) Amphotericin B is activated to a metabolite which can bind to the target only in fungal cells.
e) The transport system that is responsible for the uptake of amphotericin B into fungal cells is not
present in mammalian cells.

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21. Which of the following drugs is able to specifically target the M2 protein present in influenza A?
a) oseltamavir
b) fornivirsen
c) interferon α
d) forscarnet
e) amantidine

22. IV infusion of a high dose of acyclovir is associated with:

a) an increased risk of hepatotoxicity
b) ototoxicty
c) damage to kidney tubules as a result of precipitation
d) damage to the retina (ocular toxicity)
e) severe, dose-limiting diarrhea

23. An individual with tuberculosis, who is determined to have a low level of N-acetyltransferase:
a) cannot be effectively treated with isoniazid
b) will not be susceptible to the possible hepatoxicity associated with isonaizid treatment
c) will need to receive a higher dose of isoniazid than an individual who has a high level of N-
acetyltransferase
d) will be unable to generate sufficient active metabolite from isoniazid
e) none of the above are true

24. Which of the following must undergo integration into the host cell genome in order to complete the
cycle of life?
a) RNA virus
b) DNA virus
c) retrovirus
d) both DNA virus an retrovirus
e) RNA virus, DNA virus, and retrovirus

25. Treatment with ___________ causes an increased incidence of iritis and cataracts.
a) fomivirsen
b) foscarnet
c) cidofovir
d) ribavirin
e) none of the above

26. Which of the following would be efficacious in the treatment of an infection with a tymidine kinase-
deficient herpes simplex virus?
a) acyclovir
b) valganciclovir
c) valacyclvori
d) cidofovir

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27. Susan G. was hospitalized and treated with drug X for a well-established systemic fungal infection.
After one week of treatment, Susan’s kidney function began to diminish and her hematocrit also was
moderately decreased. What is the identity of drug X?
a) griseofulvin
b) amphotericin B
c) fluconazole
d) caspofungin acetate
e) flucytosine

28. Which of the following dose not cause chain termination?

a) delavirdine
b) zalcitabine
c) lamivudine
d) didanosine
e) zidovudine

29. A patient with a fungal infection is treated and the treatment results in the accumulation of squalene
inside the fungal cells. The drug which would be most likely to cause this effect is:
a) flucytosine
b) caspofungin acetate
c) amphotericin B
d) terbinafine
e) itraconazole

30. The function of the helper T cells includes:

a) stimulation of proliferation of B cells
b) activation of macrophages
c) stimulation of proliferation of cytotoxic T cells
d) all of the above

31. Mrs. G. has been diagnosed with primary tuberculosis. Her doctor indicates that she should be treated
with a drug which also has the potential to cause peripheral nerve damage. Mrs. G. agrees to the
treatment. The doctor should also have told Mrs. G. that the toxicity to peripheral nerves can be avoided
by:
a) taking the drug with food
b) drinking plenty of water to remain well hydrated
c) concurrent administration of vitamin B6 (pyridoxine) with the drug
d) concurrent administration of N-acetylcysteine with the drug to hasten the metabolism of the drug
e) concurrent administration of reduced folic acid with the drug

32. Which of the following may increase the risk of a false positive drug test for marijuana?
a) efavirenz
b) ritonavir
c) nevirapine
d) delavirdine
e) cidofovir

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33. Cells which lack permease would be resistant to the action of:
a) 5-Fu
b) ciproflopxacin
c) flucytosine
d) clotrimazole
e) griseofulvin

34. Concurrent administration of omeprazole would have the greatest affect on the absorption of _____ from
the gastrointestinal tract.
a) fluconazole
b) griesofulvin
c) ketoconazole
d) nitrofurantoin
e) clotrimazole

35. Which of the following shows no significant metabolism by P450?

a) efavirenz
b) ritonavir
c) delavirdine
d) amprenavir
e) fuzeon

36. If hypersensitivity to _________ is seen, rechallenge with the drug at a later date should be avoided to
prevent a possible fatal hypersensitivity reaction.
a) efavirenz
b) abacavir
c) amprenavir
d) ritonavir
e) nelfinavir

37. Protease inhibitors:

a) interfere with the synthesis of precursor viral proteins
b) are resistant to metabolism by P450
c) may cause significant increases in cholesterol and triglycerides circulating in the blood
d) generally cause significant bone marrow toxicity
e) none of the above

38. Treatment with an anti-tumor drug which slowed the progression of cells from G1 phase to S phase
would __________ the effects of a second S phase-specific drug.
a) potentiate
b) inhibit
c) not alter

39. Which of the following is an alkylating agent which does not require metabolic activation in order to
form a carbonium ion?
a) ifosfamide
b) chlorambucil
c) cyclophosphamide
d) busulfan

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40. Which of the following should be used very carefully in patients with a moderate deficiency in kidney
function?
a) lomustine
b) 6-mercaptopurine
c) cytosine arabinoside (Ara-C)
d) cisplatin

41. A significant decrease in overall hypoxanthine-guanine phosphoribosyltransferase activity would enable

a tumor cell to be resistant to the effects of:
a) thiotepa
b) acyclovir
c) 5 fluorouracil
d) 6-thioguanine
e) none of the above

42. Which of the following contributes to the effects of methotrexate?

a) specific inhibition of IMP dehydrogenase and adenylosuccinate synthetase
b) formation of a ternary complex composed of methotrexate, thymidylate synthetase, and afolate
derivative
c) incorporation into newly replicated DNA
d) selective polyglutamation within tumor cells
e) none of the above

43. Which of the following drugs is able to induce cytochrome P450?

a) griseofulvin
b) ketoconazole
c) caspofungin acetate
d) terbinafine
e) ribavirin

44. Administration of leucovorin along with 5-Fu would __________ the efficacy of the 5-Fu.
a) decrease
b) increase
c) not alter

45. The possible mechanism of resistance against isoniazid is:

a) the presence of a mutated bacterial RNA polymerase
b) a significant increase in the synthesis of arbinosyl transferase protein
c) the presence of a mutated pyrazinamidase protein
d) decreased transcription/translation of KatG gene (catalase/peroxidase)
e) production of a mutated N-acetylase protein

46. Gene amplification is associated with resistance of tumor cells to:

a) 6-thioguanine
b) cyclophosphamide
c) methotrexate
d) cisplatin
e) all of the above

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47. Which of the following can cause mispairing and ring-opening, but not cross-linking?
a) lomustine
b) ifosphamide
c) thiotepa
d) cisplatin
e) chlorambucil

48. Which of the following is converted to a metabolite which inhibits enoyl-ACP reductase?
a) ciprofloxacin
b) rifampin
c) ethambutol
d) pyrazinamide
e) isoniazid

49. Which of the following is true?

a) A palliative approach to the treatment of a solid tumor is designed to rid the body of subclinical
number of tumors that may still be present following surgery to remove the tumor.
b) The growth fraction of most solid tumors is substantially higher than that of rapidly growing
non-tumor tissues normally found in the body.
c) Well differentiated cells generally have a lower potential for proliferation than poorly
differentiated cells.
d) Sarcomas arise from epithelial cells.

50. Aluminum needles should be avoided when administering which of the following drugs?
a) lomustine
b) mechlorethamine
c) methotrexate
d) cisplatin
e) thiotepa

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ANSWERS
1. D
2. B
3. A
4. E
5. B
6. E
7. E
8. E
9. B
10. E
11. C
12. A
13. A
14. E
15. D
16. B
17. A
18. B
19. D
20. B
21. E
22. C
23. E
24. C
25. A
26. D
27. B
28. A
29. D
30. D
31. C
32. A
33. C
34. C
35. E
36. B
37. C
38. B
39. D
40. D
41. D
42. D
43. A
44. B
45. D
46. C
47. A
48. E
49. C
50. D
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