Материал: 2016_Kaplan_USMLE_Step_1_Lecture_Notes_Pharmacology

1.Which of the following chemotherapeutic drugs inhibits the polymerization of microtubules but is not associated with causing bone marrow suppression?

A.Cyclophosphamide

B.Cisplatin

C.5-Fluorouracil

D.Vinblastine

E.Vincristine

2.A patient with non-Hodgkin lymphoma is to be started on the CHOP regimen, which consists of cyclophosphamide, doxorubicin, vincristine, and prednisone. Which one of the following agents is most likely to be protective against the toxicity of doxorubicin?

A.Amifostine

B.Dexrazoxane

C.Leucovorin

D.Mesna

E.Vitamin C

3.A drug used in a chemotherapy regimen works by complexing with iron and oxygen to promote DNA strand breaks. While on this drug the patient must be monitored closely due to pulmonary side effects. In what phase of the cell cycle does this drug work?

A.G1

B.S

C.G2

D.M

E.This drug is not cell-cycle dependent.

4.Resistance to which anticancer drug, used in leukemias, lymphomas, and breast cancer, is associated with increased production of dihydrofolate reductase?

A.Doxorubicin

B.Vinblastine

C.6-MP

D.Cytarabine

E.Methotrexate

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Section IX λ Anticancer Drugs

5.A patient undergoing cancer chemotherapy has an increase in urinary frequency with much discomfort. No specific findings are apparent on physical examination. Laboratory results include hematuria and mild leukopenia, but no bacteria or crystalluria. If the symptoms experienced by the patient are drug related, what is the most likely cause?

A.Cyclophosphamide

B.5-FU

C.Methotrexate

D.Prednisone

E.Tamoxifen

Answers

1.Answer: E. Only two of the drugs listed do not cause bone marrow suppression: cisplatin and vincristine. Only two of the drugs listed inhibit microtubule plymerization: vinblastine and vincristine. The drug that fits both categories is vincristine. Patients on vincristine should be monitored for neurotoxicity, especially peripheral neuropathies.

2.Answer: B. Dexrazoxane is an iron-chelating agent that prevents the formation of free radicals and reduces the cardiotoxicity of anthracyclines such as doxorubicin. Amifostine is protective of nephrotoxicity caused by cisplatin. Folinic acid (leucovorin) reduces the toxicity of methotrexate because it provides an active form of folate to normal (nonneoplastic) cells, resulting in “leucovorin rescue.” Mesna, which inactivates acrolein, is available for protection against hemorrhagic cystitis in patients treated with cyclophosphamide.

3.Answer: C. It helps to know which anticancer drugs are cell-cycle specific and which have characteristic toxicities. Bleomycin forms a complex with iron and oxygen and promotes DNA strand breaks. Its major side effects are pulmonary

toxicities including pneumonitis and fibrosis. It acts acting mainly in the G2 phase of the cell-cycle.

4.Answer: E. Methotrexate is a widely-used chemotherapy drug that is also commonly used in moderate to severe rheumatoid arthritis. It inhibits the enzyme dihydrofolate reductase (DHFR) thereby reducing the synthesis of tetrahydrofolate and thus inhibiting DNA synthesis. Resistance occurs when cancer cells upregulate DHFR or alter the binding of methotrexate to DHFR.

5.Answer: A. These symptoms are those of a mild case of hemorrhagic cystitis. Bladder irritation with hematuria is a fairly common complaint of patients treated with cyclophosphamide. It appears to be due to acrolein, a product formed when cyclophosphamide is bioactivated by liver P450 to form cytotoxic metabolites. Mesna is the antidote used to detoxify acrolein and protect against hemorrhagic cystitis.

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SECTION X

Immunopharmacology