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STEP One > Chemo drugs > Flashcards

Chemo drugs Flashcards

1
Q

• Antimetabolites

What toxicities are associated with methotrexate other than myelosuppression?

A

Macrovesicular fatty changes in the liver (hepatotoxicity), mucositis (e.g., mouth ulcers), pulmonary fibrosis, teratogenicity

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2
Q

What cancers are commonly treated with cytarabine (arabinofuranosyl cytidine)?

A

Leukemias (AML) and lymphomas

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3
Q

What are the clinical uses for 5-fluorouracil (5-FU)?

A

Colon cancer, pancreatic cancer, basal cell carcinoma (topical)

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4
Q

All the antimetabolites interfere with which phase of DNA synthesis?

A

S phase

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5
Q

Starting with DHF, go through the steps of the folate cycle, noting where the drugs methotrexate (MTX) and 5-fluorouracil (5-FU) act.

A

DHF to THF (via DHF reductase, blocked by MTX) to CH2-THF to DHF (converting dUMP to dTMP via thymidylate synthase, blocked by 5-FU)

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6
Q

An old man is given cladribine for a disease. What is its mechanism of action?

A

Can inhibit DNA polymerase and disrupt DNA double strands (he likely has hairy cell leukemia, and cladribine is a purine analog)

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7
Q

In a patient with TRAP-positive bone marrow and a dry tap on aspiration, what side effects does the chemotherapy drug of choice cause?

A

Myelosuppression, nephrotoxicity, neurotoxicity (hairy cell leukemia is treated with cladribine)

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8
Q

What drug, used as an antineoplastic agent, is a folic acid analog that works by inhibiting dihydrofolate reductase?

A

Methotrexate (inhibiting dihydrofolate reductase results in less deoxythymidine monophosphate needed for DNA and protein synthesis)

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9
Q

Name four cancers that methotrexate can be used to treat.

A

Leukemias (ALL), lymphomas, choriocarcinomas, and sarcomas

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10
Q

Name nonneoplastic conditions for which methotrexate can be used.

A

Ectopic pregnancy, medical abortion (with misoprostol), rheumatoid arthritis, psoriasis, IBD, vasculitis.

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11
Q

How does 5-fluorouracil (5-FU), a pyrimidine analog, interact with folic acid?

A

It is converted to 5F-dUMP, which covalently binds folic acid, forming a complex that inhibits thymidylate synthase

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12
Q

What enzyme is inhibited by the 5F-dUMP/folic acid complex?

A

Thymidylate synthase, which is needed to form deoxythymidine monophosphate for DNA and protein synthesis

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13
Q

A patient is given an excessive dose of 5-fluorouracil. Can leucovorin be administered to the patient to reduce toxicity?

A

No, as myelosuppression in this case is not reversible with leucovorin (it is with methotrexate toxicity)

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14
Q

What is the mechanism by which azathioprine, 6-mercaptopurine (6-MP), and 6-thioguanine (6-TG) exert an antineoplastic effect?

A

These are purine (thiol) analogs, which inhibit de novo purine synthesis (activated by HGPRT)

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15
Q

Azathioprine, 6-mercaptopurine, and 6-thioguanine are used in the prevention/treatment of what conditions?

A

Preventing organ rejection, rheumatoid arthritis, IBD, SLE, weaning off steroids for a condition, steroid-refractory conditions

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16
Q

Azathioprine, 6-mercaptopurine, and 6-thioguanine can be used to help wean patients off what other class of drugs?

A

steroids

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17
Q

How does cytarabine (arabinofuranosyl cytidine) exert its antineoplastic effect?

A

It is a pyrimidine analog that inhibits DNA polymerase (needed in S phase)

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18
Q

What are three adverse effects of cytarabine (arabinofuranosyl cytidine)?

A

Leukopenia, thrombocytopenia, and megaloblastic anemia (Cytarabine causes pancytopenia)

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19
Q

What agent is administered to reverse myelosuppression associated with methotrexate (MTX) use?

A

Leucovorin (rescue’s bone marrow)

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20
Q

What are three neoplasms in which dactinomycin is commonly used?

A

Ewing sarcoma, Wilms tumor, and rhabdomyosarcoma (in childhood tumors, actinomycin D because children act out)

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21
Q

Which of the antitumor antibiotics has the least myelosuppression as an adverse effect?

A

Bleomycin (myelosuppression is a common adverse effect of all other antitumor antibiotics)

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22
Q

What common mechanism is seen in the antineoplastic drugs bleomycin, daunorubicin, and doxorubicin?

A

These drugs generate free radicals, which can cause DNA strand breaks and halt cell replication

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23
Q

Which malignancies are treated commonly with doxorubicin or daunorubicin?

A

Solid tumors, leukemias, lymphomas

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24
Q

Name two neoplasms commonly treated with bleomycin.

A

Testicular cancer and Hodgkin lymphoma

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25
Q

A patient develops alopecia. What two chemotherapy drugs can cause this side effect?

A

Doxorubicin and daunorubicin

26
Q

Name three antineoplastic drugs that function by intercalating into DNA strands.

A

Dactinomycin (actinomycin D), daunorubicin, and doxorubicin

27
Q

A man on chemotherapy develops new symptoms of heart failure. What antineoplastic drug was likely a part of his regimen?

A

Doxorubicin or daunorubicin can cause dilated cardiomyopathy; patients may also develop alopecia, tissue toxicity on extravasation

28
Q

A patient is started on chemotherapy that intercalates in DNA. What can you give to prevent cardiotoxicity from this drug?

A

Dexrazoxane (iron-chelating agent)

29
Q

A patient with Hodgkin lymphoma complains of shortness of breath and dark skin discoloration. Which treatment was he likely given?

A

Bleomycin (causes pulmonary fibrosis and skin changes—other side effects are mucositis and myelosuppression)

30
Q

A patient develops a dilated cardiomyopathy years after undergoing chemotherapy for breast cancer. What drug was likely part of her regimen?

A

Doxorubicin or daunorubicin (known to have cardiotoxic effects)
(also traztuzumab)

31
Q

A patient with testicular cancer is given chemotherapy that generates free radicals. What side effects should he be worried of?

A

Pulmonary fibrosis, skin hyperpigmentation, and mouth ulcers (bleomycin is used to treat testicular cancer)

32
Q

Which alkylating agent(s) require(s) activation by the liver and might not be effective in a patient with liver failure?

A

Cyclophosphamide and ifosfamide cause DNA cross-links at guanine N-7—both require bioactivation by the liver

33
Q

Which alkylating agents are able to penetrate the blood-brain barrier to access the central nervous system? Do they require bioactivation?

A

Nitrosoureas, including carmustine, lomustine, semustine, and streptozotocin; yes, they require bioactivation

34
Q

Which alkylating agent would you choose in a patient about to undergo hematopoietic stem cell transplantation?

A

Busulfan, which will ablate the host’s bone marrow before transplantation (also used in the treatment of chronic myelogenous leukemia)

35
Q

What toxicities are seen in busulfan?

A

Severe myelosuppression (in almost all cases), pulmonary fibrosis, skin hyperpigmentation

36
Q

A man with non-Hodgkin lymphoma develops hemorrhagic cystitis. What two alkylating agents can cause this side effect?

A

Cyclophosphamide and ifosfamide (myelosuppression is another side effect)

37
Q

A patient on chemotherapy for breast cancer has hematuria. This could have been avoided by using what medication?

A

Mesna, its thiol group binds toxic metabolites; this patient has hemorrhagic cystitis from cyclophosphamide use

38
Q

Which alkylating agents are used especially in treating central nervous system neoplasms?

A

Nitrosoureas cross the blood-brain barrier and are used for brain tumors (e.g., glioblastoma multiforme)

39
Q

What is the major site effect of the nitrosourea chemotherapeutic agents?

A

CNS toxicity (convulsions, dizziness, ataxia)

40
Q

A patient takes an antineoplastic drug that binds to β-tubulin during M phase, blocking microtubule formation. Which drug(s) might this be?

A

Vincristine or vinblastine

41
Q

What neoplasms are commonly treated with a vinca alkaloid (vincristine or vinblastine)?

A

Solid tumors, leukemias, Hodgkin lymphoma (vinblastine), non-Hodgkin lymphoma (vincristine)

42
Q

Vincristine Side effects?

A

Neurotoxicity, including areflexia, peripheral neuritis, and paralytic ileus

43
Q

Vinblastine side effects?

A

Bone marrow suppression (vinblastine blasts bone marrow)

44
Q

What antineoplastic drug functions by hyperstabilizing the mitotic spindle so that tumor cells are unable to complete anaphase?

A

Paclitaxel or other taxols (it is taxing to stay polymerized [the microtubule stays polymerized])

45
Q

Which neoplasms are commonly treated using taxols?

A

Ovarian and Breast Ca

46
Q

What are signs of toxicity with paclitaxel and other taxols?

A

Myelosuppression, alopecia, hypersensitivity

47
Q

What are the clinical uses of cisplatin and carboplatin? What is the mechanism of action?

A

Testicular, bladder, ovary, lung carcinomas; they cross-link DNA

48
Q

Cisplatin and Carboplatin Side effects?

A

Nephrotoxicity and ototoxicity (acoustic nerve damage)

49
Q

A patient with testicular cancer is prescribed a DNA cross-linker. What drug can be coadministered to reduce toxicity?

A

Amifostine (a free radical scavenger) and chloride (saline) diuresis, both of which prevent cisplatin-induced nephrotoxicity

50
Q

You give your cancer patient a drug that inhibits topoisomerase II. What are three of its toxicities?

A

Toxicities include myelosuppression, GI irritation, and alopecia (this is etoposide or teniposide)

51
Q

What are the clinical uses for etoposide and teniposide? What is the mechanism of action?

A

Solid tumors (e.g., testicular and small cell lung cancer), leukemias, lymphomas; etoposide blocks topoisomerase II, causing DNA degradation

52
Q

What is the mechanism of action of irinotecan and topotecan?

A

Both irinotecan and topotecan inhibit topoisomerase I and prevent DNA unwinding and replication

53
Q

What toxicities are associated with irinotecan and topotecan use?

A

Severe myelosuppression and diarrhea

54
Q

Which drug inhibits ribonucleotide reductase, acting during the S phase to decrease DNA synthesis?

A

Hydroxyurea (blocks DNA Synthesis and is S-phase specific)

55
Q

What are the three clinical uses for hydroxyurea?

A

Melanoma, chronic myelogenous leukemia, and sickle cell disease (hydroxyurea increases concentration of hemoglobin F)

56
Q

A boy with sickle cell anemia was recently prescribed hydroxyurea. How does it help him? What are two major toxicities of this medication?

A

Hydroxyurea increases concentration of hemoglobin F; bone marrow suppression and gastrointestinal upset

57
Q

A patient with colorectal cancer on monoclonal antibody chemotherapy has scarily brisk bleeding from a wound. What might be the explanation?

A

He is likely on bevacizumab, which can cause hemorrhages, impaired wound healing, and blood clot formation as side effects

58
Q

A woman develops a non-small cell lung cancer. What is a side effect of a tyrosine kinase inhibitor that can potentially help her?

A

Rash (erlotinib is often used for non-small cell lung cancer)

59
Q

What is the mechanism of action of imatinib?

A

It inhibits the tyrosine kinase formed by the BCR-ABL translocation found in CML and by c-kit found in GI stromal tumors

60
Q

A woman has morning stiffness that improves as the day goes on. She is prescribed a CD20 inhibitor. What side effect do you monitor for?

A

Progressive multifocal leukoencephalopathy (this is rituximab, a monoclonal antibody against CD20, which is found on most B-cell neoplasms)

61
Q

What is the clinical use of vemurafenib? What is its mechanism of action?

A

Metastatic melanoma; it is a small molecule inhibitor of BRAF oncogene–positive melanoma

62
Q

What are the toxicities of cisplatin/carboplatin?

A

Nephrotoxicity, acoustic nerve damage

STEP One (20 decks)

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