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LECOM pharmacology notecards > chapter 38/39: anti-neoplastic > Flashcards

chapter 38/39: anti-neoplastic Flashcards

1
Q

what is the clinical application of Gefitinib

A

non-small cell lung cancer

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2
Q

what are some adverse reactions seen with Gefitinib

A

interstitial lung disease, corneal erosion; rash, diarrhea

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3
Q

what is the mechanism of action of Gefitinib

A

reversible inhibitor of the EGFR (ErbB1) cytoplasmic tyrosine kinase domain; competes with ATP binding to the kinase domain

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4
Q

who has the most favorable response to Gefitinib

A

patients with bronchoalveolar cell carcinoma

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5
Q

what is the clinical application of Erlotinib

A

non-small cell lung cancer; carcinoma of pancreas

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6
Q

what are some adverse rxns seen with Erlotinib

A

MI, DVT, microangiopathic hemolytic anemia, elevated liver enzymes, stroke, conjunctivitis

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7
Q

what is the mechanism of action of Erlotinib

A

reversible inhibitor of EGFR (ErbB1) cytoplasmic tyrosine kinase domain

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8
Q

what is the clinical application of cetuximab

A

colorectal cancer; head and neck cancer

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9
Q

what are some adverse reactions seen with cetuximab

A

cardiac arrest, Pulmonary embolism, rash, diarrhea, hypomagnesemia, asthenia

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10
Q

what is the mechanism of action of cetuximab

A

monoclonal IgG antibody that binds to extracellular domain EGFR (ErbB1)

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11
Q

development of what is predictive of tumor response when cetuximab is used

A

development of rash

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12
Q

what is the clinical application of trastuzumab

A

breast cancer or metastatic gastric caner with HER2 over expression

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13
Q

what are some adverse reactions seen with trastuzumab

A

cardiotoxicity, nephrotic syndrome, leukopenia

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14
Q

what is the mechanism of action of trastuzumab

A

monoclonal IgG antibody against ErbB2 (HER2)

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15
Q

what is the clinical application of imatinib

A

CML expression the philadelphia chromosome; GI stroll tumor GIST expressing Kit (CD117); idiopathic hypereosinophilic syndrome

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16
Q

what are some adverse reactions see with imatinib

A

edema, myelosuppresion, nausea, muscle cramps, diarrhea, rash

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17
Q

what is the mechanism of action of sorafenib

A

inhibits both wild type and mutant B-RAF (RAS/MAP kinase pathway inhibitor)

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18
Q

what is the mechanism of action of rapamycin (sirolimus)

A

inhibits mTor but also blocks downstream targets of mTOR such as cyclin D1, c-MYC, BAD, and Hif-1

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19
Q

what is the mechanism of action of bortezomib

A

inhibits an active site N-terminal threonine residue within the 20S catalytic subunit of the proteasome

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20
Q

what is the clinical application of sorafenib

A

renal cell carcinoma, hepatocellular carcinoma

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21
Q

what is the clinical application of rapamycin (sirolimus)

A

prophylaxis for renal transplant rejection

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22
Q

what is the clinical application of bortezomib

A

multiple myeloma; mantle cell lymphoma

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23
Q

what are some adverse effects seen with sorafenib

A

CV disease, erythema multiform, hand-foot rash, elevated lipase and amylase levels; depressed blood cell counts; neuropathy

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24
Q

what are some adverse effects seen with rapamycin (sirolimus)

A

increased susceptibility to infection, lymphoma, malignancy; thrombotic microangiopathy; renal toxicity

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25
Q

what are some adverse effects seen with bortezomib

A

HF, neutropenia, thrombocytopenia, neuropathy, hypotension, arthralgia

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26
Q

what else does sorafenib inhibit besides B-RAF

A

VEGFR-2, PDGFR-2

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27
Q

what drugs should be avoided when using rapamycin (sirolimus)

A

drugs that induce or inhibit CYP 450

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28
Q

what is the clinical application of bevacizumab

A

metastatic colorectal cancer; non-small cell lung cancer

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29
Q

what are some adverse reactions seen with bevacizumab

A

arterial thromboembolism; hypertensive crisis; nephrotic syndrome

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30
Q

what is the mechanism of action of bevacizumab

A

monoclonal IgG1 antibody against VEFF-A

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31
Q

what is the clinical application of sunitinib

A

renal cell carcinoma; GI stromal tumor

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32
Q

what is the clinical application of thalidomide

A

multiple myeloma; erythema nodosum leprosum

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33
Q

what is the clinical application of lenalidomide

A

multiple myeloma; myelodysplastic syndrome

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34
Q

what are some adverse effects seen with sunitinib

A

left ventricular dysfunction, anemia; hepatotoxicity; inflammation of mucous membrane; thyroid dysfunction

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35
Q

what is the mechanism of action of sunitinib

A

inhibits VEGFR-1, VEGFR-2, PDGFR, and other receptor tyrosine kinases

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36
Q

what are some adverse effects seen with thalidomide

A

teratogenesis, thrombotic disorder, SJS; peripheral neuropathy

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37
Q

what are some contraindications for thalidomide use

A

pregnancy; women capable of becoming pregnant; males not using latex condom

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38
Q

what is the mechanism of action of thalidomide

A

inhibits basic fibroblast growth factor (bFGF)-induced angiogenesis; also costimulates T cells

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39
Q

what is thalidomide used in combination with as first line regimen for multiple myeloma

A

dexamethasone

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40
Q

what are some adverse effects seen with rituximab

A

significant immunosuppression; anaphylactoid reaction related to chimeric antibodies; hematologic abnormalities; infusion reactions

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41
Q

what is the mechanism of action of lenalidomide

A

analogue of thalidomide with enhanced inhibition of TNF-alpha and improved T-cell costimulatory properties, while maintaining antiangiogenic activity

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42
Q

what is the mechanism of action of rituximab

A

anti-CD20 antibody

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43
Q

what is the clinical application of fluorouracil (5-FU)

A

breast cancer, GI cancers, skin cancer (topical application)

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44
Q

what are some adverse reactions seen with fluorouracil

A

coronary atherosclerosis, cerebellar syndrome, visual changes, stenosis of lacrimal system; photosensitivity

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45
Q

what are some contraindications to fluorouracil use

A

severe bone marrow depression, poor nutritional state, serious infection, dihydropyrmidine dehydrogenase deficiency, pregnancy

46
Q

what is the mechanism of action of fluorouracil

A

inhibits thymidylate synthase by binding to the deoxyuridylate (substrate) site on the enzyme

47
Q

what can be used to potentiate the action of fluorouracil

A

folinic acid

48
Q

what is the clinical application of capecitabine

A

metastatic colorectal cancer; breast cancer

49
Q

what are the contraindications to capecitabine use

A

dihydropyrimidine dehydrogenase deficiency; severe renal impairment

50
Q

what is the orally available prodrug for of 5-FU

A

capecitabine

51
Q

what is the mechanism of action of 6-mercaptopurine (6-MP) and azathioprine

A

inhibits IMPDH and other synthetic enzymes, thereby interfering with AMP and GMP synthesis

52
Q

what is the main clinical application of 6-mercaptopurine

A

acute lymphoblastic leukemia

53
Q

what are the clinical applications of azathioprine

A

immunosuppression in renal transplantation, rheumatoid arthritis, IBD

54
Q

what are some adverse reactions seen with 6-mercaptopurine (6-MP) and azathioprine

A

pancreatitis, myelosuppresion, hepatotoxicity, infection; gastritis

55
Q

what is a contraindication for 6-mercaptopurine (6-MP) and azathioprine

56
Q

what is the mechanism of action of hydroxyurea

A

inhibit ribonucleotide reductase (enzyme that converts ribonucleotides to deoxyribonucleotides)

57
Q

what are the clinical applications of hydroxyurea

A

myeloproliferative disorders, hematologic malignancies, head/neck cancers, melanoma, ovarian carcinoma; sickle cell anemia (adults only)

58
Q

what are some adverse reactions seen with hydroxyurea

A

secondary leukemia with long term use; GI toxicity; skin ulcer

59
Q

what is a contraindication for hydroxyurea use

A

severe bone marrow depression

60
Q

what is the mechanism of action of thioguanine

A

incorporation into DNA and RNA results in inhibition of DNA polymerase, thereby causing cell death

61
Q

what is the clinical application of thioguanine

A

acute myelogenous leukemia

62
Q

what are some adverse reactions seen with thioguanine

A

hyperuricemia, intestinal perforation, hepatotoxicity

63
Q

what analogue is cladribine

64
Q

what is the clinical application of cladribine

A

hairy cell leukemia, multiple sclerosis

65
Q

what are some adverse reactions seen with cladribine

A

febrile neutropenia, neurotoxicity

66
Q

what analogue is cytarabine

67
Q

what are the clinical applications of cytarabine

A

acute lymphoblastic and myelogenous leukemia; CML; meningeal leukemia; hodgkin’s disease; non-hodgkin lymphoma

68
Q

what are some adverse reactions seen with cytarabine

A

neuropathy, nephrotoxicity, liver dysfunction; ulcers of mouth and anus

69
Q

what is the mechanism of action of cyclophosphamide

A

covalently bind DNA, often cross-like to DNA or associated proteins

70
Q

what are the clinical applications of cyclophosphamide

A

autoimmune diseases, leukemias & lymphomas; advanced mycosis fungoides; neuroblastoma; ovarian cancer; retinoblastoma; malignant histiocytosis

71
Q

what are some adverse reactions seen with cyclophosphamide

A

cardiomyopathy, SJS, hemorrhagic cystitis, azoospermia, alopecia, amenorrhea

72
Q

what is a contraindication for cyclophosphamide use

A

severely depressed bone marrow function

73
Q

what metabolite of cyclophosphamide can cause hemorrhagic cystitis and how can it be prevented

A

acrolein; prevented with co-administration of meson

74
Q

what is the clinical application of mitomycin

A

gastric pancreatic cancer

75
Q

what is the clinical application of thiotepa

A

bladder cancer

76
Q

what is the clinical application of carmustine

A

brain cancer

77
Q

what is the clinical application of dacarbazine

A

hodgkins disease

78
Q

what is the clinical application mom procarbazine

A

hodgkins disease

79
Q

what is the clinical application of altretamine

A

ovarian cancer

80
Q

what is a contraindication for mitomycin use

A

coagulation disorder or renal impairment

81
Q

what is a contraindication for thiotepa use

A

hepatic, renal or bone marrow dysfunction

82
Q

what is a alkylating antibiotic that targets hypoxic tumor cells

83
Q

what is the mechanism of action of cisplatin and carboplatin

A

cross-link intrastrand guanine bases

84
Q

what is the clinical application of cisplatin and carboplatin

A

genitourinary cancers; lung cancers

85
Q

what is the dose limiting toxicity of cisplatin

A

nephrotoxicity

86
Q

what are some contraindications for cisplatin and carboplatin use

A

severe bone marrow depression; renal/hearing impairment

87
Q

what can be co-administered with cisplatin to limit nephrotoxicity

A

amifostine

88
Q

what is the mechanism of action of bleomycin

A

binds oxygen and chelates Fe(II); binds DNA and leads to strand breaks via generation of oxidative intermediates

89
Q

what is the clinical application of bleomycin

A

testicular cancer; hodgkin disease

90
Q

what is the dose-limiting toxicity of bleomycin

A

pulmonary fibrosis

91
Q

what is the clinical application of irinotecan

A

colorectal cancer

92
Q

what is the clinical application of topotecan

A

small cell lung cancer, cervical carcinoma, ovarian cancer

93
Q

what are some adverse reactions seen with irinotecan and topotecan

A

life-threatening diarrhea, febrile neutropenia, alopecia, eosinophilia

94
Q

what stage in the cell cycle are irinotecan and topotecan specific for and what do they inhibit

A

S phase; inhibit topoisomerase 1

95
Q

what are the clinical applications of doxorubicin

A

leukemias, lymphomas, breast cancer, bladder cancer, thyroid cancer, GI cancer, nephroblastoma, osteosarcoma, ovarian cancer, small cell lung cancer; soft tissue sarcoma

96
Q

what is a major adverse reaction seen with doxorubicin

A

heart failure

97
Q

what are some contraindications for doxorubicin

A

preexisting heart failure, severe bone marrow depression

98
Q

what does doxorubicin inhibit and what stage of the cell cycle does it target

A

inhibits topoisomerase 2; G2 phase

99
Q

what is the clinical application of etoposide

A

testicular and lung cancer; leukemia

100
Q

what does etoposide inhibit and what stage of the cell cycle does it target

A

inhibits topoisomerase 2; action is specific to late S phase and G2 phases

101
Q

what is the mechanism of action of vinblastine

A

bind tubular subunits and prevent microtubule polymerization

102
Q

what are some adverse reactions seen with vinblastine

A

myelosuppresion, azoospermia, alopecia, bone pain

103
Q

what are some contraindications for vinblastine use

A

bacterial infection; significant granulocytopenia

104
Q

what is the dose-limiting toxicity of vinblastine

A

bone marrow suppression

105
Q

what are some contraindications for vincristine use

A

charcot-marie-tooth syndrome; intrathecal use

106
Q

what is the dose limiting effect of vincristine

A

peripheral neuropathy

107
Q

what agent that inhibits microtubule polymerization can lead to diplopia as an adverse effect

A

vincristine

108
Q

what is the dose limiting toxicity of paclitaxel

A

peripheral neuropathy

109
Q

what is the clinical application of paclitaxel

A

ovarian cancer, non-small cell lung cancer; AIDS-related kaposis sarcoma

110
Q

what are the most common clinical uses for docetaxel

A

breast cancer; non-small cell lung cancer

111
Q

what is the dose limiting toxicity of docetaxel

A

myelosuppression

LECOM pharmacology notecards (22 decks)

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