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HML II > Chemotherapy > Flashcards

Chemotherapy Flashcards

1
Q

Chemotherapy drug classes that act on mitosis (M phase)

A

Vinca alkaloids
Taxanes

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2
Q

Chemotherapy drug class that acts on G2 phase

A

Bleomycin

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3
Q

Chemotherapy drug class that acts on S phase

A

Anti-metabolites

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4
Q

General advantages of CCS drugs

A

Targeted action
Fewer side effects on non-dividing cells

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5
Q

General disadvantages of CCS drugs

A

Less effective on slow growing tumors
Toxicity on rapidly dividing cells

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6
Q

General advantages of NCCS drugs

A

Broad activity
Effective in slow growing tumors

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7
Q

General disadvantages of NCCS drugs

A

Increased toxicity
Resistance

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8
Q

Characteristic findings of tumor lysis syndrome

A

Hyperuricemia
Hyperkalemia
Hyperphosphatemia
Hypocalcemia

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9
Q

Guiding principle of combination therapy

A

Optimize therapeutic efficacy while minimizing toxicity

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10
Q

Mechanism of alkylating agents

A

Alkylation of nucleophilic groups of DNA bases, particularly N-7 guanine

Cross-linking of bases, abnormal base pairing, and DNA strand breakage

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11
Q

Examples of NCCS drug classes

A

Alkylating agents
Antitumor abx

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12
Q

Examples of CCS drug classes

A

Antimetabolites
Vinca alkaloids
Taxanes
Topoisomerase II inhibitors
Bleomycin

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13
Q

Examples of alkylating agents

A

Cyclophosphamide
Ifosfamide
Mechlorethamine
Melphalan
Nitrosoureas
Temozolomide
Platinum analogs
Decarbazine
Procarbazine
Busulfan

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14
Q

Active metabolite of cyclophosphamide

A

Phosphoramide mustard

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15
Q

Secondary metabolite of cyclophosphamide and its affect

A

Acrolein
Hemorrhagic cystitis

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16
Q

Reduction therapy of hemorrhagic cystitis

A

Mesna

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17
Q

Chemotherapy drug that can cause sterility

A

Mechlorethamine

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18
Q

Chemotherapy drug that can cause pulmonary toxicity and SIADH

A

Cyclophosphamide

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19
Q

Types of nitrosoureas

A

Carmustine
Lomustine

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20
Q

Alkylating agents that cross BBB

A

Nitrosoureas –> carmustine and lomustine
Temozolomide

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21
Q

Uses of temozolomide

A

Anaplastic astrocytoma refractory to nitrosoureas

Glioblastoma

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22
Q

Types of platinum analogs

A

Cisplatin
Carboplatin
Oxaliplatin

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23
Q

Mechanism of platinum analogs

A

Platinum binds to DNA bases, causing cross-linking

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24
Q

Method to reduce nephrotoxicity from cisplatin or carboplatin

A

Mannitol and forced hydration

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25
Q

Neurotoxicity side effects associated with cisplatin and carboplatin

A

Peripheral neuritis
Acoustic nerve damage –> tinnitus and hearing loss

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26
Q

Side effect of oxaliplatin

A

Neurotoxicity

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27
Q

Use of dacarbazine

A

Used in Hodgkin’s lymphoma

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28
Q

Mechanism of procarbazine

A

Form hydrogen peroxide that generates DNA damaging free radicals

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29
Q

Chemotherapy drug associated with disulfiram-like reaction with alcohol

A

Procarbazine

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30
Q

Chemotherapy drug that inhibits MAO

A

Procarbazine

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31
Q

Specific side effects of procarbazine

A

CNS dysfunction
Leukemogenic
Difulfiram-like reaction with ethanol
Inhibits MAO

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32
Q

Leukemogenic chemotherapy drugs

A

Procarbazine

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33
Q

Clinical use of Busulfan

A

CML

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34
Q

Busulfan lung

A

Pulmonary fibrosis
Acute lung injury
Chronic interstitial fibrosis
Alveolar hemorrhage

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35
Q

Side effects of Busulfan

A

Skin pigmentation
Adrenal insufficiency
Busulfan lung

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36
Q

Resistance to alkylating agents

A

Increased DNA repair
Decreased drug permeability
Production of trapping agents (thiols)

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37
Q

Examples of antimetabolites

A

Methotrexate
Mercaptopurine
Thioguanine
Fluorouracil
Cytarabine
Gemcitabine

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38
Q

Mechanism of methotrexate

A

Inhibit DHFR
Decreases synthesis of thymidylate, purine nucleotides, and AAs
Increases nucleic acid and protein metabolism

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39
Q

Resistance to methotrexate

A

Reduced drug accumulation
Changes DHFR sensitivity or activity
Reduced formation of polyglutamate

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40
Q

Clinical uses of methotrexate

A

Choriocarcinoma
Acute leukemia
Solid tumors
RA and psoriasis
Ectopic pregnancy

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41
Q

Long term toxicity of methotrexate

A

Hepatotoxicity
Pulmonary infiltrates and fibrosis

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42
Q

Rescue for methotrexate toxicity

A

Leucovorin/folinic acid

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43
Q

Types of purine antimetabolites

A

Mercaptopurine (6-MP)
Thioguanine (6-TG)
Cladribine

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44
Q

Mechanism of 6-MP and 6-TG

A

Activation of HGPRTase
Inhibition of enzymes in purine metabolism

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45
Q

Inhibits metabolism of 6-MP by xanthine oxidase

A

Allopurinol and febuxostat

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46
Q

General inhibitors of 6-MP and 6-TG

A

Reduced HGPRTase activity
Increased production of alkaline phosphatases

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47
Q

Clinical uses of 6-MP and 6-TG

A

Acute leukemias
CML

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48
Q

Toxicity associated with purine antimetabolites

A

Bone marrow suppression
Hepatic dysfunction

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49
Q

Mechanism of cladribine

A

Converted to deoxyadenosine triphosphate and incorporated into DNA
Causes DNA strand breakage

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50
Q

Clinical use of cladribine

A

Hairy cell leukemia

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51
Q

Pyrimidine antimetabolites

A

Fluorouracil (5-FU)
Cytarabine
Gemcitabine

52
Q

Mechanism of 5-FU

A

Converted in cells to 5-fDUMP
Inhibits thymidylate synthase
Incorporated into DNA
Inhibits DNA synthesis
Decreases dTMP

53
Q

Secondary metabolite of 5-FU and its effect

A

FUTP
Incorporated into RNA and interferes with RNA function

54
Q

Chemotherapy drug synergistic with methotrexate

A

Fluorouracil

55
Q

Clinical uses of 5-FU

A

Bladder, breast, colon, and ovarian cancers
Topically for keratosis and BCC

56
Q

Chemotherapy drug used topically for keratosis and BCC

A

Fluorouracil

57
Q

Resistance to 5-FU

A

Decreased activation
Increased thymidylate synthase activity
Reduced drug sensitivity of thymidylate synthase

58
Q

Chemotherapy drug associated with hand-foot syndrome

A

Fluorouracil

59
Q

Specific side effects of 5-FU

A

Neurotoxicity
Hand-foot syndrome

60
Q

Characteristics of hand-foot syndrome

A

Neurotoxicity
Skin toxicity

61
Q

Rescue for 5-FU toxicity

A

Thymidine

62
Q

Mechanism of cytarabine

A

Converted to AraCTP
Inhibits DNA polymerases

63
Q

Resistance to cytarabine

A

Decreased conversion to AraCTP

64
Q

Chemotherapy drug that is a deoxycytidine analog

A

Gemcitabine

65
Q

Mechanism of gemcitabine

A

Inhibits ribonucleotide reductase
Inhibits DNA synthesis and chain termination

66
Q

Active metabolite of gemcitabine

A

Gemcitabine diphosphate

67
Q

Toxicity of gemcitabine

A

Myelosuppression and neutropenia
Pulmonary toxicity

68
Q

Types of natural anticancer drugs

A

Vinca alkaloids
Taxanes
Podophyllotoxin
Camptothecins

69
Q

Types of vinca alkaloids

A

Vinblastine
Vincristine
Vinorelbine

70
Q

Mechanism of vinca alkaloids

A

Prevent assembly of tubulin dimers into microtubules
Block mitotic spindle formation

71
Q

Phase of cell cycle acted on by vinca alkaloids

A

M phase

72
Q

Neurotoxic effects specific to vinca alkaloids

A

Areflexia
Peripheral neuritis

73
Q

Clinical uses of vinblastine and vincristine

A

Acute leukemias
Lymphomas

74
Q

Clinical uses of Vinorelbine

A

Non small cell lung cancer
Breast cancer

75
Q

Types of taxanes

A

Paclitaxel
Docetaxel

76
Q

Mechanism of taxanes

A

Interferes with mitotic spindle
Prevents microtubule disassembly
Hyperstability of microtubules in M phase

77
Q

Clinical uses of taxanes

A

Breast CA
Ovarian CA
Prostate CA
Bladder CA
Lung CA
Gastroesophageal CA

78
Q

Toxicity of paclitaxel

A

Neutropenia
Thrombocytopenia
Peripheral neuropathy

79
Q

Toxicity of docetaxel

A

Neurotoxicity
Bone marrow depression

80
Q

Types of podophyllotoxins

A

Etoposide
Teniposide

81
Q

Mechanism of podophyllotoxins

A

Inhibits topoisomerase II causing DNA breakage

82
Q

Cell phase affected by podophyllotoxins

A

Late S and early G2

83
Q

Types of camptothecins

A

Topotecan
Irinotecan

84
Q

Mechanism of camptothecins

A

Inhibit topoisomerase I causing DNA damage

85
Q

Toxicity of camptothecins

A

Myelosuppression
Diarrhea

86
Q

Types of antitumor antibiotics

A

Anthracyclines
Bleomycin
Mitomycin

87
Q

Types of anthracyclines

A

Doxorubicin
Daunorubicin
Mitoxantrone

88
Q

Mechanism of anthracyclines

A

Inhibit topoisomerase II
Generate free radicals
Intercalate DNA base pairs causing DNA strand scission
Block RNA and DNA synthesis

89
Q

NCCS antitumor antibiotics

A

Anthracyclines
Mitomycin

90
Q

Clinical use of doxorubicin

A

HL and NHL
Myelomas

91
Q

Clinical use of daunorubicin

A

Acute leukemias

92
Q

Most distinctive adverse effect of anthracyclines

A

Cardiotoxicity –> ECG abnormalities, arrhythmias, cardiomyopathy, heart failure

93
Q

Anthracycline toxicity prevention and mechanism

A

Dexrazoxane

Iron chelating that inhibits iron mediated free radical generation

94
Q

Mechanism of Bleomycin

A

Generates free radicals that bind DNA
Inhibits DNA synthesis

95
Q

Clinical uses bleomycin

A

Hodgkin’s lymphoma
Testicular cancer

96
Q

Toxicity of bleomycin

A

Pulmonary dysfunction –> pneumonitis and fibrosis

Redness and hyperpigmentation

97
Q

Clinical uses of mitomycin

A

Adenocarcinomas of the cervix
Stomach CA

98
Q

Toxicity associated with mitomycin

A

Severe myelosuppression

99
Q

Tyrosine kinase inhibitor targeted chemotherapy drug

A

Imatinib

100
Q

Mechanism of imatinib

A

Inhibits tyrosine kinase of bcr-abl oncogene commonly expressed in CML

101
Q

Oncogene associated with Philadelphia chromosome translocation

A

bcr-abl

102
Q

Uses of imatinib

A

CML
GI stromal tumors

103
Q

Chemotherapy drug that inhibitis c-kit tyrosine kinase is GI stromal tumors

A

Imatinib

104
Q

Resistance to imatinib

A

bcr-abl gene mutation

105
Q

Toxicity of imatinib

A

Diarrhea
Fluid retention
CHF

106
Q

Growth factor receptor inhibitor targeted chemotherapy drug

A

Trastuzumab

107
Q

Mechanism of trastuzumab

A

Monoclonal antibody targeting HER2/neu receptor for EGF

108
Q

Use of trastuzumab

A

Breast cancer that overexpresses HER2

109
Q

Toxicity of trastuzumab

A

N/V
Fever and chills
Cardiac dysfunction

110
Q

Roles of EGFR

A

Regulates signaling pathways involved in proliferation, invasion, metastasis, and angiogenesis

Inhibits cytotoxic activity of some anticancer drugs and radiotherapy

111
Q

Chemotherapy drugs associated with EGFR

A

Cetuximab
Panitumumab
Gefitinib
Erlotinib

112
Q

Mechanism of Cetuximab

A

Chimeric monoclonal antibody that targets EC domain of EGFR

113
Q

Use of cetuximab and panitumumab

A

Colorectal cancer

114
Q

Mechanism of panitumumab

A

Fully human monoclonal antibody that targets EC domain of EGFR

115
Q

Mechanism of gefitinib and erlotinib

A

Inhibits tyrosine kinase domain of EGFR

116
Q

Use of gefitinib and erlotinib

A

Non small cell lung cancer

117
Q

Toxicity of EGFR associated chemotherapy drugs

A

Rash
Diarrhea

118
Q

Role of VEGF

A

Angiogenic growth factor

119
Q

Chemotherapy drugs associated with VEGF

A

Sorafenib
Ziv-aflibercept
Bevacizumab

120
Q

Mechanism of sorafenib

A

Inhibits multiple RTKs, including VEGF receptor

121
Q

Toxicity of sorafenib

A

HTN
Bleeding complications

122
Q

Chemotherapy drug that is a recombinant fusion protein targeting VEGF

A

Ziv-aflbercept

123
Q

Mechanism of bevacizumab

A

Binds VEGF to prevent interaction with its receptors

124
Q

Uses of bevacizumab

A

Colorectal CA
Breast CA
Renal CA
Non small cell lung CA

125
Q

Toxicity of bevacizumab

A

HTN
Arterial thrombosis
Impaired wound healing
Proteinuria

126
Q

General mechanisms of chemotherapy resistance

A

Increased DNA repair
Formation of trapping agents
Changes in target enzymes
Decreased activation of prodrugs
Inactivation of drugs
Decreased drug accumulation

127
Q

Resistance mechanism associated with increased expression of MDR1 gene

A

Decreased drug accumulation

HML II (15 decks)

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