10 Anti-neoplastic Drugs Flashcards

1
Q

Chemotherapy given to induce a remission

A

Induction chemotherapy

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2
Q

Disappearance of s/s of cancer

A

Remission

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3
Q

Reappearance of s/s

A

Relapse

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4
Q

Course of tx wherein drugs are given for a specific number of days followed by a rest period

A

Cycle

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5
Q

Chemotherapy given after the primary therapy

Usually in advanced cancers, to decrease recurrence and improve survival

A

Adjuvant chemotherapy

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6
Q

Chemotherapy given before the primary therapy

Usually to reduce tumor mass

A

Neoadjuvant chemotherapy

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7
Q

Two kinds of drugs depending on the cell cycle

A

Cell cycle-specific

Cell cycle-nonspecific

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8
Q

Kills cells in the cell cycle, sometimes they are phase-specific
Antimetabolites, bleomycin, plant alkaloids, hormones
Toxicity proportional to length of exposure, schedule dependent
Effective vs tumors with high growth fraction

A

Cell cycle-specific

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9
Q

Can kill those in cell cycle and in those in G0, dose-dependent,
Alkylating agents and antitumor antibiotics except bleomycin
Toxicity is dose dependent
Effective in low and high growth fraction tumors

A

Cell cycle-nonspecific

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10
Q

Growth at every instant is exponential but with a growth constant that is simultaneously exponentially slowing due to depletion of nutrients
Advanced cancers are less responsive to chemotherapy
Curability is inversely proportional to cell number

A

Gompertzian Growth

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11
Q

A constant fraction of cells is killed by a given drug dose

A

Log-kill hypothesis

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12
Q

Factors that affect cell-kill

A
Dose intensity
Schedule
Drug resistance
Tumor site
Px performance status
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13
Q

Drug selection

A
Single drug (choriocarcinoma, Burkitt's lymphoma)
Combination chemotherapy
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14
Q

Anti-cancer regimen for lung Ca

A

Etoposide
Cisplastin
Vincristine

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15
Q

Anti-cancer regimen for breast Ca

A

Cyclophosphamide
Methotrexate
Fluorouracil

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16
Q

General toxicities of anti-cancer regimen

A

Myelosuppression
Nausea and vomiting
Cytotoxicity to other cells

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17
Q

Usual dose-limiting toxicity, prevents you from giving a drug at a dose and schedule you want

A

Myelosuppression

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18
Q

Exceptions for myelosuppression

A
Hormones
Vincristine
Bleomycin
Asparaginase
Cisplastin
Streptozocin
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19
Q

Most common toxicity and CNS in origin

Especially cisplastin

A

Nausea and vomiting

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20
Q

Tx for nausea and vomiting

A

Ondansetron and granisetron (serotonin antagonists)

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21
Q

To manage the myelosuppression among cancer patients due to chemotherapy, give them:

A

Granulocyte colony stimulating factor (G-CSF) + filgastrim

Granulocyte-macrophage colony stimulating factor (GM-CSF) + molgramostim

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22
Q

Mechanisms of acquired drug resistance

A
Improved proficiency in DNA repair
Decrease in drug activation
Increase in drug inactivation
Decrease in cellular uptake of drug
Increase in efflux of drug due to increase in p-glycoprotein
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23
Q

Traditional chemotherapy

A

Antimetabolites
Alkylating agents
Antibiotics
Natural products

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24
Q

Specific chemotherapy

A

Hormones
Biological treatment
Targeted therapy

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25
Q

Examples of antimetabolites

A

Folic acid analogs
Purine analogs
Pyrimidine analogs

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26
Q

Examples of alkylating agents

A

Nitrogen mustard/bischloroethyl amines
Alkyl sulfonates
Nitrosureas
Platinum analogs

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27
Q

Examples of antibiotics

A

Dactinomycin

Anthracyclines

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28
Q

Examples of natural products

A

Vinca alkaloids
Podophyllotoxins
Taxanes
Camptothecins

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29
Q

Folic acid analogs are activated intracellularly by ______ forming polyglutamate metabolites

A

folylpolyglutamate synthase

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30
Q

Folic acid analog drugs

A

Methotrexate
Pemetrexed
Prelatrexate

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31
Q

Actions of folic acid analogs

A

Inhibits thymidylate synthesis, de novo purine synthesis, amino acid (serine, methionine) synthesis

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32
Q

Competes with folic acid for sites in dihydrofolate reductase, thus inhibiting DNA, RNA, protein synthesis

A

Methotrexate

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33
Q

Source of reduced folates

Prevents/treats toxic effects of folic acid analogs

A

Leucovorin (folinic acid)

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34
Q

Pharmacokinetics of MTX

A

Well absorbed orally, metabolized in liver, excreted in urine (kidney-route of elimination)

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35
Q

Adverse effects of MTX

A

Myelosuppression
Stomatitis
Diarrhea - hepatotoxicity

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36
Q

Uses of MTX

A
ALL
ChorioCa
NHL
Psoriasis
Immunosuppression
RA
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37
Q

Purine analog

A

Mercaptopurine (6-MP)

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38
Q

Mercaptopurine is converted to nucleotide form by _____, then incorporated into DNA replacing ____, thus inhibiting de novo purine synthesis

A

HGPRT

Guanine

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39
Q

Mercaptopurine is oxidized in liver by _____

A

Xanthine oxidase

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40
Q

Decrease the dose of mercaptopurine if given with _____ among gout patients
Xanthine oxidase inhibitor

A

Allopurinol

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41
Q

Adverse effects of mercaptopurine

A

Bone marrow depression

Hepatotoxicity

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42
Q

Uses of mercaptopurine

A

Leukemia: ALL, AML, CML

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43
Q

Pyrimidine analogs

A

Fluorouracil (5-FU)

Cytarabine/cytosine arabinoside

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44
Q

The metabolite of 5-FU, ______, binds with ______

A

FdUMP

Thymidylate synthetase

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45
Q

Use of 5-FU

A

IV for adenoCa (colorectal)

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46
Q

Adverse effects of 5-FU

A

Myelosuppression, mucositis, diarrhea, hand-foot syndrome (capecitabine)

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47
Q

Metabolite of cytarabine that blocks DNA synthesis and incorporated into the DNA and RNA

A

ara-CTP

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48
Q

Use of cytarabine

A
Hematologic malignancies (AML)
Not solid tumors
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49
Q

CCNS
Highly reactive compounds which form covalent bonds with electron rich sites in nucleic acids, phosphates, amino acids, proteins
Results in DNA fragmentation, cross-linking, mispairing

A

Alkylating agents

50
Q

Adverse effects of alkylating agents

A
Bone marrow suppression
Vesicant effects
Gonadal damage, azoospermia
Hemorrhagic cystits
Neurotoxicity
Pulmonary toxicity
Nephrotoxicity
Carcinogenic, teratogenic, mutagenic
51
Q

Alkylating agents causing hemorrhagic cystitis

A

Cyclophosphamide

Ifosphamide

52
Q

Alkylating agents causing neurotoxicity

A

Decarbazine
Platinum analogs
Ifosphamide

53
Q

Alkylating agents causing pulmonary toxicity

A

Busulfan
Carmusine
Melphalan

54
Q

Alkylating agents causing nephrotoxicity

A

Nitrosureas

Cisplatin

55
Q

Alkylating agents that are potentially carcinogenic (AML)

A

Melphalan
Nitrosureas
Procarbazine

56
Q

Uses of alkylating agents: cyclophosphamide, cisplatin

A

Wide spectrum

57
Q

Uses of alkylating agents: nitrosureas (carmustine, lomustine)

A

Brain tumors

58
Q

Uses of alkylating agents: chlorambucil, carboplatin

A

Ovarian cancer

59
Q

Uses of alkylating agents: busulfan

A

CML

60
Q

Pro-drug

Favorable therapeutic index and broadest spectrum of activity of all alkylating agents

A

Cyclophosphamide

61
Q

Cyclophosphamide is activated in liver and converted into in cells to ____ and ____

A

Cytotoxic phospharamide

Acrolein

62
Q

Pharmacokinetics of cyclophosphamide

A

Oral, IM or IV

Excreted via kidneys

63
Q

Adverse effects of cyclophosphamide

A

Alopecia

Sterile hemorrhagic cystitis

64
Q

CCNS
Bind to DNA thru intercalation between specific bases and block the synthesis of DNA/RNA
Cause DNA strand scission by generating free radicals and forming complexes with topoisomerase II

A

Antitumor antibiotics

65
Q

Adverse effects of antitumor antibiotics: which drugs can cause local tissue necrosis?

A

Dactinomycin

Doxorubicin

66
Q

Adverse effects of antitumor antibiotics: which drugs can cause cardiotoxicity?

A

Dactinomycin

Doxorubicin

67
Q

Antidote for the cardiotoxicity caused by antitumor antibiotics
Works by chelating iron to prevent iron-mediated lipid peroxidation

A

Dexrazoxane

68
Q

Adverse effects of antitumor antibiotics: which drugs can cause mucocutaneous and pulmonary toxicity?

A

Bleomycin

69
Q

Adverse effects of antitumor antibiotics: which drugs can cause radiation recall reaction

A

Anthracyclines

Dactinomycin

70
Q

Erythematous area of the skin that appears at the site which was previously irradiated after giving the drugs

A

Radiation recall reaction

71
Q

Adverse effects of antitumor antibiotics: which drugs can cause flare

A

Doxorubicin (adriamycin flare)

72
Q

Erythematous area on the skin overlying the vein, where the drug was administered
Local hypersensitivity reaction
Not due to extravasation of drug (pain and death)

A

Adriamycin flare

73
Q

Common among breast cancer patients who underwent mastectomy

A

Radiation recall dermatitis

74
Q

MOA of vinca alkaloids

A

Mitotic inhibitor

Binds to tubulin, thus inhibiting the assembly of the microtubules (metaphase arrest)

75
Q

Examples of vinca alkaloids

A

Vincristine

Vinblastine

76
Q

Pharmacokinetics of vinca alkaloids

A

IV, metabolized by CYP450, excreted in feces

77
Q

Adverse effects of vinca alkaloids

A

Neurotoxicity (vincristine)

Myelosuppresion (vinblastine)

78
Q

MOA of taxanes

A

Mitotic inhibitors

Promote tubulin formation but prevent depolymerization/disassembly

79
Q

Source of taxanes

A

/Taxus/ (Pacific yew trew)

80
Q

Examples of taxanes

A

Paclitaxel

Docetaxel

81
Q

MOA of epipodophyllotoxins

A

Inhibits topoisomerase II

82
Q

Epidodophyllotoxin drug

A

Etoposide

83
Q

MOA of camptothecins

A

Inhibits topoisomerase I
Binds to DNA-TOP I complex
Arrest at S phase

84
Q

From E. coli

Inhibits protein synthesis in cells that cannot synthesize L-asparagine

A

L-aspariginase (leunase)

85
Q

Use of L-asparaginase

A

ALL

86
Q

Adverse effect of L-asparaginase

A

Hypersensitivity

87
Q

Interfere with lymphoid proliferation and cause dissolution of lymphocytes

A

Glucocoticosteroids (prednisone)

88
Q

Use of glucocorticosteroids

A

Leukemia

Lymphoma

89
Q

Side effects of glucocorticosteriods

A

Cushingoid features
Na and water retention
Osteoporosis
Peptic ulcer

90
Q

Use of estrogens (estradiol, conjugated estrogens)

A

Prostate cancer

Male breast cancer

91
Q

Use of progestins (megestrol)

A

Endometrial cancer

92
Q

Use of androgens (testosterone, fluoxymesterone)

A

Female breast cancer

93
Q

MOA of anti-estrogen (tamoxifen)

A

Compete with estradiol for binding estrogen receptors

94
Q

Use of anti-estrogen

A

DOC for palliative tx of advanced breast CA

95
Q

Adverse effects of tamoxifen

A

Hot flushes
Vaginal dryness
Nausea

96
Q

Anti-androgens

A

Flutamide
Cyproterone
Acetate

97
Q

GnRH agonists

A

Leuprolide
Goserelin
Buserelin

98
Q

Use of GnRH agonists

A

Prostate cancer

99
Q

Use of living organisms, substances derived from living organisms, or laboratoy-produced versions of such substances to treat disease

A

Biological/immunotherapy

100
Q

Use of IFN-alpha

A

CML

Kaposi’s sarcoma

101
Q

Use of IL-2

A

Renal cell Ca

Melanoma

102
Q

Use of BCG

A

Urinary bladder Ca in situ

103
Q

Use of monoclonal Ab (rituximab)

A

Indolent B cell lymphomas

Autoimmune diseases

104
Q

Block fundamental mutations that cause cancer e.g. aberrant growth factor receptors, dysregulated intracellular signaling pathways, tumor angiogenesis

A

Targeted therapies

105
Q

Often inhibit multiple enzymatic sites
Plasma t1/2 (12-24 hours)
Once daily oral administration
Substrate of hepatic CYPs

A

Tyrosine kinase inhibitors

106
Q

Generally specific for a single receptor
Long plasma t1/2 (weekly)
Intermittent IV administration (weekly)

A

MAb

107
Q

TKI drugs

A

Imatinib
Nilotinib
Dasatinib

108
Q

Inhibitor of bcr-abl, c-kit, PDGFR, tyrosine kinase
Oral, metabolized by CYP3A4
Side effects include nausea, vomiting, fluid retention

A

Dasatinib

109
Q

Uses of dasatinib

A

CML

GI stromal tumors

110
Q

EGFR TKI drugs

A

Erlotinib

Gefitinib

111
Q

EGFR MAbs

A

Cetuximab

112
Q

Oral, hepatic CYP3A4
NSCLC, pancreatic Ca (erlotinib)
Adverse effects include diarrhea, pustular rash, liver/renal toxicity

A

EGFR TKIs

113
Q

IV
Head and neck squamous cell Ca, colon Ca
Adverse effects include diarrhea, acneiform rash, interstitial diseases, anaphylaxis

A

EGFR MAbs

114
Q

HER2/neu TKI drug

A

Lapatinib

115
Q

HER2/neu MAb drug

A

Trastuzumab

116
Q

Oral, hepatic CYP3A4 metabolism
Breast Ca not responsive to trastuzumab
Adverse effects include diarrhea, pustular rash

A

HER2/neu TKIs

117
Q

IV
HER2/neu-overexpressing metastatic breast Ca
Adverse effects include infusion reactions (fever, chills)

A

HER2/neu MAbs

118
Q

VEGF TKI drugs

A

Sunitinib
Sorafenib
Pazopanib

119
Q

VEGF MAbs

A

Bevacizumab

120
Q

Promotes angiogenesis

A

VEGF

121
Q

Oral, hepatic CYP3A4 metabolism
Renal cell Ca, GIST
Adverse effects include HPN, bleeding, fatigue, arterial thromboembolism

A

VEGF TKIs

122
Q

IV
Renal cell Ca, lung Ca, colorectal Ca
Adverse effects include HPN, bleeding, decreased wound healing, arterial TE, GI perforation

A

VEGF MAbs