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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
Neurotoxicity side effects associated with cisplatin and carboplatin
Peripheral neuritis Acoustic nerve damage --> tinnitus and hearing loss
26
Side effect of oxaliplatin
Neurotoxicity
27
Use of dacarbazine
Used in Hodgkin's lymphoma
28
Mechanism of procarbazine
Form hydrogen peroxide that generates DNA damaging free radicals
29
Chemotherapy drug associated with disulfiram-like reaction with alcohol
Procarbazine
30
Chemotherapy drug that inhibits MAO
Procarbazine
31
Specific side effects of procarbazine
CNS dysfunction Leukemogenic Difulfiram-like reaction with ethanol Inhibits MAO
32
Leukemogenic chemotherapy drugs
Procarbazine
33
Clinical use of Busulfan
CML
34
Busulfan lung
Pulmonary fibrosis Acute lung injury Chronic interstitial fibrosis Alveolar hemorrhage
35
Side effects of Busulfan
Skin pigmentation Adrenal insufficiency Busulfan lung
36
Resistance to alkylating agents
Increased DNA repair Decreased drug permeability Production of trapping agents (thiols)
37
Examples of antimetabolites
Methotrexate Mercaptopurine Thioguanine Fluorouracil Cytarabine Gemcitabine
38
Mechanism of methotrexate
Inhibit DHFR Decreases synthesis of thymidylate, purine nucleotides, and AAs Increases nucleic acid and protein metabolism
39
Resistance to methotrexate
Reduced drug accumulation Changes DHFR sensitivity or activity Reduced formation of polyglutamate
40
Clinical uses of methotrexate
Choriocarcinoma Acute leukemia Solid tumors RA and psoriasis Ectopic pregnancy
41
Long term toxicity of methotrexate
Hepatotoxicity Pulmonary infiltrates and fibrosis
42
Rescue for methotrexate toxicity
Leucovorin/folinic acid
43
Types of purine antimetabolites
Mercaptopurine (6-MP) Thioguanine (6-TG) Cladribine
44
Mechanism of 6-MP and 6-TG
Activation of HGPRTase Inhibition of enzymes in purine metabolism
45
Inhibits metabolism of 6-MP by xanthine oxidase
Allopurinol and febuxostat
46
General inhibitors of 6-MP and 6-TG
Reduced HGPRTase activity Increased production of alkaline phosphatases
47
Clinical uses of 6-MP and 6-TG
Acute leukemias CML
48
Toxicity associated with purine antimetabolites
Bone marrow suppression Hepatic dysfunction
49
Mechanism of cladribine
Converted to deoxyadenosine triphosphate and incorporated into DNA Causes DNA strand breakage
50
Clinical use of cladribine
Hairy cell leukemia
51
Pyrimidine antimetabolites
Fluorouracil (5-FU) Cytarabine Gemcitabine
52
Mechanism of 5-FU
Converted in cells to 5-fDUMP Inhibits thymidylate synthase Incorporated into DNA Inhibits DNA synthesis Decreases dTMP
53
Secondary metabolite of 5-FU and its effect
FUTP Incorporated into RNA and interferes with RNA function
54
Chemotherapy drug synergistic with methotrexate
Fluorouracil
55
Clinical uses of 5-FU
Bladder, breast, colon, and ovarian cancers Topically for keratosis and BCC
56
Chemotherapy drug used topically for keratosis and BCC
Fluorouracil
57
Resistance to 5-FU
Decreased activation Increased thymidylate synthase activity Reduced drug sensitivity of thymidylate synthase
58
Chemotherapy drug associated with hand-foot syndrome
Fluorouracil
59
Specific side effects of 5-FU
Neurotoxicity Hand-foot syndrome
60
Characteristics of hand-foot syndrome
Neurotoxicity Skin toxicity
61
Rescue for 5-FU toxicity
Thymidine
62
Mechanism of cytarabine
Converted to AraCTP Inhibits DNA polymerases
63
Resistance to cytarabine
Decreased conversion to AraCTP
64
Chemotherapy drug that is a deoxycytidine analog
Gemcitabine
65
Mechanism of gemcitabine
Inhibits ribonucleotide reductase Inhibits DNA synthesis and chain termination
66
Active metabolite of gemcitabine
Gemcitabine diphosphate
67
Toxicity of gemcitabine
Myelosuppression and neutropenia Pulmonary toxicity
68
Types of natural anticancer drugs
Vinca alkaloids Taxanes Podophyllotoxin Camptothecins
69
Types of vinca alkaloids
Vinblastine Vincristine Vinorelbine
70
Mechanism of vinca alkaloids
Prevent assembly of tubulin dimers into microtubules Block mitotic spindle formation
71
Phase of cell cycle acted on by vinca alkaloids
M phase
72
Neurotoxic effects specific to vinca alkaloids
Areflexia Peripheral neuritis
73
Clinical uses of vinblastine and vincristine
Acute leukemias Lymphomas
74
Clinical uses of Vinorelbine
Non small cell lung cancer Breast cancer
75
Types of taxanes
Paclitaxel Docetaxel
76
Mechanism of taxanes
Interferes with mitotic spindle Prevents microtubule disassembly Hyperstability of microtubules in M phase
77
Clinical uses of taxanes
Breast CA Ovarian CA Prostate CA Bladder CA Lung CA Gastroesophageal CA
78
Toxicity of paclitaxel
Neutropenia Thrombocytopenia Peripheral neuropathy
79
Toxicity of docetaxel
Neurotoxicity Bone marrow depression
80
Types of podophyllotoxins
Etoposide Teniposide
81
Mechanism of podophyllotoxins
Inhibits topoisomerase II causing DNA breakage
82
Cell phase affected by podophyllotoxins
Late S and early G2
83
Types of camptothecins
Topotecan Irinotecan
84
Mechanism of camptothecins
Inhibit topoisomerase I causing DNA damage
85
Toxicity of camptothecins
Myelosuppression Diarrhea
86
Types of antitumor antibiotics
Anthracyclines Bleomycin Mitomycin
87
Types of anthracyclines
Doxorubicin Daunorubicin Mitoxantrone
88
Mechanism of anthracyclines
Inhibit topoisomerase II Generate free radicals Intercalate DNA base pairs causing DNA strand scission Block RNA and DNA synthesis
89
NCCS antitumor antibiotics
Anthracyclines Mitomycin
90
Clinical use of doxorubicin
HL and NHL Myelomas
91
Clinical use of daunorubicin
Acute leukemias
92
Most distinctive adverse effect of anthracyclines
Cardiotoxicity --> ECG abnormalities, arrhythmias, cardiomyopathy, heart failure
93
Anthracycline toxicity prevention and mechanism
Dexrazoxane Iron chelating that inhibits iron mediated free radical generation
94
Mechanism of Bleomycin
Generates free radicals that bind DNA Inhibits DNA synthesis
95
Clinical uses bleomycin
Hodgkin's lymphoma Testicular cancer
96
Toxicity of bleomycin
Pulmonary dysfunction --> pneumonitis and fibrosis Redness and hyperpigmentation
97
Clinical uses of mitomycin
Adenocarcinomas of the cervix Stomach CA
98
Toxicity associated with mitomycin
Severe myelosuppression
99
Tyrosine kinase inhibitor targeted chemotherapy drug
Imatinib
100
Mechanism of imatinib
Inhibits tyrosine kinase of bcr-abl oncogene commonly expressed in CML
101
Oncogene associated with Philadelphia chromosome translocation
bcr-abl
102
Uses of imatinib
CML GI stromal tumors
103
Chemotherapy drug that inhibitis c-kit tyrosine kinase is GI stromal tumors
Imatinib
104
Resistance to imatinib
bcr-abl gene mutation
105
Toxicity of imatinib
Diarrhea Fluid retention CHF
106
Growth factor receptor inhibitor targeted chemotherapy drug
Trastuzumab
107
Mechanism of trastuzumab
Monoclonal antibody targeting HER2/neu receptor for EGF
108
Use of trastuzumab
Breast cancer that overexpresses HER2
109
Toxicity of trastuzumab
N/V Fever and chills Cardiac dysfunction
110
Roles of EGFR
Regulates signaling pathways involved in proliferation, invasion, metastasis, and angiogenesis Inhibits cytotoxic activity of some anticancer drugs and radiotherapy
111
Chemotherapy drugs associated with EGFR
Cetuximab Panitumumab Gefitinib Erlotinib
112
Mechanism of Cetuximab
Chimeric monoclonal antibody that targets EC domain of EGFR
113
Use of cetuximab and panitumumab
Colorectal cancer
114
Mechanism of panitumumab
Fully human monoclonal antibody that targets EC domain of EGFR
115
Mechanism of gefitinib and erlotinib
Inhibits tyrosine kinase domain of EGFR
116
Use of gefitinib and erlotinib
Non small cell lung cancer
117
Toxicity of EGFR associated chemotherapy drugs
Rash Diarrhea
118
Role of VEGF
Angiogenic growth factor
119
Chemotherapy drugs associated with VEGF
Sorafenib Ziv-aflibercept Bevacizumab
120
Mechanism of sorafenib
Inhibits multiple RTKs, including VEGF receptor
121
Toxicity of sorafenib
HTN Bleeding complications
122
Chemotherapy drug that is a recombinant fusion protein targeting VEGF
Ziv-aflbercept
123
Mechanism of bevacizumab
Binds VEGF to prevent interaction with its receptors
124
Uses of bevacizumab
Colorectal CA Breast CA Renal CA Non small cell lung CA
125
Toxicity of bevacizumab
HTN Arterial thrombosis Impaired wound healing Proteinuria
126
General mechanisms of chemotherapy resistance
Increased DNA repair Formation of trapping agents Changes in target enzymes Decreased activation of prodrugs Inactivation of drugs Decreased drug accumulation
127
Resistance mechanism associated with increased expression of MDR1 gene
Decreased drug accumulation

HML II (15 decks)

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