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153 Cards in this Set
- Front
- Back
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Antiobiotic anticancer drugs act where?
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In the DNA
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Antibiotic anticancer drugs form complexes with DNA by intercalation. This interaction is covalent or noncovalent?
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Noncovalent
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Name two antiobiotic anticancer drugs:
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1. Daunorubicin
2. Doxorubicin |
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What class of anticancer drug is daunorubicin?
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Antibiotic
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What class of anticancer drug is doxorubicin?
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Antibiotic
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Which antibiotic anticancer drug forms covalent linkages with DNA?
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Mitomycin C
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Mitomycin C forms covalent or noncovalent linkages with DNA?
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Covalent
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What antibiotic anticancer drug causes DNA backbone cleavages?
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Bleomycin
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Bleomycin is known to have what important adverse effect?
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Pulmonary fibrosis
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Decreased Bcl2 and increased Bax leads to what cellular change?
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Apoptosis
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DNA-interacting anticancer drugs bind to what part of DNA?
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Minor groove of DNA
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What base pairs does intercalation of antibiotic anticancer drugs occur at?
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G-C base pair
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What drug is a 3-ring chromophore and two symmetrical cyclic peptides?
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Dactinomycin
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Dactinomycin is a chomophore. This leads to what unusual reaction in the body?
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Red/yellow urine
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What is important to counsel patients about dactinomycin?
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Red/yellow urine
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For which drug is the mechanism of action intercalation into G-C rich regions of DNA?
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Dactinomycin (Actinomycin D)
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What is the net effect of intercalation at low dose of dactinomycin?
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Depression of RNA transcription - depression of rRNA synthesis
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Why is rRNA synthesis in the nucleolus the specific depression caused by dactinomycin?
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High G-C content of rRNA genes - where the drug intercalates with the minor groove of DNA
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Dactinomycin can/cannot also inhibit DNA synthesis
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Can also inhibit DNA synthesis
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What is produced when dactinomycin is metabolized?
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Free radicals which may produce DNA single strand breaks
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What is the dose-limiting toxicity of Dactinomycin?
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Myelosuppression
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What antibiotic anticancer drug is used to treat rhabdomyosarcoma, Wilm's tumor and choriocarcinoma?
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Dactinomycin
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What is the mechanism of action of Plicamycin?
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Intercalate into DNA- compete for binding sites rich in G-C base pairs
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The primary mechanism of Plicamycin is depression of what?
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DNA, RNA, and protein synthesis
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What effect does plicamycin have on calcium levels?
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Lowers calcium levels
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What drug is good to use in patients with hypercalcemia to inhibit bone resorption?
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Plicamycin
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What drug is recommended to inhibit bone resorption?
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Plicamycin
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What is the dose limiting toxicity of anthracycline?
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Cardiac toxicity
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Name two natural anthracyclines:
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Daunorubicin
Doxorubicin |
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Name two semisynthetic anthracyclines
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Idarubicin
Epirubicin |
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What antibiotic agent contains a daunosamine sugar moiety?
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Daunorubicin
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The daunosamine sugar moiety of daunorubicin can interact with what part of DNA?
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Sugar phosphate backbone of DNA
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Daunosamine's main mechanism of action is what?
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Intercalation into DNA - decreased DNA, RNA, protein synthesis
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Daunorubicin is a complex stabilizing inhibitor of what enzyme?
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Topoisomerase II
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Can daunorubicin form free radicals?
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Yes, it can
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Daunorubicin does/does not activate apoptosis signaling pathways?
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Activates apoptotic signaling pathways
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Daunorubicin is administered by what route?
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IV
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Daunorubicin is metabolized where?
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Liver
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When daunorubicin is metabolized by kidney, what can occur?
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Red urine (chromophore)
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What type of cancer is ideal for treatment with daunorubicin?
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Leukemias:
Acute lymphocytic and acute granulocytic leukemias |
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What is the dose limiting toxicity of daunorubicin?
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Cardiac toxicity
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Should daunorubicin be used in patients with cardiac disease?
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Should not be used in patients with cardiac disease
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Antibiotics are/are not cell cycle specific?
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Are not cell cycle specific
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Cells more actively dividing are more/less susceptible to antibiotics and why?
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More susceptible because they are undergoing DNA synthesis
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Daunorubicin or doxirubicin should be avoided in patients with impaired hepatic function?
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Doxirubicin because a significant fraction is metabolized in the liver
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Which drug is more active in the treatment of solid tumors (ie. ovary, breast, lung, sarcomas) Daunorubicin or doxorubicin?
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Doxorubicin
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What is one of the most active agents against metastatic breast tumors, bronchogenic CA, bladder CA, and metstatic thyroid CA?
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Doxorubicin
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What is the dose limiting toxicity of doxorubicin?
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Cardiac toxicity
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What are cardiac cells deficient in that makes it susceptible to daunorubicin and doxorubicin toxicity?
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Scavenging free radicals
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Dexrazoxane is what kind of drug?
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Iron chelator
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What is dexrazoxane used for?
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Help bind and counteract free radical formation
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Name two semisynthetic anthracyclines
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Epirubicin
Idarubicin |
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Epirubicin is what kind of anticancer drug?
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Semi-synthetic anthracycline antibiotic
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Idarubicin is what kind of anticancer drug?
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Semi-synthetic anthracycline antibiotic
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Epirubicin has lower/higher cardiac toxicity than daunorubicin and doxorubicin?
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Lower cardiac toxicity
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What drug is used in combination with Ara-C in AML?
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Idarubicin
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What is the possible mechanism for improved clinical activity against AML with idarubicin?
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Reduced multidrug resistance toward idarubicin
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Elliptacine is what kind of anticancer drug?
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Anthracycline derivative
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Amsacrine is what kind of anticancer drug?
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Anthracycline derivative
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Mitoxantrone is what kind of anticancer drug?
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Anthracycline derivative
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All anthracycline derivatives have what kind of mechanism of action?
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DNA intercalators and produce DNA strand breaks
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What other mechanism of action besides DNA intercalation do anthracycline derivatives have?
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Inhibitors of DNA topoisomerase II enzyme
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What is the difference b/w classic anthracycline and anthracycline derivatives (ellipticine, amsacrine, mitoxantrone)
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Anthracycline derivatives don't have sugar moiety
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Mitoxantrone has limited ability to produce free radicals T/F?
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True
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Mitoxantrone causes more/less cardiac toxicity than doxorubicin?
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Less cardiac toxicity
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What is the major dose limiting toxicity for mitoxantrone?
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Myelosuppression and mucositis
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DNA binding and DNA chain scission is the mechanism of action for what drug?
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Bleomycin
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DNA binding of bleomycin occurs through what kind of interaction?
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Intercalation
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Bleomycin binds Fe2+ and has what effect?
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Oxidizes Fe2+ to Fe3+
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What happens with the lost electron during Bleomycin's oxidation of Fe2+ to Fe3+?
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Forms free radicals with oxygen and produces hydroxyl radicals which attack and break DNA
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Bleomycin is administered:
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IV
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Bleomycin has a short/long half-life?
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short - <30 minutes
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Bleomycin has minimal or significant toxicity to bone marrow?
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Minimal toxicity to bone marrow
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If there is low expression of bleomycin hydrolase in lung and skin what can occur?
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Pulmonary fibrosis and skin hyperpigmentation
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Pulmonary fibrosis and skin hyperpigmentation can occur with bleomycin as a result of deficiency of what enzyme?
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bleomycin hydrolase
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What drug is reduced and active in hypoxic tissues?
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Mitomycin C
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What antibiotic produces free radicals and is an alkylating agent?
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Mitomycin C (removal of O-methyl group)
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The final metabolic product of mitomycin C is capable of producing what in DNA?
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DNA interstrand and intrastrand crosslinks
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Antimitotic drugs disrupt what?
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Microtubules
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Vincristine is what kind of drug?
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Antimitotic - Vinca alkaloid
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Vinblastine is what kind of drug?
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Antimitotic - vinca alkaloid
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Vinorelbine is what kind of drug?
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Antimitotic (semisynthetic) - vinca alkaloid
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Vindesine is what kind of drug?
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Antimitotic (semisynthetic) - vinca alkaloid
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The two semisynthetic antimitotics (Vinorelbine and Vindesine) have more/less neurotoxicity?
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Less neurotoxicity
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Vinca alkaloids bind to what part of the microtubule?
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beta-tubulin
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What occurs what vinca alkaloid binds to beta-tubulin?
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Blocks ability to polymerize with alpha-tubulin.
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Vinca alkaloids cause polymerization or depolymerization?
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Depolymerization
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Taxanes bind to what part of the microtubule?
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Beta tubulin
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Taxanes cause polymerization or depolymerization?
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Polymerization
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Vinca alkaloids are cell-specific/non specific agents?
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Cell-specific agents
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Vinca alkaloids block cells in what phase of the cell cycle?
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Mitosis
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Vinca alkaloids allows/prevents chromosomes to segregate during mitosis
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Prevents chromosome segregation during mitosis
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Disruption of microtubule structures by vinca alkaloids results in activation of what gene?
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p53 tumor suppressor gene --> apoptosis
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MRP1 stands for?
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Multidrug resistance protein 1
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Transmembrane efflux pumps and decreased binding of drug to tubulin are important resistance mechanisms for what drug?
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Vinca alkaloids
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What is the standard component of regimens to treat pediatric leukemias and solid tumors?
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Vincristine
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What is primarily used to treat testicular carcinoma?
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Vinblastine
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Do vinca alkaloids differ in their toxicologic profiles?
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Yes they do
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What is the principal toxic effec of vincristine?
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Peripheral neurotoxicity
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what is the main dose limiting toxicity of vinblastine?
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Neutropenia
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Paclitaxel is what kind of drug?
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Taxane
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Docetaxel is what kind of drug?
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Taxane
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What class of drug promotes polymerization even in the absence of GTP to form abnormal structures?
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Taxanes
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What drug binds specifically to the beta-tubulin and appears to antagonize the disassembly of cytoskeletal proteins?
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Taxanes
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Taxanes activate what pathway?
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p53 tumor suppressor pathway
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Taxanes blocks cells in what phase of the cell cycle?
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late G2 or M phase
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Increased expression of P-glycoprotein is associated with resistance to what drug?
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Paclitaxel
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Tubulin mutations can affect what drug?
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Paclitaxel
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Does taxol binding interfere with nucleotide binding site?
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No, taxol has its own binding site
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What is the main dose limiting toxicity with taxanes?
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Neutropenia, mucositis, neurotoxicity
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Etoposide is what kind of drug?
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epipodophyllotoxin
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Teniposide is what kind of drug?
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Epipodophyllotoxin
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VP-16 is also known as what drug?
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Etoposide
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VM-26 is also known as what drug?
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Teniposide
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What enzyme governs the topological interconversions of DNA by transiently break/rejoining the phosphodiester backbone of one or both strands of double helix?
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Topoisomerase
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Which enzyme breaks/rejoins only one strand of DNA?
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Topoisomerase I
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Which enzyme breaks/rejoins both strands of DNA?
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Topoisomerase II
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Which Topoisomerase prepares DNA for recombination, DNA repair, and RNA transcription?
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Topo I
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Which topoisomerase is vital for DNA replication, chromosome segregation, and maintenence of chromosome structure?
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Topo II
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VP-16 and VM-26 are/are not cell-cycle specific agents?
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Are cell cycle phase specific agents
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What phase of the cell cycle are most sensitive to VP-16 and VM-26?
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S and G2 phase
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How do "classic" inhibitors of Topo II work?
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Block religation of cleaved DNA
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What is the dose limiting toxicity of VP-16 and VM-26?
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Myelosuppression
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What kind of drug is irinotecan?
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Camptothecin analog
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What kind of drug is topotecan?
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Camptothecin analog
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What action do camptothecin analogs have?
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Topoisomerase I inhibitors
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Name two water-soluble analog of camptothecin?
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Irinotecan and topotecan
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What drugs trap and stabilize topo I:DNA intermediate?
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Irinotecan and topotecan
Camptothecin analogs |
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What drugs interfere with moving DNA replication fork?
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Irinotecan and topotecan
Camptothecin analog |
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VP-16 and VM-26 are/are not cell-cycle specific agents?
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Are cell cycle phase specific agents
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What phase of the cell cycle are most sensitive to VP-16 and VM-26?
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S and G2 phase
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How do "classic" inhibitors of Topo II work?
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Block religation of cleaved DNA
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What is the dose limiting toxicity of VP-16 and VM-26?
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Myelosuppression
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What kind of drug is irinotecan?
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Camptothecin analog
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What kind of drug is topotecan?
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Camptothecin analog
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What action do camptothecin analogs have?
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Topoisomerase I inhibitors
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Name two water-soluble analog of camptothecin?
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Irinotecan and topotecan
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What drugs trap and stabilize topo I:DNA intermediate?
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Irinotecan and topotecan
Camptothecin analogs |
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What drugs interfere with moving DNA replication fork?
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Irinotecan and topotecan
Camptothecin analog |
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What drug results in a block of DNA reclosure and persistence of multiple cleavable complexes
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Irinotecan and topotecan
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What drug is used for CRC refractory to 5-FU?
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Irinotecan
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What drug is used for second-line therapy against ovarian cancer and small cell lung cancer?
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Topotecan
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Topotecan is cleared by what route?
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Renal excretion
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Irinotecan is active or a prodrug?
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Prodrug
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Where is irinotecan activated?
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Liver
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What enzyme activates irinotecan?
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Carboxylase esterase
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What is the excretion of irinotecan?
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Biliary excretion
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What is the dose limiting toxicity of topotecan?
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Neutropenia
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What is the dose limiting toxicity of irinotecan?
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Delayed diarrhea and neutropenia
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What enzyme catalyzes Asparagine to aspartic acid and ammonia?
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L-asparaginase
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What types of cells may not have L-asparaginase and have to obtain from plasma?
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Cancer cells
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What treatment deprives cells of Asn required for protein synthesis and leads to cell death?
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L-asparaginase
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What is the major toxicity with L-asparaginase?
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Allergic reaction
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