AntiNeoplastics V.txt

  1. What are the top 3 cancers in each sex?
    • Men: prostate > lung > colon/rectum
    • Women: breast > lung > colon/rectum
  2. Which anticancer Rx act as antimetabolites? [BOOM]
    • Mercaptopurine,
    • Methotrexate,
    • Fluorouracil
  3. Which cause DNA damage? [BOOM]
    • Busulfam,
    • mechlorethamine,
    • carmustine,
    • cyclophosphamide,
    • cisplatin
  4. DNA function? [BOOM]
    Daunorubicin, doxorubicin, bleomycin, topoisomerase
  5. Transcription? [BOOM]
  6. Protein synthesis? [BOOM]
  7. What anticancer Rxs alter protein fxn? [BOOM]
    Vinblastine, vincristine, paclitaxel
  8. What normal cells are often most affected by cancer Tx?
    Fast growing cells: marrow, GI, hair follicles, renal, hepatic, reproductive, teratogenic
  9. What is radiation recall?
    Tx c chemo after radiation may cause appearance of radiation burns from previous radiation
  10. What rationale should be considered when combining chemo Tx?
    Don't use multiple Rxs that cause marrow suppression because they will not Inc the therapeutic index
  11. What are the alkylating agents?
    Mechlorethamine, cyclophosphamide, busulfan, carmustin, streptozocin, cisplatin
  12. What is their MOA?
    • Alkylate DNA --> cause miscoding, breakage, crosslinking
    • NOT cell cycle specific (can be given as a bolus)
  13. What toxicities are common to the alkylating agents?
    • Vesicants: tissue damage @ injection site (except cyclophosphamide)
    • N/V/D
    • Rapidly proliferating cells: marrow, GI, sperm, hair
    • Immunosuppression
    • Teratogenesis, sterility
  14. Why is cyclophosphamide not a vesicant?
    It is a pro-Rx that must be activated in the liver
  15. What is the MOPP regimen and when is it used?
    • Mechlorethamine, vincristine (Oncovin), prednisone, procarbazine
    • Used in: Hodgkin's, lymphocytic leukemia, lymphosarcoma
  16. What is the unique toxicity of mechlorethamine?
    Hyperuricemia --> acute renal failure, nephrolithiasis
  17. What is the Tx of hyperuricemia?
    • Alkalinize urine and use allopurinol (xanthine oxidase inhibitor)
    • Reminder: may provoke gouty attack in gout, use colchicine prophylaxis
  18. What activates cyclophosphamide?
  19. What are its uses?
    Wide use: leukemia, solid tumors, immunosuppression in transplants
  20. What are its side effects?
    • Hematologic toxicity (immune suppression)
    • Hemorrhagic cystitis [BOOM] --> prevented c MESNA
    • SIADH [BOOM]
  21. What is interesting about the pharmacokinetics of chlorambucil?
    Slow acting
  22. When is chlorambucil used?
    CLL, myeloma, autoimmune dz
  23. What are the uses of thiotepa?
    • Bladder CA
    • 2nd choice in breast and ovarian CA
  24. When is busulfan used?
    • CML
    • Reminder: Philadelphia chromosome t(9;22) BCR-ABL gene tyrosine kinase mutation, ONLY leukemia c thrombocytosis
    • Also treated c imatinib (Gleevec)
  25. What is its unique toxicity?
    Hyperuricemia --> treat c allopurinol
  26. What nitrosoureas are lipophilic and cross BBB?
    Carmustine, lomustine --> used for gliomas and other brain CA
  27. What is the MOA of nitrosureas?
    Inhibit DNA/RNA synthesis --> kill in ALL phases of cycle
  28. What are the uses of carmustine?
    Hodgkin's and non-Hodgkin's lymphoma, multiple myelomas, melanoma, GI, brain tumors
  29. What is its major toxicity?
    Profound myelosuppression --> delayed
  30. When is lomustine used?
    Brain tumors, melanoma, GI (all side effects same as carmustine)
  31. What additional unique toxicity is seen c lomustine and carmustine? [BOOM]
    Pulmonary toxicity, renal toxicity
  32. What is unique about streptozocin? [BOOM]
    Selective for Beta-islet cells in pancreas
  33. How does cisplatin differ from the other alkylating agents in structure?
    It is a platinating agent --> crosslinks DNA
  34. How does cisplatin interact c other anticancer agents?
    • Sensitizes the cells to radiation
    • Does NOT cause myelosuppression --> combine c Rx that cause myelosuppression to Inc. effectiveness
  35. What is its spectrum?
    Broad: testicular, ovarian, bladder, head, neck, lung
  36. What are its toxicities?
    • Acoustic nerve damage, anaphylaxis, renal toxicity
    • Reminder: aminoglycosides also cause ototoxicity
  37. What are the antimetabolite Rxs?
    Methotrexate, mercaptopurine, fluorouracil, cytarabine, hydroxyurea
  38. What is the methotrexate MOA?
    • Inhibits DHF reductase to prevent DHF ? THF
    • This prevents formation of thymidylate which blocks DNA, RNA, & protein synthesis
  39. What is the consequence of inhibition of DHF reductase?
  40. What is used to ? toxicity of methotrexate?
    Leucovorin (THF)
  41. What are the uses of methotrexate?
    • ALL, Burkitt's, Non-Hodgkin's lymphomas
    • Reminder: Burkitt's is t(8;14) d/t EBV, *starry sky* appearance of B-cells
    • Reminder: ALL most common CA in children, B-cell > T-cell

    • Choricoarcinoma
    • Breast, head, neck, ovary, and bladder carcinomas
    • Osteosarcoma
    • Immunosuppression: RA, psoriasis
  42. What is methotrexates unique toxicity?
  43. What are the purine antimetabolites?
    Mercaptopurine, thiguanine
  44. What is their MOA?
    • Converted to nucleotide by HGPRT --> inhibit DNA and RNA synthesis
    • Not cell cycle specific
    • Resistance is via dec. in HGPRT
    • Reminder: HGPRT in purine salvage pathway, defective in Lesch-Nyhan (XR) --> accumulation of uric acid
  45. What is the major Rx interaction of mercaptopurine? [BOOM]
    Metabolized by xanthine oxidase --> allopurinol Inc. effectiveness and toxicity
  46. When is it used?
  47. What are its toxicities?
    • Bone marrow suppression
    • Jaundice d/t cholestasis
  48. What are the pyrimidine antimetabolites?
    5-fluorouracil and cytarabine
  49. What is the the 5-FU MOA?
    Inhibits thymidylate synthase (rate limiting enzyme in DNA synthesis)
  50. Where does it act in the cell cycle?
    G1 and S phases
  51. How does it react c leucovorin?
    Needs THF to form thymidylate synthase complex, so leucovorin Inc. its effectiveness

    Leucovorin has opposite effect on methotrexate
  52. What are the uses of 5-FU?
    • Broad spectrum use in solid tumors
    • Topical for basal cell carcinoma
  53. What is the cytarabine MOA?
    Competes c dCTP --> chain termination in DNA synthesis
  54. In what phase of the cell cycle does cytarabine work?
    S phase
  55. When is it the DOC?
    AML (Reminder: t(15;17) in promyelocytic leukemia, Auer rods)
  56. What is the MOA of daunorubucin and doxorubicin?
    Intercalate and bind DNA in S-phase, generate free radicals
  57. What are their toxicities?
    • Cardiotoxicity--> 2ndary to production of free when combined c Fe
    • Based on peak concentration --> infuse Rx slowly
    • Treat c iron chelator (dexrazoxane), worse when combined c Herceptin
    • Turn urine red
    • Vesicant, depresses marrow, alopecia
  58. When is daunorubicin used?
    Leukemias (doxorubicin has a wide use)
  59. What is the bleomycin MOA?
    • Directly damages (*chops up*) DNA
    • Cell cycle specific (G2 and M)
  60. How is it given?
    Orally or into bladder
  61. When is it used?
    Highly effective for testicular and ovarian CA, used in many others
  62. What is its major toxicity?
    Pulmonary fibrosis
  63. What is the dactinomycin MOA?
    Binds DNA between C-G, causes strand breaks, stops RNA synthesis
  64. What are its uses?
    • Wilm's tumor, rhabdomyosarcoma, choriocarcinoma, sarcomas
    • Immune suppression --> transplants
  65. What is the major toxicity of dactinomycin?
    Radiation recall
  66. What are the plant alkaloids?
    Vincristine, vinblastine, paclitaxel (Taxol)
  67. What is their MOA?
    Vincristine, vinblastine --> destabilize microtubules

    Paclitaxel --> stabilizes microtubules
  68. When is vincristine used?
    Leukemia, Hodgkin's, NHL
  69. What are the vincristine toxicities?
    • Neurotoxicity--> "velvet glove" tingling in the hands [vincristine, crisps the nerves]
    • Low myelosuppression (used in many combo therapies)
  70. What are the vinblastine toxicities?
    Myelosuppression [vinblastine, blasts the blood], less neurotoxic
  71. When is vinblastine used?
    Testicular carcinoma, Hodgkin's, Kaposi's sarcoma
  72. When is paclitaxel used?
    Advanced breast, ovary, lung, head, neck
  73. What are its toxicities?
    Peripheral neuropathies, myalgia, arthralgia, hypersensitivity, myelosuppression
  74. What is the MOA of etoposide?
    Binds topoisomerase II --> DNA strand breaks
  75. When is it used?
    Testicular CA, myelosuppression
  76. What is the MOA of topotecan?
    Binds topoisomerase I --> cell cycle arrest, DNA damage
  77. When is it used?
    Ovarian CA, myelosuppression
  78. What is the MOA of asparaginase? [BOOM]
    Cancer cells require asparagine, but many lack asparagine synthase so they need exogenous forms. This Rx hydrolyzes asparagine --> aspartate
  79. When is it used?
    In combo for Tx of ALL
  80. What is the MOA of interferon alfa-2a (Roferon)?
    Dec. tumor cell proliferation
  81. When is it used?
    Hairy cell leukemia, Kaposi's sarcoma, condylomata acuminata
  82. What are the toxicities?
    • Flu-like Sx: myalgia, arthralgia
    • CNS: depression
  83. What is the MOA of IL-2?
    Inc. T cell (CD8) to tumor cells
  84. When is IL-2 used?
    Advanced malignant melanoma, renal cell CA
  85. What are the toxicities?
    • Hypotension, edema, vascular leak, resp. insufficiency
    • Anemia, thrombocytopenia
    • N/V/D
  86. What is the use of G-CSF?
    Prevent or reverse neutropenia d/t antineoplastics
  87. How are corticosteroids used in cancer Tx?
    In cancers of the immune system, to combat radiation-induced edema
  88. When are androgens used?
    Breast CA
  89. When are progestins used?
    Endometrial/breast CA
  90. What is the use of flutamide?
    Blocks androgen receptors --> used in prostate CA
  91. When are estrogens used?
    Prostate CA
  92. When are GnRH agonists used?
    To shut down androgen production (block initial surge c flutamide)
  93. What is the MOA of tamoxifen?
    Estrogen antagonist in breast, agonist in uterus
  94. What are the toxicities?
    Hot flashes, nausea, uterine changes, Dec. HDL
  95. When is trastuzumabe used?
    HER2 antibody in HER2 expressing CA
  96. What is its major toxicity?
  97. What is the imatinib (Gleevec) MOA?
    Inhibitor of Bcr-Abl fusion tyrosine kinase (CML)
  98. What is the major toxicity?
    High rate of CHF
  99. Which Rxs caue radiation recall?
    Dactinomycin, hydroxyurea
  100. Pulmonary fibrosis?
    Bleomycin, busulfan
  101. Neuropathy?
    Vincristine, vinblastine, paclitaxel
  102. Hyperuricemia?
    Mercaptopurine, busulfan
  103. Renal and acoustic nerve?
  104. Which Rx causes red urine?
  105. Hepatotoxicity?
    Mercaptopurine, BCNU, CCNU, methotrexate
  106. Cystitis?
  107. Cardiomyopathy?
    Doxorubicin, daunorubicin, imatinib
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AntiNeoplastics V.txt