Anticancer drugs

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Author:
manjinder
ID:
146885
Filename:
Anticancer drugs
Updated:
2012-04-11 01:22:33
Tags:
cancer
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Description:
drug for cancer
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  1. S phase specific
    • Cytarabine
    • 6-thioguanine
    • 6-mercaptopurine
    • 5-FU
    • methotrexate
    • Hydroxyurea
    • Etoposide
  2. G2 phase
    Bleomycin
  3. M phase
    • vinblastine
    • vincristine
    • paclitaxel
  4. G0 phase
    • alkylating agents
    • antitumor antibiotics
    • nitrosoureas (lomustine, carmustine)
  5. Cyclophosphamide
    • p450 mediated biotransformation of cyclophophamide to alkylating agent that attacks at guanine N7 (covalently X-link DNA) and acrolein (toxic form)
    • Use: non-hodgkin, ovarian, breast and neuroblastoma
    • Toxicity: myelosuppression, hemorrhagic cystitis from acrolein (mesna binds acrolein to protect the bladder, hydration also helps)
  6. Cisplatin, carboplatin
    • cross-links DNA strands
    • Testicular, ovarian, bladder, lung cancer
    • Toxicity: nephrotoxicity (prevent with amifostine-free radical scavenger) and acoustic nerve damage.
  7. Busulfan
    • Alkylates DNA
    • ablate patient's bone marrow before bone marrow tansplantation
    • Toxicity: pulmonary fibrosis, hyperpigmentation
  8. Nitrosoureas (carmustine, lomustine, semustine, streptozocin)
    • require bioactivation. cross BBB
    • Brain tumors (glioblastoma multiforma)
    • CNS toxicity (dizziness, ataxia)
  9. Procarbazine
    • reactive agent that forms hydrogen peroxide, which generates free radicals that cause DNA strand scission
    • Hodgkin's and non-Hodgkin's lymphoma and brain tumors
    • Toxicity: myelosuppressant, leukemogenic (cause cancer)
  10. Dactinomycin
    used for childhood tumors (children ACT out)
    • intercalates in DNA
    • Wilms' tumor, Ewing's sarcoma, rhabdomyosarcoma,
  11. Doxorubicin, adriamycin, daunorubicin
    • generates free radicals, noncovalently intercalate in DNA --> breaks in DNA --> dec replication
    • Use: Hodgkin, melomas, sarcomas, solid tumors (breast, endometrial, lung and ovarian)
    • Toxicity: BMS, delayed CHF (dexrazoxane is an iron-chelating agent preventing the formation of free radicals)
  12. Etoposide, teniposide
    • inhibits topoisomerase II --> inc DNA degradation
    • small cell carcinoma of the lung and prostate, testicular carcinomas
  13. Methotrexate
    • folic acid analog that inhibits dihydrofolate reductase --> dec dTMP --> dec DNA and dec protein synthesis
    • Use: cancer, abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis
    • Toxicity: myelosuppression which is reversered by leucovorin (folinic acid); macrovesicular fatty change in liver, teratogenic
  14. 5- fluorouracil
    • pyrimidine analog covalently complexes folic acid --> complex inhibits thymidylate synthase
    • use: cancer, neck cancer-topical for basal cell cancer and keratoses
    • Toxicity: photosensitivity
  15. Hydroxyurea
    • inhibits ribonucleotide reductase --> dec DNA synthesis
    • melanoma, CML, sickle cell disease
  16. 6-mercaptopurine
    • Purine analog --> dec de novo purine synthesis
    • activated by HGPRTase
    • Leukemias, lymphomas (not CLL or Hodgkin's)
    • Metabolized by xanthine oxidase thus inc toxicity w/ allopurinol
  17. Bleomycin
    • complexes w/ Fe and O2 --> DNA strand scission by creating free radicals
    • hodgkin, testicular, head, neck, skin cancer
    • Toxicity: pneumonitis, pulmonary fibrosis
  18. 6-thioguanine
    • Purine analog --> dec de novo purine synthesis
    • activated by HGPRTase
    • acute lymphoid Leukemias, lymphomas
    • can by given w/ allopurinol
  19. Vincristine, vinblastine
    • alkaloids that bind to tubulin in M-phase and block polymerization of microtubules so that mitotic spindle can't form.
    • hodgkin's lymphoma, wilms' tumor, choriocarcinoma, ALL
    • Vincristine- neurotoxicity, paralytic ileus
    • Vinblastine- bone marrow suppression
  20. Paclitaxel
    • hyperstablize polymerized microtubules in M-phase so that mitotic spindle can't break down
    • Toxicity: hypersensitivity
  21. Colchicine, vincas, paclitaxel
    inhibit microtubule. stop cell cycle in M phase
  22. Prednisone
    most commonly used glucocorticoid in cancer chemotherapy.
  23. Aldesleukin (IL-2)
    used to inc BM cells
  24. Filgrastim
    • granulocyte colony-stimulating factor
    • recovery of bone marrow
  25. Sargramostim
    • granulocyte-macrophage colony-stimulating factor
    • recovery of bone marrow
  26. Tamoxifen, raloxifene
    • SERMs- receptor antagonists in breast and agonists in bone. Block the binding of estrogen to estrogen receptor- positive cells
    • Use: breast cancer. also used to prevent osteoporosis
    • Toxicity: Tamoxifen- inc risk of endometrial carcinoma
    • Raloxifene- no inc in endometrial carcinoma
  27. Imatinib
    • Philadelphia chromosome bcr-abl tyrosine kinase inhibitor
    • Toxicity: fluid retention

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