Heme Onc and Immuno Drugs

  1. Cyclosporine
    • Inhibits calcineurin --> dec'd T-cell differentiation & activation.
    • SE's: Nephrotoxicity, lymphomas
  2. Tacrolimus
    • Inhibits cytokine release from T-cells (IL-2). Binds FK-binding protein.
    • SE's: Many systems -- nephrotoxicity, pleural effusion, peripheral neuropathy, HTN, hyperglycemia
  3. Azathioprine
    • Inhibits nucleic acid synthesis, which targets proliferating lymphocytes.
    • SE's: bone marrow suppression. Metabolized by xanthine oxidase, so allopurinol may make it toxic.
  4. Muromonab-CD3
    • Monoclonal Ab that binds CD3 (on all T-cells) --> no signal transduction.
    • SE's: Hypersensitivity reaction, cytokine release syndrome
  5. Sirolimus (rapamycin)
    • Blocks T-cell proliferation in response to IL-2, by binding mTOR.
    • SE's: leukopenia, thrombocytopenia, hyperlipidemia
  6. Mycophenolate mofetil
    Inhibits guanine synthesis --> dec'd lymphocyte production.
  7. Daclizumab
    Monoclonal Ab against IL-2 receptor on activated T-cells.
  8. Uses for aldesleukin
    (IL-2): renal cell carcinoma, metastatic melanoma
  9. Filgrastim
    G-CSF. SE's: bone pain
  10. Sargramostim
    GM-CSF. SE's: bone pain, thrombophlebitis at injection site, fever, rash, pleural effusion
  11. alpha-interferon
    Inhibits viral replication; given for Hepatitis B & C, malignant melanoma, leukemias, Kaposi's sarcoma
  12. Try treating malignant melanoma with these 2 cytokines
    Alpha-interferon and IL-2
  13. Beta-interferon
    Inhibits viral replication; given for multiple sclerosis
  14. Gamma-interferon
    Given for chronic granulomatous disease. (Neutrophils not working due to NADPH oxidase deficiency, so stimulate macrophages?)
  15. Cyclophosphamide
    • Anti-neoplastic: alkylating agent at guanine N-7 (remember that P bonds exist in DNA, & alkylating agents create bridges between DNA strands).
    • SE's: bone marrow suppression, hemorrhagic cystitis (give mesna)
    • Use for: NHL, breast, & ovarian cancer
  16. Methotrexate
    • "Tricks" DHF reductase into thinking it's folic acid --> DHF reductase inhibition --> dec'd thymine synthesis.
    • SE's: BM suppression (reverse w/leucovorin), liver fatty change (macrovesicles -- should be micro- since metabolic cause, but this is significant injury)
    • Used for: leukemias & lymphomas, choriocarcinomas, sarcomas... also abortion/ectopic pregnancy, RA, psoriasis
  17. 5-FU
    • Can be used with methotrexate, but in case some folic acid is still made... 5-F + dUMP + folic acid --> inhibit thymidylate synthase. It's a pyrimidine analog.
    • SE's: Bone marrow suppression (thymidine), photosensitivity
    • Uses: Solid tumors -- colon, breast, basal cell carcinoma. Not leukemia/lymphoma.
  18. 6-MP
    • Inhibits de novo purine nucleotide synthesis (i.e. IMP --> XMP + AMP).
    • SE's: bone marrow suppression; liver; metabolized by xanthine oxidase, so allopurinol increases toxicity (just like azathioprine)
  19. Metabolized by xanthine oxidase
    Azathioprine, 6-MP (inhib purine synthesis)
  20. Cytarabine (ara-C)
    • Anti-neoplastic; inhibits DNA polymerase. It's a pyramidine nucleoside analog.
    • Uses: AML, ALL, NHL (high-grade, obv)
    • SE's: BM suppression (the anemia is megaloblastic)
  21. Ifosfamide
    • Alkylating agent (at guanine N-7), must be activated by liver.
    • SE's: BM suppression, nephro- and neurotoxic
  22. Nitrosureas (carmustine, lomustine, semustine, streptozocin)
    Alkylating agents (anti-neoplastic). Cross blood-brain barrier, so use for glioblastomas & other brain tumors... but CNS toxicity (dizzy, ataxia), & also renal & hepatic.
  23. Cisplatin, carboplatin
    • DNA cross-linking (just like an alkylating agent).
    • SE's: not BM suppression, but nephro- and neurotoxic, plus CN 8 damage
    • Uses: Ovary, testicle, bladder, & lung cancer
  24. Busulfan
    • Alkylating agent, used for CML & P.vera.
    • SE's: pulm fibrosis, hyperpigmentation
  25. Doxorubicin, daunorubicin, dactinomycin
    • Like dogs: take bites out of DNA (i.e. intercalation of DNA).
    • Uses: ABVD for Hodgkin's, plus myelomas, & solid tumors
    • SE's: BM suppression, bald, cardiotoxic (not true for dactinomycin, which is used to treat Wilms' tumor, Ewing's sarcoma, & rhabdomyosarcoma)
  26. Bleomycin
    • Free radicals --> DNA strand breaks.
    • SE's: Minimal BM toxicity (bleomycin), but pulm fibrosis, skin changes
    • Uses: Part of ABVD for Hodgkin's; testicular cancer
  27. Hydroxyurea
    • Inhibits ribonucleotide reductase --> dec'd DNA synthesis
    • Uses: Melanoma, CML, sickle-cell (to inc fetal hemoglobin)
    • SE's: BM suppression, GI
  28. Etoposide
    • Inhibits topoisomerase II, inc's DNA degradation. Specific for G2 (right before mitosis).
    • Uses: Small-cell of lung & prostate, testicular cancer
    • Toxicity: BM suppression, GI, bald
  29. Tamoxifen, raloxifene
    • SERM: agonize estrogen receptors in bone (& endometrium --> endometrial cancer risk), but antagonize those in breast.
    • Used to prevent osteoporosis.
  30. Rituximab
    • Anti-CD20 monoclonal Ab. For NHL (since most of these = B-cells, except for lymphoblastic lymphoma & some cases of diffuse lymphoma)
    • When the drug is an Ab, cells die via complement-mediated lysis.
  31. Trastuzumab
    • TRIBE: anti-HER-2 receptor Ab, so kills breast cancer cells for which HER-2 is upregulated.
    • SE's: cardiotoxicity (this tribe doesn't have a heart)
  32. Vincristine & vinblastine
    • Bind tubulin, so microtubules can't polymerize --> no mitotic spindle.
    • Uses: Hodgkin's (MOPP), Wilms' tumor, choriocarcinoma
    • SE's: neurotoxic, paralytic ileus
  33. Paclitaxel
    • Inhibits mitotic spindle disassembly, by hyperstabilizing the polymerized microtubules. (No anaphase.)
    • Uses: ovarian & breast cancer (because women like to hang on to relationships & not disassemble)
    • SE's: BM suppression, hypersensitivity
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Heme Onc and Immuno Drugs
heme Onc and Immuno Drugs