pharm3

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Neda317
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296017
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pharm3
Updated:
2015-07-26 01:05:24
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pharm
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pharm
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340, 408-413 Endo & cancer
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  1. (conivaptan,tolvaptan)
    • ADH antagonists
    • SIADH, block action of ADH at V2-receptor
  2. Desmopressin acetate
    Central (not nephrogenic) DI.
  3. GH
    GH deficiency, Turner syndrome.
  4. Oxytocin
    Stimulates labor, uterine contractions, milk let-down; controls uterine hemorrhage
  5. Somatostatin(octreotide)
    Acromegaly, carcinoid syndrome, gastrinoma, glucagonoma, esophageal varices
  6. Demeclocycline
    MOA
    CLINICAL USE
    TOXICITY
    • -ADH antagonist (member of tetracycline family)
    • -SIADH.
    • -Nephrogenic DI, photosensitivity, abnormalities of bone and teeth.
  7. Cinacalcet
    MOA
    CLINICAL USE 
    TOXICITY
    • -Sensitizes Ca2+-sensing receptor (CaSR) in parathyroid gland to circulating Ca2+ Ž--> dec. PTH.
    • -Hypercalcemia due to 1° or 2° hyperparathyroidism.
    • -Hypocalcemia.
  8. Cladribine (2-CDA) MOA
    Purine analog -->Ž multiple mechanisms (e.g., inhibitionof DNA polymerase, DNA  strand breaks).
  9. Cladribine (2-CDA) Use
    Hairy cell leukemia.
  10. Cladribine (2-CDA) toxicity
    Myelosuppression, nephrotoxicity, and neurotoxicity.
  11. Cytarabine(arabinofuranosyl cytidine) MOA
    Pyrimidine analog -->Ž inhibitionof DNA polymerase.
  12. Cytarabine(arabinofuranosyl cytidine) 
    USE 
    Toxicity
    Leukemias (AML), lymphomas.

    Leukopenia,thrombocytopenia,megaloblastic anemia.CYTarabine causes panCYTopenia
  13. 5-fluorouracil (5-FU) MOA
    • Pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folic acid.
    • This complex inhibits thymidylate synthaseŽ --> dec. dTMP--> dec.Ž  DNA synthesis.
  14. 5-fluorouracil (5-FU) 
    Use
    Toxicity
    Colon cancer, pancreatic cancer, basal cell carcinoma(topical).

    Myelosuppression, which is not reversible with leucovorin(folinic acid).
  15. Methotrexate (MTX) MOA
    Folic acid analog that competitively inhibits dihydrofolate reductaseŽ --> dec. dTMP Ž --> dec.  DNA synthesis.
  16. Methotrexate (MTX) 
    use
    toxicity
    • Cancers: leukemias(ALL), lymphomas,choriocarcinoma, sarcomas.
    • Non-neoplastic: ectopic pregnancy, medical abortion (with misoprostol), rheumatoid arthritis, psoriasis,IBD, vasculitis.

    Myelosuppression, which is reversible with leucovorin“rescue.”Hepatotoxicity. Mucositis (e.g., mouth ulcers).Pulmonary fibrosis.
  17. Antitumor antibiotics
    • Bleomycin
    • Dactinomycin (actinomycin D)
    • Doxorubicin, daunorubicin
  18. Doxorubicin,daunorubicin 
    use
    toxicity
    Solid tumors, leukemias,lymphomas.

    • Cardiotoxicity (dilated cardiomyopathy), myelosuppression, alopecia.
    • Toxic to tissues following extravasation Dexrazoxane (iron chelating agent), used to prevent cardiotoxicity
  19. what to use to prevent cardiotoxicity of Doxorubicin, daunorubicin
    Dexrazoxane (iron chelating agent)
  20. Alkylating agents
    • Busulfan
    • Cyclophosphamide, ifosfamide
    • Nitrosoureas (carmustine,lomustine, semustine, streptozocin)
  21. Busulfan 
    MOA
    Use
    Toxicity
    Cross-links DNA.

    CML. Also used to ablate patient’s bone marrow before bone marrow transplantation.

    Severe myelosuppression (in almost all cases), pulmonary fibrosis, hyperpigmentation.
  22. Cyclophosphamide,ifosfamide
    MOA 
    Use 
    toxicity
    Cross-link DNA at guanine N-7. Require bioactivation by liver.

    Solid tumors, leukemia, lymphomas.

    Myelosuppression;hemorrhagic cystitis, partially prevented with mesna (thiol group of mesna binds toxic metabolites).
  23. w Cyclophosphamide,ifosfamide : hemorrhagic cystitis, partially prevented with
    prevented with mesna (thiol group of mesna binds toxic metabolites)
  24. Nitrosoureas are
    • carmustine,
    • lomustine,
    • semustine,
    • streptozocin
  25. Nitrosoureas(carmustine,lomustine,semustine,streptozocin)
    MOA 
    use
    toxicity
    Require bioactivation. Cross blood-brain barrier --> Ž CNS. Cross-link DNA.

    Brain tumors (including glioblastoma multiforme).

    CNS toxicity (convulsions,dizziness, ataxia).
  26. Microtubule inhibitors
    • Paclitaxel, other taxols
    • Vincristine, vinblastine
  27. Vincristine, vinblastine
    MOA
    use
    toxicity
    Vinca alkaloids that bindβ-tubulin and inhibitits polymerization intomicrotubules Ž preventmitotic spindle formation(M-phase arrest).

    Solid tumors, leukemias,Hodgkin (vinblastine) and non-Hodgkin (vincristine)lymphomas.

    Vincristine: neurotoxicity(areflexia, peripheral neuritis),paralytic ileus.Vinblastine blasts bone marrow (suppression).
  28. Paclitaxel, other taxols
    MOA
    Use
    Toxicity
    Hyperstabilize polymerized microtubules in M phase so that mitotic spindle cannot break down (anaphase cannot occur).“It is taxing to stay polymerized.”

    Ovarian and breast carcinomas.

    Myelosuppression, alopecia,hypersensitivity.
  29. Cisplatin, carboplatin 
    Prevent nephrotoxicity with
    amifostine (free radical scavenger) and chloride (saline) diuresis.
  30. Cisplatin, carboplatin
    MOA 
    use
    toxicity
    Cross-link DNA.

    Testicular, bladder, ovary, and lung carcinomas.

    Nephrotoxicity, ototoxicity. Prevent nephrotoxicity with amifostine (free radical scavenger) and chloride (saline) diuresis
  31. MOA Use toxicity
    Etoposide, teniposide
    Etoposide inhibits topoisomerase II Ž-->inc. DNA degradation.

    Solid tumors (particularly testicular and small cell lung cancer), leukemias, lymphomas.

    Myelosuppression, GI upset, alopecia.
  32. MOA Use toxicity
    Irinotecan, topotecan
    Inhibit topoisomerase I and prevent DNA unwinding and replication.

    Colon cancer (irinotecan); ovarian and small cell lung cancers (topotecan).

    Severe myelosuppression, diarrhea
  33. MOA Use toxicity
    Hydroxyurea
    Inhibits ribonucleotide reductase --> dec.Ž  DNA Synthesis (S-phase specific).

    Melanoma, CML, sickle cell disease (inc. HbF).

    Severe myelosuppression, GI upset.
  34. MOA Use toxicity
    Prednisone, prednisolone
    Various; bind intracytoplasmic receptor; alter gene transcription.

    Most commonly used glucocorticoids in cancer chemotherapy. Used in CLL, non-Hodgkinlymphoma (part of combination chemotherapy regimen). Also used as immunosuppressants (e.g.,in autoimmune diseases).

    Cushing-like symptoms; weight gain, central obesity, muscle breakdown, cataracts, acne,osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis.
  35. MOA Use toxicity
    Bevacizumab
    Monoclonal antibody against VEGF. Inhibits angiogenesis.

    Solid tumors (colorectal cancer, renal cell carcinoma).

    Hemorrhage, blood clots, and impaired wound healing.
  36. MOA Use toxicity
    Erlotinib
    EGFR tyrosine kinase inhibitor.

    Non-small cell lung carcinoma.

    Rash.
  37. MOA Use toxicity
    Imatinib
    Tyrosine kinase inhibitor of BCR-ABL (Philadelphia chromosome fusion gene in CML) and c-kit(common in GI stromal tumors).

    CML, GI stromal tumors.

    Fluid retention
  38. MOA Use toxicity
    Rituximab
    Monoclonal antibody against CD20, which is found on most B-cell neoplasms.

    Non-Hodgkin lymphoma, CLL, IBD, rheumatoid arthritis.

    inc. risk of progressive multifocal leukoencephalopathy.
  39. MOA Use toxicity
    Tamoxifen, raloxifene
    Selective estrogen receptor modulators (SERMs)—receptor antagonists in breast and agonists in bone. Block the binding of estrogen to ER ⊕ cells.

    Breast cancer treatment (tamoxifen only) and prevention. Raloxifene also useful to prevent osteoporosis.

    Tamoxifen—partial agonist in endometrium, which inc.  the risk of endometrial cancer; “hot flashes.”Raloxifene—no inc.  in endometrial carcinoma because it is an estrogen receptor antagonist inendometrial tissue.
  40. MOA Use toxicity
    Trastuzumab (Herceptin)
    Monoclonal antibody against HER-2 (c-erbB2), a tyrosine kinase receptor. Helps kill cancer cells that over express HER-2, through inhibition of HER2-initiated cellular signaling and antibody dependent cytotoxicity.

    HER-2 ⊕ breast cancer and gastric cancer (tras2zumab).

    Cardiotoxicity. “Heartceptin” damages the heart.
  41. MOA Use toxicity
    Vemurafenib
    Small molecule inhibitor of BRAF oncogene ⊕ melanoma

    Metastatic melanoma

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