Heme/onc pharm

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anddavis
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73104
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Heme/onc pharm
Updated:
2011-03-15 16:10:00
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Heme onc pharm
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Heme/onc pharm
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  1. Activates antithrombin III
    • Hepairn
    • Decreased thrombin and Xa
    • Immediate anticoagulation, anticoagulation in pregnancy
    • Parenteral
    • Follow PTT
    • Tox: bleeding, HIT, osteoporosis, drug-drug interactions
    • Reverse with protamine sulfate
  2. Enoxaparin
    • Low-molecular weight heparin
    • Acts on Xa
    • Greater bioavailability, longer 1/2 life, subQ, no lab monitoring
  3. Heparin-induced thrombocytopenia
    • Heparin binds to platelets -> autoAb production ->
    • destruction/activation of platelets -> thrombocytopenic,
    • hypercoagulable state
  4. Lepirudin, bivalirudin
    • Direct thrombin inhibitors
    • Used in pts with HIT
  5. Warfarin
    • Interferes with gamma carboxylation of vitamin K dependent clotting factors (II, VII, IX, X, protein C and S)
    • Oral
    • Metabolized by P450
    • Monitor PT/INR (extrinsic pathway)
    • Chronic anticoagulation, not in pregnancy
    • Can cause skin necrosis in protein C or S deficiency
  6. Converts plasminogen to plasmin
    • tPA (alteplase), also streptokinase and urokinase
    • Results in cleavage of thrombin and fibrin clots
    • Increased PT and PTT
    • Used in early MI and early ischemic stroke
    • Treat toxicity with aminocaproic acid
  7. Irreversibly inhibits COX1 and 2
    • Aspirin
    • Prevents conversion of arachidonic acid to TxA2, increased bleeding time
    • Antipyretic, analgesic, antiinflammatory, antiplatelet
    • Can cause CN VIII tinnitus
  8. Inhibit platelet aggregation by irreversibly blocking ADP receptors
    • Clopidogrel, ticlopidine
    • Inhibit fibrinogen binding by preventing GpIIb/IIIa expression
    • Used in acute coronary syndrome, coronary stenting, decreased thrombotic stroke
  9. Binds to GbIIb/IIIa, preventing aggregation of activated platelets
    • Abciximab (monoclonal Ab)
    • Acute coronary syndromes, coronary angioplasty
  10. Folic acid analog that binds dihydrofolate reductase
    • Methotrexate (antimetabolite)
    • Decreases dTMP and thus DNA and protein synthesis
    • Tox: myselosuppression reversible with leucovorin (folinic acid)
    • Macrovesicular fatty change in liver, mucositis, teratogen
  11. Pyrimidine analog inhibiting thymidylate synthase
    • 5-FU
    • Bioactivated to 5F-dUMP
    • Leucovorin stabilizes TS-FdUMP complex -> decreased dTMP, decreased DNA and protein synthesis
    • Tox: myelosuppression not reversible with leucovorin, photosensitivity
    • Thymidine rescue
  12. Purine analog, decreases de novo purine synthesis
    • 6-MP
    • Activated by HGPRTase
    • Tox: BM, GI, liver
    • Metabolized by xanthine oxidase -> increased tox with allopurinol
  13. 6-TG
    • Purine analog (same as 6-MP)
    • Can be given with allopurinol
  14. Pyrimidine antagonist
    • Cytarabine (ara-C)
    • Inhibits DNA polymerase
    • Leukopenia, thrombocytopenia, megaloblastic anemia
  15. Dactinomycin
    • Antitumor antibiotic, intercalates in DNA
    • Childhood tumors
    • Myelosuppression
  16. Doxorubicin/adriamycin, daunorubicin
    • Antitumor antibiotic
    • Generate free radicals, intercalate in DNA and cause breaks, inhibit Topo II
    • Cardiotoxicity
  17. Bleomycin
    • Antitumor antibiotic
    • G2-phase specific
    • Free radical formation -> breaks in DNA
    • Pulmonary fibrosis
  18. Etoposide
    • Late S to G2 phase-specific
    • Inhibit topo II
    • Myelosuppression, GI irritation, alopecia
  19. Cyclophosphamide, ifosfamide
    • Alkylating agent
    • Covalently crosslinks DNA at guanine N-7; requires activation by liver
    • Hemorrhagic cystitis from acrolein (prevented with mesna), myelosuppression
  20. Nitrosureas
    • Alkylating agent
    • -mustine, streptozocin
    • Requires bioactivation, crosses BBB
    • CNS toxicity
  21. Busulfan
    • Alkylating agents
    • Alkylates DNA
    • Pulmonaryfibrosis, hyperpigmentation
  22. Vincristine, vinblastine
    • Alkaloid, binds tubulin in M phase -> block polymerization of microtubules
    • Vincristine - neurotoxicity
    • VinBLASTine - BLASTS BM
  23. Paclitaxel
    • Hyperstabilizes polymerized microtubules in M phase
    • Myelosuppression and hypersensitivity
  24. Cisplatin
    • Cross-link DNA
    • Nephrotoxicity and acoustic nerve damage
    • Amifostene prevents nephrotoxicity
  25. Hydroxyurea
    • Inhibits ribonucleotide reductes -> decreased DNA synthesis (S phase)
    • Used in sickle cell disease (increases HbF)
    • BM suppression, GI upset
  26. Prednisone
    • May trigger apoptosis
    • Cushing-like symptoms, immunosuppression
  27. Tamoxifen, raloxifene
    • SERMs - estrogen receptor antagonists in breast, agonists in bone
    • Tamoxifen for estrogen + breast cancer
    • Raloxifene for osteoporosis
    • Tamoxifen may increase risk of endometrial cancer
  28. Trastuzumab
    • = Herceptin
    • Monoclonal Ab against HER-2 (erb-B2)
    • Metastatic breast cancer
    • Cardiotoxicity
  29. Imatinib
    • = Gleevec
    • TK inhibitor
    • CML
    • Fluid retention

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