Hematology and Oncology Pharmacology

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jknell
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211588
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Hematology and Oncology Pharmacology
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2013-04-05 11:53:15
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  1. Heparin
    • Mechanism:
    • -cofactor for activation of antithrombin
    • -decreases thrombin and factor Xa
    • -short half life

    • Clinical Use:
    • -PE
    • -acute coronary syndrome
    • -MI
    • -DVT

    • Toxicity:
    • -bleeding
    • -Heparin induced thrombocytopenia
    • -osteoporosis
    • -drug-drug interactions
    • *antidote = protamine sulfate

    • Notes:
    • -LMWH: act more on factor Xa and have longer half life, not easily reversible
    • -follow PTT
  2. Heparin Induced Thrombocytopenia
    -development of IgG antibodies against heparin bound to platelet factor 4 (PF4)

    -antibody-heparin-PF4 complex activates platelets → thrombosis and thrombocytopenia
  3. Lepirudin
    Bivalirudin
    • Mechanism:
    • -derivatives of leech anticoagulant
    • -inhibit thrombin

    • Clinical Uses:
    • -alternative to heparin for patients with HIT
  4. Warfarin (Coumadin)
    • Mechanism:
    • -interferes with synthesis and carboxylation of vitamin K dependent clotting factors (II, VII, IX, X, protein C and S)

    • Clinical Use:
    • -chronic anticoagulation
    • -STEMI
    • -venous thromboembolism prophylaxis
    • -prevent of stroke in AFib

    • Toxicity:
    • -bleeding
    • -teratogenic (CI in pregnancy)
    • -skin/tissue necrosis
    • -drug-drug interactions

    • Notes:
    • -reverse with vitamin K or fresh frozen plasma
    • -follow PT

    "The EX-PresidenT went to war(farin)"
  5. Heparin vs. Warfarin
  6. Thrombolytics
    • Ateplase (tPA)
    • Reteplase (rPA)
    • Tenecteplase (TNK-tPA)

    • Mechanism:
    • -aid conversion of plasminogen to plasmin (cleaves thrombin and fibrin clots)
    • -increase PT and PTT, no change in platelet count

    • Clinical Use:
    • -early MI
    • -early ischemic stroke
    • -direct thrombolysis of severe PE

    • Toxicity:
    • -bleeding
    • -CI: active bleeding, hx of intracranial bleeding, recent surgery, severe HTN
    • -tx toxicity with aminocaproic acid
  7. Aspirin
    • Mechanism:
    • -irreversibly binds COX (1 and 2)
    • -platelets cannot synthesize new enzymes (effects last until new platelets are produced)
    • -decrease TXA2 and PG formation
    • -increase bleeding time, no effect on PT/PTT

    • Clinical Uses:
    • -antipyretic (intermediate dose)
    • -analgesic (intermediate dose)
    • -anti-inflammatory (high dose)
    • -antiplatelet (low dose)

    • Toxicity:
    • -gastric ulceration
    • -tinnitus
    • -chronic use: renal failure, interstitial nephritis, GI bleeding
    • -Reye's syndrome in children with viral infection
    • -OD: metabolic acidosis and respiratory alkalosis
  8. ADP Receptor Inhibitors
    • Clopidogrel
    • Ticlopidine
    • Prasugrel
    • Ticagrelor

    • Mechanism:
    • -inhibit platelet aggregation by irreversibly blocking ADP receptors
    • -inhibit fibrinogen binding (block GpIIb/IIIa)

    • Clinical Use:
    • -acute coronary syndrome
    • -coronary stenting
    • -decrease incidence or recurrence of thrombotic stroke

    • Toxicity:
    • -neutropenia
  9. Cilostazol
    Dipyridamole
    • Mechanism:
    • -Phosphodiesterase III inhibitor
    • -increase cAMP in platelets (inhibiting aggregation)
    • -vasodilators

    • Clinical Uses:
    • -intermittent claudication
    • -coronary vasodilation
    • -prevention of stroke or TIA (combined with ASA)
    • -angina prophylaxis

    • Toxicity:
    • -Nausea
    • -HA
    • -facial flushing
    • -hypotension
    • -abdominal pain
  10. Gp IIb/IIIa Inhibitors
    • Abciximab
    • Eptifibatide
    • Tirofiban

    • Mechanism:
    • -bind GpIIb/IIIa and prevent platelet aggregation

    • Clinical Use:
    • -acute coronary syndrome
    • -percutaneous transluminal coronary angioplasty

    • Toxicity:
    • -bleeding
    • -thrombocytopenia
  11. Cancer Cell Drug Types
    -location of action in cell cycle


  12. Methotrexate
    • Mechanism:
    • -folic acid analog that inhibits DHFR
    • -decrease DNA and protein synthesis

    • Clinical Use:
    • -leukemias
    • -lymphomas
    • -choriocarcinoma
    • -sarcomas
    • -abortion
    • -ectopic pregnancy
    • -RA-psoriasis

    • Toxicity:
    • -myelosuppression (leucovorin rescue)
    • -macrovesicular fatty change in liver
    • -mucositis
    • -teratogenic

  13. 5-FU
    • Mechanism:
    • -pyrimidine analog
    • -inhibits DNA and protein synthesis

    • Clinical Use:
    • -colon cancer
    • -basal cell carcinoma

    • Toxicity:
    • -myelosuppression (not reversible)
    • -OD: rescue with thymidine
    • -photosensitivity

  14. Cytarabine
    • Mechanism:
    • -pyrimidine analog
    • -inhibition of DNA polymerase

    • Clinical Use:
    • -leukemias
    • -lymphomas

    • Toxicity:
    • -Leukopenia
    • -thrombocytopenia
    • -megaloblastic anemia
  15. Azathioprine
    6-MP
    6-TG
    • Mechanism:
    • -purine analogs
    • -decrease de novo purine synthesis
    • -activated by HGPRT

    • Clinical Use:
    • -leukemias

    • Toxicity:
    • -BM
    • -GI
    • -Liver
    • -increase toxicity with allopurinol
  16. Dactinomycin
    • Mechanism:
    • -antitumor antibiotics
    • -intercalates in DNA

    • Clinical Use:
    • -Wilm's tumor
    • -Ewing's sarcoma
    • -Rhabdomyosarcoma
    • -childhood tumors
    • "Children act out"

    • Toxicity:
    • -myelosuppression
  17. Doxorubicin (Adriamycin)
    Daunorubicin
    • Mechanism:
    • -antitumor antibiotics
    • -generate free radicals
    • -intercalate in DNA and generate breaks
    • -reduces replication

    • Clinical Use:
    • -solid tumors
    • -leukemias
    • -lymphomas

    • Toxicity:
    • -cardiotoxicity (dilated cardiomyopathy)
    • -myelosuppressive
    • -alopecia
    • -toxic to tissues following extravasation
    • -dexrazoxane used to prevent cardiotoxicity
  18. Bleomycin
    • Mechanism:
    • -antitumor antibiotic
    • -induces free radical formation causing breaks in DNA strands

    • Clinical Use:
    • -testicular cancer
    • -Hodgkin's lymphoma

    • Toxicity:
    • -pulmonary fibrosis
    • -skin changes
    • -minimal myelosuppression
  19. Cyclophosphamide
    • Mechanism:
    • -alkylating agent
    • -cross linked into DNA
    • -requires bioactivation by liver

    • Clinical Use:
    • -solid tumors
    • -leukemias
    • -lympomas
    • -some brain cancers

    • Toxicity:
    • -myelosuppression
    • -hemorrhagic cystitis
    • -partially prevented with mensa
  20. Nitrosoureas
    • Carmustine
    • Lomustine
    • Semustine
    • Streptozocin

    • Mechanism:
    • -alkylating agents
    • -require bioactivation
    • -cross BBB

    • Clinical Use:
    • -brain tumors (glioblastoma multiforme)

    • Toxicity:
    • -CNS toxicity (dizziness, ataxia)
  21. Busulfan
    • Mechanism:
    • -alkylates DNA

    • Clinical Use:
    • -CML
    • -ablate marrow before HSCT

    • Toxicity:
    • -pulmonary fibrosis
    • -hyperpigmentation
  22. Vincristine
    Vinblastine
    • Mechanism:
    • -microtubule inhibitors
    • -prevent mitotic spindle formation in M phase

    "microtubules are the vines of your cells"

    • Clinical Use:
    • -solid tumors
    • -leukemias
    • -lymphomas

    • Toxicity:
    • -Vincristine: neurotoxic, paralytic ileus
    • -Vinblastine: blasts BM

    • "Vinblastine blasts bone marrow"
  23. Paclitaxel
    • Mechanism:
    • -microtubule inhibitor
    • -prevent mitotic spindle breakdown in M phase

    "it's taxing to stay polymerized"

    • Clinical Use:
    • -ovarian carcinoma
    • -breast carcinoma

    • Toxicity:
    • -myelosuppression
    • -hypersensitivity
  24. Cisplatin
    Carboplatin
    • Mechanism:
    • -crosslink DNA

    • Clinical Use:
    • -testicular carcinoma
    • -bladder carcinoma
    • -ovary carcinoma
    • -lung carcinoma

    • Toxicity:
    • -nephrotoxicity (prevent with amifostine and chloride diuresis)
    • -acoustic nerve damage
  25. Etoposide
    Teniposide
    • Mechanism:
    • -inhibit topoisomerase II
    • -increased DNA degradation

    • Clinical Use:
    • -solid tumors
    • -leukemias
    • -lymphomas

    • Toxicity:
    • -myelosuppression
    • -GI irritation
    • -alopecia
  26. Hydroxyurea
    • Mechanism:
    • -inhibits ribonucleotide reductase
    • -decreases DNA Synthesis (S phase specific)

    • Clinical Use:
    • -Melanoma
    • -CML
    • -Sickle cell disease (increase HbF)

    • Toxicity:
    • -BM suppression
    • -GI upset
  27. Prednisone
    Prednisolone
    • Mechanism:
    • -may trigger apoptosis
    • -may even work on non-dividing cells

    • Clinical Use:
    • -most commonly used GC in cancer chemotherapy
    • -CLL
    • -non-Hodgkin's lymphoma
    • -immunosuppressant (autoimmune diseases)

    • Toxicity:
    • -Cushing like sx
    • -immunosuppression
    • -cataracts
    • -acne
    • -osteoporosis
    • -HTN
    • -Peptic ulcers
    • -hyperglycemia
    • -psychosis
  28. Tamoxifen
    Raloxifene
    • Mechanism:
    • -SERMs
    • -Estrogen R antagonists in breast
    • -Estrogen R agonists in bone

    • Clinical Use:
    • -breast cancer treatment and prevention
    • -prevent osteoporosis

    • Toxicity:
    • -T: partial agonist in endometrium (increased risk of endometrial cancer), hot flashes
    • -R: no increased risk of endometrial cancer
  29. Trastuzumab (Herceptin)
    • Mechanism:
    • -anti-HER2
    • -may cause antibody-dependent cytotoxicity of Her2+ cells

    • Clinical Use:
    • -HER2+ breast cancer

    • Toxicity:
    • -cardiotoxicity
  30. Imatinib (Gleevac)
    • Mechanism:
    • -philadelphia chromosome bcr-abl inhibitor

    • Clinical Use:
    • -CML
    • -GI stromal tumors

    • Toxicity:
    • -fluid retention
  31. Rituximab
    • Mechanism:
    • -anti-CD20

    • Clinical Use:
    • -Non-Hodgkin's lymphoma
    • -RA (with methotrexate)
  32. Vemurafenib
    • Mechanism:
    • -small molecule inhibitor of B-Raf with V600E mutation

    • Clinical Use:
    • -metastatic melanoma
  33. Bevacizumab
    • Mechanism:
    • -anti-VEGF
    • -inhibits angiogenesis

    • Clinical Use:
    • -solid tumors
  34. Chemo-tox Man!


    • Cisplatin/Carboplatin
    • -acoustic nerve damage
    • -nephrotoxicity

    • Vincristine
    • -peripheral neuropathy

    • Bleomycin, Busulfan
    • -pulmonary fibrosis

    • Doxorubicin
    • -cardiotoxicity

    • Trastuzumab
    • -cardiotoxicity

    • CYclophosphamide
    • -hemorrhagic cystitis

    • 5-FU
    • -myelosuppression

    • 6-MP
    • -myelosuppression

    • Methotrexate
    • -myelosuppression

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