Drugs and Disorders

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jbaalmann
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42786
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Drugs and Disorders
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2010-10-17 16:42:08
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  1. Classes of cell cycle specific and cell cycle non-specific drugs
    • Cell Cycle Specific
    • Antimetabolites
    • Topoisomerase Inhibitors
    • Microtoubule Poisons (Plant Alkaloids)
    • Signal Transduction Inhibitors
    • Cell Cycle Non-Specific
    • Alkylating Agents
    • Antitumor Antibiotics
    • Biologics (Hormone inhibitors, corticosteroids, biologic antineoplastics)
  2. The 3 classes of Plant Alkaloids
    • Vinca Alkaloids (Vincristine and Vinblastine)
    • Taxanes (Paclitaxel and Docetaxel)
    • Podoohyllotoxins (Etoposide)
  3. 3 Alkylating Agents
    • Mechlorethamine
    • Cycophosphamide
    • Cis-Platin
  4. What is the mechanism of action for alkylating agents?
    They covently interact with and bind DNA (typically cross-link), thus blockign access to DNA
  5. Which intercellular protein pumps foregin materials out of the cell and is associated with resistance?
    P-glycoprotein
  6. Irinotecan
    • Topoisomerase Inhibitor (CCS)
    • Allows topoisomerase I to make cuts, but prevents reannealing; causes DS breaks
    • S-G2 checkpoint arrest
    • Pro-drug converted by esterase to SN-38
    • UGT1A1 converts it to SN-38G to get rid of it
    • Hematologic effects at higher doses
    • Dose limiting diarrhea and n/v
  7. Methotrexate (folate analog)
    • Antimetabolite (CCS)
    • DHFR inhibitor--blocks the production of bases
    • S-G2 arrest
    • Oral, IV
    • Rescue with folinic acid
    • Hepatotoxicity
    • Resistance associated
  8. 5-FU/Cytarabine/Gemcitibine
    • Antimetabolite (CCS)
    • Pyrimidine analog--far mroe toxic than purines with more adverse side effects
    • 5-FU-->thymine-less death
    • Cy and Gem are cytosine analogs-chain terminators
  9. 6-mercaptopurine/6-thioguanine
    • Antimetabolites (CCS)
    • Purine Analogs--less severe side effects
    • Oral
    • Myelosuppression only at higher doses
    • Resistance from increase in alkaline phosphatase
  10. Imatinib
    • Signal Transduction inhibitor (CCS)
    • Blocks PDGFR, thereby blocking BCR-ABL and other tyrosine kinases
    • Most recent and selective chemo because normal cells do not have these
    • Myelosuppressive, hepatotoxic, and edema
    • Use for CML and GIST
    • Takes fatal diseae and makes it manageable--resistance associated
  11. Gefitinib
    • Signal Transduction Inhibitor (CCS)
    • Blocks EGF
    • Used in non-small cell lung cancer
    • Oral
    • Fever/dyspnea
    • Takes fatal disease and makes it manageable--resistance associated
  12. Vina Alkaloids (Vincristine and Vinblastine)
    • Plant Alkaloids (CCS)
    • Inhibit microtubule polymerization
    • Metaphase arrest with no mitotic spindles
    • IV
    • Excreted in feces
    • Cristine: peripheral neuropathy
    • Blastine: n/v, alopecia, myelosuppression
  13. Taxanes (Paclitaxel and Docetaxel)
    • Plant Alkaloids (CCS)
    • Don't allow microtubules to dissociate
    • Metaphase arrest with mitotic spindles
    • IV
    • Dissolved in Cremophor detergent--causes most negative side effects
    • Pre-treat with analgesics and anti-inflammatories
    • n/v, myelosuppression, hypersensitivity
    • Used in solid tumors
  14. Podophyllotoxins (Etoposide)
    • Plant Alkaloids (CCS)
    • Topoisomerase II inhibitor--allows it to make cut but prevents reannealing--DS breaks
    • S-G2 arrest
    • Oral and IV
    • n/v and myelosuppression
  15. Mechlorethamine
    • Alkylating Agent (CCNS)
    • Nitrogen mustard--highly reactive
    • IV only--subcutaneous causes necrosis
    • M of MOPP
    • Used for Hodgkin's
    • n/v and myelosuppression
  16. Cyclophosphamide
    • Alkylating agent (CCNS)
    • Metabolized to acrolein
    • n/v, myelosuppression, alopecia, and hemorrhagic cystitis (treat with forced hydration or Mesna)
  17. Cis-platin
    • Alkylating Agent (CCNS)
    • Bifunctional platinating agent; x-links DNA to block synthesis
    • IV
    • severe n/v and renal toxicity (treat with 1 L IV first)
    • Carboplatin and Oxaliplatin are similar
  18. Anthracyclines (Doxarubicin and Daunorubicin)
    • Antitumor Antibiotics (CCNS)
    • Squeeze between bps so topoisomerase can't come in
    • Can cause strand breaks; generates free radicals
    • Metabolized in liver
    • Minimize effects of free radicals with Dexazoxane
    • Myleosuppression, GI distress, alopeica, long-term cardiotoxicity
  19. Bleomycin
    • Antitumor antibiotic (CCNS)
    • Binds DNA--strand breaks--free radicals
    • Only active in G2 phase (CCS)
    • Hypersensitivity and dose-limiting pulmonary toxicity (long term) and fibrosis
  20. Aromatase inhibitors (Anastrazole and Letrozole)
    • Hormone Inhibitors (CCNS)
    • Aromatase converts androgen to estrogen and this inhibits process
    • Specific for ER+ cancers
    • Orally
  21. SERMS (Tamoxifen)
    • Selective estrogen receptor antagonists (ER+)
    • ER antagonist in breast tissue, agonist in endometrium, which is why 5+ years on this increases risk for ovarian cancer
    • Orally
    • Problem: CYP2D6 metabolizes tamoxifen more quickly than receptors do
  22. Androgen Receptor Antagonists (Flutamide)
    • Hormone Inhibitor (CCNS)
    • Block androgen intercellular functioning
    • Use with radiation for prostate cancer
    • Orally
  23. Hydrocortisone and Prednisone
    • Corticosteroids (CCNS-Biologic)
    • Suppress proliferation of immune cells
    • Orally
    • For lymphomas and leukemia
    • Diabetes, immune suppression, myelosuppression
  24. Interferon-alpha
    • Biologic Antineoplastics (CCNS)
    • Cytokine produced by WBCs--jacking up immune function--didn't work that well
    • Fever, chills, anorexia, weakness
    • For hematologic malignancies, metastatic melanomas, and renal cell carcinoma
  25. Trastuzumab
    • Biologic Antineoplastic (CCNS)
    • Antibody targeting HER2 and EGF receptors
    • IV
    • Can not cross BBB
    • Hypersensitivity and cardiomyopathy
    • Stops proliferation, but does not eliminate tumor
  26. What are the tyrosine kinase receptor inhibitors?
    Sutinib, temsirolimus, erlotini, cetuximab, bevatuzumab, and sorafenib
  27. Sutinib
    • Multiple receptor tyrosine kinase inhibitor (PDGFR, VEGFR, and FLT3)
    • Results in cell death and reduced angiogenesis
    • no tumor regression
    • GIST and renal cell carcinoma
  28. Temsirolimus
    • mTOR inhibitor
    • Stops proliferation and angiogenesisi by preventing synthesis of VEGF
    • G1 cell cycle arrest
    • no tumor regression
    • kidney cancer
  29. Erlotinib
    • EGFR inhibitor
    • palliative drug for metastatic lung cancer
    • <10% response rate to drug
    • No tumor regression
  30. Cetuximab
    • Bifunctional: EGFR inhibitor and antibody dependent cell cytotoxicity (helps body recognize and target cancer cells)
    • Colon cancer
  31. Bevatuzumab
    • VEGFR inhibitor
    • Colon cancer
  32. Sorafenib
    • VEGFR1-3 and RAF-1 inhibitor (Involved in signaling pathway, thereby shutting down ERK and MEK)
    • Colon cancer

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