Principles Of Chemotherapy

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  • 1. Principles of Chemotherapy: The Stages of Mitosis Mitosis (=cell division) is divided into well-defined stages; the prophase (chromosomes become visible and spindle begins to form); the metaphase (spindle is completed, chromosomes begin to separate); the anaphase (the cell begins to divide in two); and the telophase (the final step of mitosis).
  • 2. Principles of Chemotherapy: Electron Micrograph of Mitotic Cell This is an electron micrograph of a cell from ovarian tissue undergoing mitotic cell division.
  • 3. Principles of Chemotherapy: Classification of Cytotoxic Agents Twenty anticancer agents account for over 95% of all prescriptions in chemotherapy. They are divided into five major classifications.
  • 4. Principles of Chemotherapy: Action Sites of Cytotoxic Agents/Cell Cycle Level Understanding the cell cycle is important because chemnicals with different modes of action may be rationally combined to increase antitumor effects at different times in the cell cycle.
  • 5. Principles of Chemotherapy: Action Sites of Cytotoxic Agents/Cellular Level Most cytotoxic drugs target the DNA. Two exceptions are the poisons of the mitotic spindle—vinca alkaloids and taxoids—that target the tubulin.
  • 6. Principles of Chemotherapy: Action Sites of Cytotoxic Agents Knowledge of the different sites of action for cytotoxic agents permits, for example, the better understanding of how drugs act in combination.
  • 7. Principles of Chemotherapy: Metabolism of Cytotoxic Agents/Cyclophosphamide Presented here is an example of how one cytotoxic agent – cyclophosphamide – is metabolized. Cyclophosphamide is a prodrug. It needs an activation in the body and its metabolites are the active agents.
  • 8. Principles of Chemotherapy: Drug Resistance This phosphoglycoprotein (P.G.P.) is responsible for multidrug resistance. It acts by rejecting the anticancer agent from the cell. Other mechanisms of resistance exist.
  • 9. Principles of Chemotherapy: Aim of Combination Therapy The aim of combination therapy is to increase efficacy while keeping an acceptable safety profile. For example, two drugs in a combination therapy may have different mechanisms of action, and/or limiting drug resistance.
  • 10. Principles of Chemotherapy: Side Effects of Chemotherapy There are multiple side effects of chemotherapy. Some are common, such as alopecia, neutropenia. Some are rare such as cardiotoxicity. The side effects are generally the consequence of the cytotoxic effect of chemotherapy on normal cells, however they can also be related to the direct toxicity of the drug.
  • Principles Of Chemotherapy

    1. 1. ONCOLOGY Principles of chemotherapy Interphase Prophase Daughter cells Telophase Anaphase Metaphase The mitosis stages
    2. 2. ONCOLOGY Principles of chemotherapy Electron micrograph of mitotic cell
    3. 3. <ul><li>Busulfan Cytosine Etoposide Bleomycin L-asparaginase </li></ul><ul><li>Carmustine Arabinoside Teniposide Dactinomycin Hydroxyurea </li></ul><ul><li>Chlorambucil Floxuridine Vinblastine Daunorubicin Procarbazine </li></ul><ul><li>Cisplatin Fluorouracil Vincristine Doxorubicin </li></ul><ul><li>Cyclophosphamide Mercaptopurine Vindesine Mitomycin-c </li></ul><ul><li>Ifosfamide Methotrexate Taxoids Mitoxantrone </li></ul><ul><li>Melphalan Plicamycin </li></ul>ONCOLOGY Principles of chemotherapy Alkylating Agents Anti- Metabolites Mitotic Inhibitors Antibiotics Others Classification of cytotoxic agents
    4. 4. <ul><li>Antibiotics Antimetabolites </li></ul>ONCOLOGY Principles of chemotherapy S (2-6h) G 2 (2-32h) M (0.5-2h) Alkylating agents G 1 (2-  h) G 0 Vinca alkaloids Mitotic inhibitors Taxoids Cell cycle level Action sites of cytotoxic agents
    5. 5. <ul><li>DNA synthesis </li></ul>ONCOLOGY Principles of chemotherapy Antimetabolites DNA DNA transcription DNA duplication Mitosis Alkylating agents Spindle poisons Intercalating agents Cellular level Action sites of cytotoxic agents
    6. 6. <ul><li>6-MERCAPTOPURINE </li></ul><ul><li>6-THIOGUANINE </li></ul><ul><li>METHOTREXATE </li></ul><ul><li>5-FLUOROURACIL </li></ul><ul><li>HYDROXYUREA </li></ul><ul><li>CYTARABINE </li></ul>ONCOLOGY Principles of chemotherapy PURINE SYNTHESIS PYRIMIDINE SYNTHESIS RIBONUCLEOTIDES DEOXYRIBONUCLEOTIDES DNA RNA PROTEINS MICROTUBULES ENZYMES L-ASPARAGINASE VINCA ALKALOIDS TAXOIDS ALKYLATING AGENTS ANTIBIOTICS ETOPOSIDE Action sites of cytotoxic agents
    7. 7. <ul><li>CYCLOPHOSPHAMIDE </li></ul>ONCOLOGY Principles of chemotherapy 4-OH CYCLOPHOSPHAMIDE ALDOPHOSPHAMIDE PHOSPHORAMIDE MUSTARD 4-KETOCYCLOPHOSPHAMIDE CARBOXYPHOSPHAMIDE ACROLEIN HEPATIC CYTOCHROMES P 450 ACTIVATION CYTOTOXICITY TOXICITY INACTIVATION ALDEHYDE DEHYDROGENASE Cyclophosphamide Metabolism of cytotoxic agents
    8. 8. <ul><li>EXTRACELLULAR INTRACELLULAR </li></ul>ONCOLOGY Principles of chemotherapy ATP PGP 170 ATP Drug Drug Plasma Membrane Drug resistance
    9. 9. <ul><li>INCREASED EFFICACY </li></ul>ONCOLOGY Principles of chemotherapy Different mechanisms of action Compatible side effects Different mechanisms of resistance ACTIVITY SAFETY Aim of combination therapy
    10. 10. <ul><li>Mucositis </li></ul><ul><li>Nausea/vomiting </li></ul><ul><li>Diarrhea </li></ul><ul><li>Cystitis </li></ul><ul><li>Sterility </li></ul><ul><li>Myalgia </li></ul><ul><li>Neuropathy </li></ul>ONCOLOGY Principles of chemotherapy Alopecia Pulmonary fibrosis Cardiotoxicity Local reaction Renal failure Myelosuppression Phlebitis Side effects of chemotherapy

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