Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Principles of chemotherapy.

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Presentation transcript:

Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Principles of chemotherapy

Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Principles of chemotherapy Stages of Mitosis Interphase Prophase Daughter cells Telophase Anaphase Metaphase

Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Electron micrograph of mitotic cell Principles of chemotherapy Electron micrograph of mitotic cell

Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Classification of cytotoxic agents Principles of chemotherapy Classification of cytotoxic agents BusulfanCytosineEtoposideBleomycinL-asparaginase CarmustineArabinosideTeniposideDactinomycinHydroxyurea ChlorambucilFloxuridineVinblastineDaunorubicinProcarbazine CisplatinFluorouracilVincristineDoxorubicin CyclophosphamideMercaptopurineVindesineMitomycin-c IfosfamideMethotrexateTaxoidsMitoxantrone MelphalanPlicamycin AlkylatingAgents Anti-Metabolites MitoticInhibitors AntibioticsOthers

Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Action sites of cytotoxic agents Principles of chemotherapy Action sites of cytotoxic agents Antibiotics Antimetabolites S (2-6h) G 2 (2-32h) M (0.5-2h) Alkylating agents G 1 (2-  h) G0G0 Vinca alkaloids Mitotic inhibitors Taxoids Cell cycle level

Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Action sites of cytotoxic agents Principles of chemotherapy Action sites of cytotoxic agents DNA synthesis Antimetabolites DNA DNA transcriptionDNA duplication Mitosis Alkylating agents Spindle poisons Intercalating agents Cellular level

Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Action sites of cytotoxic agents Principles of chemotherapy Action sites of cytotoxic agents 6-MERCAPTOPURINE 6-THIOGUANINE METHOTREXATE 5-FLUOROURACIL HYDROXYUREA CYTARABINE PURINE SYNTHESIS PYRIMIDINE SYNTHESIS RIBONUCLEOTIDES DEOXYRIBONUCLEOTIDES DNA RNA PROTEINS MICROTUBULESENZYMES L-ASPARAGINASE VINCA ALKALOIDS TAXOIDS ALKYLATING AGENTS ANTIBIOTICS ETOPOSIDE

Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Metabolism of cytotoxic agents Principles of chemotherapy Metabolism of cytotoxic agents CYCLOPHOSPHAMIDE 4-OH CYCLOPHOSPHAMIDE ALDOPHOSPHAMIDE PHOSPHORAMIDEMUSTARD 4-KETOCYCLOPHOSPHAMIDECARBOXYPHOSPHAMIDE ACROLEIN HEPATICCYTOCHROMES P 450 ACTIVATION CYTOTOXICITY TOXICITY INACTIVATION ALDEHYDEDEHYDROGENASE Cyclophosphamide

Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Drug resistance Principles of chemotherapy Drug resistance EXTRACELLULARINTRACELLULAR ATP PGP 170 ATP Drug Drug PlasmaMembrane

Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Aim of combination therapy Principles of chemotherapy Aim of combination therapy INCREASED EFFICACY Different mechanisms of action Compatible side effects Different mechanisms of resistance ACTIVITY SAFETY

Clinical Division of Oncology Department of Medicine I Mediacal University of Vienna, Austria Side effects of chemotherapy Principles of chemotherapy Side effects of chemotherapy Alopecia Pulmonary fibrosis Cardiotoxicity Local reaction Renal failure Myelosuppression Phlebitis Mucositis Nausea/vomiting Diarrhea Cystitis Sterility Myalgia Neuropathy