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Therapy of cancer disease

Therapy of cancer disease.

Mercy
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Therapy of cancer disease

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  1. Therapy of cancer disease This study material is recommended specifically for practical courses from Pharmacology II for students of general medicine and stomatology. These brief notes could be used to prepare for the lesson and as a base for own notes during courses. Addititonal explanations and information are given in single lessons.

  2. Cytostatics Definition chemiotherapeutics = chemoprotectives –

  3. Cytostatics Cancerdisease Classification: • Benign • Malign

  4. Cytostatics Cabcerogenesis • processofchangeofsomatic cell to cancer cell • 3 phases: initiation promotion progression

  5. Cytostatics Exogenous factors involved in cancerogenesis

  6. Cytostatics Endogenous factors involved in cancerogenesis

  7. Cytostatics Modes of action Target sites:

  8. Adverse effects 1. Early

  9. Nežádoucí účinky cytostatik • Delayed

  10. Adverse effects

  11. Adverse effects

  12. Adverse effects

  13. Adverse effects

  14. Adverse effects Analgesics • basic analgesics are NSAIDs • in strong pain opioids • bone pain – kalcitonin, bisphosphonates • combination with corticoids and psychoactive agents (antidepressants, neuroleptics, anxiolytics)

  15. Adverse effects Bisphosphonates ibandronate clodronate pamidronate zoledronate

  16. Cytostatics Particularity of cancer pharmacotherapy • DDF • „nonspecificity“ of target site • combination with othrt types of therapy • dosing, administration routes and combinations

  17. Cytostatics Classification with regard to cell cycle • cycle specific/nonspecific • phase specific/nonspecific

  18. Cytostatics Classification • monoclonal antibodies and other drugs of „biological“ (targeted) therapy • alkylating • platin cytostatics • cytotoxic antibiotics • antimetabolites • herbal alkaloids • hormones • others

  19. Alkylating cytostatics Mode of action • alkylation of cellular structures, namely DNA → loss of function and cellular death

  20. Alkylating cytostatics • β-chloretylamines (N-yperite derivatives): chlorambucil, melphalan • oxazaphosphorines: cyclophosphamide, ifosfamide • methanesulphonic acid derivatives: busulphan

  21. Alkylating cytostatics nitrosourea derivatives: lomustine, carmustine, fotemustine, streptozocine triazenes: procarbazine, dacarbazine platin compounds: cisplatin, carboplatin, oxaliplatin mitomycin

  22. Intercalating agents MofA • bounds between DNA strands with non-covalent binding (Van der Waals forces, hydrogen bonds) doxorubicine daunorubicine mitoxantrone

  23. Antimetabolites Folic acid antagonists MofA: dihydrofolate reductase inhibition methotrexate

  24. Antimetabolites Purine antagonists 6-merkaptopurine 6-thioguanine azathioprine cladribine fludarabine

  25. Antimetabolites Pyrimidine antagonists cytarabine 5-fluorouracil gemcitabine

  26. Herbal alkaloids irinotecan, topotecan MofA: topoisomerase I inhibition

  27. Herbal alkaloids etoposid, teniposid MofA: topoisomerase II inhibition

  28. Herbal alkaloids Vinca alkaloids MofA: destruction of mitotic spindle vincristine vinblastine vindesine vinorelbine

  29. Herbal alkaloids Taxans MofA: inhibition of tubulin depolymerization = block of mitotic spindle paclitaxel docetaxel

  30. Androgens Antiandrogens Oestrogens Antioestrogens Gestagens Gonadoliberin inhibitors Aromatase inhibitors Glucocorticoids Octreotide Estramustine, prednimustine Hormones and theit antagonists

  31. Others bleomycine, (peplomycine) MofA: ROS production→ DNA fragmentation AE: pyretic reactions, pulmonary fibrosis • low myelosuppression hydroxycarbamid arsenic trioxide celekoxib anagrelide asparaginase

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