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8  anticancer drugs
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8 anticancer drugs

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Pharmacology

Pharmacology
Third Year

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8  anticancer drugs 8 anticancer drugs Presentation Transcript

  • ANTICANCER DRUGS
  • Introduction Cancer Disease of cells characterized by progressive, abnormal & uncontrolled proliferation of tissues. Both normal as well as cancerous cells must pass through the following phases of cell cycle. 1. G1 phase: Synthesis of enzymes and other cellular components needed for DNA synthesis. 2. Synthetic phase: DNA synthesis takes place 3. G2 phase: Synthesis of cellular components for mitosis (proteins and RNA synthesis) 4. M phase: Mitotic cell division takes place 5. G0 phase: Cells stop dividing temporarily or permanently.
  • Anticancer drugs Cell cycle-specific drugs : act mainly on dividing cells • Antimetabolites: Methotrexate, 5 Fluorouracil • Antibiotic: Bleomycin • Vinca alkaloids: Vinblastine, vincristine Cell cycle non-specific drugs: act on dividing as well as resting cells • Alkylating agents: Cyclophosphamide, Busulphan • Antibiotics: Doxorubicin, daunorubicin, • Metal complexes: Cisplatin Hormonal agents • Glucocorticoids – Prednisone • Gonadal hormone antagonists – Tamoxifen, Flutamide
  • METHOTREXATE Mech of action: • Inhibits dihydrofolate reductase ↓ nucleic acid synthesis. Uses: • Acute leukemias, Non-Hodgkin’s lymphoma, Breast cancer, • As Immunosuppresant - Rheumatoid arthritis, Inflammatory bowel diseases Adv effects • Mucositis, Myelotoxicity, hepatotoxicity & pulmonary fibrosis - prevented by Leucovorin (folinic acid)
  • FLUOROURACIL (5-FU) Mech of action: • Converted in cells to 5 fluoro-2-deoxyuridine-5’- monophosphate (5-dUMP) which inhibits thymidylate synthase and leads to ‘thymineless’ death of cells. Uses: • Bladder, breast, colon cancers. Adv effects: GI distress, myelotoxicity, Alopecia
  • Uses: • Non Hodgkin’s lymphoma, breast & ovarian cancers • As immunosuppressant - Rheumatoid arthritis, nephrotic syndrome & organ transplantation Adv effects: • Hemorrhagic cystitis – prevented by vigorous hydration & MESNA –Sodium mercaptoethane sulfonate • Myelosuppression CYCLOPHOSPHAMIDE
  • CISPLATIN Uses: Testicular CA & cancers of bladder, lung and ovary Adv effects • Nephrotoxicity, • Vomiting ( prevented by Ondansetron), • Myelotoxicity Carboplatin is less nephrotoxic, has greater myelotoxicity.
  • Vinca alkaloids Mech of action : • Bind to tubulin & prevent its polymerization into microtubules thereby block the formation of mitotic spindles Uses: • Vincristine: Acute leukemias, lymphomas, Wilm’s tumour, • Vinblastine: Testicular CA, lymphomas, neuroblastoma, Adv effects : • Myelotoxicity (Vinblastine) • Neurotoxicity (Vincristine )
  • ANTIBIOTICS DOXORUBICIN & DAUNORUBICIN – Inhibit topoisomerase II & generate free radicals causing DNA damage. Uses : • Doxorubicin -Hodgkin’s lymphoma, breast, endometrial, lung, ovarian, & thyroid cancers. • Daunorubicin – Acute leukemias Toxicity : • Cardiotoxicity (prevented by Dexrazoxane) • Myelotoxicity,
  • HORMONAL AGENTS TAMOXIFEN • Antiestrogenic action Uses : Breast carcinoma Adv effects: • Endometrial hyperplasia • Thromboembolism, FLUTAMIDE • Androgen receptor antagonist Use: Prostatic cancer Adv effects: Gynecomastia, hot flushes
  • Specific toxicities • Haemorrhagic cystitis : Cyclophosphamide • Megaloblastic anaemia : Methotrexate • Nephrotoxicity : Cisplatin • Neuropathy : Vincristine • Pulmonary fibrosis & pigmentation of skin : Busulphan & Bleomycin • Cardiotoxicity : Doxorubicin & Daunorubicin • Severe vomiting : Cisplatin, Doxorubicin • Extravasation : vesicant drugs like Doxorubicin, Vinblastine
  • Management of Cancer Chemotherapy induced Adverse drug reactions • Nausea & Vomiting : Ondansetron • Bone marrow Suppression: Filgrastim (CSF) • Methotrexate toxicity: Leucovorin • Cyclophosphamide toxicity : MESNa • Cisplatin toxicity : Amifostine • Doxorubicin toxicity: Dexrazoxane • Hyperuricemia (rapid tumor cell lysis): Allopurinol