Anticancer drugs 4 cytotoxic drugs and antibiotics


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Anticancer drugs 4 cytotoxic drugs and antibiotics

  1. 1. Anticancer drugs Dr. S. Parasuraman Faculty of Pharmacy, AIMST.
  2. 2. Classification of anticancer agents Cytotoxic drugs 1. Alkylating agents 2. Platinum coordination: Cisplatin, Carboplatin, Oxaliplatin 3. Antimetabolites 4. Microtubule damaging agents: Vincristine, Vinblastine, Vinorelbine, Paclitaxel, Docetaxel 5. Topoisomerase-2 inhibitor: Etoposide 6. Topoisomerase-1 inhibitor: Topotecan, Irinotecan 7. Antibiotics: Actinomycin D, Doxorubicin, Daunorubicin, Epirubicin, Bleomycins, Mitomycin C. 8. Miscellaneous: Hydroxyurea, L-Asparaginase, Tretinoin, Arsenic trioxide
  3. 3. Classification of anticancer agents Targeted drugs 1. 2. 3. 4. 5. Tyrosine proteinkinase inhibitors: Imatinib, Nilotinib EGF receptor inhibitor: Gefitinib, Erlotinib Angiogenesis inhibitors: Bevacizumab Proteasome inhibitor: Bortezomib Unarmed monoclonal antibody: Rituximab, Trastuzumab
  4. 4. Classification of anticancer agents Hormonal drugs 1. 2. 3. 4. 5. 6. 7. 8. 9. Glucocorticods: Prednisolone Estrogens: Fosfestrol, ethinylestradiol Selective estrogen receptor modulators: Tamoxifen Selective estrogen receptor down: Fulvestrant Aromatase inhibitors: Letrozole, Anastrozole Antiandrogen: Flutamide 5-α reductase inhibitor: Finasteride GnRH analogues: Nafarelin, Triotorelin Progestins: Hydroxyprogesterone acetate
  5. 5. Platinum coordination Cisplatin: • Cisplatin hydrolysed intracellularly to produce a highly reactive moiety which causes cross linking of DNA. • Effect is resemble those of alkylating agents and radiation. • Bound to plasma proteins, penetrates tissues and is slowly excreted unchanged in urine with t½ of about 72 hr. • Very effective in metastatic testicular and ovarian carcinoma. Widely used in many solid tumours like lung, bladder, esophageal, gastric, hepatic, head and neck carcinomas. • Dose: 50-100 mg/m2
  6. 6. Microtubule damaging agents Vinca alkaloids (Vincristine & vinblastine): • MoA: – – • Inhibits microtubular protein and prevents polymerization and assembly of microtubules and cause disruption of mototic spindle and interfere with cytoskeletal function. Cell cycle specific, acts on MITOTIC phase. Use: – Administered in combination with other drugs. Used in POMP regimen for leukemia and the MOPP regimen for Hodgkin lymphoma – Vinca alkaloids are used in the treatment of acute lymphoblastic leukemia in children, Wilms tumor, Ewing soft-tissue sarcoma, and Hodgkin and non-Hodgkin lymphomas as well as some other rapidly proliferating neoplasms.
  7. 7. Microtubule damaging agents Vinca alkaloids (Vincristine & vinblastine): • MoA:
  8. 8. Microtubule damaging agents Vinca alkaloids (Vincristine & vinblastine): • Resistance: – • Pharmacokinetics: – – – • Resistant cells have enhanced efflux of vinca alkaloids via Pglycoprotein in the cell membrane. IV administration has rapid cytotoxic effects and cell destruction. Metabolized in the liver by the CYP450 pathway. Excreted in bile and feces. Adverse effects: – – phlebitis or cellulitis, if the drugs extravasate during injection Nausea, vomiting, diarrhea, and alopecia – Myelosuppressant, Inappropriate ADH secreaction. • Dose: – – Vincristine 1.5-5 mg/m2 BSA Vinblastine 0.1-0.15mmg/kg i.v. weekly X 3 doses
  9. 9. Taxanes Paclitaxel, Docetaxel: • Paclitaxel is a diterpin taxane obtained from bark of the Western yew tree. • Paclitaxel has shown good activity against advanced ovarian cancer and metastatic breast cancer. • Docetaxel effective in breast and ovarian cancer. • Both the drugs active in the G2/M phase of the cell cycle and inhibiting the beta tubulin. • Paclitaxel used for metastatic breast cancer after failure of first line chemotherapy and relapse cases. • Docetaxel effective in breast and ovarian cancer refractory to first line drug. • Dose: Paclitaxel – 135-175 mg/m2 i.v; Docetaxel 20-120 mg/vial inj
  10. 10. Antibiotics Drug Actinomycin D Use • Very potent antineoplastic drug, highly efficacious in Wilms' tumour and rhabdomyosarcoma • Mtx resistant choriocarcinoma Daunorubicin Doxorubicin Epirubicin ADR vomiting, stomatitis, diarrhoea, erythema and desquamation of skin, alopecia Dose 15 µg/kg i.v. daily for 5 days • effective in many solid tumours • capable of causing breaks in DNA strands by activating topoisomerase II and generating quinone type free radicals Marrow depression, Daunorubicin alopecia, stomatitis, : 20 mg/vial vomiting and local inj tissue damage Doxorubicin: 60-75 mg/m2 • Newer drugs similar to doxorubicin Adj. therap. For breast cancer, GIT, bladder cancer Dose: 60-90 mg/m2
  11. 11. Antibiotics Drug Mitomycin C Use • highly toxic drug is used only in resistant cancers of stomach, cervix, colon, rectum, bladder, etc. • kills cells in G1-M phases ADR Dose Bone marrow and • 10 mg/m2 g.i.t are the primary BSA targets of toxicity.
  12. 12. Miscellaneous Drug Use ADR Dose Hydroxyurea blocks the conversion of Myelosuppressio ribonucleotides to n is the major deoxyribonucleotides by toxicity inhibiting the enzyme ribonucleoside diphosphate reductase- interferes with DNA synthesis (active in s phase) 20-30 mg/kg daily or 80 rng/kg twice weekly L-Asparaginase The enzyme Lasparaginase (from E. coli) degrades L-asparagine to Laspartic acid, depriving leukaemic cells of an essential metabolite Dose: SG-200 KU/kg i.v. daily for 2-4 weeks liver damage, allergic reactions, anaphylaxis
  13. 13. Miscellaneous Drug Use Tretinoin • Trans-retinoic acid, a form of vit. A. • Degradation of PLLRARα fusion gene. Arsenic trioxide • Traditional poison for ages. • Used for Acute Promyelocytic Leukemia (APL) ADR Dose Dryness of skin, eye, nose, mouth, prutitus, epistaxis, rise in serum lipids and intraocular pressure. Most important ADR is ‘retinoic acid syndrome’ Nausea, fatigue, sensory disturbances, effusions, hyperglycemia, QT prolongation, A-V block.
  14. 14. Thank you