09 antineoplastic drugs-ii
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09 antineoplastic drugs-ii

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09 antineoplastic drugs-ii 09 antineoplastic drugs-ii Presentation Transcript

  • PSALM OF THE DAY Psalm 150 verse 6 Let everything that hath breath praise the LORD. Praise ye the LORD.
  • And JESUS answered him, The first of all the commandments is, HEAR O ISRAEL; THE LORD OUR GOD IS ONE LORD: AND THOU SHALT LOVE THE LORD THY GOD WITH ALL THY HEART, AND WITH ALL THY SOUL, AND WITH ALL THY MIND, AND WITH ALL THY STRENGTH: this is the first commandment. And the second is like namely, THOU SHALT LOVE THY NEIGHBOUR AS THYSELF. There is none other commandment greater than these. Mark 12:29-31 c.f. Matthew 22:37-40
  • ANTINEOPLASTIC DRUGS LECTURE 2
  • NATURAL PRODUCTS/ Plant Subtances Vinca Alkaloids Podophyllotoxins Camptothecins Taxanes Vincristine, Vinblastine Etoposide, teniposide Topotecan, Irinotecan Paclitaxel (Taxol)
  • VINCA ALKALOIDS Vincristine, vinblastine: Inhibits tubulin assembly-M phase specific Toxicity: Nausea,Vomiting, Bone marrow suppression, Alopecia, Neurotoxicity Therapeutic uses: (MVPP), Lymphomas
  • Vinca Alkaloids Mechanism of Action Cell cycle specific Binds to the microtubular protein tubulin in a dimeric form The drug-tubulin complex adds to the forming end of the microtubules to terminate assembly Depolymerization of the microtubules occurs Resulting in mitotic arrest at metaphase, dissolution of the mitotic spindle, and interference with chromosome segregation
  • Vinca Alkaloids Vinblastine Vincristine Vindesine Inhibit microtubules (spindle), causing metaphase cell arrest in M phase.
  • EPIPODOPHYLLOTOXINS Etoposide, teniposide Semi-synthetic glycosides Present in may apple, mandrake plant Inhibits topoisomerase II Given PO and i.v.
  • NATURAL PRODUCTS Topotecan, Irinotecan) Are Camptothecins Active metabolites formed in vivo Inhibit topoisomerase I Taxol (Paclitaxel) and Docetaxel Are Taxanes Inhibit disassembly of microtubules Given i.v. for ovarian and breast cancer
  • ENDOCRINE THERAPY Many endocrine cancers retain hormone receptors e.g. ER in breast Androgens oppose the effects of estrogens, and vice versa Have different toxicities from the other antineoplastic drugs
  • HORMONES (a) Glucocorticoids e.g. Prednisone Use: Lymphoma (b) Androgens e.g. Testosterone S/E: Masculinisation Use: Breast cancer (c) Estrogens e.g. Oestradiol S/E: Gynaecomastia Use: Testicular cancer, Prostate cancer
  • HORMONES Progestins e.g. Megestrol S/E : Fluid retention Main use: Endometrial cancer GnRH analogs: Goserelin, Leuprolide Stimulate ,then inhibit release of FSH and LH Use: Prostate cancer
  • ENDOCRINE THERAPY Antiestrogen: Tamoxifen Competitive antagonist at estrogen receptor Use: Breast cancer Given orally, highly protein bound, active metabolite S/E: Nausea, hot flashes, amenorrhoea
  • ENDOCRINE THERAPY Antiandrogens e.g. Flutamide, Nilutamide Competitive antagonist at androgen receptor Use: Prostate cancer S/E: Fluid retention, gynaecomastia Finasteride (Proscar®) 5- -Reductase enzyme inhibitor Use: Prostate cancer
  • MISCELLANEOUS Immunotherapy: lL-2, InterferonMonoclonal antibodies: Trastuzumab (Herceptin®) for breast cancer L-Asparaginase : for acute lymphoblastic leukemia, S/E hepatotxicity Hydroxyurea : inhibits deoxyribonucleotides, S/E: myelosuppression
  • Avastin (Bevacizumab)     A recombinant humanized antibody to Vascular Endothelial Growth Factor (VEGF) Avastin binds to and inhibit VEGF, a protein that plays a critical role in tumor angiogenesis At present, Genentech is pursuing broad latestage clinical trials examining its potential use in multiple tumor types.
  • MISCELLANEOUS Mitoxanthrone: topoisomerase II inhibitor Procarbazine: forms active metabolites which cause DNA strand breaks, D/I with alcohol Radioactive isotopes e.g. 131-Iodine, 60Cobalt
  • Cancer Vaccines in Development: Cervarix In Phase III studies, Cervarix, one of the new vaccines highlighted by GSK, demonstrated 100% effectiveness in preventing persistent infection by the two human papillomaviruses (HPV) with the highest risk for causing cervical cancer: HPV16 and HPV18. Cervarix has the potential to prevent more than 70% of cervical cancers. Phase III trials enrolling 25,000 women has began. Filing is expected in 2008.
  • JOHN 14: 6 JESUS saith unto him, I am the way, the truth, and the life: no man cometh unto the Father, but by me.