PHARM 471 Phytopharmaceuticals and Veterinary Medicine PDF

Kwame Nkrumah University of Science & Technology, Kumasi, Ghana PHARM 471 PHYTOPHARMACEUTICALS AND VETERINARY MEDICINE TOPIC: ANTICANCER AGENTS...

Kwame Nkrumah University of Science & Technology, Kumasi, Ghana PHARM 471 PHYTOPHARMACEUTICALS AND VETERINARY MEDICINE TOPIC: ANTICANCER AGENTS Dr. BERNARD KOFI TURKSON Department of Herbal Medicine, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences. 1  Outline Introduction Classification of anti-cancer drugs Anticancer drugs mechanisms of action -Alkylating agents -Antimetabolites -Cytotoxic antibiotics -Plant delivatives -Hormones -Monoclonal antibodies -Miscellaneous www.knust.edu.gh 2  Introduction Cancer is a term used for diseases in which abnormal cells divide without control and are able to invade other tissues. Cancer cells can spread to other parts of the body through the blood and lymph systems. The utilization of anticancer medications, whether synthesized or obtained from natural sources, to inhibit and cure cancer is known as chemotherapy. These medications can be utilized to treat various cancers, including breast, cervical, and lung cancers, as well as lymphomas and leukemia www.knust.edu.gh 3  Treatment of cancers Cancer if diagnosed early, the better a person’s chances for survival. The most effective treatments of cancer are obtained using a multidisciplinary approach (collaboration and co-decision of many branches of science). Chemotherapy Rapidly dividing cells metastasized cancers (leukaemia and lymphoma) Radiotherapy In combination with other therapies iodine-131 (thyroid cancer), iridium-192 (breast CA) Surgery Not metastasized cancers, prostate, breast or testicular CA’s www.knust.edu.gh 4  Treatment of cancers Immunotherapy Immune system made strong to fight against cancers Hormone therapy Killing cancer cells by altering hormone levels Gene therapy Replacing defective gene www.knust.edu.gh 5  Anticancer Anticancer agents, are also known as antineoplastic or chemotherapeutic drugs, are medications used in the management or treatment of malignant, or cancerous, disease. The anticancer drug either kill cancer cells or modify their growth. Aim of the cancer therapy Cure or prolong remission Palliation (the act of relieving suffering and symptoms without curing an underlying disease) Adjuvant chemotherapy (treatment given after the initial treatment to reduce the risk of cancer returning) www.knust.edu.gh 6  Categories of anti-cancer agents The anti-cancer agents are not easily classified. Historically, they are categorized as; Alkylating agents Antimetabolites Plant derived products Hormones and antagonists Miscellaneous. In recent years, however, the miscellaneous group has come to include some of the most important agents. www.knust.edu.gh 7  Classification of anti-cancer agents Anticancer agents are classified by; Indication (lymphoma, leukemia, melanoma, solid tumor), Mechanism of action (such as alkylating agents, antibiotics, biological response modifiers, antiandrogens, topoisomerase inhibitors or protein kinase inhibitors), Chemical structure (folic acid analog, platinum coordination complex, purine or pyrimidine analog, monoclonal antibody) Cytotoxic or nonspecific Noncytotoxic or targeted. www.knust.edu.gh 8  Alkylating Agents C) Alkyl Sulfonates A) Nitrogen Mustards -Busulfan -Mechlorethamine D) Triazine -Cyclophosphamide -Dacarbazine -Melphalan -Procarbazine -Chlorambucil E) Ethylenimine B) Nitrosoureas -Thio-TEPA -Carmustine -Lomustine -semustine www.knust.edu.gh 9  Antimetabolites Antibiotics Immunomodulators A) Folate antagonist -Actinomycin(D- A. Levamisole -Methotrexate actinomycin) B. Interferons B) Purine antagonist -Doxorubicin -Interferon alfa-2a and 2 b -6-mercaptopurine -Rubidomycin -6-thioguanine - C. Interleukins -Mitoxantrone Azathioprine -Aldesleukin -Bleomycins C) Pyrimidine antagonist -5-Fluorouracil -Mitomycin C -Cytarabine -Mithramycin(plicamycin) www.knust.edu.gh 10  Cell cycle specific agents Plant-derived Products Vinca Alkaloids A. Vinca Alkaloids Taxanes -Vincristine Antimetabolites -Vinblastine Bleomycins B. Taxanes -Paclitaxel Cell cycle non- specific agents -Docetaxel Alkylating Agents C. Epipodophyllo Toxin Antibiotics -Etoposide -Teniposide www.knust.edu.gh 11  Hormones And Hormone E) Progestin Antagonists -Medroxy Progesteron Miscellaneous agents A) Glucocorticoids Acetate -Hydroxyurea ( Hydrea ) -Prednisolone -Mitotane -Prednisone Monoclonal antibodies -Cisplatin B) Estrogen -Carboplatin -Trantuzumab -Mitoxantrone -Diethylstilbestreol - Rituximab Enzymes C) Anti-estrogen -L- Asparaginase (Elspar ) -Tamoxifen -Imatinib D) Androgens and Anti- androgens -Testosteron -Flutamide www.knust.edu.gh 12  Mechanism of action Anticancer agents primarily work by interfering with critical cellular processes such as; DNA replication Cell division Protein synthesis, often by damaging DNA, disrupting the cell cycle, or inhibiting essential enzymes, ultimately leading to cell death in rapidly dividing cancer cells. Their specific mechanism of action varies depending on the class of the agent. www.knust.edu.gh 13 www.knust.edu.gh 14 www.knust.edu.gh 15  MOA Antimetabolites These block or subvert one or more of the metabolic pathways involved in DNA synthesis a. Folate antagonists eg; methotrexate – Folates are essential for the synthesis of purine nucleotides and thymidylate, which in turn are essential for DNA synthesis and cell division Methotrexate inhibits dihydrofolate reductase b. Purine antagonists –e.g 6-mercaptopurine, inhibits several enzymes for purine biosynthesis. Also forms metabolites like 6-methylmercaptopurine ribotide (MMPR) which contribute to its cytotoxic action. Fludarabine in its trisphosphate form inhibits DNA polymerase c. Pyrimidine antagonist – eg 5-fluorouracil, also inhibit thymidylate synthetase hence inhibiting thymidilate synthesis -Cytarabine; inhibits DNA polymerase www.knust.edu.gh 16  Cytotoxic Antibiotics Is a widely used group of medications that mainly produce their effects through direct action on DNA As a rule, they should not be given together with radiotherapy, as the cumulative burden of toxicity is very high www.knust.edu.gh 17  Plant derivatives; Vinca Alkaloids Are derived from the Madagascar periwinkle The principal members are vincristine, vinblastine and vindesine The drugs bind to tubulin and inhibit its polymerisation into microtubules, preventing spindle formation in dividing cells and causing arrest at metaphase Their effects become manifest only during mitosis. www.knust.edu.gh 18 MOA-Vinca alkaloids www.knust.edu.gh 19  Hormones Hormone-dependent tumors have steroid receptors in the malignant cells Their growth can be inhibited by hormones with opposing actions, by hormone antagonists or by agents that inhibit the endogenous hormone synthesis Hormones or their analogues that have inhibitory actions on target tissues can be used in treatment. Such procedures alone rarely effect a cure but do mitigate the symptoms of the cancer Glucocorticoids such as prednisolone and dexamethasone have marked inhibitory effects on lymphocyte proliferation and are used in the treatment of leukaemias and lymphomas www.knust.edu.gh 20  Monoclonal antibodies Are immunoglobulins, of one molecular type, produced by hybridoma cells in culture, that react with defined target proteins expressed on cancer cells In some cases, binding of the antibody to its target activates the host's immune mechanisms and the cancer cell is killed by complement-mediated lysis or by killer cells Other attach to and inactivate growth factor receptors on cancer cells, thus inhibiting the survival pathway and promoting apoptosis. www.knust.edu.gh 21  Miscellaneous agents Crisantaspase; is a preparation of the enzyme asparaginase It breaks down asparagine to aspartic acid and ammonia, active against tumour cells that have lost the capacity to synthesize asparagine and therefore require an exogenous source The drug has a fairly selective action www.knust.edu.gh 22  Anticancer herbs Aloe africana A. maculata A. secundiflora A. vera www.knust.edu.gh 23  Anticancer herbs Common names: Madagascar periwinkle, rose periwinkle, or rosy periwinkle. Catharanthus roseus is native to Madagascar but grown elsewhere as an ornamental and medicinal plant. It is the source of the drugs vincristine and vinblastine (for treatment of leukaemia). www.knust.edu.gh 24 Local Name Botanical Name Part Used Akura aso Cissampelos mucronata shoot Twea pea Garcinia cola seed Ntropo (fanti) Solanum macrocarpon leaves and unripe fruit Ananse dokono Lantana camara Nyaya Momordica charantia shoot Aboma agu wakyi Phyllanthus spp Obireku ani, KƆtƆ ani Abrus precatorius www.knust.edu.gh 25  General toxicity of cytotoxic drugs Cytotoxic drugs have more profound effect on rapidly multiplying cells, because its targeting action in nucleic acid and there precursors. Bone marrow: Depression of bone marrow results in granulocytopenia, agranulocytosis, thrombocytopenia, aplastic anaemia. Lymphoreticular tissue: Lymphocytopenia and inhibition of lymphocyte function results in suppression of cell mediated as well as humoral immunity. Oral cavity: Stomatitis, neutropenia, thrombocytopenia www.knust.edu.gh 26  GIT: Diarrhoea, shedding of mucosa, haemorrhages, Nausea and vomiting Skin: Alopecia (due to damage of cells in hair follicles) Gonads: Oligozoospermia in males; amenorrhoea in females. Foetus: Cytotoxic agents causes abortion, foetal death, teratogenesis in pregnant women. Carcinogenicity: Secondary cancers, especially leukaemias, lymphomas and histocytic tumours appear with greater frequency many years after the use of cytotoxic drugs. Hyperuricaemia Individual drugs may produce specific adverse effects, e.g. neuropathy by vincristine, Cardiomyopathy by doxorubicin, cystitis and alopecia by cyclophosphamide. www.knust.edu.gh 27  References 1. Rang and Dale’s Pharmacology 6E 2007. 2. Lippincott’s Illustrated Reviews - Pharmacology - 2nd Edition. 3. Katzung Pharmacology Tenth Ed. 4. Google images www.knust.edu.gh 28