ANTI CANCER DRUGS.powerpoint presentation

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1. ANTI CANCER DRUGS

2. DIFFERNCES BETWEEN CHEMOTHERAPY OF INFECTION AND MALIGNANT CELLS. INFECTION The invading microbe is biologically foreign to the host tissue and its metabolic reactions are so different from those of the host cells that a chemotherapeutic agent can attack it selectively without affecting the host tissue cells. The body helps the antimicrobial drug with its own defence system in the form of antibodies,phagocytosis etc. MALIGNANCY No clear cut differences in metabolic reactions between normal and malignant cells. host defence is usually lacking or ineffective.

3. INDIAN CELEBRIRTIES WHO SURVIVED CANCER

4. YUVRAJ SINGH

5. SANJAY DUTT

6. CHARACTERISTICS WHICH DISTINGUISH CANCER CELLS FROM NORMAL CELLS Uncontrolled(autonomous) proliferation Differentiation and loss of function Tissue invasiveness/metastasis.

7. DIVISION OF NORMAL CELL G0(gap 0 or resting):non-proliferative phase. G1(gap 1 i.e presynthetic ) phase:the cell determines its readiness to commit to DNA synthesis. S(synthetic)phase: DNA synthesis. G2(gap 2,i.e postsynthetic )phase: accuracy of DNA replication is determined,and errors are corrected. M(mitotic phase):the replicated chromosomes are separated into two nuclei for the two daughter G1 cells. These cells may reenter the cycles or pass into the G0 phase.

8. Cell cycle Prophase (before) Metaphase (after) Anaphase (upword) Telophase (end) Interphase + Mitosis :18 – 24 hours Mitosis 1-2 hours

9. DEREGULATION OF CELL CYCLE IN CANCER CELL Abnormal growth factor function. Abnormal cyclins and /or cDK function. Abnormal DNA synthesis. Abnormal decrease in negative regulatory factors due to mutation in the tumour suppressor gene p53.

10. TREATMENT APPROACHES TO CANCER

11. KILL OR REMOVE THE CANCER CELLS Cytotoxic chemotherapy: act on all rapidly dividing normal and cancerous cells and kill them.not specific for cancer cells. Radiotherapy Targeted cytotoxic agents:e.g antibodies linked to toxins. Surgery

12. TARGETED CANCER THERAPY Uses drugs that block the growth and spread of cancer by interfering with specific molecules that are involved in the growth and spread of cancer. Targets are identified first(specific genes,proteins,tissue environment) and the drugs are designed to interact with the targets. Two types of drugs are used in targeted therapies: Small molecules which enter the cells to act on the target located within the cells. Monoclonal antibodies which act on targets on the cell surface.

13. CYTOTOXIC CHEMOTHERAPY PHASE SPECIFIC S phase:antimetabolites . G1-S phase:epipodophyllotoxin M phase:taxane and vinca alkaloids. G2-M phase:bleomycin . these injure DNA at a specific phase of the cell cycle but do not act on the resting phase. PHASE NON SPECIFIC Alkylating agents Anti tumor antibodies Platinum analouges Campothecin Doxorubicin. These injure DNA at any phase of the cell cycle including the resting phase(G0) to block the check points before the cell division.

14. ALKYLATING AGENTS These compounds,first used in chemical warfare have anti cancer properties.

15. NITROGEN MUSTARDS MOA Alkylating agents in neutral or alkaline solution,form highly reactive quaternary ammonium derivatives,ethyleniminium cations. These cations react with (alkylate) groupings like amini,sulphadryl,hydroxy or phosphate in the physiologically important molecules in the cells and render them unavailable for the normal metabolic ractions .

16. PHARMACOLOGICAL ACTIONS Cytotoxic action: damage the nuclei of growing and multiplying cells. Damage the epithelial cells of cornea,oral mucosa and intestinal mucosa causing ulceration. Immunosuppressant action:suppress antibody production and hence act as immunosuppressants,thus encouraging opportunistic infections. Miscellaneous actions: severe emitics,mutagenic and leukemiogenic .

17. MECHLORETHAMINE Acts locally as a vesicant. Acts on on the skin,eyes and the respiratory tract. Undergoes very rapid chemical transformation to the active form when dissolved in water. Used for cutaneous T-cell lymphoma as local application. Very toxic drug and is now replaced by other alkylating agents.

18. CYCLOPHOSPHAMIDE Pharmacoligical action similar to mechlorethane . It is a prodrug. Given orally as well as parenterally.

19. ABSORPTION,FATE AND EXCRETION Well absorbed from the GIT. Converted to active metabolites,hydroxyphosphamide and aldophsphamide . Metabolised further to inactive compounds. 14% of the drug appears in the urine unchanged.

20. ADVERSE RECTIONS Hemorrhage Cystitis Hepatic damage.

21. PREPARATION AND DOSAGE Supplied as 50 mg tablets and in vials containing powder. Solution for injection is prepared by adding sterile water which remains stable for 3 hours. Given intravenously,intrapleurally,intraperitoneally,intraarterially,intraperitoneally, intraarterially and directly into the tumour . Administered as a single dose(mg/kg) for 10-20 days. Low dose(2-6) Moderate dose(10-15) High dose(20-40)

22. INDIACATIONS chronic lymphatic leukaemia Lymphomas Solid tumours Immunosuupressing agent.

23. IFOSAMIDE Analouge of cyclophosphamide with similar action and safety profile.

24. MELPHALAN Properties similar to other alkylating agents. Orally effective. Less irritant Used ti treat multiple myeloma.

25. CHLORAMBUCIL Properties similar to mechlorethamine. Shortest acting nitrogen mustard. Orally effective Predominantly against malignant cells of lymphoid series. Given orally in the dose of 0.1-0.2mg/kg of body weight daily for 3-6 weeks. Used in chronic lymphocytic laukaemia .

26. ANTIMETABOLITES A chemical agent which by virtue of its close structural similarity to the metabolite , blocks its actions,is called a metabolite. It achieves this either by preventing the combination of the metabolite with its specific enzyme and thus getting transformed into a compound which is either metabolically inactive or harmful. Damage cell directly.

27. CLASSIFICATION Substances essential for the synthesis of the nucleic acid bases,e.g folic acid antagonist methotrexate. Substances which get incorporated into the nucleic acid chains e.g purine and pyrimidine antagonists.

28. METHOTREXATE MOA: competes with for the folate reductase enzyme and binds to the folate reductase(which us essential for the production of tetrahydrofolic acid) ireeversibly,thus restricting the production of THF. Lack of THF leads to inhibition of DNA synthesis and thus cell replication.

29. PHARMACOLOGICAL ACTIONS Bone marrow: inhibits erythropoiesis,myelopoiesis , and finally causes aplasia of the bone,causing marked granulocytopenia,reticulocytopenia and moderate lymphopenia. Immunosuppressive action: acts by preventing the clonal expansion of both B and T cells. Anti-inflammatory action: reduces lymphocyte proliferation, rheumatoid factor

30. ABSORPTION,FATE AND EXCRETION Methotrexate is well absorbed from the intestines. Remains in the tissue longer than folate causing a prolonged inhibitory effect. Poor concentration in CSF 50%-90% of the dose is rapidly excreted via both glomerular filtration and tubular secretion.

31. ADVERSE REACTIONS Megaloblastic anemia Leucopenia Aplasia Dermatitis Liver damage

32. PREPARATIONS AND DOSES TABLET(mg) 2.5 7.5 10 15 SOLUTION(mg) 2.5 7.5 15 20 25 50 100

33. INDIACATIONS Acute lymphatic leaukaemia in children Choriocarcinoma Soft tissue sarcoma Breast cancer Acute myeloid leukaemia Rheumatoid arthritis Psoriasis Immunosuppressant in steroid-resistant asthma,crohn’s disease and transplant rejection. Medical termination of pregnancy.

34. ANTIMITOTIC NATURAL PRODUCTS

35. Vinca alkaloids : Vincristine & vinblastine are obtained from vinca rosea. Vincristine : it is neurotoxic. Uses – leukaemias , hodgkin’s lymphoma, & brain tumour Vinblastin : it causes bone depression, alopecia & vomiting. Uses - Testicular tumour hodgkin’s lymphoma

36. Antibiotics : These drugs bind to DNA , they block the synthesis of new DNA & of DNA dependenat RNA and thus inhibit cell replication. These are cell cycle non specific drugs except for bleomycin which blocks G 2 phase of cell cycle. AE : Myelosupression ,, Hepatotoxicity, alopecia, nausea, vomiting, stomatitis, Cardiotoxicity, pulmonary toxicity, nephrotoxicity.

37. Uses : Acute leukaemia Testicular toxicity Hodgkin’s disease Pancreatic , colon, breast , lung carcinoma