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Anticancer Drugs

Anticancer Drugs. Anticancer Drugs. Introduction. Cancer refers to a malignant neoplasm or new growth. Cancer cells manifest uncontrolled proliferation, loss of function due to loss of capacity to differentiate, invasiveness, and the ability to metastasize.

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Anticancer Drugs

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  1. Anticancer Drugs Anticancer Drugs

  2. Introduction • Cancer refers to a malignant neoplasm or new growth. Cancer cells manifest uncontrolled proliferation, loss of function due to loss of capacity to differentiate, invasiveness, and the ability to metastasize. • Cancer arises as a result of genetic changes in the cell, the main genetic changes being, inactivation of tumor suppressor genes and activation of oncogenes.

  3. Management of cancer • There are three approaches for the management of cancer: 1. Radiotherapy 2. Surgery 3. Chemotherapy

  4. Anticancer drugs • The anticancer drugs either kill cancer cells or modify their growth. However selectivity of majority of drugs is limited and they are one of the most toxic drugs used in therapy. • In malignant diseases, drugs are used with the aim of: • Cure or prolonged remission • Palliation • Adjuvant chemotherapy

  5. Classification of drugs • Drugs acting directly on cells (cytotoxic drugs): • Alkylating agents • Mechlorethamine • Cyclophosphamide • Ifosfamide • Chlorambucil • Melphalan

  6. Continue 2. Antimetabolities • Methotrexate • 6-mercaptopurine • 6-thioguanine • Azathioprine • 5-fluorouracil • Cytarabine

  7. Continue 3. Vinca alkaloids • Vincristine • Vinblastine 4. Taxanes • Paclitaxel • Docetaxel

  8. Continue 5. Antibiotics • Actinomycin D • Doxorubicin • Daunorubicin • Mitoxantrone • Bleomycins • Mitomycin C

  9. Continue 6. Miscellaneous • Hydroxyurea • Procarbazine • L-asparaginase • Cisplatin • Carboplatin • Imatinib

  10. Continue • Drugs altering hormonal milieu • Glucocorticoids • Prednisolone 2. Estrogens • Fosfestrol • Ethinylestradiol

  11. Continue 3. Selective estrogen receptor modulators • Tamoxifen • Toremifene 4. Aromatase inhibitors • Letrozole • Anastrozole • Exemestane

  12. Continue 5. Antiandrogen • Flutamide • Bicalutamide 6. 5 alpha reductase inhibitors • Finasteride • Dutasteride

  13. Continue 7. GnRH analogues • Nafarelin • Triptorelin 8. Progestins • Hydroxyprogestrone acetate

  14. General toxicity of cytotoxic drugs • Bone marrow depression • Lymphoreticular tissue: lymphocytopenia and inhibition of lymphocyte function. • Oral cavity: the oral mucosa is particularly susceptible to cytotoxic drugs because of high epithelial cell turnover.

  15. Continue • GIT: Diarrhea, shedding of mucosa, hemorrhages occur due to decrease in the rate of renewal of the mucous lining. Drugs that frequently cause mucositis are Bleomycins, Actinomycin, and Methotrexate. • Nausea and vomiting are prominent with many cytotoxic drugs, this is due to direct stimulation of CTZ.

  16. Continue • Gonads: Inhibition of gonadal cells causes oligozoospermia and impotence in males; inhibition of ovulation and amenorrhea are common in females. • Fetus: practically all cytotoxic drugs given to pregnant women profoundly damage the developing of the fetus. • Hyperuricaemia: this is a secondary to a massive cell destruction (uric acid is a product of purine metabolism). Gout and urate stones in the urinary tract may develop. Allopurinol is protective by decreasing uric acid synthesis.

  17. Mechanism of actions • Alkylating agents and related compounds (e.g. cyclophosphamide, lomustine, thiotepa, cisplatin): These groups of drugs act by forming covalent bonds with DNA and thus impending DNA replication. • Antimetabolites (e.g. methotrexate, fluorouracil, mercaptopurine): These drugs blocks or destabilize pathways in DNA synthesis.

  18. Continue • Cytotoxic antibiotics (e.g. Doxorubucin, bleomycin, dactinomycin): These drugs inhibit DNA or RNA synthesis or cause fragmentation to DNA chains or interfere with RNA polymerase and thus inhibit transcription. • Plant derivatives (e.g. vincristine): Inhibits mitosis

  19. Mechlorethamine • It is the first nitrogen mustard, highly reactive and local vesicant, can only be given i.v route. • It produces many acute effects like nausea, vomiting, and haemodynamic changes. • Dose is 0.1mg/kg i.v daily times 4 days, doses may be repeated at suitable intervals. • It is available 1omg dry powder in vial.

  20. Cyclophosphamide • It is inactive, produces few acute effects and is not locally damaging. Transformation into active metabolities occurs in the liver and a wide range of antitumour actions is excerted. • It has prominent immunosuppressant property. Thus it is one of the most popular anticancer drugs. • It is less damaging to platelets, but alopecia and cystitis are prominent. • Dose is 2-3mg/kg/day, 10-15mg/kg i.v, every 7-10days, i.m use is also possible.

  21. Ifosfamide • Ifosfamide has a longer and dose dependent halflife. • It has found utility in bronchogenic, breast, testicular, bladder, headache, neck and some other carcinoma. • Ifosfamide causes less alopecia, and is less emetogenic than cyclophosphamide. • Dose is available 1g vial, 200mg inj.

  22. Chlorambucil • It is very slow acting Alkylating agent specially active on lymphoid tissue. • It is the drug of choice for long term maintenance therapy for chronic lymphatic leukemia and some solid tumors also resolve. • It has some immunosuppressant property. • Dose is 4-10mg daily for 3-6 weeks.

  23. Melphalan • It is very effective in multiple myeloma and has been used in advanced ovarian cancer. • Bone marrow depression is the most important toxicity. • Infections, diarrhea, and pancreatitis are the complications. • Dose is 10mg daily for 7 days or 6mg per day for 2-3 weeks. • It is available 2, 5, 50mg for i.v injection.

  24. Busulfan • It is highly specific for myeloid elements, granulocyte precursors being the most sensitive, followed by those platelets and RBC. It produces little effect on lymphoid tissue and G.I.T. • Hyperuricaemia is common and pulmonary fibrosis is a speacific adverse effect. Sterility also occurs. It is the drug of choice for chronic myeloid leukemia. • The dose is 2-6mg/day orally.

  25. Dacarbazine • It is different from other Alkylating agents in having primary inhibitory action on RNA and protein synthesis (others mainly effect DNA). • It is activated in the liver. The most important indication is malignant melanoma, also used Hodgkin's disease. • Nausea and vomiting are the prominent side effects. • The dose is 3.5mg/kg per day i.v for 10 days. • Available 100, 200, 500mg injection.

  26. Methotrexate • It is one of the oldest and highly efficacious antineoplastic drugs, inhibits dihydrofolate reductase- blocking the conversion of DHF to THF which is an essential co-enzyme required for one carbon transfer reactions in purine synthesis. • Methotrexate is absorbed orally. Little is metabolized and largely excreted in the urine. • Methotrexate is apparently curative in choriocarcinoma, 15-30mg/day for 5 days orally or 20-40mg i.m or i.v.

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