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ANTINEOPLASTIC AGENTS

LECTURE 9 B. ANTINEOPLASTIC AGENTS. PHARMACOLOGY. OBJECTIVE. To cause a lethal lesion that can arrest tumor’s progression. The attack is generally against the metabolic sites that are essential for cell replication. Ideally, only malignant cells should be targeted.

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ANTINEOPLASTIC AGENTS

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  1. LECTURE 9 B ANTINEOPLASTIC AGENTS PHARMACOLOGY

  2. OBJECTIVE • To cause a lethal lesion that can arrest tumor’s progression. • The attack is generally against the metabolic sites that are essential for cell replication. • Ideally, only malignant cells should be targeted. • However, currently no such drugs are available that specifically recognize neoplastic cells, resulting in the appearance of adverse drug reactions (ADRs).

  3. CLASSIFICATION • Antimetabolites • Antibiotics • Alkylating agents • Microtubule inhibtors • Steroids • Others

  4. ANTIMETABOLITES • Methotrexate, mercaptpurine • Act at S phase of the cell cycle • They inhibit the synthesis of nucleotides by altering various genetic mechanisms • Used in leukemia, lymphoma, inflammatory diseases. • ADRs: Neurological, renal, hepatic, pulmonary, resistance.

  5. METHOTREXATE MOA

  6. Mercaptopurine MOA

  7. ANTIBIOTICS • Dactinomycin , Bleomycin, Daunorubicin, Doxorubicin • Interaction with DNA, leading to disruption of DNA function • Usually in combination with other anticancer agents • Choriocarcinoma, Breast, lung, leukemia, lymphoma • ADRs: Same as for antimetabolites plus skin reactions and immunosuppression

  8. ALKYLATING AGENTS • Cyclophophamide, nitrosoureas (carmustine) • Covalently binding to nucleophilic groups on the DNA. Resulting in the disruption of cell growth • Used in lymphomas, leukemias and solid tumors • Same as above plus nausea, latent viral infections (why?), alopecia, neutropenia.

  9. MICROTUBULE INHIBITORS • Vincristine, vinblastine, paclitaxel • Act on the spindle fibers to halt cell division • The most commonly used anticancer agents. • Lekemia, lymphoma, soft and hard tissue tumors. • ADRs: Same as above plus neuropathy (ataxia, foot drop)

  10. STEROIDS • Prednisone, tamoxifen, estrogens • Only good for hormone responsive tumors • Breast, ovarian, prostatic (plus sometimes in addition to other agents for decreasing inflammation) • ADRs: Same as above

  11. OTHERS • Cisplatin – similar to alkylating agents • Carbaplatin - similar to alkylating agents • Etoposide – irreversible DSBs (double stranded breaks) • Interferons – active against tumor cells by initiating immune response against them.

  12. THANK YOU

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