Pharmacology: Antineoplastic And Immunomodulating Drugs

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Most antineoplastic drugs inhibit

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DNA synthesis or disrupt DNA structure and function.

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DNA synthesis inhibitors include

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folate antagonists (methotrexate and trimetrexate), purine antagonists (mercaptopurine, thioguanine, and others), pyrimidine antagonists (cytarabine, floxuridine, and fluorouracil), and a ribonucleotide reductase inhibitor (hydroxyurea).

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DNA alkylating drugs that cross-link DNA include

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nitrogen mustards (cyclophosphamide and others), nitrosoureas (carmustine and others), and miscellaneous drugs (busulfan, dacarbazine, and mitomycin). Platinum compounds (cisplatin and others) also cross-link DNA strands.

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DNA intercalating drugs include

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anthracycline drugs (doxorubicin and others), bleomycin, and dactinomycin

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Inhibitors of mitosis include

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vinca alkaloids (vincristine and others) and taxane drugs (docetaxel and paclitaxel).

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Topoisomerase inhibitors include

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podophyllotoxin drugs (etoposide and teniposide) and camptothecin analogues (irinotecan and topotecan).

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Biologic response modifiers used in the treatment of cancer include

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IFN alfa-2b, aldesleukin, and monoclonal antibodies (bevacizumab, cetuximab, rituximab, and trastuzumab).

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Myelosuppression is the

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dose-limiting toxicity of most antineoplastic drugs.

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Doxorubicin and other anthracycline drugs produce

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cardiotoxicity

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cyclophosphamide and ifosfamide cause

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hemorrhagic cystitis

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bleomycin and busulfan produce

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pulmonary fibrosis

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vincristine, docetaxel, and related drugs cause

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neurotoxicity

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cisplatin produces

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renal toxicity

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Hormonal agents are used to treat some cancers, especially estrogen antagonists to treat

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breast cancer

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androgen antagonists are used to treat

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prostate cancer

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corticosteroids (e.g., prednisone) are used to treat

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lymphocytic leukemias and lymphomas.

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• Immunosuppressant drugs used to prevent organ transplant rejection or to treat autoimmune diseases include

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monoclonal antibodies (basiliximab, daclizumab, and muromonab-CD3), microbial products (cyclosporine, sirolimus, and tacrolimus), corticosteroids (e.g., prednisone), and cytotoxic drugs (e.g., azathioprine).

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CLASSIFICATION OF ANTINEOPLASTIC AND IMMUNOMODULATING DRUGS

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DNA Synthesis Inhibitors
DNA Alkylating Drugs
DNA Intercalating Drugs
DNA Topoisomerase Inhibitors
Mitotic Inhibitors
Monoclonal Antibodies
Protein Kinase Inhibitors
Antineoplastic mTOR Inhibitor
Cytokines and Interferons
Immunomodulating Drugs

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DNA Synthesis Inhibitors

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Folate Antagonists
Purine Antagonists
Pyrimidine Antagonists
Ribonucleotide Reductase Inhibitor

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Folate Antagonists

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Methotrexate, pemetrexed (Alimta)

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Purine Antagonists

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Cladribine,
clofarabine,
fludarabine,
mercaptopurine,
nelarabine,
thioguanine

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Pyrimidine Antagonists

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Capecitabine (Xeloda),
Cytarabine,
Floxuridine,
Fluorouracil,
Gemcitabine (Gemzar)

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Ribonucleotide Reductase Inhibitor

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Hydroxyurea

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DNA Alkylating Drugs

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Nitrogen Mustards
Nitrosourea Drugs
Platinum Compounds
Other DNA Alkylating Drugs

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Nitrogen Mustards

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Chlorambucil,
cyclophosphamide (Cytoxan),
Ifosfamide,
Mechlorethamine,
Melphalan

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Nitrosourea Drugs

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Carmustine,
lomustine
streptozocin

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Platinum Compounds

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Cisplatin,
carboplatin,
oxaliplatin

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Other DNA Alkylating Drugs

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Busulfan,
dacarbazine,
mitomycin

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DNA Intercalating Drugs

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• Bleomycin
• Doxorubicin (Adriamycin), Daunorubicin, Idarubicin
• Mitoxantrone, dactinomycin

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DNA Topoisomerase Inhibitors

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• Etoposide, teniposide
• Irinotecan, topotecan

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Mitotic Inhibitors

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• Paclitaxel (Taxol), docetaxel
• Vincristine (Oncovin), Vinblastine, Vinorelbine
• Ixabepilone

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Monoclonal Antibodies

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• Alemtuzumab, bevacizumab, cetuximab, gemtuzumab ozogamicin, panitumumab, rituximab, trastuzumab, 90Y-ibitumomab, 131I-tositumomab

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Protein Kinase Inhibitors

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• Dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, sorafenib, sunitinib

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Antineoplastic mTOR Inhibitor

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• Temsirolimus

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Cytokines and Interferons

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• Aldesleukin, Interferon alfa-2b

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Immunomodulating Drugs

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Microbial Products
Monoclonal Antibodies
Other Drugs

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Microbial Products

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• Cyclosporine, sirolimus, tacrolimus

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Monoclonal Antibodies

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• Basiliximab, daclizumab, muromonab-CD3, palivizumab

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Other Immunomodulating Drugs

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• Azathioprine, prednisone
• Thalidomide

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Cancer occurs when

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normal cells are transformed into neoplastic cells through alteration of their genetic material, leading to abnormal gene expression

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This transformation usually results from

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genetic mutations that cause expression of oncogenes and inhibition of tumor suppressor genes