Pharmacology
Summary
Cytotoxic antibiotics--- which include strong>bleomycin, anthracyclines, and actinomycin D--- are antineoplastic drugs that interact directly with DNA, either by intercalating between specific bases or causing strand breaks, which results in the blocking of DNA and RNA synthesis and inhibition of cell division.
Bleomycin is a small peptide that binds to DNA by chelating metal ions and producing a pseudoenzyme. When this pseudoenzyme reacts with oxygen, it produces superoxide and hydroxide free radicals which cleave DNA. It's a cell cycle-specific agent that arrests cells in the G2 phase, and is used in the treatment of Hodgkin’s and non-Hodgkin’s lymphoma as well as numerous solid tumors, like germ cell tumors and squamous cell carcinoma. Its main dose-limiting toxicity is pulmonary toxicity, and other side effects include skin toxicity, stomatitis, mucositis and alopecia. Similarly, anthracyclines, like doxorubicin and daunorubicin, induce cytotoxicity through the generation of oxygen free radicals and by binding avidly to DNA through intercalation. These cytotoxic antibiotics, however, are associated with irreversible dose-dependent cardiotoxicity and myelosuppression. Actinomycin D also acts as an intercalating agent and is used in numerous pediatric malignancies (e.g. Wilms tumor, Ewing sarcoma, rhabdomyosarcoma).
Lesson Outline
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FAQs
Bleomycin is a cytotoxic antibiotic that binds to DNA and catalyzes the production of free radicals, such as superoxide and hydroxide. These free radicals subsequently cause both single and double-strand breaks in DNA, which cleaves DNA. In addition, bleomycin halts the progression of the cell cycle by blocking the G2 phase, further contributing to its antineoplastic effects.
Bleomycin is effective in the treatment of various hematologic and solid malignancies, including Hodgkin and non-Hodgkin lymphomas, germ cell tumors, and squamous cell carcinoma of the skin, cervix, and vulva. However, it does have potential side effects, including pulmonary toxicity, which can present as pneumonitis or pulmonary infiltrates, and skin toxicity, which can manifest as rash, exfoliation, hyperpigmentation, or atrophic striae. Bleomycin can also cause mucositis, stomatitis, and alopecia.
Anthracyclines, like doxorubicin and daunorubicin, are cytotoxic antibiotics that exert their effects by intercalating with DNA, which then blocks DNA and RNA synthesis. Additionally, they also produce free radicals, which can cause further damage.
Anthracyclines are used in the treatment of a broad range of solid and hematologic malignancies. They do, however, come with potential side effects, such as cardiotoxicity (which can lead to dilated cardiomyopathy), myelosuppression, and alopecia. Dexrazoxane, an iron chelator, is often used to prevent anthracycline-induced cardiotoxicity.
Actinomycin D is another antineoplastic antibiotic that works similarly to anthracyclines in that it intercalates with DNA and blocks both DNA and RNA synthesis. It is particularly effective in treating numerous pediatric malignancies, such as Wilms tumor, Ewing sarcoma, and rhabdomyosarcoma. Like other antineoplastic antibiotics, actinomycin D can cause side effects, including alopecia.
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