Antibiotic antineoplastic drugs

Antibiotic antineoplastic drugs

Antibiotic antineoplastic drugs are antimicrobial products thatproduce tumoricidal (tumor-destroying) effects by binding with DNA. These drugs inhibit the cellular processes of normal and ma-lignant cells. They include:

anthracyclines (daunorubicin, doxorubicin, idarubicin)

·                 bleomycin

·                 dactinomycin

·                 mitomycin

·                 mitoxantrone.

Pharmacokinetics

Antibiotic antineoplastic drugs are usually administered I.V.

Direct deliveries

Some drugs are also administered directly into the body cavity be-ing treated. Bleomycin, doxorubicin, and mitomycin are some-times given as topical bladder instillations, resulting in minimal systemic absorption. When bleomycin is injected into the pleural space for malignant effusions, up to one-half of the dose is ab-sorbed systemically.

Distribution, metabolism, and excretion

Distribution of antibiotic antineoplastic drugs throughout the body varies; their metabolism and elimination also vary.

Pharmacodynamics

With the exception of mitomycin, antibiotic antineoplastic drugs intercalate, or insert themselves, between adjacent base pairs of a DNA molecule, physically separating them.

Taking the extra base

Remember, DNA looks like a twisted ladder with the rungs made up of pairs of nitrogenous bases. These drugs insert themselves between those nitrogenous bases. Then, when the DNA chain replicates, an extra base is inserted opposite the intercalated an-tibiotic, resulting in a mutant DNA molecule. The overall effect is cell death.

Clean break

Mitomycin is activated inside the cell to a bifunctional or even tri-functional alkylating drug. Mitomycin produces single-strand breakage of DNA. It also cross-links DNA and inhibits DNA syn-thesis.

Pharmacotherapeutics

Antibiotic antineoplastic drugs act against many cancers, includ-ing:

·                 acute leukemia

·                 breast, ovarian, bladder, and lung cancer

·                 cancers of the GI tract

·                 choriocarcinoma

·                 Ewing’s sarcoma (a malignant tumor that originates in bone marrow, typically in long bones or the pelvis) and other soft-tissue sarcomas

·                 Hodgkin’s disease and malignant lymphomas

·                 melanoma

·                 osteogenic sarcoma and rhabdomyosarcoma (malignant neo-plasm composed of striated muscle cells)

·                 squamous cell carcinoma of the head, neck, and cervix

·                 testicular cancer

·                 Wilms’ tumor (a malignant neoplasm of the kidney, occurring in young children).

Drug interactions

Antibiotic antineoplastic drugs interact with many other drugs. (See Adverse reactions to antibiotic antineoplastic drugs.)

§    Concurrent therapy with fludarabine and idarubicin isn’t recom-mended because of the risk of fatal lung toxicity.

§    Bleomycin may decrease serum digoxin and serum phenytoin levels.

§    Doxorubicin may reduce serum digoxin levels.

§    Combination chemotherapies enhance leukopenia and thrombo-cytopenia (reduced number of platelets).

§    Mitomycin plus vinca alkaloids may cause acute respiratory dis-tress.