Antibiotics cancer chemotherapy

A thorough discussion of the mechanisms of absorption is provided in Chapter 4. Water-soluble vitamins (B2, B12, and C) and other nutrients (e.g., monosaccharides, amino acids) are absorbed by specialized mechanisms. With the exception of a number of antimetabolites used in cancer chemotherapy, L-dopa, and certain antibiotics (e.g., aminopenicillins, aminoceph-alosporins), virtually all drugs are absorbed in humans by a passive diffusion mechanism. Passive diffusion indicates that the transfer of a compound from an aqueous phase through a membrane may be described by physicochemical laws and by the properties of the membrane. The membrane itself is passive in that it does not partake in the transfer process but acts as a simple barrier to diffusion. The driving force for diffusion across the membrane is the concentration gradient (more correctly, the activity gradient) of the compound across that membrane. This mechanism of... 

In the case of antibiotic chemotherapy, the ideal pharmacodynamic response is usually no pharmacodynamic response the pharmacological target is not normal human cells but rather a parasite, a virus-infected human cell, or a cancerous cell. The less selective the chemotherapeutic drug, the greater the severity of adverse effects. Cancer chemotherapy is often severely toxic, even life threatening. Suppression of a viral infection, such as occurs in the treatment of HIV with antiviral drugs, is often complicated by serious drug-associated toxicity, such as hepatotoxicity or bone marrow suppression. 

Screening of microbial products has led to the discovery of a number of growth-inhibiting compounds that have proved to be clinically useful in cancer chemotherapy. Many of these antibiotics bind to DNA through intercalation between specific bases and block the synthesis of RNA, DNA, or both cause DNA strand scission and interfere with cell replication. All of the anticancer antibiotics now being used in clinical practice are products of various strains of the soil microbe Streptomyces. These include the anthracyclines, bleomycin, and mitomycin. 

Complex glycosylated compounds like macrolides, anthracyclines, aureolic acids, cardiac glycosides, orthosomycines and tetronic acids are of considerable scientific as well as pharmaceutical interest. Obviously, each of them is responsible for certain therapeutic effects with respect to different diseases. Anthracyclines and aureolic acids are applied in cancer chemotherapy, orthosomycines are active as antibiotics against Gram-positive bacteria, and the cardiac glycosides are used in the treatment of cardiac insufficiency. 

Plicamycin is a cytotoxic antibiotic (see Chapter 55 Cancer Chemotherapy) that has been used clinically for two disorders of bone mineral metabolism Paget s disease and hypercalcemia. The cytotoxic properties of the drug appear to involve its binding to DNA and interruption of DNA-directed RNA synthesis. The reasons for its usefulness in the treatment of Paget s disease and hypercalcemia are unclear but may relate to the need for protein synthesis to sustain bone resorption. The doses required to treat Paget s disease and hypercalcemia are about one tenth the amounts required to achieve cytotoxic effects. 

Members of this group feature tricyclic carbon framework decorated with two oligosaccharide chains. Mithramycin 48 and chromomycin A3 49 are two aureolic acids that have found their use in cancer chemotherapy. These compounds, interacting with Mg2+, bind GC-rich DNA in a nonintercalative way, and sugar chains are indispensable in stabilizing metal-antibiotic complexes. Carbohydrates are... 

Actinomycin D is a selective inhibitor of RNA synthesis but its use in cancer chemotherapy is severely limited owing to its toxicity. It is thought that the two cyclic peptide moieties of the antibiotic whose three-membered aromatic ring system is intercalated into doublestranded DNA occlude the minor groove of duplex DNA and impede the progression of the enzyme, RNA polymerase. 

The antibiotics used in cancer chemotherapy are mostly DNA-intercalating agents. An example is provided by daunorubicin (Figure 13.10). This drug molecule has a large, flat polycyclic system, which will intercalate between the stacked base pairs of the DNA. However, there is more to it The ring is also able to chelate iron, and the complex... 

Freifeld A, Marchigiani D, Walsh T, et al. A double-blind comparison of empirical oral and intravenous antibiotic therapy for low-risk febrile patients with neutropenia during cancer chemotherapy. N Engl J Med 1999 341 305-311. 

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