Toxicity and nephrotoxicity

Cyclosporin A, a fungal metabolite, is a cyclic polypeptide that consists of 11 amino acids. It has a biologic half-life of 4 to 6 h and displays a preferential T cell cytotoxic property, in that it inhibits the factors that stimulate T lymphocyte proliferation. Cyclosporin A has been used as the sole immunosuppressant (without prednisone or other drugs) for cadaveric transplants of the kidney, pancreas, and liver. Cyclosporin A has been observed to cause reversible hepatic toxicity and nephrotoxicity. 

Lerner AM, Reyes MP, Cone LA, Blair DC, Jansen W, Wright GE, Lorber RR. Randomised, controlled trial of the comparative efficacy, auditory toxicity, and nephrotoxicity of tobramycin and netilmicin. Lancet 1983 l(8334) 1123-6. 

A large, randomized, multicenter trial that compared voriconazole with hposomal amphotericin B for empirical antifungal therapy showed comparable composite success rates however, voriconazole did not fulfill the protocol-defined criteria for noninferiority to liposomal amphotericin. Voriconazole was superior in reducing documented breakthrough infections, infusion-related toxicity, and nephrotoxicity. However, patients who received voriconazole had more frequent... 

It bears repeating that there is a significantly higher risk of bladder toxicity and nephrotoxicity with ifosfamide than with cyclophosphamide. This is because ... 

Effects of repeated ethylene glycol peroral overexposure in treated rats and mice can result in kidney, Hver, and nervous system damage. The most sensitive indicators of ethylene glycol toxicity are disturbances in acid—base balance and nephrotoxic (kidney) effects. Effects of repeated chronic peroral overexposure of diethylene glycol in treated rats result in kidney and Hver damage (48). 

Xylan-based microparticles were also evaluated regarding their in vitro toxicity. In fact, cross-liked (CLM) and spray-dried microparticles (SDM) based on xylan and ESIOO were produced in order to carry UA and avoid its side effects, namely hepatotoxicity and nephrotoxicity. Additionally, CLM and SDM dispersions at concentrations of 50, 125, 250, and 500 pg/ml were placed in contact with human embiyonic Ixmg fibroblasts (MRC-5 cells)... 

Williams, P.D., Hottendorf, G.H. and Bennett, D.B. (1986a). Inhibition of renal membrane binding and nephrotoxicity of aminoglycosides. J. Pharmacol. Exp. Ther. 237 919-925. Williams, P.D., Laska, D.A. and Hottendorf, G.H. (1986b). Comparative toxicity of aminoglycoside antibiotics in cell cultures derived from human and pig kidney. In Vitro Toxicol. 1 23-32. 

Flufenamic acid is used for moderate pain and dysmenorrhea, but it should not be used for more than 1 week due to the possibility of nephrotoxicity, gastrointestinal toxicity, and anemia. It is frequently used in combination with the anticoagulant warfarin, the effect of which is strengthened when combined with flufenamic acid. Synonyms for this drug are arlef, flexocutan, romazal, and others. 

Vancomycin can cause red-man syndrome consisting of diffuse flushing, presumably mediated by histamine-release. This problem can be prevented by limiting the infusion rate. The most serious adverse reactions are ototoxicity and nephrotoxicity. The toxicity for both organ systems is potentiated by aminoglycosides. Vancomycin will cross the placenta barrier and has the potential to cause fetal ototoxicity. 

The adverse effects of methotrexate include gastrointestinal complaints, bone marrow suppression, alopecia and nephrotoxicity. The toxic effects of methotrexate may be terminated by administering the fully reduced folate coenzyme leucovorin (folinic acid). Leucovorin rescue permits the administration of high doses of methotrexate, for example in situations where partially resistance has occurred or to obtain cytotoxic concentrations of methotrexate in the CNS. 

Ototoxicity and nephrotoxicity are the major concerns during administration of streptomycin and other aminoglycosides. The toxic effects are dose related and increase with age and underlying renal insufficiency. All aminoglycosides require dose adjustment in renal failure patients. Ototoxicity is severe when aminoglycosides are combined with other potentially ototoxic agents. 

Streptomycin is ototoxic and nephrotoxic. Vertigo and hearing loss are the most common adverse effects and may be permanent. Toxicity is dose-related, and the risk is increased in the elderly. As with all aminoglycosides, the dose must be adjusted according to renal function (see Chapter 45). Toxicity can be reduced by limiting therapy to no more than 6 months whenever possible. 

Apart from its ototoxic and nephrotoxic potential, kanamycin may also cause liver disturbances and both peripheral and central neuropathies including encephalopathy, lethargy, and convulsions. Cochlear toxicity is more frequent... 

Neomycin is particularly ototoxic and nephrotoxic when given parenterally. As with gentamicin and kanamycin, the nephrotoxicity may be reversible but the ototoxicity is usually irreversible and deafness may occur following oral administration, instillation into cavities, or topical use. It may block neuromuscular action and respiratory depression has been reported. Local treatments may cause hypersensitivity, rashes, pruritus, and anaphylaxis. Neomycin is not geno-toxic. 

The different biosynthetic pathways through which mycotoxins are produced result in a broad diversity of chemical structures and, consequently, in a variety of toxic effects in humans and animals. An excellent review of the toxic effect of mycotoxins (3) is based on a system approach, where the toxic effects are discussed on the basis of the body systems affected by the mycotoxins. Hepatotoxic, gastrointestinal, hematopoietic, and nephrotoxic effects are treated, as well as... 

Most biologically active natural peptides are linear, but bacitracin is a leading member of the so-called cyclic peptide type of antibiotics. The commercial material, extracted from Bacillus subtilis, is a mixture of several compounds in which bacitracin A predominates. It exerts its action by inhibiting peptidoglycan synthesis and membrane function. Bacitracin has been a useful antibiotic since the 1960s, but its systemic use results in a number of toxic side effects, including nephrotoxicity. One cannot be sure which components of the mixture are responsible for the toxicity, and separation of natural constituents is complex and difficult. For this reason, an efficient synthesis of bacitracin A would be useful. 

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