Nephrotoxicity of aminoglycosides

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. 

Rankin GO, Sutherland CH. Nephrotoxicity of aminoglycosides and cephalosporins in combination. Adverse Drug React Acute Poisoning Rev 1989 8(2) 73-88. 

Martinez-Salgado C, Lopez-Hernandez FJ, and Lopez-Novoa JM. Glomerular nephrotoxicity of aminoglycosides. Toxicol AppI Pharmacol 223 86-98,2007. 

Williams PD, Flottendorf GFI, Bennett DB, Inhibition of renal membrane binding and nephrotoxicity of aminoglycosides, J Pharmacol Exp Therap, 1986, 237(3) 919-25. 

KojimaR, Ito M, Suzuki Y. Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects (4). Effects oftobramycin alone and in combination with latamoxef on the stability of rat kidney lysosomal membranes. Jpn J Pharmacol 1987 43(1) 73-80. 

The use of D -glucaro-6-lactam (K salt) reduced the nephrotoxicity of aminoglycosides in rats.14 Postmortem studies revealed the accumulation of gentamicin and amikacin in human kidneys.15 Certain aminoglycosides... 

The most important and common acute toxicity caused by aminoglycoside treatment is renal dysfunction or nephrotoxicity, and comprehensive review articles on the molecular mechanisms of nephrotoxicity of aminoglycosides have been published [205,206,207]. Clinically, renal toxicity is manifested by the increase of blood urea and serum creatinine levels, as well as by alteration of the glomerular filtration rate (GFR). Although the effects of aminoglycosides on the kidney are reversible and rarely cause death, since renal clearance is affected, kidney dysfunction leads to complications in patients who are on multiple drugs and in other hospitalized patients. 

Martinez-Salgado, C., Lopez-Hernandez, F. J., Lopez-Novoa, J. M. (2007 Aug 15). Glomerular nephrotoxicity of aminoglycosides. Toxicology and Applied Pharmacology, 223 1), 86—98. 

Another example Dehydration greatly enhances the sensitivity of rats to the nephrotoxicity of aminoglycosides. 

The ability to develop resistance when monotherapy (less often with aminoglycosides) is used to treat infections caused by P. aeruginosa is well described (17). Therefore, traditional therapy has consisted of a combination of an antipseudomonal P-lactam (or P-lactam/p-lactamase inhibitor, carbo-penem, monobactam) with an aminoglycoside because of in vitro demonstration of synergy however, critically ill patients have many risk factors that render them more susceptible to the nephrotoxicity of aminoglycosides. The... 

Renal cell lines have been utilized to a limited extent for evaluation nephrotoxins. A rabbit kidney cell line (LLC-RKi) has been utilized for evaluating nephrotoxic antibiotics (Viano et al., 1983 Hottendorf et al., 1987 Williams et al., 1988). LLC-PKi cells have by far been the most widely employed cell line for studying drug-induced nephrotoxicity, specifically in the evaluation of aminoglycoside antibiotics (Hori et al., 1984 Schwertz et al., 1986 Williams et al., 1986b Holohan et al.,... 

Hori, R., Yamamoto, S., H., Kohno, M. and Inui, K. (1984). Effect of aminoglycoside antibiotics on cellular functions of kidney epithelial cell line (LLC-PKi) a model system for aminoglycoside nephrotoxicity. Pharmacol. Exp. Ther. 230 742-748. 

Gentamicin is an aminoglycoside. All aminoglycosides tend to be nephrotoxic and ototoxic. The dose must be reduced and serum concentrations must be monitored in patients with impaired renal function. Concomitant administration of aminoglycosides and other nephrotoxic drugs, such as certain diuretics, ciclosporin, teicoplanin and vancomycin should be avoided. 

Disp Tabs, susp SE D, dizziness, rash, eosinophilia, T transaminases Interactions T Nephrotox W/ aminoglycosides, loop diuretics T effects W/probenecid i effects W/ antacids, chloramphenicol EMS T Risk of nephrotox w/ loop diuretics monitor for signs of electrolyte disturbances and hypovolemia d/t D monitor pt for super Infxn OD May cause NA /D, Szs, muscles spasms symptomatic and supportive... 

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