Nephrotoxicity furosemide

Information seems to be limited to the case cited and its general clinical importance is uncertain. Although mannitol is by far the more usual drug used to induce diuresis during the use of eisplatin in order to reduce the risk of nephrotoxicity, furosemide may also be used for this indication. ... 

Uses Severe, systemic fungal Infxns oral cutaneous candidiasis Action Binds ergosterol in the fungal membrane to alter permeability Dose Adults Peds. Test dose 1 mg IV adults or 0.1 mg/kg to 1 mg IV in children then 0.25-1.5 mg/kg/24 h IV over 2-6 h (range 25-50 mg/d or qod). Total dose varies w/ indication PO 1 mL qid Caution [B, ] Disp Inj SE -1- K /Mg from renal wasting anaphylaxis reported, HA, fever, chills, n hrotox, -1- BP, anemia, rigors Notes -1- In renal impair pre-Tx w/ APAP antihistamines (Benadryl) X SE Interactions T Nephrotoxic effects W/ antineoplastics, cyclosporine, furosemide, vancomycin, aminoglycosides, T hypokalemia W/ corticost oids, skeletal muscle relaxants EMS May cause electrolyte imbalances, monitor ECG OD May effect CV and resp Fxn symptomatic and supportive... 

The severity of aminoglycoside nephrotoxicity is additive with that of vancomycin, polymixin, gallium, furosemide, enflurane, cisplatin, and cephalosporins. Aminoglycoside nephrotoxicity is synergistic with that of amphotericin B and cyclosporine. 

Cephalosporins Ethacrynic acid, furosemide, gentamycin Increased nephrotoxicity. 

Furosemide is eliminated in equal portions by renal and non-renal (glucuronidation) routes. Its half-life is prolonged in renal failure, but hepatic failure has little effect, Bumetanide and torasemide are eliminated via CYP isoenzymes and so their half-life is affected by hepatic disease more than renal disease. They are known to cause thrombocytopenia (hut decrease activity of oral anticoagulants), ototoxicity and nephrotoxicity. 

Among the agents that promote the nephrotoxic effects of the aminoglycosides, the loop diuretics furosemide and etacrynic acid are often mentioned. However, this... 

Smith CR, Lietman PS. Effect of furosemide on amino-glycoside-induced nephrotoxicity and auditory toxicity in humans. Antimicrob Agents Chemother 1983 23(l) 133-7. 

The nephrotoxic effects of cefaloridine are potentiated by concurrent administration of furosemide (36,37), perhaps by a direct interaction and probably also because furosemide lowers the clearance of the antibiotic (38). Such combinations are better avoided. 

Plouvier B, Baclet JL, de Coninck P. Une association nephrotoxique mannitol et furosemide. [A nephrotoxic combination mannitol and furosemide.] Nouv Presse Med 1981 10(21) 1744-5. 

A report from Italy has suggested that intravenous saline 0.4% before and after administration of the contrast medium, an infusion of dopamine 3 micrograms/kg/ minute for 24 hours after the contrast medium, intravenous furosemide 80 mg 30 minutes before the contrast medium, or intravenous mannitol (20%) 250 ml 1 horn-before and 1 hour after the contrast medium each prevented the reduction in renal function caused by the nonionic agents iobitridol, ioversol, or iodixanol (193). However, the protocol of the study was not described, and previous studies have shown that dopamine, furosemide, and mannitol do not offer good protection against contrast media-induced nephrotoxicity. On the other hand, volume expansion with intravenous saline has been found to offer some protection (190). 

In a similar vein, Leehey et al. [201] have reported on the frequency of aminoglycoside-induced nephrotoxicity using three different dosing schemes, including two that were based on pharmacokinetic principles. It is noteworthy that despite careful calculation of the dosing scheme, this did not alter the incidence of nephrotoxicity. However, the duration of dosing correlated positively with nephrotoxicity incidence, as did treatment with furosemide, old age, and liver disease. 

Beta-lactam induced renal toxicity can results from their use in monotherapy or when used in combination with other nephrotoxic drugs such as aminoglycosides, amphotericin B, cisplatin, cyclosporine, furosemide, ifosfamide, vancomycin and nephrotoxic p-lactams. While the risk of nephrotoxic injury from monotherapy with p-lactams is relatively low, this risk is substantially increased when multiple drug combinations are required. 

Results from animal studies indicate that while furosemide enhanced cephaloridine nephrotoxicity no increased renal toxicity was observed by combining of piperacillin with furosemide [142]. Latamoxef and flo-moxef may decrease nephrotoxicity of vancomycin by inhibiting its uptake into the kidney [146,147]. The results of a retrospective study including renal transplant patients indicate that aztreonam can be safely administered with cyclosporine [148]. Combination therapy with ampicillin/aztreonam in neonates showed a lower renal toxicity than in the group with concurrent administration of oxacillin/ amikacin [149]. 

Wade JC, Smith CR, Petty BG, Lipski JJ, Conrad G, Ellner J, Lietman PS. Nephrotoxicity of piperacillin combined with furosemide in rats. Jpn J Antibiot 2000 53(8) 582-591. 

Theoretically, any of the protective interventions mentioned in the previous section may be applicable to a clinical setting, but few have actually been studied, in some instances, because there are practical limitations to their use. For example, the duration of protection conferred by furosemide is brief, being confined to the time furosemide is present in the renal tubule. Furosemide would exacerbate electrolyte imbalance by causing sodium and potassium depletion, which, if not adequately monitored and replaced, would be expected to potentiate AmB-induced nephrotoxicity. Furthermore, none of the advocated drug interventions are itmocuous. Of all the alternatives, manipulation of sodium status or of the method of administration offer simple interventions that can be readily and usually... 

Gerkens JF, Branch RA. The influence of sodium status and furosemide on canine acute amphotericin B nephrotoxicity. J Pharmacol Exp Ther 1980 214 306-11. 

While several experimental reports have suggested that diuretics [mannitol and furosemide] decrease cisplatin nephrotoxicity [36, 41] others have shown that they may aggravate it [43]. Further, in humans, there is no convincing evidence than diuretics may attenuate cisplatin nephrotoxicity as shown in a randomized study by Alsarraf et al. [44] hydration + cisplatin was compared to hydration + mannitol + cisplatin. 

Heldemann HTH, GerkensJF, Jackson EK, Branch RA. Attenuation ofcisplatin-induced nephrotoxicity in the rat by high salt diet, furosemide and acetazolamide. Naunyn-Schmiedeberg s Arch Pharmacol 1985 329 201-5. 

Pera MF Jr, Zook BC, Harder HC. Effects of mannitol or furosemide diuresis on the nephrotoxicity and physiological disposition of cis-dichlorodiammine platinum [II] In rats. Cancer Res 1979 29 1269-78. 

Adelman RD, Spangler WL, Beasom F, Ishizaki G, Conzelman GM. Furosemide enhancement of experimental gentamicin nephrotoxicity comparison of functional and morphological changes with activities of urinary enzymes. J Infect Dis 1979 ... 

Mannitol and furosemide reduce the concentration of platinum in the urine, suggesting that these agents might attenuate cisplatin nephrotoxicity [40,41]. However, plasma and renal platinum content were unchanged and the degree of cellular necrosis did not improve with use of these diuretics [41]. Platinum does not appear to undergo tubular reabsorption based on the nearly complete urinary recovery of microinjected platinum [13]. Hence, renal platinum content is independent of its luminal concentration. 

Conclusions regarding the renoprotective action of mannitol and furosemide to decrease experimentally induced cisplatin nephrotoxicity are conflicting [36,41, 43]. However, in humans, a randomized study hy Alsarraf et al. [44] comparing hydration + cisplatin to hydration + mannitol + cisplatin concluded that mannitol did not attenuate cisplatin nephrotoxidly. 

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