Nephrotoxicity acute effects

In studies of acute effects on humans caused by exposure to Pb, nephrotoxic effects as well as gastrointestinal effects have been observed [40], Encephalopathy can affect both children and adults. Acute encephalopathy has been shown to increase the incidence of neurological and cognitive impairments. 

Benzylpenicillin is a p-lactam with low or no renal toxicity [21]. However, when administered in large doses, benzylpenicillin or amoxicillin [22] have the potential to induced nephrotoxicity. Acute interstitial nephritis and disturbances of blood electrolytes have also been reported [23]. By comparison, dicloxacillin induced a pathological increase of creatinine, while cloaxicillin had only a marginal effect on the renal function [24]. 

Lithium carbonate 0.9-1.2gq.24hr Renal 100% 50-75% 25-50% Nephrotoxic adverse effects include nephrogenic diabetes insipidus, nephrotic syndrome, renal tubular acidosis, and interstitial fibrosis acute toxicity when serum levels > 1.2 mEq/L serum levels should be measured periodically 12 hr after dosing half life does not reflect extensive tissue accumulation plasma levels rebound after dialysis toxicity enhanced by volume depletion, NSAIDs, and diuretics Dose after dialysis NC Dose for GFR 10-50 ml/min... 

Chapters 6 and 7 split the field of toxicology and human effects into acute and chronic effect areas. While this is artificial to some extent, it is useful for label classification and development. Typically, acute data is obtained first, and, at relatively modest cost. Although hepatotoxicity, neurotoxicity, and nephrotoxicity are usually thought of as chronic effects, they may in fact be acute effects. The real division between the two fields is in immediacy of effect following exposure. Thus, acute effects follow directly and immediately upon exposure, while chronic effects may be delayed for many years, e.g. cancer. 

Effects Solvents are potent CNS depressants. The acute effects of excessive exposure are nausea, vertigo, locomotor disturbances, headache, and coma. Chronic exposure to halogenated hydrocarbons leads to both hepatic dysfunction and nephrotoxicity. Long-term exposure to tetrachloroethylene—or to trichloroethane—has caused peripheral neuropathy. 

Lead exposures in diverse human populations produce both acute and chronic nephrotoxic effects. The chronic kidney disease association with occupational Pb exposures in the clinical literature, dating to the nineteenth century, was typically characterized as a glomerulonephritic disease histo-pathologically. This traced to the absence of evaluation of the temporal course of Pb-induced nephropathy, particularly the acute effects. 

A, Vock P, C Boesch C, Frey FJ, Vogt B BOLD-MRI for the assessment of renal oxygenation in humans acute effect of nephrotoxic xenobiotics. Kidney hit 2006 70 144-150. Pruijm M, Hofmann L, Charollais-Thoenig J, Forni V, Maillard M, Coristine A, Stuber M, Burnier M, Vogt B Effect of dark chocolate on renal tissue oxygenation as measured by BOLD-MRI in healthy volunteers. Clin Nephrol 2013 80 211-217. 

Methotrexate -antifolate antimetabolite cell cycle dependent -bone marrow suppression -nausea and vomiting—mild to moderate -mucocutaneous effects (mucositis, stomatitis, diarrhea) -hepatotoxicity—more common in high-dose therapy -CNS toxicity—dizziness, malaise, blurred vision, encephalopathy -nephrotoxicity—including acute renal failure, particularly at high doses... 

Immunosuppressive agents such as azathioprine and mercaptopurine (a metabohte of azathioprine) are sometimes used for the treatment of IBD. These agents are generally reserved for cases that are refractory to steroids and may be associated with serious adverse effects such as lymphomas, pancreatitis, or nephrotoxicity. Cyclosporine has been of short-term benefit in acute, severe ulcerative colitis when used in a continuous infusion. 

Larson JL, Wolf DC, Butterworth BE. 1993. Acute hepatotoxic and nephrotoxic effects of chloroform in male F-344 rats and female B6C3Fi mice. Fundam Appl Toxicol 20(3) 302-315. 

In addition to intensive supportive care, prompt chelation with oral or intravenous unithiol, intramuscular dimercaprol, or oral succimer may be of value in diminishing nephrotoxicity after acute exposure to inorganic mercury salts. Vigorous hydration may help to maintain urine output, but if acute renal failure ensues, days to weeks of hemodialysis or hemodiafiltration in conjunction with chelation may be necessary. Because the efficacy of chelation declines with time since exposure, treatment should not be delayed until the onset of oliguria or other major systemic effects. 

Aminoglycoside use is limited somewhat by problems with toxicity.66 Nephrotoxicity, as indicated by bloody urine, acute renal tubular necrosis, and so on, is one of the more common and serious adverse effects.49,66 Ototoxicity, as indicated by dizziness and ringing or fullness in the ears, may also occur. This effect can be irreversible in severe cases.67 Toxicity may occur more frequently in certain individuals, such as patients with liver or kidney failure, or in elderly patients. To reduce the risk of toxicity, drug levels in the bloodstream must be periodically monitored so dosages can be adjusted for individual patients. Other adverse effects include hypersensitivity (e.g., skin rashes, itching) in susceptible individuals. 

Studies in laboratory animals have shown that intravenous administration of a high dose of GSH (up to 500 mg/kg) within 30 min of cisplatin injection protects against cisplatin-induced neurotoxicity and nephrotoxicity. Subcutaneous injection of GSH or GSH monoisopropyl ester 2.5 h before injection of cisplatin also protected mice against nephrotoxicity and the acute lethal toxicity of cisplatin, although the GSH ester was far more effective than GSH itself. In these studies, treatment with GSH or GSH ester did not interfere with the antitumor effectiveness of cisplatin, which can be explained by the characteristics of uptake of GSH and cisplatin. GSH and cisplatin are cleared rapidly from the circulation. 

Mercaptopurine and thioguanine are both given orally (Table 55-3) and excreted mainly in the urine. However, 6-MP is converted to an inactive metabolite (6-thiouric acid) by an oxidation catalyzed by xanthine oxidase, whereas 6-TG requires deamination before it is metabolized by this enzyme. This factor is important because the purine analog allopurinol, a potent xanthine oxidase inhibitor, is frequently used with chemotherapy in hematologic cancers to prevent hyperuricemia after tumor cell lysis. It does this by blocking purine oxidation, allowing excretion of cellular purines that are relatively more soluble than uric acid. Nephrotoxicity and acute gout produced by excessive uric acid are thereby prevented. Simultaneous therapy with allopurinol and 6-MP results in excessive toxicity unless the dose of mercaptopurine is reduced to 25% of the usual level. This effect does not occur with 6-TG, which can be used in full doses with allopurinol. 

Powers WJ, Gad SC, Siino KM, et al. 1986. Effects of therapeutic agents on chromium-induced acute nephrotoxicity. In Serrone DM, Ed. Chromium symposium 1986 An update. Pittsburgh, PA Industrial Health Foundation, Inc., 79-86. 

A substantial body of literature documents the side effects of platinum compounds. The nephrotoxicity of the parent compound cisplatin almost led to its abandonment, until Cvitkovic et al. introduced aggressive hydration, which prevented the development of acute renal failure [2] [3], As noted above, the toxicity of cisplatin was a driving force both in the search for less toxic analogues and for more effective treatments for its side effects, especially nausea and vomiting. 

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