Nephrotoxicity long-term

Rahn KH, BarenbrockM, Fritschka E, Heinecke A, Lippert J, SchroederK, Hauser I, Wagner K, NeumayerHH. Effect of nitrendipine on renal function in renal-transplant patients treated with cyclosporin a randomised trial. Lancet 1999 354 1415-1420. Rodicio JL. Calcium antagonists and renal protection from cyclosporine nephrotoxicity long-term trial in renal transplantation... 

Rodicio JL. Calcium antagonists and renal protection from cyclosporine nephrotoxicity Long-term trial in renal transplantation patients. J Car-diovasc Pharm 2000 35 S7-11. 

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. 

Previous reactions to these agents. With the exception of the use of streptomycin in tuberculosis, these agents generally are not indicated in long-term therapy because of the ototoxic and nephrotoxic hazards of extended administration. 

WARNING Systemic absorption of oral route may cause neuro/oto/nephrotox may result resp paralysis possible w/ any route of administration Uses Hepatic coma, bowel prq) Action Aminoglycoside, poorly absorbed PO -1- GI bacterial flora Dose Adults. 3-12 g/24- h PO in 3-4 doses Peds. 50-1 (X) mg/kg/24 h PO in 3-4 doses Caution [C, /-] Renal failure, neuromuscular disorders, hearing impair Contra Intestinal obst Disp Tabs, PO soln SE Hearing loss w/ long-term use rash, NA EMS Use neuromuscular blockers w/ caution, reduced dose may be necessary t bleeding risk w/ concurrent anticoagulant use OD May cause neuromuscular block and kidney failure calcium salts can be used to revise neuromuscular block... 

The principal advantage of MMF over alternative systemic immunosuppressive agents (e.g., methotrexate, cyclosporine) is its relative lack of hepatotoxicity and nephrotoxicity. Adverse effects produced by MMF most commonly include nausea, abdominal cramps, diarrhea, and possibly an increased incidence of viral and bacterial infections. Whether MMF may be associated with an increased long-term risk of lymphoma or other malignancies is controversial however, any such risk is likely to be lower in patients treated for skin disease with MMF monotherapy than in transplant patients treated with combination immunosuppressive therapy. 

Nephrotoxicity is the most common and the most serious long-term toxicity of amphotericin B administration. This drug reduces glomerular and renal tubular blood flow through a vasoconstrictive effect on afferent renal arterioles, which can lead to destruction of renal tubular cells and disruption of the tubular basement... 

L A. Nephrotoxicity is the most common and most serious toxicity associated with amphotericin B administration. This is manifested by azotemia (elevated serum blood urea nitrogen and creatinine), and by renal tubular acidosis, which results in the wasting of potassium and magnesium in the urine (leading to hypokalemia and hypomagnesemia, requiring oral or intravenous replacement therapy). Normochromic normocytic anemia is also seen with long-term amphotericin B administration. Elevation of hver enzymes is not associated with the use of amphotericin B. 

Rare react ions with long-term use include peptic ulcer disease, G1 bleeding, gastritis, a severe hepatic reaction (jaundice), nephrotoxicity (hematuria, dysuria, proteinuria), and a severe hypersensitivity reaction (bronchospasm or angioedema). 

Rare reactions with long-term use include peptic ulcer disease, GI bleeding, gastritis, nephrotoxicity (dysuria, cystitis, hematuria, proteinuria, nephrotic syndrome), severe hepatic reactions (cholestasis, jaundice), and severe hypersensitivity reactions (bronchospasm, angioedema). 

Not usually used for long-term therapy secondary to nephrotoxicity and ototoxicity Patient/Family Education... 

Adverse effects include nausea, vomiting, headache, fever, breathlessness, anaemia, thrombophlebitis on IV administration. On long term use, dose related nephrotoxicity and anaemia occurs. 

Sirolimus is used for tissue transplantation where its major advantage over calci-neurin inhibitors is that it is not nephrotoxic. Chronic renal failure in transplant patients who have taken calcineurin inhibitors for the long term can be prevented by the administration of sirolimus. Steroid-free immunosuppression can be achieved by administering sirolimus alone or in combination with mycophenolate mofetil and cyclosporine or tacrolimus. Since impaired wound healing is one of its potential side effects, some transplant centers use sirolimus only after several weeks of surgery. 

Adverse Effects. Cyclophosphamide is used very cautiously as an immunosuppressant because of the possibility of severe side effects, including carcinogenic effects during long-term use. Other side effects include hematologic disorders (leukopenia, thrombocytopenia), cardiotoxicity, nephrotoxicity, and pulmonary toxicity. 

The array of industrial chemicals, negligence during use, and the long-term health consequences need to be understood by workers. The rational understanding of the mechanism of nephrotoxicity in animals and man provides the basis for safe use. Reports of Kluwe et al. and Porter and Bennett indicate the type of adverse health effects vis-a-vis nephrotoxicity caused by aminoglycosides, halogenated hydrocarbons and aromatic amines produce chronic kidney injury in humans and species of mammals. 

Thus it is feasible that a specific profile of toxicity is seen to occur in repeat-dose animal studies at a dose/concentration below the guidance value, eg. <100 mg/kg bw/day by the oral route, however the nature of the effect, e.g. nephrotoxicity seen only in male rats of a particular strain known to be susceptible to this effect, may result in the decision not to classify. Conversely, a specific profile of toxicity may be seen in animal studies occurring at above a guidance value, eg. at or above 100 mg/kg bw/day by the oral route, and in addition there is supplementary information from other sources, e.g. other long-term administration studies, or human case experience, which supports a conclusion that, in view of the weight of evidence, classification would be the prudent action to take. 

Two patients with long-standing ulcerative colitis developed what seemed to be a drug-induced chronic interstitial nephritis after taking sulfasalazine for several years, with no other detectable cause (73) the same problem has arisen with mesalazine. However, in a long-term stndy (mean treatment time 10 years) in 36 patients taking sulfasalazine for ulcerative cohtis, there was no nephrotoxicity (74). 

Although the pattern of long-term toxicity of ciclosporin and tacrohmus is remarkably similar for most serious adverse effects (particularly nephrotoxicity), a higher incidence of several minor adverse effects with ciclosporin, namely hirsutism, gingivitis or gum hyperplasia, has been thought to underlie a moderate but significant decrease in the quahty of life with ciclosporin compared with tacrolimus (2). 

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