Paracetamol nephrotoxicity

Thus in some cases, enzyme expression is directly influenced in a particular organ by testosterone or estrogens. For example, in the mouse kidney, testosterone directly regulates the expression of cytochrome P-450 isozymes, and this leads to the particular sensitivity of the female kidney to the nephrotoxicity of paracetamol. 

It has been shown by using NMR spectroscopy in conjunction with isotopelabelling studies that there is a significant degree of deacetylation followed by reacetylation (futile deacetylation) of paracetamol metabolites in vivo in the rat [58]. If this also occurs in humans, then it may help to explain the observed incidence of nephrotoxicity of paracetamol in that the process would result in levels of the potent nephrotoxin 4-aminophenol in vivo. Confirmation of the levels of futile deacetylation in individual metabolites of isotopically labelled paracetamol in man has been achieved by using directly coupled HPLC-NMR... 

Paracetamol causes skin rashes, blood dyscrasia, and liver damage and nephrotoxicity in overdose. Large doses of paracetamol cause nephritis and... 

Aspirin, paracetamol, and hydrocortisone are used to control febrile reactions of amphotericin. Patients with a history of adverse effects with amphotericin should be prophylactically treated with antipyretics and hydrocortisone. Antiemetics and pethidine also are used for the treatment of adverse effects of amphotericin. With sodium supplements and hydration therapy, damage to the kidney can be reduced. If conventional amphotericin is not well tolerated by the patient, colloidal carriers can be used as alternative options. Administration of amphotericin with a nephrotoxic drug, such as cyclosporin, may further increase toxicity. Diuretics and anticancer drugs should be avoided with amphotericin. 

Supportive measures that would complement antimicrobial effectiveness and assist recovery of the animal from the infection should be provided. In neonatal animals, care must be taken to avoid a too-rapid rate of intravenous fluid administration. Fever may serve a useful purpose in infectious diseases, and the change in body temperature may be used to assess the progress of the infection. In the presence of an infectious diseased, the only indication for an antipyretic drug, e.g. aspirin or paracetamol (acetaminophen) in dogs but not in cats metamizole (dipyrone) or sodium salicylate administered intravenously to horses, is to decrease body temperature to below a dangerous level, 41°C (105.8°F). Concurrent therapy with a NSAID and an aminoglycoside antibiotic increases the risk of nephrotoxicity. If the infection is suspected to be contagious, the diseased and in-contact animals should be isolated. 

Siegers, C.R Moller-Hartmann, W. Cholestyramine as an antidote against paracetamol-inducedhepato-and nephrotoxicity in the rat. Toxicol.Lett., 1989, 47, 179-184 [rat urine extracted metabolites] Lam, S. Malikin, G. An improved micro-scale protein precipitation procedure for HPLC assay of therapeutic drugs in serum. J.Liq.Chromatogr., 1989, 12, 1851-1872 [serum also amiodarone, aspirin, caffeine, chloramphenicol, flecainide, pentobarbital, procainamide, pyrimethamine, quinidine, theophylline, tocainide, trazodone fluorescence detection UV detection]... 

Acetaminophen (APAP, N-acetyl-p-aminophenol, paracetamol) is a widely used over-the-counter analgesic. At erapeutic doses it is a safe drug. However, at high doses it may produce severe hepatic necrosis and has also been reported in some individuals to be nephrotoxic (1-3). Available evidence indicates that acetaminophen hepatotoxicity is not a result of the parent compound but is mediated by a reactive metabolite N-acetyl-g-benzoquinone imine (NAPQI). This metabolite is the two-electron oxidation product of acetaminophen and is formed by the microsomal cytochrome P-450 mixed function oxidase system (4-8). Following a therapeutic dose of acetaminophen the reactive metabolite is detoxified Current address National Institutes of Health, Bethesda, MD 20892 Current address Rohm and Haas Company, Spring House, PA 19477... 

Urinary tract Among 2068 patients with paracetamol overdose, nephrotoxicity occurred in eight (0.4%) [19 ]. The onset of... 

Drug overdose In a retrospective cohort study the presence of gastrointestinal manifestations after paracetamol poisoning predicted a risk of subsequent hepatotoxicity and nephrotoxicity [22 ]. 

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