Aspirin nephrotoxicity

COX-2 inhibitors such as celecoxib are associated with adverse effects such as nephrotoxicity and a potential increased risk of myocardial infarction (see Chaps. 55 and 15 for additional information). Combination of COX-2 inhibitors with alcohol may increase GI adverse effects. All NSAIDs should be used with caution in patients with aspirin-induced asthma.31... 

Clinical use Phenidine (Clissold, 1986) is a weak analgesic and antipyretic compound without antiinflammatory action. It has been used in combination with other compounds like aspirin, caffeine or codeine, but due to hematological and nephrotoxic side-effects (Dubach et al., 1983) has been withdrawn from many markets. 

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. 

Antrafenine closely resembles glafenine and floctafenine (SED-9,153) (SEDA-7,116) (SEDA-11, 96) (1). The same adverse effects must be expected and some have been described, for example nephrotoxicity (SEDAA, 69) (2). Gastrotoxicity is claimed to be less than with aspirin (3), again no doubt merely because it is a weak anti-inflammatory drug. 

Large doses of caffeine cause diuresis. Daily consumption of caffeine citrate increased the mean urinary excretion rate of tubular cells and erythrocytes in volunteers (25). The nephrotoxicity of analgesic antipyretic drug combinations may result from a combined effect, in which aspirin, phenacetin, and caffeine all play a role (SEDA-4, 5). In 10 asymptomatic women and 20 women with confirmed detrusor instability, caffeine caused a significant increase in detrusor pressure on bladder filling in the latter, but no difference in volume at first contraction, height of contraction, or bladder capacity (26). 

Aspirin also has the potential to increase acetaminophen nephropathy. Aspirin inhibits the cyclooxygenase component of prostaglandin H synthase without effect on the prostaglandin hydroperoxidase component, while salicylic acid (the deacetylated metabolite of aspirin) decreases renal glutathione concentrations. Thus, coadministration of aspirin with acetaminophen (or phenacetin) results in a synergistic nephrotoxicity. 

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. 

Cooper K, Bennett WM. Nephrotoxicity of common drugs used in clinical practice. Arch Intern Med 1987 147 1213-1218. Perneger TV, Whelton PK, Klag MJ. Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs. N Engl J Med 1994 331 1675-1679. 

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]... 

Drugs with nephrotoxic potential include ACE inhibitors, acetazolamide. aminoglycosides, aspirin, amphotericin B, cyclosporine, furosemide, gold salts, lithium, methicillin, methoxyflurane, NSAIDs, pentamidine, sulfonamides, tetracyclines (degraded), thiazides, and triamterene. 

Medications beta-biockers, aspirin, nonsteroidai antiinflammatory drugs, aminogiycosides, interieukin-2, cyciosporine, cispiatin, other nephrotoxic drugs... 

There is much evidence of the nephrotoxicity of aspirin (140 ). Administration of aspirin (4 g daily) was associated with a rise in plasma creatinine (average increase 38%) and a fall in creatinine clearance (average decrease 25%). These changes were observed in 8 of 9 patients with rheumatoid arthritis and 10 of 11 healthy volunteers. There was no change in the clearance of chromium edetate (150 ). In another study aspirin produced similar changes in plasma creatinine and creatinine clearance. However, the blood urea was also increased and the inulin clearance was reduced in parallel with the creatinine clearance, suggesting that glomerular filtration was reduced (151 =). Aspirin also reduces the urinary excretion of canrenone, a metabolite of spironolactone. This effect may be caused by competition for active renal tubular secretion (152). 

The mechanisms of salicylate-induced renal lesions are uncertain, but inhibition of medullary prostaglandin synthesis with resultant ischaemia has been proposed (137, 139 ). Further studies have confirmed that aspirin causes acute tubular damage (160, 161). It also inhibits renal tubular gluconeo-genesis (162). Aspirin readily produces typical renal papillary necrosis in rats in doses as low as 200 mg/kg/day and dehydration predisposes to nephrotoxicity (139 , 140 ). In another study, no comparable lesions were produced in rats in a short-term study using daily doses of 24-125 mg/kg. It was claimed that these doses were equivalent to consumption of 8—40 aspirin tablets daily in man (163). However, these calculations were based on comparisons of estimated total salicylate in the body derived from urinary excretion data. Such an approach is quite inappropriate since it does not take into account species differences in the extent or rate of absorption, distribution, protein binding, metabolism and renal medullary concentrations of salicylate. Experimental analgesic nephropathy has been critically reviewed (164 ). 

Nanra, R. S. (1973) Nephrotoxicity of aspirin. Bull. Postgrad. Comm. Med. Univ. Sydney, 29, 221. 

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