Nonsteroidal anti-inflammatory drugs renal effects

Many nonsteroidal anti-inflammatory drugs of different chemical structures (Fig. 5) have been introduced for the treatment of inflammatory and painful conditions. Many years of clinical experience with these drugs have shown that there is no induction of tolerance or dependence and no respiratory depression as seen with opioids. The major side-effects of these compounds with COX-1 selectivity or balanced COX-1 and COX-2 inhibition are damage to the gastric mucosa, prolongation of bleeding time and renal failure. 

Tarako et al. (1991) evaluated oxygen supply and energy state in the isolated perfused rat kidney. Metabolic activities of the isolated perfused rat kidney were described by Nishiitsutsuji-Uwo et al. (1967). Cox et al. (1990) used the isolated perfused rat kidney as a tool in the investigation of renal handling and effects of nonsteroidal anti-inflammatory drugs. 

Prostaglandin synthesis. Nonsteroidal anti-inflammatory drugs (NSAIDs), e.g. indomethacin, attenuate the antihypertensive effect of p-adrenoceptor blockers and of diuretics, perhaps by inhibiting the synthesis of vasodilator renal prostaglandins. This effect can also be important when a diuretic is used for severe left ventricular failure. 

The antihypertensive effect of beta-blockers can be impaired by the concurrent administration of some nonsteroidal anti-inflammatory drugs (NSAIDs), possibly because of inhibition of the synthesis of renal vasodilator prostaglandins. This interaction is probably common to all beta-blockers, but may not occur with aU NSAIDs for example, sulindac appears to affect blood pressure less than indometacin (405-407). 

Murray MD, Brater DC. Adverse effects of nonsteroidal anti-inflammatory drugs on renal function. Ann Intern Med 1990 112(8) 559-60. 

De long PE, Statius van Eps LW. Sickle cell nephropathy new insights into its pathophysiology. Kidney Int 1985 27 711-719. Allen M, Lawson L, Eckman IR, Delaney V, Bourke E. Effects of nonsteroidal anti-inflammatory drugs on renal function in sickle cell anemia. Kidney Int 1988 34 500-506. 

Bennett WM, Henrich WL, Stoff JS, Bennett WM, Henrich WL, Stoff JS.The renal effects of nonsteroidal anti-inflammatory drugs summary and recommendations. American Journal of Kidney Diseases 1996,-28 S56-S62. 

Field TS, Gurwitz JFI, Glynn RJ et al.The renal effects of nonsteroidal anti-inflammatory drugs in older people findings from the Established Populations for Epidemiologic Studies of the Elderly. Journal of the American Geriatrics Society 1999 47 507-511. 

Forrester S D, Troy G C 1999 Renal effects of nonsteroidal anti-inflammatory drugs. Compendium on Continuing Education for the Practicing Veterinarian 21 910-919 Fry S W, Seeff L B 1995 Hepatotoxicity of analgesics and anti-inflammatory agents. Gastroenterology Clinics of North America 24 875-905... 

Brater DC. Effects of nonsteroidal anti-inflammatory drugs on renal... 

Chronic renal effects associated to the use of nonsteroidal anti-inflammatory drugs (NSAID) is discussed in chapter 14. 

Whelton A, Scott H, Stout RL. Effects of misoprostol on nonsteroidal anti-inflammatory drug induced renal insufficiency in patients with stable chronic renal failure a double-blind, crossover study. Am J Therap 1995 2(11) 858-863. 

DiBona, G.F. (1986). Prostaglandins and nonsteroidal anti-inflammatory drugs. Effects on renal hemodynamics. Am. ]. Med., 80 (Suppl. lA), 12-21... 

Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the clearance of MTX (121). However, the effect is relatively small and does not appear to have a clinically significant effect (118,122,123). Conversely, if NSAIDs induce acute renal failure, high levels of MTX and toxicity can be encountered. We have observed two patients who developed severe MTX-induced leukopenia associated with NSAID-induced renal failure. 

Clinical pharmacology of synthetic opioid analgesics (fentanyl, sufentanil, remifentanil) is not substantially altered by renal failure. In contrast, morphine is a poor choice in patients with severe renal impairment, particularly when given repetitively. Morphine effects maybe prolonged due to very slow elimination of active metabolites. Postoperative analgesic regimens should also avoid nonsteroidal anti-inflammatory drugs. 

Interactions. Several types of drug interfere with lithium excretion by the renal tubules, causing the plasma concentration to rise. These include diuretics (thiazides more than loop type), ACE inhibitors and angiotensin-11 antagonists, and nonsteroidal anti-inflammatory analgesics. Theophylline and sodium-containing antacids reduce plasma lithium concentration. The effects can be important because lithium has such a low therapeutic ratio. Diltiazem, verapamil, carbamazepine and pheny-toin may cause neurotoxicity without affecting the plasma lithium. Concomitant use of thioridazine should be avoided as ventricular arrhythmias may result. 

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