Prostaglandin renal effects

Adverse effects that are not unequivocally related to inhibition of prostaglandin synthesis include hepatic effects (hepatitis, hepatic necrosis, cholestatic jaundice, increased serum aminotransferases), dermal effects (photosensitivities, Stevens-Johnson syndrome, toxic epidermal necrolysis, onycholysis), central nervous system (CNS) effects (headaches, dizziness, tinnitus, deafness, drowsiness, confusion, nervousness, increased sweating, aseptic meningitis), ocular effects (toxic amblyopia, retinal disturbances), and certain renal effects (acute interstitial nephritis, acute papillary necrosis). 

Lee JB. Cardiovascular-renal effects of prostaglandins the antihypertensive, natriuretic renal endocrine function. Arch Intern Med 1974 133(l) 56-76. 

Renal effect of aspirin inhibition of prostaglandin synthesis. 

NSAIDs inhibit prostaglandin synthesis, and in so doing can reduce GFR in susceptible patients, including those with cirrhosis. A number of renal complications can occur, including acute renal failure. All NSAIDs have been associated with nephrotoxicity. There is a small amount of data suggesting that renal effects are less likely to occur with sulindac, but studies relate to short-term therapy only, and there have been case reports of acute renal failure developing in high-risk patients [4,27,35]. 

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. 

Several renal syndromes can comphcate NSAID use [1-3, 3-5, 24]. Generally, individuals who have normal renal function and are properly hydrated, are not at risk for developing adverse renal effects [1]. NSAID-induced deterioration in renal function depends on the specific drug, the dose and duration of pharmacologic effect and the state of health of the recipient [25]. Patients who have prostaglandin-dependent states associated with co-morbid diseases, such as high renin states or chronic renal insufficiency, are especially susceptible... 

In clinical studies, urinary prostaglandin levels and renal effects were unchanged in patients with normal... 

Perinotto P, Biggi A, Carra N et al. Angiotensin II and prostaglandin interactions on systemic and renal effects of L-NAME in humans. Journal ofthe American Society of Nephrology 2001,-12 1706-1712. 

NSAIDs have an overall favorable safety profile resulting in OTC availability in the United States of ibuprofen, naproxen, and keto-profen for short-term therapy. WWle potential adverse renal effects from OTC NSAIDs have been a concern, activity of vasodilatory prostaglandins is not necessary to maintain renal function in healthy individuals. NSAIDs are unlikely to impair renal function in the absence of renal ischemia or excess renal vasoconstrictor activity. Nevertheless, given the fact that 50 million U.S. citizens report NSAID use, it has been estimated that 500,000 to 2.5 million people will develop NSAID nephrotoxicity in this country annually. ... 

Dunn, M.J. and Zambraski, E.J. (1980). Renal effects of drugs that inhibit prostaglandin synthesis. Kidney Int., 18, 609-622... 

Garella, S. and Matarese, R.A. (1984). Renal effects of prostaglandins and clinical adverse effects of nonsteroidal anti-inflammatory agents. Medicine, 63, 165-81... 

Prostaglandins - The effects of prostaglandins on cardiovascular responses would appear to be critically dependent on dose levels infused into humans at the appropriate dose, PGA and RGE cause a fall in blood pressure and renal dilatation without the release of renin. However,these effects are not simply dose related. Experiments on the cat spleen have led to the suggestion that there is a continuous basal secretion of vasodilating prostaglandins at very low infusion rates of PGA and PGE in the dog, effects due to direct vasodilation can be separated from sympathetic inhibition. ... 

Evaluation of inhibition of the other isoforms is still in the preclinical stages. Inhibition of NHE2 with prostaglandin E2 or with amiloride hastens the reestablishment of barrier function after intestinal ischemic damage in pigs and the use of S-3226 in rats with renal ischemia improved outcomes. Further work examining the effect of inhibition of the other isoforms is still required. 

There are several underlying mechanisms responsible for posttransplant HTN. Some causes of HTN in transplant recipients may include renal dysfunction, increased sensitivity to endothelin-1 and angiotensin, increased density of glucocorticoid receptors in the vascular smooth muscle, and decreased production of vasodilatory prostaglandins.57 However, one of the most easily recognized causes of posttransplant HTN is the use of corticosteroids and calcineurin inhibitors.58,59 Corticosteroids usually cause sodium and water retention,57 thus increasing blood pressure, whereas calcineurin inhibitors are associated with a number of effects that may result in HTN, including... 

Li+ also inhibits several hormone-stimulated adenylate cyclases which, in some cases, appear to be related to side effects of Li+ therapy. For instance, Li+ inhibits the hydro-osmotic action of vasopressin, the antidiuretic hormone which increases water resorption in the kidney [136]. This effect is associated with polyuria, a relatively harmless side effect sometimes experienced with Li+ treatment, which arises from the inability of the kidney to concentrate urine. Li+ has been shown to inhibit vasopressin-stimulated adenylate cyclase activity in renal epithelial cells. Additionally, Li+ is reported to enhance the vasopressin-induced synthesis of prostaglandin E2 (PGE2) in vitro in kidney. PGE2 inhibits adenylate cyclase activity by stimulation of Gj, and, therefore, this effect may contribute to the Li+-induced polyuria. 

Foop diuretics (furosemide, bumetanide, torsemide) are usually necessary to restore and maintain euvolemia in HF. In addition to acting in the thick ascending limb of the loop of Henle, they induce a prostaglandin-mediated increase in renal blood flow that contributes to their natriuretic effect. 

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