T1 - Electrolyte and acid-base disturbances associated with non-steroidal anti-inflammatory drugs. N2 - Inhibition of renal prostaglandin synthesis by non-steroidal anti-inflammatory drugs NSAIDs causes various electrolyte and acid-base disturbances including sodium retention edema, hypertension , hyponatremia, hyperkalemia, and decreased renal function. AB - Inhibition of renal prostaglandin synthesis by non-steroidal anti-inflammatory drugs NSAIDs causes various electrolyte and acid-base disturbances including sodium retention edema, hypertension , hyponatremia, hyperkalemia, and decreased renal function.
Overview Fingerprint. Abstract Inhibition of renal prostaglandin synthesis by non-steroidal anti-inflammatory drugs NSAIDs causes various electrolyte and acid-base disturbances including sodium retention edema, hypertension , hyponatremia, hyperkalemia, and decreased renal function.
Keywords Acute renal failure Edema Hyponatremia Non-steroidal anti-inflammatory agents Renal tubular acidosis. Access to Document Link to publication in Scopus.
J Assoc Physicians India ; NSAIDs inhibit the cascade of arachidonic acid, selectively or not, causing a nonpermissive effect on the formation of prostaglandins.
Effects of nonsteroidal anti-inflammatory meloxicam on stomach, kidney, and liver of rats. Toxicol Ind Health ; In the kidneys, prostaglandins - mainly prostacyclins, PGE2, PGD2 - will act as vasodilators in the afferent arteriole, increasing renal perfusion, with distribution of the cortex flow to the nephrons in the renal medullary region. This vasodilatation acts as a negative feedback on the mechanisms, such as the performance of the renin-angiotensin-aldosterone system and the sympathetic nervous system, culminating with compensation to ensure adequate flow to the organ.
NSAIDs inhibit this mechanism and may result in acute vasoconstriction and spinal cord ischemia, which can lead to acute renal injury. In addition to the vasodilatation action, through the stimulation of tubular receptors PGE2 will inhibit the transport of sodium and chloride in the ascending loop of Henle and in the collecting ducts, by means of stimulating of the EP1 receptor, leading to natriuresis. Eur Rev Med Pharmacol Sci ; Nonsteroidal Anti-Inflammatory Drugs and the Kidney.
Pharmaceuticals Basel ; NSAIDs may also cause higher sodium and water retention by inhibiting PGE2 production, leading to the formation of edema, which is often subclinical. Clinical trials comparing different NSAIDs show the development of hypertension, especially when using high doses and for a prolonged time, with ibuprofen being more involved.
Cardiovascular safety of nonsteroidal anti-inflammatory drugs revisited. Postgrad Med ; In addition to its actions in the kidneys, prostaglandins perform several functions related to homeostasis, such as protection of the gastrointestinal mucosa, platelet activation, inflammation, bronchodilation, and others. Kidney damage caused by the use of NSAIDs is not common, especially when it comes to individuals who are previously healthy and who do not use abusive or high doses of these drugs.
Some factors, such as advanced age and comorbidities, which in themselves already lead to a decrease in GFR, increase the risk of NSAID-related nephrotoxicity, contributing to the development of side effects.
One of the risk factors is systemic arterial hypertension, which causes an even higher activation of the renin-angiotensin-aldosterone system RAAS and the sympathetic nervous system, leading to vasoconstriction; and the inhibition of prostaglandin synthesis causes the loss of the compensatory mechanism of renal vasodilation. The same applies to comorbidities that lead to a decrease in effective arterial volume, such as nephrotic syndrome with a high level of proteinuria, liver cirrhosis, especially in those with ascites, heart failure and lupus nephritis.
Patients with these conditions using NSAIDs have an inhibition of the kidney-compensation mechanism, as it happens in hypertensive patients, which contributes to renal damage. As already explained above, prostaglandins PGs play an important role in maintaining renal activity. The main hydroelectrolytic and acid-basic changes caused by this class of drugs are sodium retention causing edema and hypertension , hyperkalemia and metabolic acidosis due to the lower activity of COX-1 and COX Electrolyte and Acid-base disturbances associated with non-steroidal anti-inflammatory drugs.
Electrolyte Blood Press ; The inhibition of prostaglandin-mediated vasodilatation PGE-2 prevents adequate renal perfusion. In circulating arterial volume dysregulation situations, in which there is higher RAAS stimulation, there is a high production of prostaglandins PGE-2, PGI-2 by the afferent arteriole endothelium.
These prostaglandins are a self-regulating mechanism in cases of decreased renal perfusion, such as heart failure, hypovolemia, and as compensatory vasodilatation of the afferent arteriole mediated by PGE2, that occurs in response to norepinephrine or angiotensin II action. If production is reduced, it is only natural for plasma retention to occur due to afferent arteriolar vasoconstriction, leading to hydroelectrolytic and acid-base disturbances, especially water retention resulting from increased sodium reabsorption and hyperkalemia.
Thus, patients with such conditions associated with the use of NSAIDs are more vulnerable to developing nephrotoxicity. Drug-induced renal disorders. J Renal Inj Prev ; Aldosterone is able to increase potassium excretion. Since prostaglandin PGI2 stimulates renal juxtaglomerular cells to release renin and, consequently, aldosterone a state of hypoaldosteronism , inhibition of the production of this molecule by NSAIDs can cause less distal tubular flow, resulting in hyperkalemia, as well as metabolic acidosis.
Recent evidence from case-control and retrospective studies suggest that there is no correlation between a higher incidence of hyperkalemia with selective COX-2 inhibitors the coxibs , as already described in clinical trials of the s, and thus the incidence of hypokalemia with any class of NSAIDs.
Effect of Cyclooxygenase COX -1 and COX-2 inhibition on furosemide-induced renal responses and isoform immunolocalization in the healthy cat kidney. BMC Vet Res ; Blocking both enzymes prevents PGE2 production. This enzyme regulates the reabsorption of sodium and water in the renal tubules diuretic and natriuretic effect , besides optimizing blood perfusion to the renal medulla, which contributes to this effect.
However, in physiological situations, such enzymes are not primary components of the hydroelectrolytic homeostasis generated in the kidneys, since the baseline production rate of prostaglandins is relatively low.
Nonsteroidal anti-inflammatory drugs and their effects in the elderly. Aging Health ; Cyclooxygenasespecific inhibitors and cardiorenal function: a randomized, controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis patients. Am J Ther ; Am J Cardiol ; Serum urea decreased to pre-admission values by day 5 when he was discharged. The case was discussed with his primary physician, and with the consent of the patient, telmisartan and a low salt supplement were carefully restarted one at a time.
On follow-up at 2 months, he had restarted all his previous medications including telmisartan, and his electrolyte and renal parameters were at his usual baseline levels. The NSAID etoricoxib is a selective inhibitor of cyclo-oxygenase 2 COX-2 approved for treatment of patients with chronic arthropathies and musculoskeletal and dental pain [ 5 ]. Like parecoxib, celecoxib and other selective COX-2 inhibitors, it has demonstrated a significant reduction in gastrointestinal toxicity, although its renal adverse effects appear to be similar to those of other NSAIDs.
They are widely prescribed in Europe, South America and Asia for musculoskeletal pain. They are preferred over other NSAIDS mainly due to the favorable gastrointestinal profile and convenience of single-day dosing.
It is available as an off-the-counter drug in India. Specific COX-2 inhibition may induce renal ischemia, electrolyte imbalance and increased blood pressure, ultimately leading to fluid and sodium retention and decreased GFR [ 8 ]. In elderly patients on a sodium-depleted diet, a drop in GFR may be significant after a single dose of COX-2 inhibitor [ 9 ]. The time course of events, absence of other precipitating causes of renal dysfunction or hyperkalemia, rapid improvement on stopping the drug with no recurrence on reintroduction of the other medications and diet make etoricoxib the most probable cause Naranjo score 7.
It may exacerbate pre-existing hypertension. The number and spectrum of these side effects have been greater with rofecoxib than with the other COX-2 inhibitors, presumably due to the non-class effects of these drugs as their chemical structures are different [ 11 ]. In 14 cases of COX-2 inhibitor celecoxib and rofecoxib associated acute renal failure reported by Perazella et al.
Acute renal failure, disturbances in volume status heart failure, edema , acidosis and hyponatremia were common. Similar to our case, treatment before the development of clinically recognized renal failure ranged from 4 days to 3 weeks, and resolution of the renal dysfunction took 2 days to 3 weeks after discontinuation of drugs and supportive therapy.
Diclofenac Arthritis Long Term program, which enrolled 34, arthritis patients over 18 months, show clinically important increases in renal function endpoints.
There was no significant increase in the incidence of hyperkalemia [ 13 ]. Unlike in healthy people, patients with edematous conditions requiring dietary sodium restriction and diuretics, such as those with chronic renal insufficiency, congestive heart failure, chronic liver disease and hypertension, should be treated cautiously with COX-2 inhibitors.
Electrolytes and renal function should be checked 1—2 weeks after initiation of COX-2 inhibitors in these patients to screen for hyperkalemia and renal insufficiency [ 14 , 15 ]. Even a short duration of treatment with the new COX-2 inhibitor etoricoxib may have the potential to precipitate renal failure and life-threatening hyperkalemia when administered to selected patients.
Perazella MA Drug induced hyperkalemia: old culprits and new offenders. Am J Med — Arch Int Med — Harris RC Cyclooxygenase-2 inhibition and renal physiology. Intern Med J 35 9 — Clin Pharmacokinet — BMJ — Young D Few options available for arthritis pain refief. Am J Health Syst Pharm — PubMed Article Google Scholar.
Scientific World Journal — Heart Fail Clin 4 4 — Pharm World Sci — Article Google Scholar. Zhang J, Ding EL, Song Y Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: meta-analysis of randomised trials.
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