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NSAIDs: Electrolyte complications

Author
Richard H Sterns, MD
Section Editor
Michael Emmett, MD
Deputy Editor
John P Forman, MD, MSc

INTRODUCTION

Nonsteroidal antiinflammatory drugs (NSAIDs) are the most commonly prescribed analgesics worldwide. These agents reduce pain, inflammation, and fever by inhibiting cyclooxygenase (COX), which results in decreased synthesis of prostaglandins. COX has two isoforms; inhibition of COX-1 is responsible for the gastrointestinal side effects of NSAIDs, while their desired antiinflammatory effects are due to inhibition of COX-2 [1]. The COX-2 isoform is constitutively present in the kidney, and, therefore, both nonselective NSAIDs and more selective COX-2 inhibitors reduce renal prostaglandins. (See "NSAIDs: Pharmacology and mechanism of action".)

Renal vasodilatory prostaglandins promote the secretion of renin, impair sodium reabsorption in the loop of Henle and cortical collecting tubule, and partially antagonize the ability of antidiuretic hormone (ADH) to increase water reabsorption in the collecting tubules [2-5]. Locally generated prostaglandins also may mediate part of the natriuretic effect of dopamine and of natriuretic peptides [6,7].

These actions are not of major importance in normal subjects in whom basal renal prostaglandin production is relatively low. However, they may become clinically significant when prostaglandin synthesis is stimulated by underlying renal disease or by the vasoconstrictors angiotensin II or norepinephrine. Secretion of these vasoconstrictors is increased in states of effective volume depletion: true volume depletion due to gastrointestinal or renal losses (as with diuretic therapy) or reduced tissue perfusion due to heart failure or cirrhosis.

In the setting of effective volume depletion, NSAIDs, which inhibit prostaglandin synthesis, can produce a variety of complications related to renal dysfunction, each of which is reversible with discontinuation of therapy [2,3]. These include hyperkalemia, hyponatremia, and edema. These complications are mediated in part by reductions in the secretion of renin and aldosterone and by increased activity of ADH [2,3,8].

In addition, vasoconstriction due to decreased synthesis of vasodilator prostaglandins can impair renal function and exacerbate underlying hypertension and heart failure. These issues are discussed separately. (See "NSAIDs: Acute kidney injury (acute renal failure)" and "NSAIDs and acetaminophen: Effects on blood pressure and hypertension" and "Nonselective NSAIDs: Adverse cardiovascular effects", section on 'Patients with heart failure' and "COX-2 selective inhibitors: Adverse cardiovascular effects".)

       
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Literature review current through: Nov 2017. | This topic last updated: Sep 28, 2017.
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References
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