Alterations in GFR
Sodium retention and edema
Other effects (rare):
• Nephrotic Syndrome
• Acute interstitial nephritis
• Chronic interstitial nephritis
What You Should Know About COX-2 Inhibitors
- Volume 15 - Issue 10 - October 2002
- 10339 reads
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Are COX-2 inhibitors good alternatives to nonsteroidal antiinflammatory drugs (NSAIDs)? Yes, traditional NSAIDs inhibit both COX enzymes but they have well-documented gastrointestinal side effects. NSAIDs can cause severe electrolyte disturbances and renal complications such as hyponatremia, hyperkalemia, edema, hypertension, acute and chronic tubulointerstitial nephritis, papillary necrosis and glomerular lesions. Patients with prostaglandin-depleted disease states (cirrhosis, congestive heart failure, chronic renal failure, volume depletion, and nephrosis) who use NSAIDs often develop acute renal insufficiency.1
There are 100,000 hospitalizations per year and 16,000 deaths per year in the U.S. alone due to NSAID complications.2 The development of COX-2 inhibitors has reduced the GI toxicity, however recent studies have revealed potential renal and cardiac complications with COX-2 inhibitors.
Understanding The Dynamics Of NSAIDs And COX-2 Inhibitors
In order to use these medications appropriately, it is essential to have a clear understanding of how they work and a strong awareness of possible side effects.
NSAIDs work by inhibiting COX, the rate-limiting enzyme in the metabolic conversion of arachidonic acid into prostanoids. COX-1 enzymes are found in most tissues and are important in hemostasis and in protecting gastric mucosa. COX-2 enzymes are induced in inflammatory states and tumorigenesis and can be found in neural and renal tissues.
The COX-2 protein is located in the macula densa along the cortical thick ascending loop of Henle and medullary interstitial cells. Cyclooxygenase stimulates the conversion of arachidonic acid into prostanoids. During the inflammatory process, COX-2 can be induced by a variety of stimuli, including endotoxins, cytokines, interleukin-1 and tumor necrosis factor-alpha.3 The most important prostanoids in the kidney are prostacyclin (PGI2) and prostaglandin (PGE2).
Prostaglandins contribute to pain and inflammation. They are potent vasodilators, producing painful edema and sensitize pain receptors to histamine thus lowering the threshold for pain response. PGE2, produced by COX-2, inhibits salt and water reabsorption by the ascending limb and collecting duct. PGE2 is necessary for rejection of NaCl reabsorption. Blockage of PGE2 production by NSAIDs can inhibit salt excretion, leading to peripheral edema, weight gain and increased blood pressure.4 COX-2 inhibitors are not without renal side effects (see “Renal Side Effects of COX-2 Inhibitors” below).4 Increased circulatory volume causes greater tubular flow and secretion of potassium. In healthy individuals, renal prostaglandins do not play a major role in sodium and water homeostasis.5