Millions of people worldwide take nonsteroidal antiinflammatory drugs (NSAIDs) on a regular basis to treat pain and inflammation. Patients with an acute overdose of NSAIDs often present to emergency departments and represent a sizable percentage of cases reported to regional poison centers . As aging populations have increasingly come to rely on NSAIDs, chronic toxicity and acute poisonings have become more commonplace. Emergency and primary care clinicians need to understand the toxicity of NSAIDs; lack of appropriate medical intervention is believed to be partly responsible for 44 fatal NSAID-related poisonings in 2008.
Acute NSAID poisoning is reviewed here. A summary table to facilitate emergent management is provided (table 1). A general approach to suspected drug intoxication and discussions of chronic NSAID toxicity are provided elsewhere. (See "General approach to drug poisoning in adults" and "Nonselective NSAIDs: Overview of adverse effects".)
Nonsteroidal antiinflammatory drugs (NSAIDs) are competitive inhibitors of the enzyme cyclooxygenase (COX) (figure 1). NSAIDs prevent COX-mediated production of prostaglandins and thromboxanes, but not leukotrienes and other eicosanoids. (See "NSAIDs: Mechanism of action".) There are two COX isoforms, COX-1 and COX-2. The constitutive enzyme, COX-1, is expressed in most tissues and enables regulation of basal cellular homeostasis (platelet function, gastric mucosal integrity, and regulation of renal blood flow). The activity of the inducible COX-2 isoenzyme increases in inflammatory and pain states .
Numerous animal and human studies have demonstrated the role of COX-1 in inflammation [3,4]. In general, all NSAIDs inhibit both isoforms, with most adverse reactions believed to be attributable to COX-1 inhibition. The development of newer COX-2 selective NSAIDs arose from the desire to maintain therapeutic antiinflammatory function, while decreasing the rates of adverse drug effects, most notably gastrointestinal and renal toxicity. (See "Nonselective NSAIDs: Overview of adverse effects".)
Oral absorption of NSAIDs approaches 100 percent and peak serum levels usually occur within one to two hours. Large toxic ingestions or concomitant food consumption can delay peak levels up to three to four hours. NSAIDS are weak acids that are extensively (up to 99 percent) protein bound, with a small volume of distribution (0.1 to 0.2 L/kg). Diseases causing low protein levels or large NSAID ingestions can decrease plasma protein binding, resulting in an increased volume of distribution and greater penetration into body tissues, including the central nervous system.