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High-Yield Facts

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  • Nonsteroidal anti-inflammatory drugs (NSAIDs) are relatively devoid of toxicity in the overdose setting.

  • Patients who develop toxicity exhibit central nervous system or gastrointestinal (GI) toxicity.

  • Overdose of NSAIDs has been associated with an anion-gap acidosis.

  • Long-term use of NSAIDs is associated with nephrotoxicity, including acute tubular necrosis, acute interstitial nephritis, and acute renal failure.

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Introduction

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Nonsteroidal anti-inflammatory drugs (NSAIDs) have analgesic, antipyretic, and anti-inflammatory effects and are among the most commonly used drugs in the world. While acute therapeutic use is regarded as safe in most patients, adverse reactions at therapeutic doses and with chronic use has resulted in a reevaluation of its safety in recent years. The introduction and, subsequent, withdrawal of cyclooxygenase (COX)-2-selective agents have resulted a decrease in the use of these agents. Ibuprofen and naproxen are currently the only nonprescription NSAIDs available in the United States. They are also available in combination cough and cold preparations as well as the prescription combination drug, Vicoprofen® (ibuprofen and hydrocodone). Other prescription forms of NSAIDs are also available in the United States and globally.

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Due to its nonprescription status and wide use, unintentional and intentional ingestions are common. The 2011 Annual Report of the American Association of Poison Control Centers listed 48 deaths in which NSAIDs were a contributing factor with 2 deaths related to a single substance (ibuprofen and colchicine). NSAIDs accounted for more than 79,000 single exposures, of which more than 65,000 were attributed to ibuprofen. As expected, children younger than 6 years had the majority of exposures with over 51,000 single exposures to NSAIDs.1 Symptoms in the overdose setting are rare; however, severe toxicity can occur.

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Pharmacology

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NSAIDs have numerous classifications including their cyclooxygenase (COX) activity, biochemical properties and pharmacologic action.(Table 115-1)2 Largely, NSAIDs are similar in their biochemical characteristics in that they are relatively lipophilic, weak acids. While most are absorbed readily in the GI tract, their pharmacokinetic properties differ. Thus the clinician can select for specific indications. The duration of action and half-life guides dosing with short half-life NSAIDs (e.g., ibuprofen) administered every 6 to 8 hours and longer half-life NSAIDs (e.g., naproxen) dosed once or twice daily. Metabolism and elimination are important pharmacokinetic properties to consider when dosing NSAIDs as adverse reactions are likely to occur with hepatic and renal disorders. In addition, drug interactions can result in adverse effects when taking into account metabolism, and other substrates that can affect enzyme function.

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Table Graphic Jump Location
TABLE 115-1   Pharmacology and Biochemical Properties of Non-Steroidal Anti-Inflammatory Drugs 

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