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The Ancient Egyptians recognized the pain-relieving effects of concoctions made from myrtle and willow leaves. Hippocrates may have been among the first to use willow bark and leaves from the Salix species to relieve fever, but it was not until 1829 that the glycoside salicin was extracted from the willow bark and used as an antipyretic. Seven years later, salicylic acid was isolated, and by the late 1800s, it was being used to treat gout, rheumatic fever, and elevated temperatures. The less irritating acetylated salicylate compound was first synthesized in 1833, and in 1899 acetylsalicylic acid was commercially introduced as aspirin by Bayer. With that, the modern era of aspirin therapy and salicylate toxicity began.

The American Association of Poison Control Centers (AAPCC) National Poison Data System (NPDS) collects and reports annual exposure data in the United States. Analgesics, which include both aspirin and acetaminophen (APAP), continue to rank first among pharmaceuticals most frequently reported in human exposures (Chap. 136). Salicylate toxicity and fatalities have long been a major toxicological “concern.” From the 1950s to 1970s, salicylate was the leading cause of fatal childhood poisoning. The association with Reye syndrome; safer packaging; and the increased use of nonsteroidal antiinflammatory drugs (NSAIDs), APAP, and other alternatives to aspirin has decreased the incidence of unintentional salicylate poisoning. In the last 5 years of data available (2008–2012), there were 20 to 30 deaths per year reported (Chap. 136). Despite this decline in reported deaths and general use, it is still imperative that clinicians are adept at early recognition and swift management of patients with salicylate overdose.

Aspirin and other salicylate containing products continue to be some of the most common prescription and nonprescription xenobiotics used by the general public. Since landmark trials demonstrated the inhibition of platelet function by aspirin in the 1970s, its use became the standard of care for cardiovascular disease prevention and treatment. Subsequent investigations have demonstrated that aspirin can decrease the incidence of myocardial infarction, colon cancer, and transient ischemic attack. Its antiinflammatory properties have also continued to make it an active investigational xenobiotic for cancer.1

Bayer, a company once associated exclusively with aspirin, several years ago turned to making products containing ibuprofen or APAP. But in a very recent move of re-branding, Bayer is now marketing a return of aspirin for pain relief with three new products containing aspirin alone; aspirin with caffeine; and aspirin, caffeine, and APAP. Salicylates continue to be readily available and will continue to lead to significant morbidity and mortality in overdose.


Aspirin and other salicylates have analgesic, antiinflammatory, and antipyretic properties, a combination of traits shared by all of the NSAIDs (Chap. 37). Most of the beneficial effects of NSAIDs result from their inhibition of cyclooxygenase (COX). This enzyme enables the synthesis of prostaglandins, ...

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