ACETAMINOPHEN HEPATOTOXICITY - 09/09/11
Résumé |
Acetaminophen (APAP) is a drug with dramatic characteristics and a dramatic history. First synthesized in 1893, it languished in obscurity for the next half-century, coming to clinical attention in the 1950s and achieving over-the-counter status in 1960.3, 58 With that emergence on the clinical scene, it achieved rapid popularity as a safe and effective analgesic and antipyretic without the gastrointestal side effects of the NSAIDs, the drugs with which it competed for use. APAP is available in several hundred preparations under a variety of trade names; unfortunately, however, within a few years APAP showed itself to be a potent hepatotoxin.
The fame and notoriety of the drug derive from the fact that it is a mild, but effective, analgesic and antipyretic with apparently few side effects in ordinary therapeutic doses, but a potent hepatotoxin in large overdose.3, 62 Indeed, its hepatotoxic effects are of such importance and interest that they seem to have attracted more attention in the medical literature than any other agent except the classic hepatotoxin, carbon tetrachloride. Within a few years of its entry into popular use, reports of suicidal overdoses leading to hepatic necrosis began to appear. The first clinical evidence of the toxicity of APAP appeared in 1966 in reports of two suicide attempts, one successful, involving intake of a large overdose.16, 63 News of the suicidal effectiveness of the drug spread rapidly and within a few years, APAP became the most popular means of attempting suicide in the United Kingdom and the most frequent cause of fulminant hepatic failure.9, 29, 64, 65 Many thousands of cases of APAP overdose have been admitted to British hospitals, many with hepatic injury.
The incidence of suicidal overdose in the United States, fortunately, has lagged behind, with the first report appearing in 1971.6 By now, thousands of cases of hepatic necrosis have been reported. In 1995, over 100,000 instances of presumed poisoning by APAP alone (72,880 cases) or with other drugs (38,047 cases) were reported to the Toxic Exposure Surveillance Program of the American Association of Poison Control Centers.28 Indeed, APAP is the most common pharmaceutical agent involved in suicidal overdose in the United States today. It is exceeded only by the sum of all antidepressants.29 Acetaminophen also is the most common cause of fulminant hepatic failure in the United States57 (Figure 1). The phenomenon has spread to other countries.9, 40
The apparent reasons for the popularity of APAP as a means of suicide include the ease of obtaining this over-the-counter preparation and the relative mild, immediate symptoms. An ironic aspect of APAP toxicity that may have some effect on its popularity is the long period (1 to 2 days) of relative well being before the onset of liver failure, a period during which the suicide victim may experience the response of others to the effort and perhaps regret it.
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| Address reprint requests to Hyman J. Zimmerman, MD, Hepatic Department, AFIP, 14th and Alaska Avenue, NW, Washington, DC 20306–6000 |
Vol 2 - N° 3
P. 523-541 - août 1998 Retour au numéro
Article précédent
- DRUG-INDUCED CHRONIC LIVER DISEASE
- Doris B. Strader, Leonard B. Seeff
- NSAID-INDUCED HEPATOTOXICITY
- James H. Lewis
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