Poisoning with acetaminophen

Acute acetaminophen poisoning or toxicily can occur after a single 10- to 15-g dose of acetaminophen. Dosses of 20 to 25 g may be fatal. With excessive dosages die liver cells necrose or die Death can occur due to liver failure The risk of liver failure increases in patients who are chronic alcoholics. 

The skin often appears flushed, hot, and dry in poisoning with atropine and other antimuscarinics. Excessive sweating occurs with organophosphates, nicotine, and sympathomimetic drugs. Cyanosis may be caused by hypoxemia or by methemoglobinemia. Icterus may suggest hepatic necrosis due to acetaminophen or Amanita phalloides mushroom poisoning. 

Acetaminophen (paracetamol JV-acetyl-p-aminophenoF, TYLENOL, others) is an effective alternative to aspirin as an analgesic-antipyretic agent however, its anti-inflammatory effects are much weaker. While it is indicated for pain relief in patients with noninflammatory osteoarthritis, it is not a suitable substitute for aspirin or other NSAIDs in chronic inflammatory conditions such as rheumatoid arthritis. Acetaminophen is well tolerated and has a low incidence of GI side effects. It is available without a prescription. Acute overdosage can cause severe hepatic damage, and the number of accidental or deliberate poisonings with acetaminophen continues to grow. Chronic use of less than 2 g/day is not typically associated with hepatic dysfunction. 

N-acetylcysteine (NAC) (MUCOMYST, MUCOSIL, PARVOlek) is indicated for those at risk of hepatic injury. NAC therapy should be instituted in suspected cases of acetaminophen poisoning before blood levels become available, with treatment terminated if assay results subsequently... 

Boutis K, Shannon M Nephrotoxicity after acute severe acetaminophen poisoning in adolescents. J Toxicol Clin Toxicol 2001 39(5) 441-445. [PMID 11545233] (Nephrotoxicity occurred in about 9% of adolescents with severe acetaminophen poisoning.)... 

Administration of chloroform to laboratory animals resulted in the depletion of renal GSH, indicating that GSH reacts with reactive intermediates, thus reducing the kidney damage otherwise caused by the reaction of these intermediates with tissue MMBs (Hook and Smith 1985 Smith and Hook 1983, 1984 Smith et al. 1984). Similarly, chloroform treatment resulted in the depletion of hepatic GSH and alkylation of MMBs (Docks and Krishna 1976). Other studies demonstrated that sulfhydryl compounds such as L-cysteine (Bailie et al. 1984) and reduced GSH (Kluwe and Hook 1981) may provide protection against nephrotoxicity induced by chloroform. The sulfhydryl compound N-acetylcysteine is an effective antidote for poisoning by acetaminophen, which, like chloroform, depletes GSH and produces toxicity by reactive intermediates. 

Intravenous silymarin has been demonstrated to lower mortality from Amanita mushroom poisonings, but this formulation is available only in Europe. Animal studies have demonstrated hepatic protection against alcohol, acetaminophen, and mushroom toxins and protection against hepatic fibrosis with bile duct occlusion. There is also evidence of silybin protecting against cis-platin-induced nephrotoxicity in rats. It is not yet clear whether milk thistle extract offers any renal protection to humans. 

When a specific antidote or other treatment is under consideration, quantitative laboratory testing may be indicated. For example, determination of the acetaminophen serum level is useful in assessing the need for antidotal therapy with acetylcysteine. Serum levels of salicylate (aspirin), ethylene glycol, methanol, theophylline, carbamazepine, lithium, valproic acid, and other drugs and poisons may indicate the need for hemodialysis (Table 58-3). 

Acetaminophen is one of the drugs commonly involved in suicide attempts and accidental poisonings, both as the sole agent and in combination with other drugs. Acute ingestion of more than 150-200 mg/kg (children) or 7 g total (adults) is considered potentially toxic. A highly toxic metabolite is produced in the liver (see Figure 4-5). 

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