Acetaminophen poisoning

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. 

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. 

Acetaminophen (paracetamol) poisoning is common in Western countries and is increasing elsewhere. Single doses as low as 7.5 g in adults or 150 mg/kg in a child can cause severe toxicity. Very occasionally, lower doses cause harm. Mortality, from hepatic or occasionally renal failure, is related to blood concentration and the time between ingestion and the initiation of antidotal treatment. Even severely poisoned patients may be asymptomatic, although nausea and vomiting are fairly common. 

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. 

Ethanol Multiple effects on neurotransmitter receptors, ion channels, and signaling pathways Antidote in methanol and ethylene glycol poisoning Zero-order metabolism duration depends on dose Toxicity Acutely, CNS depression and respiratory failure chronically, damage to many systems, including liver, pancreas, GI tract, and central and peripheral nervous systems Interactions Induces CYP2E1 Increased conversion of acetaminophen to toxic metabolite... 

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. 

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). 

More ODs, at least one fatal 213 another acetaminophen poisoning from abuse of an OTC preparation113... 

The chemical and toxicologic characterization of the electrophilic nature of the reactive acetaminophen metabolite has led to the development of effective antidotes—cysteamine and N-acetylcysteine. Administration of A-acetyl cysteine (the safer of the two) within 8-16 hours following acetaminophen overdosage has been shown to protect victims from fulminant hepatotoxicity and death (see Chapter 59 Management of the Poisoned Patient). 

Tamper-Resistant Packaging Regulations Issued for OTC Products. Tragedy Acetaminophen-capsule poisoning by cyanide causes seven deaths. Result Revision of GMPs to require tamper-resistant packaging. 

Vale JA, Proudfoot AT. Paracetamol (acetaminophen) poisoning. Lancet 1995 346(8974) 547-52. 

Biochemical differences also contribute to differential susceptibility between and within species. Cats are more susceptible to acetaminophen poisoning than other domestic animals. The cat s glucuronyl... 

Dogs and cats are commonly poisoned by pesticides, herbicides, household products such as antifreeze, and drugs such as acetaminophen applied by humans to their pets. By far the most common toxicities in these small animals involve various insecticides and the overzealous use of these products by owners attempting to control fleas and ticks on their pets. 

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