Non-opioid analgesic poisoning

Abstract

In most developed countries, analgesics top the list of the most frequent causes of poisoning. Currently, paracetamol overdose remains the most frequent, whilst ibuprofen has overtaken aspirin in keeping with changes in usage. Paracetamol (acetaminophen)Since the first cases of severe and fatal liver damage were reported in 1966, 1,2 overdose of paracetamol has become the cause of 100-200 deaths in the UK each year. 3 Paracetamol toxicity remains the leading cause of fulminant hepatic failure in the UK and is a common reason for liver transplantation. 4,5 Knowledge of the toxic mechanism (Fig 1) has led to effective antidotes which provide substrates for increased glutathione production. Intravenous acetylcysteine (Parvolex®) is the treatment of choice in the UK. (Methionine is an oral alternative 7 that can be considered only within the first 12 hours of overdose.) Although treatment of acute paracetamol overdose is well defined, decisions are complicated by late presentation, staggered overdoses and marked variation in individual susceptibility (Table 1). Table 2 lists the expected clinical features of paracetamol overdosage, but clinical information is of little help in determining the risk of toxicity. The interpretation of the plasma paracetamol concentration using a nomogram (Fig 2) is the established method for determining diagnosis, assessing risk (see Table 3 also) and deciding on management. Management of overdoseActivated charcoal can be given within one hour of ingestion. This is unnecessary in most children because self-administration of paracetamol elixir by a child rarely results in toxicity. Blood should be taken no earlier than four hours post-ingestion for measurement of the plasma paracetamol concentration in any patient following a single ingestion of more than 150 mg/kg or 12 g, whichever is smaller. The risk of liver damage can then be assessed using the paracetamol nomogram. Acetylcysteine should be commenced if the concentration is above the treatment line. An alternative treatment line exists for 'high-risk' patients (those fulfilling any of the criteria listed in Table 1). Doses as low as 75 mg/kg may be hepatotoxic in such patients; although there is little evidence supporting this figure, there are reasonable empirical reasons to accept it.The plasma paracetamol concentration provides a good diagnostic indicator, and treatment is successful in patients presenting early with an accurate history, particularly with regard to time of ingestion which is essential for interpreting a paracetamol concentration. If the time of ingestion is unknown, or paracetamol has been taken chronically or in a staggered fashion (eg 2 hours between doses), the plasma paracetamol concentration cannot be interpreted accurately. Acetylcysteine should therefore be given if the total dose in 24 hours exceeds 150 mg/kg or 12 g, whichever is the smaller ( 75 mg/kg for high risk patients).If the patient presents more than eight hours from ingestion, treatment should be commenced immediately (since the efficacy of t...

An Overview of Clinical Pharmacology of Ibuprofen

“…38 Toxic effects are unlikely at doses below 100 mg/kg but can be life-threatening or severe above 400 mg/kg. 39 However, large doses do not indicate that the clinical course is likely to be lethal. 40…”