Acute Poisoning Due to Non-Steroidal Anti-Inflammatory Drugs

Summary

Despite the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs), the current number of reported cases of poisoning is small However, with the introduction of ‘over-the-counter’ preparations of NSAIDs in some countries (e.g. ibuprofen in the UK and USA) an increased incidence of acute poisoning from this group of drugs can be expected. Conventionally, NSAIDs are divided into the following groups based on their chemical structure: arylpropionic acids, indole and indene acetic acids, heteroarylacetic acids, fenamates, phenylacetic acids, pyrazolones and oxicams.

Unless NSAIDs are ingested in substantial overdose, acute poisoning with these agents does not usually result in significant morbidity or mortality. In most cases the clinical features are mild and confined to the gastrointestinal and central nervous systems, though acute renal failure, hepatic dysfunction, respiratory depression, coma, convulsions, cardiovascular collapse and cardiac arrest may complicate severe poisoning.

Arylpropionic acid derivatives were thought initially to have a low order of toxicity in overdose but, in addition to anticipated gastrointestinal symptoms, headache, tinnitus, hyperventilation, sinus tachycardia, hypoprothrombinaemia, haematuria, proteinuria and acute renal failure have been described. In addition, drowsiness, coma, nystagmus, diplopia, hypothermia, hypotension, respiratory depression and cardiac arrest have been reported in severe cases of poisoning.

Oxyphenbutazone and phenylbutazone are considerably more toxic in overdose. Complications of severe poisoning include coma, convulsions, hepatic dysfunction, acute renal failure, sodium and water retention, haematuria, cardiovascular collapse, respiratory alkalosis, metabolic acidosis, hypoprothrombinaemia and thrombocytopenia.

In contrast, indomethacin appears to be much less toxic. In addition to gastrointestinal symptoms, indomethacin taken in overdose induces headache, tinnitus, dizziness, lethargy, drowsiness, confusion, disorientation and restlessness. Only 1 case of acute sulindac poisoning has been reported in the literature. A 16-year-old boy was admitted with hypokalaemia (2.2 mmol/L), transient granulocytosis and ‘scanty’ haematemesis after ingesting 12g sulindac. No cases of acute tolmetin poisoning have been reported.

The fenamates (flufenamic acid, meclofenamic acid, mefenamic acid, tolfenamic acid) are, with the exception of mefenamic acid, not as widely prescribed as other groups of NSAIDs. In overdose, mefenamic acid may result in nausea, vomiting, diarrhoea, muscle twitching, convulsions and coma. Convulsions appear more frequently following overdose with mefenamic acid than with other NSAIDs; other complications include hypoprothrombinaemia, acute renal failure and cardiorespiratory arrest.

Azapropazone (a pyrazolone derivative) may produce gastrointestinal irritation, nausea, vomiting, epigastric pain, haematemesis, giddiness, abnormal limb movements, coma, hyperventilation and acute renal failure following overdose. In 11 cases of acute poisoning due to feprazone, another pyrazolone, symptoms reported included nausea, vomiting, drowsiness, headache, hypertonia, twitching and tachypnoea.

Worldwide, piroxicam is probably the most widely prescribed NSAID and it appears to be at least moderately toxic in acute overdose. Nausea, vomiting, diarrhoea, abdominal pain, gastrointestinal bleeding, dizziness, blurred vision, excitability, hyperventilation, hyperreflexia, coma, convulsions, haematuria, proteinuria, acute renal failure, hepatic dysfunction and hypoprothrombinaemia have been described in 5 reports (24 patients) published in the literature between 1983 and 1985.

The management of NSAID overdose is essentially supportive and symptomatic. If a substantial overdose of an NSAID has been ingested (e.g. more than 10 therapeutic doses in an adult or 5 therapeutic doses in a child) and the patient presents not more than 4 hours later, an attempt may be made to reduce absorption by either gastric lavage or the administration of syrup of ipecacuanha. It should be recognised, however, that neither technique has been validated by a clinical trial to confirm their efficacy in NSAID poisoning. Furthermore, syrup of ipecacuanha itself induces symptoms indistinguishable from NSAID overdose and this makes diagnosis more difficult. Activated charcoal is unlikely to prevent significant absorption of ingested NSAID if administered more than 1 to 2 hours after overdose. Forced diuresis, dialysis and haemoperfusion are not useful as most NSAIDs are highly protein-bound and extensively metabolised. Repeated doses of activated charcoal to increase non-renal elimination may have an important role to play in cases of severe poisoning but this has yet to be confirmed.