Acute Poisoning Due to Non-Steroidal Anti-Inflammatory Drugs

Abstract

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 12 g sulindac. No case 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.(ABSTRACT TRUNCATED AT 400 WORDS)

Application of engineered cytochrome P450 mutants as biocatalysts for the synthesis of benzylic and aromatic metabolites of fenamic acid NSAIDs

“…Metabolite 1a was found to co-elute with the major metabolite 3-hydroxymethyl-meclofenamic acid formed after incubation of 1 with human liver microsomes (HLM). 30 Metabolites 1b and 1c were identified as products of aromatic hydroxylation at position C-5 of carboxy phenyl ring and at position C-4'of the dichloro phenyl ring, respectively (see Supplementary Information). All three hydroxylated metabolites of 1 which are produced by engineered P450 BM3 were also formed in incubations with HLM.…”

An Overview of Clinical Pharmacology of Ibuprofen

“…66 Based on clinical trial data, serious GIT reactions prompting withdrawal of treatment because of hematemesis, peptic ulcer, 67 and severe gastric pain or vomiting showed an incidence of 1.5% with ibuprofen compared to 1% with placebo and 12.5 % with aspirin. 68 Ibuprofen was a potential cause of GI bleeding, 69,70 increasing the risk of gastric ulcers and damage, renal failure, epistaxis, 71-74 apoptosis, 75 heart failure, hyperkalaemia, 76 confusion and bronchospasm. 77 It has been estimated that 1 in 5 chronic users (lasting over a long period of time) of NSAIDs will develop gastric damage which can be silent.…”

“…The symptoms of high dose include seizures, apnea, and hypertension, as well as renal and hepatic dysfunction. [91][92][93][94] Ibuprofen has been implicated in elevating the risks of myocardial infraction, particularly among those chronically using high doses. [95][96][97][98][99][100] Desmopressin and NSAIDs should not be used in combination in patients with bleeding disorders.…”

Piroxicam induced submassive necrosis of the liver.

“…Normal liver function tests were recorded after a reported ingestion of 1800 mg piroxicam. 18 Previous case reports of piroxicam induced submassive necrosis have described the onset of jaundice three days'4 and three weeks'5 after beginning piroxicam. Our second patient fits this pattern, with an onset of jaundice approximately six weeks after piroxicam was begun.…”