SPECIFIC SUBSTANCES
Non-steroidal anti-
inflammatory drugs
Euan A Sandilands
D Nicholas Bateman
Abstract
Non-steroidal anti-inflammatory drugs are widely available and a com-
mon component of overdose. Toxic effects are principally renal. At
high doses, coma and hepatic injury are rarely reported. Mefenamic
acid is notable as it causes convulsions, although these are usually
short-lived. Treatment is to a large extent supportive.
Keywords Mefenamic acid; non-steroidal anti-inflammatory drugs
Introduction
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely
prescribed and also available for over-the-counter sale. NSAIDs
come in different chemical groupings; oxicams (meloxicam,
piroxicam, tenoxicam) and phenylpropionic (arylpropionic) acid
derivatives (e.g. fenbufen, ibuprofen, naproxen, tiaprofenic acid,
mefenamic acid). Coxibs (e.g. celecoxib, etoricoxib) are
cyclooxygenase-2 (COX-2)-selective agents. Mefenamic acid is
frequently prescribed for dysmenorrhoea. As a result, most
overdoses occur in young females as this is the market for whom
the drug has been used.
The chemical differences between NSAIDs make little differ-
ence to their toxicity in overdose. All the drugs, including the
COX-2-selective agents, are also potentially nephrotoxic in
overdose due to inhibition of renal prostaglandin synthesis.1e3
Mechanisms of action and toxicity
All compounds in this class act by inhibiting COX enzymes,
which are involved in inflammation and are responsible for the
synthesis of prostaglandins involved in normal physiological
processes. Inhibition of these actions is responsible for the ma-
jority of the adverse effects of NSAIDs in clinical use, and for
their main toxicity in overdose. The newer, so-called COX-2-se-
lective agents are thought to inhibit the inducible form of COX
more than other forms of the enzyme. The main toxicity of
NSAIDs seen in overdose involves the kidney; this can be
Euan A Sandilands MD FRCPE PGCert Med Ed is a consultant in Clinical
Toxicology at the National Poisons Information Service (Edinburgh),
Royal Infirmary of Edinburgh and an honorary Senior Clinical Lecturer
at the University of Edinburgh, UK. Competing interests: none
declared.
D Nicholas Bateman MD FRCP FRCPE FBPhS FAACT FEAPCCT is
honorary Professor in Clinical Toxicology at the University of
Edinburgh. Formerly he was Consultant Physician and Director of
the National Poisons Information Service (Edinburgh Unit) at the
Royal Infirmary, Edinburgh, UK. Competing interests: none
declared.
MEDICINE 44:3
exacerbated in the elderly, in patients with pre-existing renal
impairment or in the presence of other nephrotoxic medication.
In very large doses, neurological or hepatic effects can be seen,
but these are uncommon.
Clinical features
Following acute overdose, NSAIDs are usually of low toxicity
unless taken in very large doses. Toxicity, however, can be
more pronounced in children.4,5 Common clinical features
include nausea and vomiting. Gastrointestinal haemorrhage can
occur but is unusual. Alterations in renal blood flow due to
inhibition of prostaglandin synthesis cause disturbance of
electrolyte excretion, with initial kaliuresis, followed by acute
tubular damage and renal failure at higher doses.6 The risk of
renal damage is likely to be increased by co-ingestion of other
potentially nephrotoxic agents. These risks are greater in the
elderly and those with existing renal disease. More serious
poisoning may be associated with metabolic acidosis, electro-
lyte disturbance, renal and liver injury, coma and
convulsions.4,5,7
Mefenamic acid in particular is associated with convulsions in
overdose, with a recent study of single-agent overdoses reporting
convulsions in 11% of patients with mefenamic acid poisoning.8
As in the case of therapeutic use, asthmatics can suffer
bronchospasm following an overdose with NSAIDs and this
should be treated conventionally.
Pregnancy
Exposure to NSAIDs in the third trimester of pregnancy has also
been associated with premature closure of the ductus arteriosus
in neonates due to inhibition of prostaglandin synthesis.9
Management
Treatment of poisoning with NSAIDs is generally symptomatic
and supportive. Administration of activated charcoal can be
considered in patients who have ingested large doses of NSAIDs
and present to medical services within 1 hour of ingestion.
It is important to check renal function and acidebase status 12
hours after ingestion in patients who have ingested large doses. A
reduction in estimated glomerular filtration rate and/or an in-
crease in serum creatinine concentration is to be expected in such
patients. Mild metabolic acidosis secondary to renal tubular bi-
carbonate loss can precede a rise in creatinine. Treatment of
renal impairment is conventional, although haemodialysis may
rarely be required in very severe cases.
Convulsions with mefenamic acid, if persistent, should be
managed with diazepam 10e20 milligrams intravenously or
lorazepam 3e4 milligrams intravenously. A
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 SPECIFIC SUBSTANCES
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