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SPECIFIC SUBSTANCES

Non-steroidal anti- exacerbated in the elderly, in patients with pre-existing renal


impairment or in the presence of other nephrotoxic medication.

inflammatory drugs In very large doses, neurological or hepatic effects can be seen,
but these are uncommon.

Euan A Sandilands
Clinical features
D Nicholas Bateman
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
Abstract
include nausea and vomiting. Gastrointestinal haemorrhage can
Non-steroidal anti-inflammatory drugs are widely available and a com-
occur but is unusual. Alterations in renal blood flow due to
mon component of overdose. Toxic effects are principally renal. At
inhibition of prostaglandin synthesis cause disturbance of
high doses, coma and hepatic injury are rarely reported. Mefenamic
electrolyte excretion, with initial kaliuresis, followed by acute
acid is notable as it causes convulsions, although these are usually
tubular damage and renal failure at higher doses.6 The risk of
short-lived. Treatment is to a large extent supportive.
renal damage is likely to be increased by co-ingestion of other
Keywords Mefenamic acid; non-steroidal anti-inflammatory drugs 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-
Introduction lyte disturbance, renal and liver injury, coma and
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely convulsions.4,5,7
prescribed and also available for over-the-counter sale. NSAIDs Mefenamic acid in particular is associated with convulsions in
come in different chemical groupings; oxicams (meloxicam, overdose, with a recent study of single-agent overdoses reporting
piroxicam, tenoxicam) and phenylpropionic (arylpropionic) acid convulsions in 11% of patients with mefenamic acid poisoning.8
derivatives (e.g. fenbufen, ibuprofen, naproxen, tiaprofenic acid, As in the case of therapeutic use, asthmatics can suffer
mefenamic acid). Coxibs (e.g. celecoxib, etoricoxib) are bronchospasm following an overdose with NSAIDs and this
cyclooxygenase-2 (COX-2)-selective agents. Mefenamic acid is should be treated conventionally.
frequently prescribed for dysmenorrhoea. As a result, most
overdoses occur in young females as this is the market for whom Pregnancy
the drug has been used. Exposure to NSAIDs in the third trimester of pregnancy has also
The chemical differences between NSAIDs make little differ- been associated with premature closure of the ductus arteriosus
ence to their toxicity in overdose. All the drugs, including the in neonates due to inhibition of prostaglandin synthesis.9
COX-2-selective agents, are also potentially nephrotoxic in
overdose due to inhibition of renal prostaglandin synthesis.1e3
Management
Mechanisms of action and toxicity Treatment of poisoning with NSAIDs is generally symptomatic
All compounds in this class act by inhibiting COX enzymes, and supportive. Administration of activated charcoal can be
which are involved in inflammation and are responsible for the considered in patients who have ingested large doses of NSAIDs
synthesis of prostaglandins involved in normal physiological and present to medical services within 1 hour of ingestion.
processes. Inhibition of these actions is responsible for the ma- It is important to check renal function and acidebase status 12
jority of the adverse effects of NSAIDs in clinical use, and for hours after ingestion in patients who have ingested large doses. A
their main toxicity in overdose. The newer, so-called COX-2-se- reduction in estimated glomerular filtration rate and/or an in-
lective agents are thought to inhibit the inducible form of COX crease in serum creatinine concentration is to be expected in such
more than other forms of the enzyme. The main toxicity of patients. Mild metabolic acidosis secondary to renal tubular bi-
NSAIDs seen in overdose involves the kidney; this can be 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
Euan A Sandilands MD FRCPE PGCert Med Ed is a consultant in Clinical
Toxicology at the National Poisons Information Service (Edinburgh), lorazepam 3e4 milligrams intravenously. A
Royal Infirmary of Edinburgh and an honorary Senior Clinical Lecturer
at the University of Edinburgh, UK. Competing interests: none
declared.
REFERENCES
D Nicholas Bateman MD FRCP FRCPE FBPhS FAACT FEAPCCT is
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Edinburgh. Formerly he was Consultant Physician and Director of
the National Poisons Information Service (Edinburgh Unit) at the 2 Kulling PE, Backman EA, Skagius AS, Beckman EA. Renal
Royal Infirmary, Edinburgh, UK. Competing interests: none impairment after acute diclofenac, naproxen, and sulindac over-
declared. doses. J Toxicol Clin Toxicol 1995; 33: 173e7.

MEDICINE 44:3 185 Ó 2015 Elsevier Ltd. All rights reserved.


SPECIFIC SUBSTANCES

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MEDICINE 44:3 186 Ó 2015 Elsevier Ltd. All rights reserved.