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- cyclo-oxygenase-2 inhibitors
- COX-2 inhibitors
- non-steroidal anti-inflammatory drugs
There has been a great deal written about the use of selective cyclo-oxygenase-2 (COX-2) inhibitors in the adult population. Yet despite this there is still controversy over their place in treatment and in the interpretation of evidence from the major clinical trials.1 In the UK the National Institute for Clinical Excellence (NICE) recommended COX-2 inhibitors only be prescribed for osteoarthritis and rheumatoid arthritis patients at high risk of developing serious gastrointestinal adverse effects.2
Their role in children is even less well defined, with only a small number of published studies. Yet despite this lack of published evidence there is an undercurrent among paediatric practitioners to prescribe these agents. The aim of this review is to highlight the current published literature on the use of COX-2 inhibitors in children.
The major mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) is inhibition of cyclo-oxygenase (COX) enzymes, which catalyse prostaglandin synthesis from arachidonic acid. There are at least two isoforms of cyclo-oxygenase: COX-1 is found in high concentrations in platelets, vascular endothelial cells, stomach, and in the kidney. It is accountable for the production of prostaglandins necessary for the maintenance of normal endocrine and renal function, gastric mucosal integrity, and haemostasis. The COX-2 isoform, under normal physiological conditions, is almost undetectable in most tissues; however, it increases up to 20 fold at the site of tissue damage.
It is suggested that COX-2 plays a role in the inflammation process, while inhibition of COX-1 is responsible for the adverse effects of NSAIDs. Based on this hypothesis, drugs that selectively inhibit COX-2 enzymes should have the beneficial anti-inflammatory activity of traditional NSAIDs without the toxicity.
Available COX-2 inhibitors
NSAIDs may be classified in terms of their COX-2 selectivity. However, there are international differences regarding COX-2 classification. The Food and Drug Administration in the USA classifies meloxicam …