Current problems with non-specific COX inhibitors

Patricia McGettigan, David Henry

Research output: Contribution to journalReview articleResearchpeer-review

45 Citations (Scopus)

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and effective treatments for pain and inflammation. They have a substantial toxicity profile with side effects mainly affecting the gastrointestinal tract, heart and kidneys. Although they comprise a chemically diverse group of drugs, NSAIDs are unified by a common mode of action - the ability to inhibit the enzyme cyclo-oxygenase (COX). This also accounts for much of their toxicity. The enzyme exists in at least 2 isoforms. COX-1 generates prostaglandins with physiological functions, COX-2 is induced by inflammation and its physiologic functions are unclear at present. Conventional NSAIDs, like diclofenac, ibuprofen, and naproxen, are non-selective COX inhibitors, blocking the production of both physiologic and inflammatory prostaglandins. In this chapter, we describe the main 'predictable' gastrointestinal, cardiac and renal toxicities that can be explained by such blockade and review the supporting clinical and epidemiological evidence. In the gastrointestinal tract, the side effects associated with conventional NSAIDs are both local and systemic, and include ulceration, bleeding, perforation, and obstruction. The upper gastrointestinal tract is more commonly affected than the lower. The cardiac and renal side effects are most likely to occur in patients with existing heart or kidney disease, where prostaglandins play an essential role in maintaining the vasoconstrictor/dilator balance necessary for homeostasis. The patients at highest risk of toxicity are the elderly, those with a prior history of ulceration or bleeding, and those with a history of cardiac disease. Among such patients, the decision to prescribe NSAIDs requires careful consideration of the: potential benefits and harms.

Original languageEnglish
Pages (from-to)1693-1724
Number of pages32
JournalCurrent Pharmaceutical Design
Volume6
Issue number17
DOIs
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Cyclooxygenase Inhibitors
Anti-Inflammatory Agents
Prostaglandin-Endoperoxide Synthases
Pharmaceutical Preparations
Prostaglandins
Kidney
Gastrointestinal Tract
Heart Diseases
Hemorrhage
Inflammation
Naproxen
Upper Gastrointestinal Tract
Aptitude
Diclofenac
Ibuprofen
Kidney Diseases
Vasoconstrictor Agents
Enzymes
Protein Isoforms
Homeostasis

Cite this

McGettigan, Patricia ; Henry, David. / Current problems with non-specific COX inhibitors. In: Current Pharmaceutical Design. 2000 ; Vol. 6, No. 17. pp. 1693-1724.
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Current problems with non-specific COX inhibitors. / McGettigan, Patricia; Henry, David.

In: Current Pharmaceutical Design, Vol. 6, No. 17, 2000, p. 1693-1724.

Research output: Contribution to journalReview articleResearchpeer-review

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