Cyclooxygenase inhibition: between the devil and the deep blue sea

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) account for more reports of drug related toxicity than any other class of drugs. Their most widely recognised adverse effects are on the gastrointestinal tract. They cause acute erosions and chronic ulcers that result in hospitalisation and death because of ulcer bleeding and perforation. Between them, aspirin and non-aspirin NSAIDs may account for more than half of all episodes of ulcer bleeding and perforation.

Figure 1

Schematic representation of COX selectivity assay.

Figure 2

Selectivity ratios of selected drugs. Derived from IC₈₀ data.³¹

Figure 3

Effect of naproxen 1 g daily and rofecoxib 50 mg daily on ex vivo gastric mucosal prostaglandin synthesis. Volunteers received placebo, naproxen, or rofecoxib for seven days. Twelve standardised gastric mucosal biopsy samples were taken and prostaglandin synthesis stimulated by vortex mixing. Reproduced from Gastroenterology with permission.³³

Figure 4

Acute volunteer studies. Lanza grade 2 = one or more erosions. Data derived from Lanza.^{35, 43}

Figure 5

Ulcer development over 12 weeks in patients receiving placebo, rofecoxib 25 mg, rofecoxib 50 mg, or ibuprofen 2.4 g daily. Combined data from two studies covering 1516 patients. Reproduced by permission from Arthritis & Rheumatism.³⁹

Figure 6

Ulcer development in patients receiving celecoxib in endoscopic studies. Reproduced with kind permission of the Journal of the American Medical Association.⁴⁴