Update in Rheumatology

Nonsteroidal Anti-Inflammatory Drugs

One of the two isoforms of COX, known as COX-1, is expressed in most tissues and promotes formation of the prostaglandins needed for normal physiology. Inhibiting COX-1 suppresses the formation of beneficial prostaglandins and may lead to ulceration of the mucosa of the upper gastrointestinal tract as well as acute renal insufficiency. The other form of the enzyme, COX-2, is evoked by inflammatory cytokines and leads to the production of prostaglandins that mediate inflammation, as in rheumatoid joints. This form is also expressed in the brain, kidneys, ovaries, and bone (1). To combat inflammation, ideally only COX-2 should be inhibited; unfortunately, all traditional prostaglandin inhibitors, until the release of celecoxib 1 year ago, suppressed both forms of COX.

All Traditional Cyclooxygenase-Inhibiting Nonsteroidal Anti-Inflammatory Drugs—Even Those “Selective” for Cyclooxygenase-2—Blocked Prostaglandin Production in Gastric Mucosa

Cryer B, Feldman M. Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med. 1998; 104:413-21.

This study examined the extent to which current NSAIDs inhibit the respective COX isoforms in humans. Blood samples from 16 healthy young to middle-aged men and women were incubated with 25 anti-inflammatory or analgesic drugs at six concentrations. Assays were then done for serum-generated thromboxane B₂ synthesis (COX-1 assay) and lipopolysaccharide-stimulated prostaglandin E₂ synthesis by monocytes (COX-2 assay). In addition, gastric biopsy samples from the volunteers were incubated with each of the drugs, and mucosal prostaglandin E_{2 …}