Pharmacology of antiarthritic drugs.

The clinical use of corticosteroids and second-line antirheumatic drugs provides relief in many patients but is associated with short-term and long-term toxicity. The beneficial effects are evident but are not well understood, particularly for the second-line agents. Rheumatoid arthritis is associated with abnormalities in macrophage, lymphocyte, and fibroblast functions. Corticosteroids and second-line agents appear to alter many of these responses (Table 2). Effects on macrophage and other antigen processing and phagocytic cells are common, but T- and B-lymphocytes also may be affected. Some of these agents have direct anti-inflammatory properties by inhibiting prostaglandin or leukotriene synthesis. A few are able to inhibit fibroblast proliferation and secretion of inflammatory mediators. Many other activities are possible. Understanding pharmacokinetics also should assist in determining dosing, possible consequences of other disorders, and predicting duration of acute effects. A better understanding of the disease process in rheumatoid arthritis and other disorders treated with these agents will lead to the better therapeutic approaches and, it is hoped, the discovery of more specific and less toxic agents.