Anti-inflammatory drug mechanisms.

Abstract

The approach to management of disordered inflammation via pharmacological modification of the chemical mediators thereof is reviewed. Anti-inflammatory drug effects seem unlikely to be exerted to an important degree by way of actions on histamine or serotonin, neither is there any clear evidence that anti-inflammatory drugs achieve their effects by intervening in kinin formation. Activation of complement components is an important influence in the development of the inflammatory process and some aspects may be subject to modification by drugs, e.g. corticosteroids. Lysosomal enzymes are capable of compounding inflammatory reactions if lysosomal membrane integrity is prejudiced. Anti-inflammatory drugs such as steroids and chloroquines may stabilise lysosomal membranes and gold salts may inhibit lysosomal hydrolases. Although an action in uncoupling oxidative phosphorylation is shared by a number of anti-inflammatory drugs, this seems unlikely to be of importance in the conditions operating under therapeutic use. Prostaglandin synthesis in situ has now been shown to be potentially important in medication of inflammation. Non-steroidal anti-inflammatory acidic drugs inhibit prostaglandin bio-synthesis under a variety of conditions, indomethacin being consistently highly active, as are other of the more potent non-steroidal anti-inflammatory agents; aspirin also being effective. Connective tissue activating peptide (CTAP) which can reproduce many of the features characterising rheumatoid arthritis is inhibited by cortisol and a variety of non-steroidal agents. Non-steroidal acidic anti-inflammatory drugs share characteristics such as protein-binding and capacity to displace endogenous substances from serum protein binding sites. However, such displacement capacity is shared by other drugs without anti-inflammatory effects. The inflammatory process is an exceedingly complex reaction made up of numerous interacting systems with a variety of mediators. Relative importance of the various factors changes with the phase of the process. To imagine that the effects of a diverse group of drugs are likely to be attributable to an action at a single specific point is probably ingenuous. However, convincing inhibitory effects on the part of the drugs effective in this context may be seen on several of the specific chemical mediators. It may be the capacity to interfere at several different points in the chain of events involved in the inflammatory reaction that endows effective anti-inflammatory drugs with their special therapeutic properties.