Prostaglandins, specific agents

Inflammation is a non-specific reaction which can be induced by a variety of agents apart fiom microorganisms. Lymphokines and derivatives of arachidonic acid, including prostaglandins, leukotrienes and thromboxanes are probable mediators of the inflammatory response. The release of vasoactive amines such as histamine and serotonin (5-hydroxytryptamine) firm activated or damaged cells also contribute to inflammation. 

Topical corticosteroids (Table 16-1) may halt synthesis and mitosis of DNA in epidermal cells and appear to inhibit phospholipase A, lowering the amounts of arachidonic acid, prostaglandins, and leukotrienes in the skin. These effects, coupled with local vasoconstriction, reduce erythema, pruritus, and scaling. As antipsoriatic agents, they are best used adjunc-tively with a product that specifically functions to normalize epidermal hyperproliferation. 

Arachidonic acid is not present in significant amounts in tissues as the free acid but is stored as a fatty acid at the sn-2 position of phospholipids. Prostaglandin biosynthesis is initiated by the interaction of a stimulus with the cell surface. Depending on the cell type, the stimulus can take the form of a hormone, such as angiotensin II or antidiuretic hormone, or a protease such as thrombin (involved in blood clotting), or both hormone and protease. These agents bind to a specific receptor that activates a phospholipase A2 that specifically releases the arachidonic acid from a phospholipid such as phosphatidylcholine. The release of arachidonic acid by phospholipase A2 is believed to be the rate-limiting step for the biosynthesis of eicosanoids. 

Other molecules have been suggested as being useful lung-specific bioadhesive agents [137,138], for example, insulin, transferrin, prostaglandins, hirudin-inhibited thrombin (which binds thrombomodulin), anionic polysaccharides, oligosaccharides (such as dextran sulfate, dermatan sulfate, chondroitin sulfate, hyaluronic acid), peptides (such as benzoyl-phe-ala-pro [BPAPI] that... 

Summary - Many diverse novel compounds that inhibit different platelet functions show great promise, not only for potential anti-thrombotic agents, but also for more specific effects on prostaglandin and/or thromboxane A2 synthesis, and serotonin or calcium uptake and release. Many active compounds can be used as tools in the search toward a more complete understanding of the physiologic interactions of the hemostatic mechanisms. This better understanding would lead to the development and use of more potent and selective synthetic compounds in the inhibition of platelet aggregation and fibrin formation, and in the enhancement of fibrinolysis for the control of both arterial and venous thrombosis. It is hoped that some of these new compounds will be evaluated clinically in the near fu ture. 

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