Analgesics : from chemistry and pharmacology to clinical by Helmut Buschmann; Gregor Bahrenberg; et al

By Helmut Buschmann; Gregor Bahrenberg; et al

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1987). Additional Effects of COX-inhibitors Some NSAIDs show anti-inflammatory and antiproliferative effects Independent of their COX activity. , 2001). A key question with respect to those additional activities Is whether or not concentrations of the respective compound at the presumed sites of actions is sufficient in order to add to the main mode of action, COX inhibition. NSAIDs as Transcriptional Modulating Drugs In addition to bioactive eicosanoids, the inflammatory response involves the sequential activation of various signaling pathways, including reactive oxygen intermediates, cytokines, growth factors, enzymes, 2 Cyclooxygenase Inhibition 41 receptors, and adhesion molecules.

Increased expression of most of these proteins is the result of enhanced gene transcription. Changes in gene transcription of proteins involved in inflammation are usually regulated by transcription factors such as modulators of activated T cells (NF-AT), nuclear factors (NF-KB), and activated protein (AP-1). Therefore, drugs able to Inhibit transcription of genes involved in the inflammatory process could be potent antiinflammatory agents. Thus among the most effective antiinflammatory drugs are the glucocorticoids, whose actions occur by inhibition of the transcription of several genes which are responsible for the induction of cytokines, chemoklnes and COX-2 in response to Inflammation.

The metabolic pathway of acetylsalicylic acid is shown in scheme 6. 5-8 g/day) for pain and inflammation and for antiplatelet therapy (75-100 mg/day). It is also available in rectal and topical formulations and as a soluble lysine derivative for intravenous or intramuscular application. Acetylsalicylic acid is often used in multi-drug preparations. The main side-effects are gastrointestinal disorders. , 1982). The lithium, magnesium, calcium, and aluminium salts of acetylsalicylic acid are used in some special preparations.

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