[Aspirin--the prodigious panacea? Molecular mechanisms of the action of acetylsalicylic acid in the organism].
Aspirin (acetylsalicylic acid) is a commonly used non-steroidal anti-inflammatory drug capable of acetylating proteins in the course of a simple, non-enzymatic chemical reaction. Its main physiological effect is inhibiting prostanoid synthesis. Cyclooxygenases, COX-1 and COX-2, are crucial in the metabolic pathway leading to the generation of prostanoids. Both enzymes are major cellular targets for aspirin. The physiological spectrum of the biological activity of the prostanoids is very broad, and underlies the high clinical effectiveness of aspirin as an anti-inflammatory, antipyretic, and analgesic drug. Apart from the inhibition of prostanoid synthesis aspirin shows a variety of pharmacological activities, including reduction of ATP storage pools, increased extracellular adenosine, lowered inducible nitric oxide synthase activity, modulation of mitogen-activated protein kinases, and the expression of a plethora of genes induced under conditions of cell stress via the regulation of transcription factor NFkappaB activity. Such multipotent action explains its wide use in clinical practice. Regardless of the accumulated evidence on the molecular mechanisms of aspirin's action, the rationale of the appropriate dosing and monitoring of aspirin therapy and prophylaxis remains obscure. Hence, an evaluation and reasonable weighing of the cost/benefit ratio of aspirin therapy in various diseases seems appropriate.
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Zakład Chemii Medycznej, Instytut Fizjologii i Biochemii, Uniwersytetu Medycznego, Łódz.
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D000700:Analgesics / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D004351:Drug Resistance; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000517:prevention & control; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D013927:Thrombosis / Q000188:drug therapy
D000700:Analgesics; D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D001241:Aspirin