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Informationen zum Autor ZAHER A. RADI is a Research Fellow and Toxicologic Anatomic Pathologist in Drug Safety R&D at Pfizer Worldwide Research & Development. He has published over fifty-five research papers and review articles, in addition to book chapters and numerous abstracts and presentations. Klappentext The first thorough review of cyclooxygenase inhibitors, including their toxicity mechanisms and toxicopathological risksCyclooxygenases (COXs) are enzymes responsible for the formation of an important class of biological mediators called prostanoids. Prostanoids such as prostaglandins mediate inflammatory and anaphylactic reactions. For those suffering from inflammation and pain, the pharmacological inhibition of COXs, with non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, can provide relief. Yet the use of NSAIDs can trigger toxicological effects as well, leading to potential health risks.Comparative Pathophysiology and Toxicology of Cyclooxygenases provides a comprehensive overview of how COX inhibitors affect various bodily systems, specifically the toxicity mechanisms triggered when the COX enzyme is inhibited. The book provides an introduction to the discovery of cyclooxygenases, their use as therapeutic agents, as well as an historical perspective. Shedding light on the differences in expression, pathophysiology, and toxicology of COX inhibitors across species, the book offers a systematic examination of the effects and pathophysiology of COX inhibitors and their mechanisms of toxicity, beginning with the GI tract. Subsequent chapters cover:* The pathophysiology of COX inhibition on bone, tendon, and ligament healing* COX inhibitors and renal system pathophysiology and mechanisms of toxicity* The pathophysiologic role of COX inhibition in the ocular system* COX inhibition and the respiratory and cardiovascular systemsThe book also sheds light on the latest research devoted to developing COX inhibitors with no adverse side-effects. The first book to offer a thorough comparative look at the toxicological effects of COX inhibitors throughout the body, this invaluable resource will help advance the research and development of safer and more effective COX drugs. Zusammenfassung The first thorough review of cyclooxygenase inhibitors, including their toxicity mechanisms and toxicopathological risks Cyclooxygenases (COXs) are enzymes responsible for the formation of an important class of biological mediators called prostanoids. Inhaltsverzeichnis PREFACE xi INTRODUCTION: DISCOVERY OF CYCLOOXYGENASES AND HISTORICAL PERSPECTIVE 1 Aspirin 1 Prostaglandins 2 Cyclooxygenases 4 COX-2 Selective NSAIDs 7 References 8 CHAPTER 1 GASTROINTESTINAL TRACT 11 Introduction 11 Comparative COX-1 and COX-2 Expression in the GI Tract 13 Effects of ns-NSAIDs on the GI Tract 15 Effects of Arylpropionic Acid ns-NSAIDs on the GI Tract 17 Effects of Enolic Acid (Oxicam) ns-NSAIDs on the GI Tract 22 Effects of Acetic Acid Derivative ns-NSAIDs on the GI Tract 23 Effects of Aminonicotinic Acid Derivative ns-NSAIDs on the GI Tract 26 Effects of Pyrazolone Derivative ns-NSAIDs on the GI Tract 27 Effects of Salicylic Acid Derivative ns-NSAIDs on the GI Tract 28 Effects of Anthranilic Acid Derivative ns-NSAIDs on the GI Tract 30 Effects of COX-1 Inhibitors on the GI Tract 30 Effects of COX-2 s-NSAIDs on the GI Tract 31 Pathophysiology and Mechanisms of NSAID-Associated GI Toxicity 38 Role of Cyclooxygenase Potency 39 Species Differences in NSAID-Associated Susceptibility to GI Injury 39 GI Anatomical Differences 40 Enterohepatic Recirculation and NSAID Toxicity 41 Role of Xenobiotic Glucuronidation 42 Aging and Stress and NSAID GI Effects 43 Disruption of GI Physiologic...
