Comparison of the Effects of Deracoxib, Buffered Aspirin, and Placebo on the Gastric Mucosa of Healthy Dogs

...........................................................................................ii ACKNOWLEDGEMENTS........................................................................iv DECLARATION OF WORK PERFORMED....................................................v TABLE OF CONTENTS...........................................................................vi LIST OF TABLES AND FIGURES............................................................viii LIST OF ABBREVIATIONS......................................................................ix INTRODUCTION....................................................................................1 CHAPTER I: Literature Review A. Anatomy and physiology of gastroprotection........................................3 Gastric function......................................................................3 Gastric microanatomy..............................................................3 Gastric mucosal defense...........................................................4 B. Gastric Ulceration........................................................................8 Ulcer development and healing...................................................8 Gastric ulceration in canine patients............................................11 Helicobacter spp. induced gastric injury.......................................11 Drug induced gastric injury......................................................12 Studies demonstrating gastric injury due to corticosteroid use or concurrent corticosteroid and non-steroidal anti-inflammatory drug use in dogs..................................................................................15 C. Gastrointestinal injury, non-steroidal anti-inflammatory drugs and cyclooxygenase.............................................................................17 Cyclooxygenase 1 and 2.........................................................17 Studies demonstrating cyclooxygenase activity in dogs, cats and horses...............................................................................18 Aspirin as the prototypical cyclooxygenase-1 inhibitor.....................20 Studies utilizing aspirin-induced gastric injury in dogs.....................22 Cyclooxygenase-2 selective inhibitors.........................................24 Studies evaluating cyclooxygenase-2 preferential inhibitors in dogs ....26 Inconsistencies in the cyclooxygenase-1 and 2 theory.........................28 D. Deracoxib................................................................................30 Structure and function............................................................30 Deracoxib: efficacy and safety studies.........................................31 CHAPTER II: Comparison of the Effects of Deracoxib, Buffered Aspirin, and Placebo on the Gastric Mucosa of Healthy Dogs. A. Introduction.............................................................................36 B. Materials and Methods................................................................38 C. Results...................................................................................42 D. Discussion..............................................................................45 CHAPTER III: Conclusions.......................................................................51 FOOTNOTES.......................................................................................52 REFERENCES......................................................................................53