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Comparison of Oral Non-Steroidal Anti-Inflammatory Drugs in Cautery Dehorned Calves" (2015)

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Comparison of Oral Non-Steroidal Anti-Inflammatory Drugs in Cautery Dehorned Calves Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2015 Comparison of oral non-steroidal anti- inflammatory drugs in cautery dehorned calves Matthew Lloyd Stock Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Pharmacology Commons, and the Veterinary Medicine Commons Recommended Citation Stock, Matthew Lloyd, "Comparison of oral non-steroidal anti-inflammatory drugs in cautery dehorned calves" (2015). Graduate Theses and Dissertations. 14735. https://lib.dr.iastate.edu/etd/14735 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Comparison of oral non-steroidal anti-inflammatory drugs in cautery dehorned calves by Matthew Lloyd Stock A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Biomedical Sciences (Pharmacology) Program of Study Committee: Johann F. Coetzee, Major Professor Jesse P. Goff Walter H. Hsu Douglas E. Jones Michael J. Kimber Suzanne T. Millman Iowa State University Ames, Iowa 2015 Copyright © Matthew Lloyd Stock, 2015. All rights reserved. ii DEDICATION To my parents who told me to never stop learning and always work hard. To my brother and his wife, Cam and Veronika, who remind me every day to be better and that perseverance has its rewards. To my wife, Laura, who always anchored me when adrift. iii TABLE OF CONTENTS Page NOMENCLATURE ................................................................................................. v ABSTRACT. ............................................................................................................. vii CHAPTER 1 GENERAL INTRODUCTION .................................................... 1 Dissertation organization ................................................................................... 1 Introduction ........................................................................................................ 2 References ......................................................................................................... 7 CHAPTER 2 LITERATURE REVIEW ............................................................ 9 Abstract ......................................................................................................... 9 Literature Review ................................................................................................ 10 References ......................................................................................................... 43 CHAPTER 3 PHARMACOKINETICS OF FIROCOXIB IN PREWEANED CALVES AFTER ORAL AND INTRAVENEOUS ADMINISTRATION ............................................................................................. 81 Abstract ......................................................................................................... 81 Introduction ......................................................................................................... 82 Materials and Methods ......................................................................................... 84 Results ......................................................................................................... 90 Discussion ......................................................................................................... 91 Acknowledgements .............................................................................................. 96 References ......................................................................................................... 96 CHAPTER 4 THE EFFECTS OF FIROCOXIB ON CAUTERY DISBUDDING PAIN AND STRESS RESPONSES IN PREWEANED DAIRY CALVES ................................................................................................... 105 Abstract ......................................................................................................... 105 Introduction ......................................................................................................... 106 Materials and Methods ......................................................................................... 109 Results ......................................................................................................... 119 Discussion ......................................................................................................... 122 Conclusion ......................................................................................................... 128 Acknowledgments................................................................................................ 129 References ......................................................................................................... 129 iv CHAPTER 5 IMPACT OF CARPROFEN ADMINISTRATION ON STRESS AND NOCICEPTION RESPONSES OF CALVES TO CAUTERY DEHORNING .................................................................................... 141 Abstract ......................................................................................................... 141 Introduction ......................................................................................................... 143 Materials and Methods ......................................................................................... 144 Results and Discussion ........................................................................................ 156 Conclusion ......................................................................................................... 169 Acknowledgments................................................................................................ 169 References ......................................................................................................... 169 CHAPTER 6 A FIELD TRIAL COMPARING FOUR ORAL NON-STEROIDAL ANTI-INFLAMMATORY DRUGS ON CONTROLLING CAUTERY DEHORNING PAIN AND STRESS IN CALVES ......................................................................................................... 186 Abstract ......................................................................................................... 186 Introduction ......................................................................................................... 188 Materials and Methods ......................................................................................... 189 Results and Discussion ....................................................................................... 197 Conclusion ......................................................................................................... 207 Acknowledgments .............................................................................................. 207 Reference ......................................................................................................... 208 CHAPTER 7 DERIVATION OF A PAIN-STRESS INDEX ........................... 218 Introduction ......................................................................................................... 218 Methods ......................................................................................................... 218 Results and Discussion ....................................................................................... 219 References ......................................................................................................... 220 CHAPTER 8 GENERAL CONCLUSIONS ...................................................... 223 ACKNOWLEDGMENTS ....................................................................................... 231 v NOMENCLATURE A Y-intercept for the distribution phase Α distribution slope ALP alkaline phosphatase AST aspartate aminotransferase AUC area under the curve extrapolated to infinity B Y-intercept for the elimination phase Β elimination slope BUN blood urea nitrogen Cmax maximum plasma concentration CL plasma clearance CL/F plasma clearance per bioavailability COX cyclooxygenase F bioavailability GGT γ-glutamyltransferase IC50 concentration producing 50% of the maximum inhibition effect IC80 concentration producing 80% of the maximum inhibition effect K01 absorption constant for central compartment K10 elimination constant for central compartment K12 intercompartmental distribution rate constant from central to peripheral compartment vi K21 intercompartmental redistribution rate constant from peripheral to central compartment NSAID: non-steroidal anti-inflammatory drug PK/PD Pharmacokinetic / Pharmacodynamic PSI Pain-Stress Index SEM standard error of the mean T1/2 K10 elimination half-life T1/2α distribution half-life T1/2β terminal half-life Tmax time to maximum plasma concentration Vss volume of distribution in a steady state Vc volume of distribution of the central compartment V/F volume of distribution per bioavailability Varea volume of distribution during the elimination phase vii ABSTRACT Dehorning is a commonly performed husbandry procedure in cattle to limit injury and conform to modern facility design. Prior research provides evidence that dehorning results in increased nociception and stress through changes in behavioral, neuroendocrine, and physiological responses. Alterations in these actions allow investigators
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