Comparative and Veterinary Pharmacology (eBook)

Preface 5
Contents 7
Contributors 9
Part I: Topics in Veterinary Pharmacology 11
Introduction 12
From Materia Medica to Veterinary Pharmacology and Therapeutics 12
Aims of This Volume and Rationale for Inclusion of the Chapters 16
References 26
Species Differences in Pharmacokinetics and Pharmacodynamics 27
Introduction 28
Diversity of Species and Breeds of Interest for Veterinary Medicine 29
Origin of Interspecies Differences in Modalities of Drug Administration 32
Origin of Interspecies Differences in Drug Disposition and Drug Action 34
Origin of Interspecies Differences in Dosage Regimens 38
Pour-on Formulations: Dermal or Oral Route of Administration? 40
Consequence of Coprophagia on Drug Disposition and Responses 41
Interspecies Differences in Drug Disposition in Relation to Digestive Tract Physiology 42
Species Variation in Drug Metabolism 45
Kidney Function and Urinary pH 48
Specificity in Drug Administration and Disposition in Poultry 49
Species Variability in Drug Administration and Disposition in Fish 51
Conclusions 53
References 53
Comparative and Veterinary Pharmacogenomics 57
Introduction 58
Drug Disposition 59
Oxidative Enzymes 59
Cytochrome P450 2D15 in Dogs 59
Cytochrome P450 2D in Rats 61
Cytochrome P450 2C41 in Dogs 61
Cytochrome P450 1A2 in Dogs 62
Cytochrome P450 2B11 in Dogs 63
Esterases in Horses and Rabbits 65
Conjugative Enzymes 67
N-acetyltransferase in Mice, Rats, Hamsters, Rabbits and Rhesus Macaques 67
UDP-Glucuronosyltransferase 1A in Rats 68
UDP-Glucuronosyltransferase 2B2 in Rats 69
Thiopurine Methyltransferase in Cats, Dogs and Mice 69
Transporters 70
P-glycoprotein in Dogs and Mice 70
MRP2 in Rats 72
Other 73
Albumin in Rats and Dogs 73
Arylhydrocarbon Receptor in Mice and Rats 73
Drug Effect 74
Malignant Hyperthermia in Pigs, Dogs, Cats and Horses 74
Warfarin Resistance in Rats 77
Future Directions 78
References 78
Drug Delivery Systems in Domestic Animal Species 86
Introduction to Veterinary Drug Delivery: Comparison with Drug Delivery in Human Medicine 87
Controlled-Release Principles in Veterinary Medicine 89
Exogenous Regulation: Devices and Formulations 90
Oral Formulations 90
Airway Delivery: Pulmonary and Nasal 93
Topical Formulations and Transdermal Patches 95
Intravaginal Delivery for Fertility Regulation 98
Intramammary Formulations for Ruminants 99
Ocular and Periodontal Adhesives 101
Sustained-Release Parenteral Veterinary Drug Delivery 102
Endogenous Regulation: The Role of Drug Transporters in Regulating Delivery 104
ABC Efflux Transporters in Veterinary Medicine 105
Potential Veterinary Drug Interactions Based on Transporters 107
Conclusions 110
References 111
Population Medicine and Control of Epidemics 120
Introduction 121
Helminth Control 121
Helminth Parasites of Ruminants 121
Helminth Parasites of Dogs and Cats 123
Gastro-Intestinal Nematodes 123
Cestodes 126
Heartworm 128
Anthelmintic Agents 129
Anthelmintic Resistance 129
Mastitis Control in Dairy Cows 131
Control of Respiratory Disease in Cattle and Swine 134
Conclusion 139
References 140
Interspecies Allometric Scaling 146
Introduction 147
History of Scaling 150
Linear ExtrapolationLinear extrapolation 151
Metabolic ScalingMetabolic scaling 151
Allometric ScalingAllometric scaling 153
Discussion and Conclusions 156
References 162
Pain and Analgesia in Domestic Animals 165
Introduction 166
Animal Pain 167
Significance of Pain Evaluation in Animals 167
Relevance to the Human Experience 168
Analgesic Factors 169
Analgesic Strategies and Techniques 170
Pain Perception in Animals 171
Recognition of Animal Pain 173
Laboratory Animals 173
Dogs and Cats 174
Horses and Other Equines 177
Cattle, Sheep, Goats and Camels 178
Birds 179
Other Non-mammalian Vertebrates 179
Analgesic Agents and Their Use in Domestic Animals 180
Local Anaesthetics 180
Opioids 182
Non-steroidal Anti-inflammatory Drugs 184
Alpha 2 Adrenergic Agonists 186
Tramadol 188
Treatment of Neuropathic Pain 188
Conclusions 189
References 189
New Technologies for Application to Veterinary Therapeutics 196
Introduction and Historical Background 197
Major Dynamics Affecting Veterinary Pharmacology 198
Technological Developments 200
Continued Advances in Computer Technology 202
Microfluidics 205
Nanotechnology 206
High-Throughput Screening 208
Increased Ability to Control and Target Drug Delivery 209
Increased Knowledge of Pharmacogenomics 210
Potential Impact on Veterinary Medicine 211
Conclusion 213
References 213
Part II: The Interface of Veterinary Pharmacology and Man 216
Genetically Modified Animals and Pharmacological Research 217
Introduction 218
The Potential of Detailed Animal Genomes 220
Use of Transgenic Mice to Reveal Drug Targets 221
The Development and Use of Transgenic Farm Animals 222
Farm Animal Pharming 223
Gene Therapy for Diseases of Companion and Farm Animals 224
Summary 226
References 226
Antimicrobial Drug Resistance 231
Introduction 232
Antimicrobial Mechanisms of Action 233
Resistance 237
Resistance Mechanisms 237
Defining the Term ``Resistance´´ 237
Monitoring Programmes: Points to Consider 241
Impact of Antibiotic Use on Resistance 243
Pharmacokinetic Considerations 245
General Considerations 245
Mutation Selection Window 248
Duration of Dosing 249
PK/PD is More Than MICs 251
Clinical Susceptibility Breakpoints 253
Tolerance Versus Resistance 254
New Approaches in Antimicrobial Therapy 259
Conclusions 261
References 262
Drug Residues 269
Introduction 270
The Food Safety Risk Analysis Framework 271
Risk Assessment 272
Hazard Identificationhazard identification 273
Hazard Characterisationhazard characterisation 273
Exposure Assessmentexposure assessment 275
Risk Characterisationrisk characterisation 277
Analysing for Residues of Veterinary Drugs in Depletion Studies 282
Good Practice in the Use of Veterinary Drugsgood practise in the use of veterinary drugs 282
Residues of Veterinary Drugs at Injection Sites 282
Risk Managementrisk management 284
Residues of Veterinary Drugs and Food Safety 284
Calculating a Withdrawal Periodwithdrawal period for Edible Tissues 284
Calculating a Withdrawal Periodwithdrawal period for Milk 285
Residues of Veterinary Drugs in International Trade 287
Estimating an Export Slaughter Interval 287
Risk Communicationrisk communication 289
Post-approval Monitoring 289
Residue Control Programmes 289
Non-regulatory Mechanisms for the Control of Drug Residuesnon-regulatory mechanisms for the control of drug residues 290
The Role of the Veterinary Pharmaceutical Industryveterinary pharmaceutical industry 290
The Roles of Producersproducers, Veterinariansveterinarians and Food Processorsfood processors 290
Perspectives and Future Challenges 291
References 293
Veterinary Medicines and the Environment 295
Introduction 296
Routes of Input to the Environment 296
Manufacturing 297
Livestock Treatment 297
Aquaculture 298
Fate and Behaviour 299
Sorption in Soil 299
Persistence in Soil 301
Transport in Soil Systems 301
Leaching to Groundwater 301
Runoff 302
Drain Flow 302
Surface Waters 303
Uptake Into Biota 303
Occurrence 304
Aquaculture 304
Livestock Treatments 304
Impacts of Veterinary Drugs in the Environment 306
Effects in Regulatory Studies 306
Chronic and Subtle Effects 308
Avermectins and Terrestrial and Aquatic Invertebrates 309
Antibiotics and Soil Microbes 310
Diclofenac and Vultures 311
Human Health Risks 311
Recommendations for Future Research 312
References 313
Veterinary Medicines and Competition Animals: The Question of Medication Versus Doping Control 319
Introduction 321
Rationale for Anti-doping Versus Medication Control 321
Medication Versus Doping Control: Progress Towards a General Policy Giving Priority to the Welfare and Safety of the Horse 322
Doping Agents and Doping Control Issues 323
Medication Issues and Medication Control 326
Analytical Method and Doping Testing 327
Blood Versus Urine Testing and the Rationale for Selecting a Matrix for Doping and Medication Control 328
Substances Requiring a Threshold 330
Testing Exposure and the End of a Zero Tolerance Approach for Medication Control 331
The Decision Making Process on No Significant Effect Levels: A Risk Analysis Integrated Approach 334
Risk Assessment 334
Exposure Assessment 336
Risk Characterisation 337
Risk Management 337
Risk Communication: Detection Times Versus Withdrawal Times 338
From a Detection Time to a Withdrawal Time 339
Conclusion 340
References 341
Index 344