Clinical Pharmacology (eBook)

Front Cover 1
Clinical Pharmacology 4
Copyright Page 5
Table of Contents 6
Introduction 10
Part 1: The Individual Factor in Drug Response 12
Chapter 1. Genetic and Environmental Factors Responsible for Interindividual Variations in Drug Response 14
INTRODUCTION 14
REFERENCES 23
Chapter 2. Interindividual Differences in Plasma Concentrations and Effect of the Adrenergic Beta-receptor Blocking Drug Alprenolol and its Metabolite 4-hydroxy-alprenolol in Man 24
VARIATION IN PLASMA CONCENTRATION OF ALPRENOLOL 24
VARIATION IN EFFECT AND RESPONSIVENESS TO ALPRENOLOL 27
CONTRIBUTION OF 4-HYDROXY-ALPRENOLOL TO ADRENERGIC BETA-RECEPTOR BLOCKADE OF ALPRENOLOL IN MAN 28
CONCLUSIONS 32
ACKNOWLEDGEMENTS 32
REFERENCES 32
Chapter 3. Interindividual Differences in Drug Response· Studies with Indomethacin and Oral Contraceptive Steroids 34
ABSTRACT 34
INTRODUCTION 34
MATERIALS AND METHODS 35
RESULTS 36
DISCUSSION 40
REFERENCES 40
Chapter 4. Pharmacogenetic Investigation of Amobarbital Disposition 42
ABSTRACT 42
CONCLUSIONS 50
REFERENCES 50
ACKNOWLEDGEMENT 51
Chapter 5. New Methods and Models for the Isoniazid Acetylation Polymorphism 52
OBSERVATIONS ON METABOLIC ACTIVATION OF CARCINOGENIC ARYLAMINES AND THE INH ACETYLATION POLYMORPHISM 52
HEAT STABILITY DIFFERENCES OF HUMAN LYMPHOCYTE PABA NAT FROM RAPID AND SLOW INH ACETYLATOR DONORS 55
POLYMORPHIC DRUG ACETYLATION IN INBRED MICE: DISSOCIATION OF SPONTANEOUS AND PROCAINAMIDE INDUCIBLE ANTI-NUCLEAR ANTIBODIES (ANA) IN GENETIC SLOW ACETYLATORS 56
REFERENCES 60
Chapter 6. Polymorphic Drug Acetylation and Systemic Lupus Erythematosus 62
HYDRALAZINE 62
ISONIAZID 62
PROCAINAMIDE 63
SPONTANEOUS SYSTEMIC LUPUS ERYTHEMATOSUS 65
REFERENCES 65
Chapter 7. Problems of Drugs Administration in the Neonatal Period 68
1- ABSORPTION 69
2- DRUG PLASMA PROTEINS BINDING AND DISTRIBUTION 70
3- METABOLIC DEGRADATION 71
4- RENAL EXCRETION 73
5- CONCLUSIONS 74
REFERENCES 74
Chapter 8. The Effect of Disease on the Response to Drugs 78
ABSORPTION 78
DISTRIBUTION 80
METABOLISM 81
RENAL ELIMINATION 84
CONCLUSIONS 86
REFERENCES 86
Part 2: Drug Utilization: Geographical Differences and Clinical Implications 88
Chapter 9. Drug Utilization - Geographical Differences and Clinical Implications 90
REFERENCES 92
Chapter 10. Methodologies and Approaches in Drug Utilisation Studies 94
ABSTRACT 94
INTRODUCTION 94
WHOIESALE DATA 94
HOSPITAL DATA 96
PRESCRIPTION DATA 96
QUESTIONNAIRES AND INTERVIEW DATA 99
ALL METHODOLOGIES USE EDP 100
MAIN APPROACHES 100
UTILISATION OF RESULTS 100
CONCLUSIONS 101
REFERENCES 101
Chapter 11. Drug Prescribing in Hospitals: An International Comparison 104
Drugs in Hospital 105
Adverse Effects of Drug Treatment 108
Drugs Prescribed on Discharge 108
Drugs Consumed before Admission 109
Discussion 109
REFERENCES 110
Chapter 12. Drug Utilization Strategies within Regional Programs on Drug Control and Evaluation 112
INTRODUCTION 112
FROM UNCONTROLLED MARKET TO DRUG SELECTION 112
FROM DRUG SELECTION TO MONITORING QUALITY OF THEIR USE 114
DISCUSSION AND CONCLUSION 121
REFERENCES 122
Chapter 13. Drug Utilization — Geographical Differences and Clinical Implications — Psychotropic Drugs 124
MATERIAL AND METHODS 124
RESULTS AND COMMENTS 126
REFERENCES 131
Chapter 14. Drug Utilization — Geographical Differences and Clinical Implications — Antidiabetic Drugs 134
MATERIAL AND METHODS 134
RESULTS AND DISCUSSION 135
ACKNOWLEDGEMENT 142
REFERENCES 142
Chapter 15. Antihypertensive Drugs 144
METHODS 144
RESULTS AND DISCUSSION 144
CONCLUSION 151
ACKNOWLEDGEMENTS 151
REFERENCES 152
Chapter 16. Digoxin - Compliance as a Factor in Drug Utilisation 154
Acknowledgement 162
References 162
Chapter 17. Drug Utilization, the Role and Effect of Clinical Pharmacology 164
ABSTRACT 164
INTRODUCTION 164
RESULTS 165
DISCUSSION 169
REFERENCES 170
Chapter 18. Controls of Drug Utilization: National and International Implications 172
BACKGROUND TO CONTROL OF DRUG USE 172
MEASURING THE IMPACT OF UTILIZATION CONTROLS 173
CONCLUSIONS 175
REFERENCES 178
Chapter 19. Drug Utilization — Geographical Differences and Clinical Implications 180
Part 3: Surveillance of Drugs in Therapeutic Use 182
Summary 183
Chapter 20. Surveillance of Drugs in Therapeutic Use 184
Chapter 21. Registered Release: a Method for Detecting Adverse Drug Reactions 186
EXISTING METHODS 186
REGISTERED OR MONITORED RELEASE 186
DISCUSSION 189
Chapter 22. Surveillance of Drugs in Therapeutic Use in Developing Countries 190
ABSTRACT 190
INTRODUCTION 190
DRUG SURVEILLANCE 191
AOVERSE DRUG REACTION MONITORING 196
CONCLUSION 197
REFERENCES 197
Chapter 23. Methods of " Audit" in Drug Use 200
ABSTRACT 200
INTRODUCTION 200
CONCLUSION 205
ACKNOWLEDGMENTS 206
REFERENCES 206
Chapter 24. The Value and Limitations of Patient Registers in Drug Surveillance 208
Introduction 208
Registers, Classification and Coding 208
Patient Register 208
Mortality Register 210
Malformation Register and Medical Registration of Births 211
Cancer Register 211
Concluding Remarks 212
REFERENCES 212
Chapter 25. Experiences of the Boston Collaborative Drug Surveillance Program 214
1. Descriptive papers 214
2. Patient factors related to acute toxicity 215
3. Drug interactions 216
4. Event analysis 216
5. Other papers on acute drug effects 216
6. Long-term toxicity 216
Part 4: New Development in Antiarrhythmic Drugs 220
Chapter 26. Relevance of "in Vitro" Electrophysiologic Effects of Antiarrhythmic Drugs to their Efficacy under "in vivo" Conditions 222
SUMMARY 228
REFERENCES 229
Chapter 27. Arrhythmias Caused by Cardiac Glycosides 232
ABSTRACT 232
INTRODUCTION 232
TOXICITY IN DIFFERENT TISSUES 233
CHANGES IN AUTOMATICITY VERSUS REPETITIVE ACTIVITY 233
THE MECHANISM OF REPETITIVE ACTIVITY 234
CHANGES IN AUTOMATIC DISCHARGE 236
THE POISONING OF THE SODIUM-POTASSIUM PUMP 237
THE MECHANISM OF TRANSIENT DEPOLARIZATION 237
DIGITALIS TOXICITY IN THE SINUS NODE 238
AGENTS MODIFYING DIGITALIS TOXICITY 238
THE THERAPEUTIC EFFECT OF POTASSIUM 239
CONCLUSIONS 239
ACKNOWLEDGMENTS 240
REFERENCES 240
Chapter 28. From Experiment to Therapeutic Application in the Field of Antiarrhythmics 244
ABSTRACT 244
INTRODUCTION 244
PHARMACOLOGICAL RESULTS 244
CLINICAL RESULTS 249
REFERENCES 250
Chapter 29. Clinical use of Antiarrhythmic Drugs. The Relevance of Experimental Data 252
REFERENCES 255
Chapter 30. New Antiarrhythmics. The need for bridging the gap between the pharmacologist and the clinician 256
REFERENCES 262
Chapter 31. Theoretical Considerations Concerning Drug Treatment of Dysrhythmias due to Coronary Insufficiency 264
SUMMARY 280
REFERENCES 281
Index 284