Combined Effects of Drugs and Toxic Agents
Modern Evaluation in Theory and Practice
(Sprache: Englisch)
Scientists struggling with the pharmaco- and toxicodynamic interactions of drugs and chemicals will find this book a valuable reference to the relevant theoretical background of this complex field and an indispensible guide to practical, analytical...
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Klappentext zu „Combined Effects of Drugs and Toxic Agents “
Scientists struggling with the pharmaco- and toxicodynamic interactions of drugs and chemicals will find this book a valuable reference to the relevant theoretical background of this complex field and an indispensible guide to practical, analytical procedures for evaluation of experimental data.A new, straightforward mechanistically based analysis of observed combination effects is backed up by numerous examples as well as by computer-assisted plotting and curve fitting - using popular graphical software systems. The reader thus can gain not only a modern understanding of this complex area but proceed directly to the evaluation of his own dose-response experiments with respect to independent actions, and additive interactions, where appropriate. The meanings of terms and acronyms in the literature, most of them used in this book also, are elucidated by a comprehensive glossary.This book represents a modern, theoretical and practical guide for all scientists dealing with this controversial and complex area of the action and interaction of drugs and chemicals.
Inhaltsverzeichnis zu „Combined Effects of Drugs and Toxic Agents “
1 Principle considerations of drug actions and interactions1.1 Introduction
1.2 Dose-response curves
1.2.1 The parameters of dose-response curves
1.2.2 Models and curve-fitting
1.2.3 Comparison of curves
1.3 Time course of effects
1.4 Phenomena and mechanisms: interactions between drugs - antagonism and synergism
1.4.1 Simple interactions
1.4.2 Complex interactions
- Phenomena
- Mechanisms of interaction
2 Concepts and models of interactions - additivity and independence
2.1 Concept and phenomenon of additivity
2.1.1 Historical perspective
2.1.2 The isobologram
2.1.3 Dose-response curves
2.1.4 Mechanism underlying additivity
2.1.5 Additive dose-response curves
2.1.6 Comparison of effect-additive with dose-additive combinations
2.2 Site-directed analysis
2.3 Concept of independence
2.3.1 Calculation of independent effects
2.3.2 Independent dose-response curves
2.4 Relationship between additivity and independence
2.4.1 Dose-additive and independent combinations
2.4.2 Effect-additive and independent combinations
2.5 Summary and conclusions
2.6 Tips and hints
3 Synergism/potentiation and antagonism - phenomena and mechanisms
3.1 The current dilemma
3.1.1 The "effect approach"
3.1.2 The "dose approach" (evaluation of isobolograms)
3.2 Towards a uniform characterization of synergism/potentiation and antagonism
3.3 Potentiation (synergism)
3.3.1 Net effects
3.3.2 Total effects
3.4 Antagonism
3.4.1 The "effect approach"
3.4.2 The "dose approach" (evaluation of isobolograms)
3.5 Comparison of complex with simple interactions
3.6 Quantitative expression of combined effects
3.6.1 The combination index (CI)
3.6.2 Comparison of CI and combined-effect graph
3.7 Suggestions for quantitation of combined effects
3.8 Tips and hints
4 Evaluation by dose-response curves
4.1 New methodological approach: fixed-dose studies
4.1.1 Construction of experimental and theoretical dose-response curves
4.1.2 Statistical comparison of
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observed and expected response 58 Chi-square goodness-of-fit test 58 - F-test
4.1.3 Expression of results and examples
4.2 Fixed dose-ratio combinations
4.2.1 Dose-additive interactions
4.2.2 Independent actions
4.2.3 Multiple combinations
4.3 Tips and hints
5 Evaluation by time-course studies
5.1 Time course of independent actions
5.2 Dose-additive time course
5.3 Statistical comparison of observed and expected time course
5.4 Time-course studies with log response scale
5.5 Comparison of time-course studies and dose-response studies
5.6 Conclusions
6 Single-dose and other studies
6.1 Single-dose studies
6.1.1 Comparison with effect-additive
6.1.2 Comparison with independence
6.1.3 Comparison with additivity
6.1.4 Tips and hints
6.2 Other studies
7 Combined-effect graph and other graphs
7.1 The construction of the combined-effect graph
7.1.1 Percent of maximum response
7.1.2 Percent of control response
7.2 Comparison of observed with independent effects
7.3 Yonetani-Theorell plot for enzyme inhibitors
7.4 Tips and hints
8 Applications of the new approach and observations
8.1 Biochemistry and physiology/pathophysiology
8.1.1 Dual inhibition of enzyme activity
8.1.2 Physiology
8.1.3 Pathophysiology
8.2 Experimental pharmacology
8.2.1 Dose-response studies: site of action
8.2.2 Extent of enhancement
8.2.3 "Unspecifically" acting agents in combination
8.3 Clinical pharmacology - drug combinations
8.3.1 Dose-response studies
8.3.2 Drug mixtures: dose-response studies
8.3.3 Drug mixtures: time-course studies
8.3.4 Single-dose studies
8.4 Chemotherapy of infections and tumors
8.4.1 Therapy of infections
8.4.2 Tumortherapy
8.5 Experimental and environmental toxicology
8.5.1 Examples of toxic interactions
8.6 Epidemiology - risks
8.7 Herbicides
8.8 Conclusions and discussion
8.8.1 Methods
8.8.2 Comparison with model interactions
9 A new and critical view of isobolograms
9.1 Inappropriate conclusions
9.2 Pitfalls
10 Comparison of the new with the conventional approach
10.1 Experimental dose-response curves and isobolograms
10.1.1 Concurring interpretation
10.1.2 Different and controversial interpretation
- Envelope of additivity in isobolograms
- Nonconsideration and incorrect calculation of independence
10.2 Evaluation of combined effects in the future
- Epilog
- Appendix A - Glossary of terms and abbreviations
- Appendix B - Guide to practical work: exercise examples
- References
4.1.3 Expression of results and examples
4.2 Fixed dose-ratio combinations
4.2.1 Dose-additive interactions
4.2.2 Independent actions
4.2.3 Multiple combinations
4.3 Tips and hints
5 Evaluation by time-course studies
5.1 Time course of independent actions
5.2 Dose-additive time course
5.3 Statistical comparison of observed and expected time course
5.4 Time-course studies with log response scale
5.5 Comparison of time-course studies and dose-response studies
5.6 Conclusions
6 Single-dose and other studies
6.1 Single-dose studies
6.1.1 Comparison with effect-additive
6.1.2 Comparison with independence
6.1.3 Comparison with additivity
6.1.4 Tips and hints
6.2 Other studies
7 Combined-effect graph and other graphs
7.1 The construction of the combined-effect graph
7.1.1 Percent of maximum response
7.1.2 Percent of control response
7.2 Comparison of observed with independent effects
7.3 Yonetani-Theorell plot for enzyme inhibitors
7.4 Tips and hints
8 Applications of the new approach and observations
8.1 Biochemistry and physiology/pathophysiology
8.1.1 Dual inhibition of enzyme activity
8.1.2 Physiology
8.1.3 Pathophysiology
8.2 Experimental pharmacology
8.2.1 Dose-response studies: site of action
8.2.2 Extent of enhancement
8.2.3 "Unspecifically" acting agents in combination
8.3 Clinical pharmacology - drug combinations
8.3.1 Dose-response studies
8.3.2 Drug mixtures: dose-response studies
8.3.3 Drug mixtures: time-course studies
8.3.4 Single-dose studies
8.4 Chemotherapy of infections and tumors
8.4.1 Therapy of infections
8.4.2 Tumortherapy
8.5 Experimental and environmental toxicology
8.5.1 Examples of toxic interactions
8.6 Epidemiology - risks
8.7 Herbicides
8.8 Conclusions and discussion
8.8.1 Methods
8.8.2 Comparison with model interactions
9 A new and critical view of isobolograms
9.1 Inappropriate conclusions
9.2 Pitfalls
10 Comparison of the new with the conventional approach
10.1 Experimental dose-response curves and isobolograms
10.1.1 Concurring interpretation
10.1.2 Different and controversial interpretation
- Envelope of additivity in isobolograms
- Nonconsideration and incorrect calculation of independence
10.2 Evaluation of combined effects in the future
- Epilog
- Appendix A - Glossary of terms and abbreviations
- Appendix B - Guide to practical work: exercise examples
- References
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Bibliographische Angaben
- Autor: Gerald Pöch
- 1993, XI, 167 Seiten, Masse: 24,4 cm, Kartoniert (TB), Englisch
- Verlag: Springer
- ISBN-10: 3211824340
- ISBN-13: 9783211824344
Sprache:
Englisch
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