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.
Sprache
Verlagsort
Verlagsgruppe
Illustrationen
53 s/w Abbildungen
XI, 167 p. 53 illus.
Dateigröße
ISBN-13
978-3-7091-9276-4 (9783709192764)
DOI
10.1007/978-3-7091-9276-4
Schweitzer Klassifikation
1 Principle considerations of drug actions and interactions.- 1.1 Introduction.- 1.2 Dose-response curves.- 1.3 Time course of effects.- 1.4 Phenomena and mechanisms: interactions between drugs - antagonism and synergism.- 2 Concepts and models of interactions - additivity and independence.- 2.1 Concept and phenomenon of additivity.- 2.2 Site-directed analysis.- 2.3 Concept of independence.- 2.4 Relationship between additivity and independence.- 2.5 Summary and conclusions.- 2.6 Tips and hints.- 3 Synergism/potentiation and antagonism - phenomena and mechanisms.- 3.1 The current dilemma.- 3.2 Towards a uniform characterization of synergism/potentiation and antagonism.- 3.3 Potentiation (synergism).- 3.4 Antagonism.- 3.5 Comparison of complex with simple interactions.- 3.6 Quantitative expression of combined effects.- 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.- 4.2 Fixed dose-ratio 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.- 6.2 Other studies.- 7 Combined-effect graph and other graphs.- 7.1 The construction of the combined-effect graph.- 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.- 8.2 Experimentalpharmacology.- 8.3 Clinical pharmacology - drug combinations.- 8.4 Chemotherapy of infections and tumors.- 8.5 Experimental and environmental toxicology.- 8.6 Epidemiology - risks.- 8.7 Herbicides.- 8.8 Conclusions and discussion.- 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.- 10.2 Evaluation of combined effects in the future.- Epilog.- Appendix A - Glossary of terms and abbreviations.- Appendix B - Guide to practical work: exercise examples.- References.
