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Selective Toxicity Adrien Albert

Selective Toxicity By Adrien Albert

Selective Toxicity by Adrien Albert


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Summary

This book is about selectively toxic agents. Selective toxicity covers an immense field: most of the drugs used for treating illness in man and his economic animals, as well as all of the fungicides, insecticides, and weed killers that are used in agriculture.

Selective Toxicity Summary

Selective Toxicity: The physico-chemical basis of therapy by Adrien Albert

This book is about selectively toxic agents. That is to say, it is about those substances that affect certain cells without harming others, even when they are close neighbours. Toxicity need not be fatal. It can be made easily reversible, as is the case with general anaesthetics. Selective toxicity covers an immense field: most of the drugs used for treating illness in man and his economic animals, as well as all of the fungicides, insecticides, and weed killers that are used in agriculture. Essentially, this book is a discussion of the physical and chemical means which contribute to selectivity, and this is the basis of molecular pharmacology. _Selective Toxicity began as a course of lectures that Professor F. G. Young encouraged me to give in University College London, in 1948 and again in 1949. The first edition appeared in 1951, as a very small book because little was then known about the factors that provide selectivity. Since those early days, the subject has undergone tremendous development. At first, industry was un receptive to the word 'toxicity', however qualified! Yet the market was being supplied with biologically powerful substances of which several had the potential to cause harm. This aspect was brought to light by two events of the early 1960s. The first of these was the discovery that a sedative, thalidomide, administered to expectant mothers, after what was then considered to be adequate testing, had caused permanent deformities in about 10000 children.

Table of Contents

One: Topics of General Interest.- 1 Selectivity in the service of man.- 1.0 What is Selectivity?.- 1.1 Beneficial results from the use of selectivity toxic agents.- 1.2 The physical basis of selectivity: the three principles.- Steps in the correlation of structure with biological action.- 2.0 The earliest correlations.- 2.1 The concept of receptors. The receptor as part of an enzyme, permease, or other protein.- 2.2 The receptor as part of a nucleic acid.- 2.3 The receptor as a coenzyme or other small molecule.- 2.4 Reversibility, and other aspects of receptors.- 2.5 How a small change in a molecule can lead to a large change in biological properties.- 2.6 Correlations: Todays perspective.- 3 Comparative distribution: the first principle of selectivity.- 3.0 Examples of selectivity through distribution.- 3.1 How drugs are absorbed, distributed, and eliminated.- 3.2 The permeability of natural membranes.- 3.3 The significance of partition coefficients.- 3.4 Mechanisms that produce loss. Storage and elimination.- 3.5 Metabolic change as an early step in excretion. Synergism and antagonism.- 3.6 Metabolic change as an early step in activation. Pro-drugs.- 3.7 Quantitative aspects of distribution. Pharmacokinetics. 97 Sustained release.- Sustained release.- 4 Comparative biochemistry: the second principle of selectivity.- 4.0 Nucleic acids.- 4.1 Proteins.- 4.2 Analogous enzymes and coenzymes.- 4.3 Nitrogen and phosphorus metabolism.- 4.4 Carbohydrate and lipid metabolism.- 4.5 The tricarboxylic acid cycle, and electron transport.- 4.6 Photosynthesis.- 4.7 Hormones and pheromones.- 4.8 Metabolism of foreign substances.- 4.9 Quantitative aspects of comparative biochemistry.- 5 Comparative cytology: the third principle of selectivity.- 5.0 The variations of cell architecture.- 5.1 Cytological aspects of cancer therapy.- 5.2 Cytological aspects of immunotherapy.- 5.3 The cell wall.- 5.4 Sub-cellular architecture.- 5.5 Viruses.- 6 Chemotherapy: history and principles.- 6.0 The early history of chemotherapy.- 6.1 Ehrlichs fundamental contributions.- 6.2 Chemotherapeutic drugs available before 1935. The chemotherapeutic index.- 6.3 1935 and afterwards.- 6.4 Parallel developments in crop-protecting agents: agrochemicals.- 6.5 Resistance to drugs and other agents.- 6.6 Therapeutic interference.- 7 Pharmacodynamics.- 7.0 Pharmacodynamics and chemotherapy compared.- 7.1 Early history of the use of synthesis to find new drugs.- 7.2 Some common molecular patterns in pharmacodynamic drugs.- 7.3 Simplification of the structure of natural products.- 7.4 Recognition of the importance of measurement.- 7.5 How agonists and antagonists act on receptors.- 7.6 The natural divisions of pharmacodynamics.- The forces available for binding an agent. Chemical bonds. Adsorption.- 8.0 Types of chemical bonds.- 8.1 Adsorption.- 8.2 Non-biological aspects of selectivity.- Two: Studies, in Depth, of Topics from Part One.- 9 Anti-metabolites: antagonistic analogues of coenzymes and enzymic substrates.- 9.0 Enzymes.- 9.1 Anti-metabolites (antagonistic analogues): definition, derivation, and mode of action.- 9.2 History of analogue antagonism prior to 1940.- 9.3 The folic acid antagonists.- 9.4 Other metabolite analogues of proven value in prophylaxis and therapy.- 9.5 Transition-state inhibitors.- 9.6 Sequential blocking.- 9.7 Analogues that form a covalent bond.- 9.8 Special relationships between agonists and antagonists.- 9.9 Pharmacogenetics.- 10 Ionization.- 10.0 The nature of ionization.- 10.1 The ionization constant (Ka).- 10.2 Differences in ionization that can bring about selectivity.- 10.3 Substances that are more biologically active when ionized.- 10.4 Substances that appear to be less active when ionized.- 10.5 Substances of which both ion and molecule play a part in the biological action.- 10.6 The ionization of receptors.- 10.7 Conclusions.- 11 Metal-binding substances.- 11.0 Metals in the living cell.- 11.1 Biochemical differences that can assist selectivity.- 11.2 The chemistry of chelation.- 11.3 Quantitative treatment of metal binding.- 11.4 Chemical differences that can assist selectivity.- 11.5 The various modes of biological action of chelating agents (an introduction).- 11.6 Diminution, by chelation, of the toxic effect of a metal.- 11.7 Augmentation, by chelation, of the toxic effect of a metal.- 11.8 The tetracyclines.- 11.9 Substances whose biological action is at least partly due to chelation.- 11.10 The special case of robust complexes.- 11.11 Fundamental considerations in designing new chelating agents. Promising avenues of application.- 12 Steric factors.- 12.0 Some fundamental considerations.- 12.1 Optical isomerism.- 12.2 Geometrical isomerism.- 12.3 Conformational behaviour.- 12.4 Catecholamine receptors.- 12.5 Acetylcholinesterase.- 12.6 Acetylcholine receptors.- 12.7 The GABA receptor and the benzodiazepines.- 12.8 Morphine and the opioid receptors.- 12.9 Psychotherapeutic agents.- 12.10 Conclusion.- 13 The covalent bond in selective toxicity.- 13.0 Arsenicals, antimonials, and mercurials.- 13.1 The penicillins.- 13.2 Cephalosporins. Other -lactam inhibitors of the formation of new cell walls.- 13.3 Organic phosphates and carbamates.- 13.4 Alkylating agents.- 13.5 Lethal synthesis.- 13.6 Miscellaneous examples.- 14 Surface chemistry. The modification of membranes by surface-active agents.- 14.0 Surface phenomena in vitro.- 14.1 Surface phenomena and drug action. Diuretics. Cardiac glycosides.- 14.2 Ionophores.- 14.3 The injury of membranes by biologically active agents.- 14.4 The preservation of membranes by biologically active agents.- 15 Biological activity unrelated to structure.- 15.0 General biological depressants (hypnotics, general anaesthetics, and volatile insecticides).- 15.1 Mitotic disorganizers.- 16 The perfection of a discovery.- 15.0 Multiple regression analysis.- 15.1 Alternative methods.- 15.2 Steric considerations.- 17 Some numerical assistance.- 17.0 Table: Calculation of percentage ionized, given pH and pKa.- 17.1 Table and discussion: Fragmental constants and partition coefficients.- 17.2 Table and discussion: Electronic effects in molecules (Hammett and Taft sigma values).- 17.3 Table and discussion: Nuclear magnetic resonance.- 17.4 Searching the literature.- References.- Formula index.

Additional information

NPB9780412260209
9780412260209
0412260204
Selective Toxicity: The physico-chemical basis of therapy by Adrien Albert
New
Paperback
Chapman and Hall
1985-01-17
750
N/A
Book picture is for illustrative purposes only, actual binding, cover or edition may vary.
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