General pharmacology
Author(s)
Bibliographic Information
General pharmacology
（Handbuch der experimentellen Pharmakologie / hrsg. von A. Heffter, Ergänzungswerk Bd.4）
Springer, 1970
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Note
Reprint. Originally publised: Berlin : J. Springer, 1937
2nd reprint, 1973
Description and Table of Contents
Description
The author's general aim has been to survey as wide a field of evidence as possible and this had involved excursions into subjects of which he has little first hand knowledge. This width of range also has necessitated a somewhat arbitrary selection of evidence and has prevented full discussion of any indi- vidual problem. The author trusts that he has not misrepresented anyone's results or opinions, and if this has occurred, he can only plead in excuse the peculiar difficulty of giving a brief and yet accurate account of evidence of such a wide variety. The diagrams reproduced in the article have all been redrawn and in many cases the original figures or diagrams have been modified as, for instance, by recalculating dosage on the logarithmic scale. The original authors therefore have no direct responsibility for the diagrams in their present form. The author desires to thank Messrs Arnold and Co. for permitting the repro- duction of Figs. 9 and 23 from similar figures which appeared in his book "The Mode of Action of Drugs on Cells"; portions of other figures from this book also have been reproduced in modified form. The author also desires to thank Dr. J. M.
ROBSON for help in correction of the proofs. Edinburgh, July, 1937. A. J. CLARK. Contents.
Table of Contents
- 1: Methods of General Pharmacology.- General Considerations p. 4. - Selection of Material p. 5. - Employment of Physico-chemical Methods p. 5. - The Mathematical Interpretation of Biological Data p. 6. - Favourable Factors in Pharmacological Measurements p. 7. - Curves Relating Exposure to Drugs with Biological Effect p. 7. - Classes of Curves p. 8. - Discussion p. 9.- 2: The Cell as a Physico-chemical System.- The Structure of Protoplasm p. 10. - The Cell Surface p. 12. - Cell Permeability p. 12. - Structure of Plasmatic Membrane p. 14. - Cell Organisation p. 15.- 3: General Characteristics of the Cell-Drug System.- Dimensions of Molecules and Cells p. 17. - The Number of Molecules in Single Cells p. 19. - The Number of Enzyme Molecules per Cell p. 19. - Lethal Doses of Drugs per Cell p. 20. - Effective Doses of Drugs per Cell p. 21. - Minimum Active Doses of Drugs per Organism p. 22. - Minimum Active Dilutions of Drugs p. 22. - Intracellular Administration of Drugs p. 23. - Types of Action of Drugs on Cells p. 25. - Discussion p. 25.- 4: Reactions between Drugs and Active Proteins.- Symplex Compounds p. 26. - Combination of Haemoglobin with Oxygen and Carbon Monoxide p. 27. - Antagonism of Oxygen and Carbon Monoxide p. 29. - Discussion p. 30.- 5: The Action of Drugs on Catalysts and Enzymes.- Poisoning of Inorganic Catalysts p. 31. - General Characters of Enzymes p. 33. - Enzyme Activity p. 34. - General Characters of the Poisoning of Enzymes p. 34. - Diphasic Actions of Enzyme Poisons p. 36. - The Rate of Action of Enzyme Poisons p. 37. - Relation between Concentration of Poison and Inhibitien of Enzyme p. 37. - Discussion p. 40.- 6: Action of Heavy Metals on Enzymes in vitro and in vivo.- Action of Heavy Metals on Saccharase p. 40. - Concentration-action Relations of Heavy Metals and Enzymes p. 42. - The Action of Metals on Living Cells p. 44. - Relation between Metal Concentration and Action on Cells p. 44. - Minimum Lethal Concentrations of Heavy Metals p. 44. - Relative Toxicity of Metals p. 46. - Course of Reaction between Metals and Cells p. 47. - Diphasic Actions of Metals on Cells p. 48. - Discussion p. 49.- 7: Action of Various Enzyme Poisons in vitro and in vivo.- The Action of Dyes on Enzymes p. 50. - Action of Quinine on Enzymes p. 51. - Action of Quinine on Cells p. 52. - Action of Cyanide on Enzymes and Cells p. 52. - Diphasic Actions of Cyanide p. 55. - Phenol Compounds p. 55. - The Action of Narcotics p. 56. - Action of Narcotics on Enzymes p. 56. - Action of Narcotics on Cells p. 59. - Theories of Narcotic Action p. 60. - Discussion p. 61.- 8: Concentration-action Relations I.- (1) Classification of Concentration-action Curves.- Relations Depending on Mass-action p. 63. - All-or-None Effects p. 64.- (2) Concentration-action Relations Attributable to Mass-action Laws.- The Mode of Action of Acetylcholine p. 66. - Amount of Acetylcholine Acting on Cells p. 69. - Individual Variation p. 70. - Site of Action of Acetylcholine p. 70. - Influence of Temperature on Acetylcholine Response p. 72. - Specificity of Acetylcholine Action p. 72. - Possible Nature of Acetylcholine Receptors p. 73. - Acetylcholine Esterase p. 74. - Concentration-action Relations of Adrenaline p. 74. - Dosage of Adrenaline p. 75. - Concentration-action Relations Found with Various Hormones p. 76. - Insulin p. 76. - Thyroxin p. 77. - Posterior Pituitary Principles p. 77. - Sex Hormones p. 77. - Various Alkaloids p. 78. - Nicotine p. 78. - Physostigmine p. 79. - Other Alkaloids p. 79.- 9: Concentration-action Relations II.- (3) Linear Relations
- Action of Narcotics.- (4) All-or-None Responses.- Instrumental Errors p. 83. - Distortion by the Cell of some Chemical Relation p. 83. - Obligatory All-or-None effects p. 84. - All-or-None Cellular Responses p. 85. - Concentration-action Curves with Guinea Pig's Uterus p. 86. - Drugs Producing All-or-None Effects p. 87. - Discussion p. 89.- 10: Quantitative Pharmacology and the Theory of Humoral Transmission.- p. 90. - Quantitative Data p. 91. - Rate of Action p. 92. - Concentration-action Relations p. 93. - Specific Antagonisms p. 95. - Discussion p. 96.- 11: Kinetics of Drug Action.- Sources of Error in Kinetic Measurements.- (1) Kinetics of Reactions in Heterogenous Systems.- (2) Kinetics of Cell Reaction.- Delays in Drug Action Due to Diffusion to Cell Surface p. 98. - Penetration of Cells p. 100. - Delay in Biological Response p. 102.- (3) Maximum Rate of Drug Action.- 12: The Rate of Action of Drugs on Cells.- (1) Curves Relating Time and Graded Action.- The Shapes of Time-action Curves p. 107.- (2) Curves Relating Time and All-or-None Effects.- Kinetics of Protein Precipitation p.110. - Precipitation of Protein by Phenol p. 111.- (3) Time Action Curves as Expressions of Variation.- Calculation of Time-action Curves p. 114. - Time Relations of Toxic Action of Copper on Algae p. 115.- (4) Implications of Monomolecular Theory.- Quantitative Measurements of Drug Uptake p. 118. - Drug Actions as Chain Processes p. 119.- (5) Mortality Curves.- (6) Action of Radiations.- Discussion p. 122.- 13: Time-concentrations Curves.- (1) Form of Curves and Possible Significance.- (2) Time-concentration Curves of Nerve Paralysis.- (3) Time-concentration Curves with Various Drugs.- (4) Time-concentration Relations in Disinfection.- (5) Toxic Vapours.- Deviation of Narcotics p. 139. - Time-concentration Curves of Anaesthetics p. 140. - Time-concentration Curves of Hydrocyanic Acid p. 141. - Irritant Gases p. 141. - Discussion p. 142.- 14: Individual Variation of Response to Drugs.- Methods of Measurement of Individual Variation p. 142. - Skew Variation in Biological Material p. 144. - Normal Equivalent Deviation p. 146. - Errors in Construction of Characteristic Curves p. 148. - Uniformity of Population p. 148. - Errors of Sampling p. 149.- 15: Relation between Various Types of Curves Expressing Response of Cells to Drugs.- (1) Concentration-action Curves as Expressions of Individual Variation.- Virus Infections p. 151. - Discussion p. 153.- (2) Characteristic Curves as Expressions of Chemical Processes.- (3) Correlation between Concentration-action Curves and Characteristic Curves.- Examples of Skewed Characteristic Curves p. 156. - All-or-None Effects p. 161. - Discussion p. 162.- (4) Drug Responses and Individual Variation.- 16: Special Problems Relating to Variation of Populations.- Uniformity of Population p. 165. - Influence of Sex, Age and Weight on Response to Drugs p. 166. - Seasonal Variations in Sensitivity p. 169. - Variation in Human Populations p. 169. - Hypersensitivity and Idiosyncrasy p. 171. - Margin of Safety with Massive Doses p. 173. - Disinfection, etc. p. 175.- 17: Quantitative Aspects of Drug Antagonism and of Drug Synergism.- p. 176. - The antagonism of cyanides by narcotics p. 177. - Selective Antagonisms with Haemoglobin p. 180. - Antagonism in Enzyme Poisoning p. 181. - Acetyl Choline-Atropine Antagonism p. 184. - AdrenalineErgotoxine Antagonism p. 186. - Synergists of Adrenaline p. 187. - Comparison of Antagonisms found with Enzymes and with Hormones p. 188.- 18: Qualitative Aspects of Drug Antagonism.- p. 190. - Antagonism of Adrenaline p. 191. - Chemical Structure of Acetyl Choline Antagonists p. 191. - Acetyl Choline Antagonism in Different Tissues p. 193. - Analysis of Drug Actions by Drug Antagonisms p. 196. - General Theory of Drug Antagonisms p. 198.- 19: Alternative Theories of Drug Action.- Monomolecular Theory p. 199. - The Potential Theory of Drug Action p. 200. - Phasic response of cells p. 201. - Arndt-Schulz Law p. 204. - Drug Responses as Expression of Individual Variation p. 204. - Weber-Fechner Law p. 205. - Discussion p. 205.- 20: Quantitative Aspects of Chemotherapy.- p. 206. - Action of Metallic Compounds p. 207. - Action of Non-metallic Compounds p. 212. - Drug-resistance p. 213. - Discussion p. 214.- 21: Conclusion.- Index of Authors.- Index of Subjects.
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