Inhalt

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.