Drugs and Enzymes (eBook)

Front Cover 1
Drugs and Enzymes 4
Copyright Page 5
Table of Contents 6
LIST OF AUTHORS 10
INTRODUCTION 14
PART 1: RELATIONSHIP BETWEEN BIOCHEMICAL EFFECTS OF DRUGS IN VITRO AND THEIR PHARMACOLOGICAL EFFECT IN VIVO 20
Chapter 1. Reversible Binding as a Complication in Relating the in vitro Effect of Drugs to their in vivo Activity 22
DIFFICULTIES IN DETERMINING DRUG LEVELS IN VIVO 23
THEORETICAL ASPECTS OF REVERSIBLE BINDING OF DRUGS TO TISSUES 25
THE EFFECT OF BINDING ON THE APPARENT ACTIVITY OF DRUGS 30
DISCUSSION 34
REFERENCES 34
DISCUSSION 35
Chapter 2. Correlations between the Action of Substances on Isolated Smooth Muscle and on the Central Nervous System 36
ACETYLCHOLINE 36
CATECHOLAMINES 38
5-HYDROXYTRYPTAMINE 40
REFERENCES 42
Chapter 3. Drugs and Enzymes of Ion Movement in the Central Nervous System 44
ACTIONS ON ELECTRICAL CHARACTERISTICS OF CEREBRAL TISSUES 44
ACTIONS ON ION MOVEMENTS OF CEREBRAL TISSUES 46
ACTIONS AT SUBCELLULAR AND ENZYMIC SYSTEMS 47
REFERENCES 51
Chapter 4. Metabolism, Activity and Some Effects of Drugs in Mammalian Non-myelinated Nerve Fibers 54
REFERENCES 66
Chapter 5. Neurophysiological and Biochemical Correlationsin Isolated Nerve Cell Preparations at Rest and during Impulse Activity 68
Chapter 6. Effect of Digitalis on Membrane Adenosine Triphosphatase of Cardiac Muscle 78
INTRODUCTION 78
RESULTS AND DISCUSSION 79
CLOSING REMARKS 96
REFERENCES 96
DISCUSSION 99
REFERENCES 100
Chapter 7. Discussion to paper by K. Repke 102
REFERENCES 106
Chapter 8. In vivo Factors Influencing the Efficacy of Chelating Compounds as Therapeutic Agents for Metal Toxicity 108
MOBILIZATION OF METALS BY CHELATING AGENTS 108
INTRODUCTION 108
CHEMISTRY OF CHELATES 110
TISSUE METAL BINDING AGENTS – THE SOFT TISSUES 115
TISSUE METAL BINDING SYSTEMS – THE SKELETON 117
CATION CONTENT OF TISSUES AND BODY FLUIDS 118
ENVIRONMENTAL CHARACTERISTICS OF METAL BINDING SITES 118
METABOLIC CHARACTERISTICS OF THE CHELATING AGENT 119
REFERENCES 122
DISCUSSION 123
Chapter 9. Effets metaboliques de quel ques radio-protecteurs 124
ABRÉVIATIONS UTILISÉES 124
INTRODUCTION 124
RADIO-PROTECTION PAR HYPOXIE 125
RADIO-PROTECTION PAR LES THIOLS ET DISULFURES 130
RADIO-PROTECTION ET MÉTABOLISME ÉNERGETIQUE 144
CONCLUSIONS 148
SUMMARY 150
TRAVAUX CONSULTÉS 151
DISCUSSION 156
Chapter 10. A Contribution to the Effects of Protective Drugs 158
ACKNOWLEDGMENTS 161
REFERENCES 161
DISCUSSION 161
Chapter 11. Carbonic Anhydrase Inhibitors 162
REFERENCES 166
DISCUSSION 166
Chapter 12. The Kinetics of Carbonic Anhydrase and its Inhibition in vivo 168
I. REACTION RATES 170
II. INHIBITION KINETICS, APPLIED IN VIVO 173
III. SULFONAMIDE CHLORURETICS AND CARBONIC ANHYDRASE 183
REFERENCES 185
Chapter 13. Comparison by Direct Measurement of Sulfonamide Carbonic Anhydrase Inhibition in Whole Cells and in Enzyme Solutions 188
I. MATERIAL AND METHODS 188
II. RESULTS AND DISCUSSION 193
REFERENCES 199
Chapter 14. Monoamine Oxidase Inhibitors 200
REFERENCES 209
Chapter 15. Discussion to paper by S. Spector 210
REFERENCES 212
Chapter 16. Enzymes as Therapeutic Agents 214
REFERENCES 220
Chapter 17. Modifiers of Adrenocortical Function 222
ACKNOWLEDGEMENT 235
REFERENCES 236
Chapter 18. Modifiers of Adrenocortical Function— Some Clinical Aspects 238
SUMMARY 244
ACKNOWLEDGMENT 244
REFERENCES 244
Chapter 19. Xenon Bonding to Proteins — Relationship to Anesthetic Action 246
REFERENCES 250
Chapter 20. Discussion to paper by R. M. Featherstone 252
REFERENCES 254
PART 2: BIOCHEMICAL MECHANISMS OF DRUG TOXICITY 256
Chapter 21. Individual Variation in Drug Metabolism as Cause of Drug Toxicity 258
REFERENCES 267
DISCUSSION 268
Chapter 22. Discussion to paper by W. Kalow 270
REFERENCES 273
Chapter 23. Impairment of Drug Metabolism in Drug Toxicity 274
PHYSIOLOGICAL AND PATHOLOGICAL CONDITIONS AFFECTING DRUG METABOLISM 275
RELATIONSHIP BETWEEN HEPATIC GLYCOGEN AND MICROSOMAL DRUG METABOLISM 276
SOME UNUSUAL STIMULATORS OF DRUG-METABOLIZING ENZYME ACTIVITY 279
RELATIONSHIPS BETWEEN HEPATIC ULTRASTRUCTURE AND MICROSOMAL DRUG METABOLISM 282
SUMMARY 287
ACKNOWLEDGMENTS 288
REFERENCES 288
Chapter 24. Enzyme Induction and Drug Toxicity 290
EFFECT OF ENZYME INDUCTION ON THE ACUTE TOXICITY OF DRUGS 294
ENZYME INDUCTION IN CHRONIC TOXICITY STUDIES 295
INDUCTION OF DRUG-METABOLIZING ENZYMES IN NON-HEPATIC TISSUES 298
SPECIFICITY OF POLYCYCLIC HYDROCARBONS AND DRUGS AS ENZYME INDUCERS 299
MECHANISM OF THE STIMULATORY EFFECT OF POLYCYCLIC HYDROCARBONS AND DRUGS ON MICROSOMAL ENZYME ACTIVITY 300
STIMULATORY EFFECT OF DRUGS ON THE METABOLISM OF NORMAL BODY CONSTITUENTS 305
SUMMARY 306
ACKNOWLEDGEMENTS 307
REFERENCES 307
Chapter 25. Morphological Changes in the Endoplasmic Reticulum of the Liver Cells with Enzyme Induction after Pretreatment with Several Drugs 312
REFERENCES 320
Chapter 26. Biochemical Factors in the Formation of Active and Toxic Metabolic Products 322
THE FORMATION OF TOXIC AND ACTIVE PRODUCTS BY BIOCHEMICAL TRANSFORMATION 322
THE FORMATION OF ACTIVE AND TOXIC METABOLITES BY MICROSOMAL ENZYMES 326
TISSUE STORAGE AND THE ACTIVITY AND TOXICITY OF DRUGS 333
REFERENCES 334
Chapter 27. Discussion to paper by J. Axelrod 338
REFERENCES 342
Chapter 28. Biochemistry of Rodenticides 344
BIOCHEMICAL ASPECTS 345
ARYLTHIOUREAS AS RODENTICIDES 350
REFERENCES 353
Chapter 29. Mechanisms of Drug-induced Carcinogenesis 356
REFERENCES 362
Chapter 30. Biochemical Factors in Carbon Tetrachloride Toxicity 364
REFERENCES 373
Chapter 31. Investigations on the Early Effects of CCI4 on Lipid Transport 376
REFERENCES 382
Chapter 32. Hepatic Lipid Transport and Lipoprotein-protein Synthesis: Effects of CCI4 Intoxication 384
REFERENCES 393
Chapter 33. Cumulative Effects of Reserpine on the Pituitary-adrenocortical and Sympathetic Nervous System 394
REFERENCES 404
DISCUSSION 405
Chapter 34. Inactivation of SH-Enzymes in Drug-induced Hemolysis 406
REFERENCES 411
Chapter 35. Discussion to paper by S. Rapoport and D. Scheuch 412
REFERENZEN 416
Chapter 36. Hepatotoxic Drugs Causing Porphyria in Man and Animals 418
TOXIC PORPHYRIA IN ANIMALS 420
TOXIC PORPHYRIA IN MAN 427
REFERENCES 429
Chapter 37. Photosensitivity to Drugs 432
ACKNOWLEDGMENTS 449
REFERENCES 449
DISCUSSION 454
Chapter 38. Specificity in Delayed-type Reactions to Simple Chemicals 456
METHODS 457
RESULTS 458
DISCUSSION 463
SUMMARY 464
REFERENCES 465
Chapter 39. Metabolische Studien mit Thalidomid und seinen Stoffwechselprodukten 466
DIE FRAGE DER HYDROXYLIERTEN METABOLITEN VON THALIDO 468
DER MECHANISMUS DER HYDROLYTISCHEN SPALTUNG DES THALIDOMID-MOLEKÜLS 469
DIE BIOLOGISCHEN EIGENSCHAFTEN DER METABOLITEN VON THALIDOMID 471
SUMMARY 473
REFERENZEN 474
DISCUSSION 474
Chapter 40. Discussion to paper by J. W . Faigle et al 476
REFERENCES 480
DISCUSSION 480
Chapter 41. Chloroquine Toxicity 482
MATERIALS AND METHODS 484
CLINICAL STUDIES 485
ASSAY OF CHLOROQUINE AND METABOLITE 485
RESULTS 487
DISCUSSION 495
SUMMARY 500
REFERENCES 500
INDEX 504