Evaluation of Drug Activities (eBook)

Front Cover 1
Evaluation of Drug Activities: Pharmacometrics 4
Copyright Page 5
Contents of Volume 2 6
Contents of Volume 1 7
PART II: Particular Applications CHAPTERS 20-41 10
CHAPTER 20. Anticholinesterases 12
A. Physiological and Pharmacological Actions 12
B. Uses 18
C. Methods of Test and Assessment 18
D. Antagonism 27
E. Specificity of Action 29
F. Measurements of in vivo Inhibition 34
G. Duration of in vivo Inhibition 36
H. Special Routes of Application 37
J. Toxicity 37
K. Conclusions 40
References 41
CHAPTER 21. Histamine Antagonists 44
A. Physiological and Competitive Antagonists 44
B. Protection (Guinea Pig) against Histamine Activity 45
C. Antagonism to Cardiovascular Activity 47
D. Antagonism in Isolated Tissues 48
E. Modification of Anaphylactic Response 49
F. Modification of (Human)Response to Intradermal Administration 50
References 50
CHAPTER 22. Selective Brain Stem Depressants: Antiemetics, Antitussives, Antihypertensives, Antipyretics 52
A. General 52
B. Antiemetics 53
C. Antitussives 57
D. Antihypertensives 58
E. Antipyretics 58
References 59
CHAPTER 23. Agents Acting on the Alimentary Tract 60
A. Introductory 60
B. Secretion 60
C. Motility 67
D. PurgativeActivity 72
E. Conclusions 73
References 73
CHAPTER 24. Agents Acting on the Respiratory Tract 76
A. Antitussive Drugs 76
B. Drugs Actingon Airway Smooth Muscle 80
C. Drugs Influencing Bronchial Secretion 83
References 85
CHAPTER 25. Iron-containing Haematinics 88
A. Introductory 88
B. Iron Preparations 89
C. AcuteToxicity 95
D. Tests of Oral Iron Preparations 97
E. Assessment of Parenteral Forms of Iron 109
F. Iron Utilisation 116
G. Chronic Toxicity and Carcinogenicity 124
References 131
Appendix 136
CHAPTER 26. Coagulants and Anticoagulants 138
A. Introductory 138
B. Anticoagulants 139
C. Coagulants and Haemostatics 150
References 152
CHAPTER 27. Cardioactive Agents 154
A. Introductory. 154
B. Cardiac Glycosides 154
C. Antiarhythmic Agents 158
D. Coronary Vasodilators 161
References 165
CHAPTER 28. Diuretics and Antidiuretics 168
A. Diuretics 168
B. Antidiuretics 172
References 178
CHAPTER 29. Biologically Active Polypeptides 180
A. Introductory 180
B. Oxytocin 181
C. Vasopressin (Antidiuretic Hormones, ADH) 185
D. Angiotensin 187
E. Substance P 190
F. Kinins 192
G. Eledoisin 196
H. Conclusion 197
References 197
CHAPTER 30. Dermatological Agents 202
A. Introductory 202
B. Available Methods 203
C. Conclusions 215
References 216
CHAPTER 31. Agents Acting on the Uterus 218
A. Introductory 219
B. Uterine Muscle Preparations 221
C. Uterus Preparations for Special Purposes 225
D. Preparations of Cervix Uteri, Fallopian Tubes, Round Ligament and Vagina 230
E. Preparations for in situ Studies 233
F. Uterine Activity in the Conscious Animal 243
G. Experimental Abortion and Parturition 245
H. Biochemical Studies of the Myometrium 246
J. Uterine Blood Flow 247
K. Conclusions 247
References 248
CHAPTER 32. Oestrogens, Androgens and Progestagens 256
A. Introductory 256
B. Oestrogen Tests 256
C. Androgen Tests 262
D. Progestagen Tests 268
E. Conclusions 276
References 276
Appendix 280
CHAPTER 33. Adrenocorticoid Activity 282
A. Introductory 282
B. Influence on Survival and Growth 282
C. Effects on Electrolyte Metabolism 285
D. Effects on Carbohydrate Metabolism 286
E. Eosinophil Depression 289
F. Thymus Involution 290
G. Anti-inflammatory Effect 292
H. Conclusion 294
References 295
CHAPTER 34. Adrenocortical Antagonists 298
A. Introductory 298
B. Mineralocorticoid Antagonists 298
C. Glucocorticoid Antagonists 309
D. Inhibitors of Corticoid Biosynthesis 310
References 313
CHAPTER 35. Thyroxine Analogues (Thyroxine Antagonists and Thyromimetics) 316
A. Introductory 316
B. Standards 317
C. Routes of administration 318
D. Methods 318
E. Conclusions 328
References 330
Appendix 332
CHAPTER 36. Antithyroid Agents 334
A. Introductory 334
B. Test Methods 334
C. Conclusions 339
References 339
CHAPTER 37. Hypoglycaemic Agents 342
A. Introductory 342
B. General Considerations 343
C. Quantitative Tests 345
References 352
CHAPTER 38. Antifertility Agents 354
A. Introductory 354
B. Agents Active on Males 355
C. Agents Active on Females 361
D. Conclusions 365
References 366
CHAPTER 39. Anti-inflammatory Agents 368
A. Introductory 368
B. Suppression of Increased Vascular Permeability 369
C. Leucocyte Emigration 376
D. Granulation Tissue Formation 376
E. Conclusions 378
References 379
CHAPTER 40. Antitumour Agents 380
A. Introductory 380
B. Tests with Transplantable Tumours 384
C. Certain Commonly Used Transplantable Tumours 398
D. Transplantable Tumours from Specialised Tissues or Used as Models for Studying Particular Forms of Human Cancer 398
E. Tests for Activity against Spontaneous Tumours 403
F. Tests for Activity against Induced Tumours 404
G. Tests on Heterotransplanted Human Tumours 405
H. Tests with Tumour Cells Grown in vitro 407
J. Microbial Systems 410
K. Miscellaneous Test Systems 411
L. Tests for Inhibition of Metastasis 413
M. Multiple and Sequential Tests 414
N. The Need for New Thinking and New Types of Test 416
References 422
CHAPTER 41. Blood Cholesterol Depressants 428
A. Introductory 428
B. Methods of Test 429
C. Effects on Cholesterol Biosynthesis 433
D. Effects on Lipid Mobilisation 436
E . Effects on Cholesterol Absorption 438
F. Effects on Cholesterol Catabolism and Excretion 438
G. Effects on Lipoprotein Secretion and Turnover 440
H. Conclusions 440
References 441
Appendix The Compositions of some Organ Bath Solutions 444
Alphabetical Guide to Chapter Contents 452