Pharmacology of Antihypertensive Drugs (eBook)

Front Cover 1
Pharmacology of Antihypertensive Drugs 4
Copyright Page 5
Table of Contents 12
Contributors 6
Foreword 8
Preface 10
Chapter 1. General introduction: the classification of antihypertensive drugs 14
Chapter 2. Animal models in experimental hypertension: relevance to drug testing and discovery 19
I. HYPERTENSION MODELS AND DRUG EFFECTIVENESS 20
II. METHODS OF MEASURING BLOOD PRESSURE 20
III. EXPERIMENTAL HYPERTENSION 23
IV. HYPERTENSION OF RENAL ORIGIN 24
V. RENAL HYPERTENSION 27
VI. DIETARY OR ENDOCRINE-INDUCED EXCESSIVE SODIUM INTAKE AND HYPERTENSION 35
VII. HYPERTENSION AND INCREASED SYMPATHETIC ACTIVITY 39
VIII. HYPERTENSION AND HEREDITARY FACTORS 41
IX. CONCLUSIONS 45
ACKNOWLEDGMENTS 46
REFERENCES 46
Chapter 3. The interaction of antihypertensive drugs with mechanisms of blood pressure regulation 59
I. BLOOD PRESSURE CONTROL MECHANISMS 59
II. INTERACTIONS OF ANTIHYPERTENSIVE DRUGS WITH BLOOD PRESSURE CONTROL MECHANISMS 70
III. CONCLUSIONS 72
REFERENCES 72
Chapter 4. Diuretic drugs in hypertension 79
I. ACTION OF DIURETICS ON RENAL ELECTROLYTE EXCRETION AND RENAL HEMODYNAMICS CLASSIFICATION OF DIURETIC DRUGS
II. EFFECTS OF DIURETICS ON CARDIAC OUTPUT AND PERIPHERAL VASCULAR RESISTANCE 86
III. EFFECTS OF DIURETICS ON EXTRACELLULAR FLUID COMPARTMENTS 87
IV. MECHANISM OF THE ANTIHYPERTENSIVE EFFECTS OF DIURETICS 89
V. THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM AS A COUNTERREGULATING MECHANISM 98
VII. CONCLUSIONS 100
REFERENCES 101
Chapter 5. Centrally acting hypotensive drugs 115
I. METHODS USED TO DETECT CENTRAL HYPOTENSIVE ACTIVITY OF DRUGS 115
II. WHICH COMPOUNDS DISPLAY CENTRAL HYPOTENSIVE ACTIVITY? 118
III. STRUCTURE-ACTIVITY RELATIONSHIPS IN CENTRALLY ACTING HYPOTENSIVE AGENTS 122
IV. MODE OF ACTION OF CENTRALLY ACTING HYPOTENSIVE DRUGS 124
V. SIDE-EFFECTS AND CONTRAINDICATIONS FOR CENTRALLY ACTING HYPOTENSIVE DRUGS INTERACTIONS WITH OTHER DRUGS
VI. PHARMACOKINETIC CHARACTERISTICS AND BIOTRANSFORMATION OF CENTRALLY ACTING HYPOTENSIVE DRUGS 152
VII. DRUGS EXPECTED TO DISPLAY CENTRAL HYPOTENSIVE ACTIVITY BUT WHICH PROVED TO BE INACTIVE 155
VIII. CONCLUSIONS 156
REFERENCES 157
Chapter 6. a-Methyldopa and related compounds 167
I. BASIC CONCEPTS OF ADRENERGIC PHARMACOLOGY 168
II. CHEMISTRY OF METHYLDOPA AND RELATED COMPOUNDS 172
III. PHARMACODYNAMIC ACTIONS OF METHYLDOPA 173
IV. PHARMACOLOGY OF SOME STRUCTURAL ANALOGS OF METHYLDOPA 192
V. CONCLUDING REMARKS 196
REFERENCES 197
Chapter 7. Depressants of peripheral sympathetic nerve function 207
I. GANGLION-BLOCKING AGENTS 208
II. ADRENERGIC NEURON-BLOCKING AGENTS 211
III. RESERPINE 233
IV. INHIBITORS OF NOREPINEPHRINE SYNTHESIS 240
ACKNOWLEDGMENTS 242
REFERENCES 242
Chapter 8. a-Adrenoceptor antagonists 252
I. PRAZOSIN 252
II. TRIMAZOSIN 255
III. DOXAZOSIN (UK-33,274) 255
IV. URAPIDIL 256
V. KETANSERIN (R-41468) 256
VI. CONCLUSIONS 258
REFERENCES 258
Chapter 9. ß-Adrenoceptor antagonists 262
I. ADRENOCEPTORS 262
II. GENERAL PHARMACOLOGY OF ß-ANTAGONISTS 265
III. CARDIOVASCULAR ACTIONS OF ß-ANTAGONISTS 273
IV. EFFECTS OF ß-ANTAGONISTS ON BLOOD VESSELS 286
V. EFFECTS OF ß-ANTAGONISTS ON THE CARDIAC CONDUCTING SYSTEM 292
VI. ß-ANTAGONISTS AND CARDIAC METABOLISM 295
VII. ß-ANTAGONISTS AND THE RESPIRATORY SYSTEM 297
VIII. ß-ANTAGONISTS AND THE KIDNEY 300
IX. ß-ANTAGONISTS AND THE CENTRAL NERVOUS SYSTEM 302
X. VOLUNTARY NEUROMUSCULAR JUNCTION AND ß-ANTAGONISTS 304
XL METABOLIC AND ENDOCRINE EFFECTS OF ß-ANTAGONISTS 304
XII. ß-ANTAGONISTS AND EXPERIMENTAL HYPERTENSION 306
XIII. ß-ANTAGONIST PHARMACOKINETICS 307
XIV. CONCLUSIONS 311
REFERENCES 311
Chapter 10. Vasodilator drugs with direct action on smooth muscle 320
I. ARTERIOLAR AND/OR VENOUS RELAXATION INDUCED BY VASODILATOR DRUGS 321
II. VASODILATORS WITH A DIRECT ACTION: COMPOUNDS AND THEIR MODE OF ACTION 322
III. HYDRALAZINE AND DIHYDRALAZINE 326
IV. MINOXIDIL 330
V. SODIUM NITROPRUSSIDE 331
VI. DIAZOXIDE 334
VII. INDAPAMIDE 336
VIII. NEWER VASODILATOR DRUGS 336
IX. CONCLUSIONS 338
REFERENCES 338
Chapter 11. Calcium entry blockers (calcium antagonists) 344
I. CALCIUM ENTRY BLOCKERS AND THE HEART 344
II. CALCIUM ENTRY BLOCKERS AND BLOOD VESSELS: MODE OF ACTION AT THE CELLULAR LEVEL 344
III. HEMODYNAMIC PROFILE 350
IV. TISSUE DISTRIBUTION, BIOTRANSFORMATION AND KINETIC PROPERTIES 351
V. PHARMACOLOGICAL BASIS OF THE THERAPEUTIC EFFECTS 351
VI. SIDE-EFFECTS 352
VII. CONCLUSIONS 352
REFERENCES 353
Chapter 12. Angiotensin-Converting enzyme inhibitors 356
I. HISTORICAL BACKGROUND 356
II. ENZYME PROPERTIES 356
III. DESIGN OF NEW ANGIOTENSIN-CONVERTING ENZYME INHIBITORS: DEVELOPMENT OF CAPTOPRIL 358
IV. IN-VITRO AND IN-VIVO CONVERTING-ENZYME INHIBITORY CHARACTERISTICS OF CAPTOPRIL 358
V. ANTIHYPERTENSIVE ACTIVITY IN SPONTANEOUSLY HYPERTENSIVE RATS 361
VI. ANTIHYPERTENSIVE EFFECT OF ANGIOTENSIN-CONVERTING ENZYME INHIBITORS IN RENAL HYPERTENSIVE RATS 364
VII. MINERALOCORTICOID HYPERTENSION 366
VIII. ANTIHYPERTENSIVE ACTIVITY OF ANGIOTENSIN-CONVERTING ENZYME INHIBITORS IN DOGS 366
IX. EVIDENCE FOR A ROLE OF THE KALLIKREIN-KININ SYSTEM IN THE ANTIHYPERTENSIVE ACTION OF CONVERTING-ENZYME INHIBITORS 367
X. CONVERTING-ENZYME INHIBITION AND THE KIDNEY 368
XI. CONCLUSIONS 371
REFERENCES 371
Index 378