Handbook of Experimental Pharmacology Continuation of Handbuch der experimentellen Pharmakologie
Vol. 54111
Editorial Board G.V. R. Born, Cambridge . A. Farah, Rensselaer, New York H. Herken, Berlin . A. D. Welch, Memphis, Tennessee
Advisory Board S. Ebashi . E. G. Erdos· V. Erspamer . U. S. von Euler· W. S. Feldberg G. B. Koelle· O. Krayer· M. Rocha e Silva· J. R. Vane· P. G. Waser
Adrenergic Activators and Inhibitors Part II
Contributors
D. M. Aviado . W C. Bowman· G. Burnstock . 1. Greven J. Hannappel . P. J uul . A. Kahan . L. Kovacs M. S. Micozzi . H. Osswald· C. W I. Owens· D. E. Potter B. N. C. Prichard· K. H. Rahn . D. Robertshaw· M. Sas A.1. Smith· H. A. J. Struyker-Boudier . G. T. Tucker J. Tuckman . H. Wong
Editor
L. Szekeres
Springer-Verlag Berlin Heidelberg New York 1981
Professor Dr. LAszLO SZEKERES
Institute of Pharmacology, University Medical School of Szeged, Dom ter 12, H-6701 Szeged, Hungary
With 118 Figures
ISBN-13: 978-3-642-67586-7 e-ISBN-13: 978-3-642-67584-3 DOl: 10.1007/978-3-642-67584-3
Library of Congress Cataloging in Publication Data. Main entry under title: Adrenergic activators and inhibitors. (Handbook of experimental pharmacology; v. 54) Includes bibliographies and index. 1. Sympathomimetic agents. 2. Sympatholytic agents. 3. Neuropharmacology. I. Anden, N. E. II. Szekeres, L. III. Series: Handbuch der experimentellen Pharmakologie New series; v. 54. QP905.H3 vol. 54 [RM323.6] 615'.1 [615'.78]. 79-23866
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© by Springer-Verlag Berlin Heidelberg 1981. Softcover reprint of the hardcover lst edition 1981
The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.
List of Contributors
Professor Dr. D.M. AVIADO, New Jersey Medical School, P.O. Box 307, Short Hills, NJ 07078jUSA
Professor Dr. W.e. BOWMAN, University of Strathdyde, Department of Physiology and Pharmacology, Royal College, 204 George Street, GB-Glasgow G 1 1XW
Professor Dr. G. BURNSTOCK, Department of Anatomy and Embryology, University College London, Gower Street, GB-London WC lE 6BT
Professor Dr. J. GREVEN, Abteilung Pharmakologie der Medizinischen Fakultiit der RWTH, Melatener StraBe 213, 0-5100 Aachen
Dr. J. HANNAPPEL, FranzstraBe 46,0-5100 Aachen Professor Dr. P. JUUL, Department of Pharmacology, Royal Danish School of
Pharmacy, Universitetsparken 2, DK-2100 Copenhagen Professor Dr. A.. KAHAN, Clinic of Ophthalmology, Koninyi Sandor rkp. 16, H-6701
Szeged Dr. L. KOVACS, Clinical Obstet. et Gynaec., Universitatis, Semmelweis ~ 1.,
H-6725 Szeged Dr. M. S. MICOZZI, Department of Research Medicine, University of Pennsylvania,
Medical School, Department of Pathology, Pennsylvania Hospital, Philadelphia, PNjUSA
Priv.-Doz. Dr. H. OSSWALD, Abteilung Pharmakologie der Medizinischen Fakultiit der RWTH, Melatener StraBe 213, 0-5100 Aachen
Dr. e. W.1. OWENS, University College Hospital, Medical School, University Street, GB-London WClE 6JJ
Professor Dr. D. E. POTTER, Department of Pharmacology and Therapeutics, School of Medicine, Texas Technical University, Health Sciences Center, P.O. Box 4569, Lubbock, TX 79409jUSA
Dr. B. N. C. PRICHARD, Clinical Pharmacology, University College Hospital, Medical School, University Street, GB-London WClE 6JJ
Professor Dr. K.H. RAHN, Department of Pharmacology, University of Limburg, P.O. Box 616, NL-6200 MD-Maastricht
Professor Dr. D. ROBERTSHAW, Department of Physiology and Biophysics, Colorado State University, Fort Collings, CO 80523jUSA
Professor Dr. M. SAS, Clinical Obstet. et Gynaec., Universitatis, Semmelweis 11. 1., H-6725 Szeged
Professor Dr. A.J. SMITH, Clinical Pharmacology, Faculty of Medicine, Division of Clinical Investigation, The University of Newcastle, AUS-2308 New South Wales
Dr. H.A.J. STRUYKER-BoUDIER, Department of Pharmacology, University of Limburg, P.O. Box 616, NL-6200 MD-Maastricht
VI List of Contributors
Dr. G. T. TUCKER, Clinical Pharmacology and Therapeutics, Department of Therapeutics, Hallamshire Hospital, Glossop Road, GB-Sheffield S10 2JF
Dr. J. TUCKMAN, Institute of Rehabilitation Medicine, New York University Medical Center, 400 East 34th Street, New York, NY l0016/USA
Dr. H. WONG, Department of Pharmacology, University of Melbourne, Parkville, AUS-3052 Victoria
Contents of Part 11*
Section IV: Effects on Organ Systems Other Than the Nervous and the Cardiovascular System
CHAPTER 1
Systemic Pharmacology of Adrenergic Activators and Inhibitors: Effects on the Respiratory System. D. M. A VIADO and M. S. MICOZZI
A. Introduction ..................... 3 B. Epinephrine: A Unique Example of Direct Activator of Alpha- and
Beta-Adrenoceptors ................ 4 I. Alpha- and Beta-Receptors in the Respiratory System 5
1. Upper Respiratory Tract 5 2. Lower Respiratory Tract 6 3. Pulmonary Circulation 6 4. Bronchial Circulation 7 5. Ventilation - Perfusion Relationship 7
II. Antiasthmatic Use and Airway Resistance 7 1. Classic Physiologic Concept . . . . . 8 2. Recent Biochemical Concepts . . . . 8
III. Adverse Effects on the Pulmonary Circulation 9 1. Pulmonary Arterial Hypertension 9 2. Acute Pulmonary Edema . . . . . . . . 10
IV. Tachyphylaxis and Status Asthmaticus . . . 10 V. Epinephrine as Neurohumoral Transmitter of the Airways 11
C. Direct Activator of Alpha-Receptors . . . . . . . . . . . 11 I. Norepinephrine . . . . . . . . . . . . . . . . . . 12
1. Pulmonary Vasoconstriction and Pulmonary Edema 12 2. Uptake of Norepinephrine in the Pulmonary Circulation 13
II. Dopamine 14 III. Phenylephrine 14 IV. Methoxamine 15 V. Nasal Decongestants 16
D. Direct Activators of Beta-Receptors 16 I. Isoproterenol . . . . . . . 17
1. Antiasthmatic Use and Airway Resistance 17 2. Paradoxical Bronchospasm . . . . . . 18
----* Contents of Part I, Section I to III see p. XXI
VIII
3. Pulmonary Vasodilation and Venous Admixture 4. Toxicity of Aerosol Propellants
II. Protokylol ...... . III. Ethylnorepinephrine . . .
E. Bronchoselective Beta-Activators I. Isoetharine
II. Metaproterenol .... III. Terbutaline . . . . . .
1. Bronchomotor System 2. Pulmonary Circulation
IV. Salbutamol V. Carbuterol ..... .
VI. Pirbuterol ..... . VII. Bronchoselective Drugs Under Clinical Investigation
1. Albuterol 2. Hexoprenaline 3. Ibuterol 4. Rimiterol 5. Zimterol
F. Adrenergic Transmitter Releasing Agents I. Ephedrine as an Antiasthmatic Drug
II. Pseudephedrine and Phenylprppanolamine as Oral-Nasal Decongestants ................. .
III. Mephentermine and Metaraminol as Vasopressor Agents IV. Aminorex and Chlorphentermine as Anorexigenics . .
G. Adrenergic Alpha-Receptor Blocking Agents . . ..... . I. Phenoxybenzamine and Acute Pulmonary Insufficiency .
1. Correction of Pulmonary Vascular Consequences of Hypoxemia 2. Blockade of Pulmonary Vasoconstriction Induced by Catecholamines . . . . . . . . . . . . . .
II. Tolazoline and Chronic Pulmonary Hypertension III. Phentolamine and Acute Ventricular Failure IV. Thymoxamine and Acute Bronchial Asthma ..
H. Adrenergic Beta-Receptor Blocking Agents . . ... I. Nonselective Adrenergic Beta-Receptor Blocking Agents
1. Propranolol 2. Sotalol ..... . 3. Pindolol . . . . . . 4. Dichloroisoproterenol
II. Cardioselective Beta-Receptor Blocking Agents 1. Practolol . 2. Acebutolol 3. Atenolol . 4. Bunitrolol
I. Adrenergic Neuron Blocking Agents I. Bretylium
II. Reserpine
Contents
18 19 19 20 20 21 22 22 22 23 23 24 25 25 25 25 26 26 26 26 27
27 28 28 28 29 29
29 30 30 30 31 32 33 33 33 34 34 34 35 35 35 35 36 36
Contents
III. Guanethidine IV. Methyldopa
J. Concluding Remarks 1. Nasal Congestion and Decongestion 2. Bronchial Mucosal Decongestion. 3. Bronchodilation 4. Bronchoconstriction . . . . . . 5. Pulmonary Vasodilation . . . . 6. Pulmonary Vasoconstriction, Congestion, and Edema 7. Bronchial Circulation
References
CHAPTER 2
Effects of Adrenergic Activators and Inhibitors on the Skeletal Muscles. W.e. BOWMAN. With 14 Figures
A. Introduction . . . . . . . . . . . . . . . . . . .
B. Direct Action on Contractions of Nonfatigued Muscles I. Fast-Contracting Muscles . . . . . . . . . . .
II. Slow-Contracting Muscles. . . . . . . . . . . III. Other Sympathomimetic Amines and Adrenoceptor Blocking Drugs IV. Adrenoceptors . . . . . . . . V. Electrical and Ionic Changes . .
1. Resting Membrane Potential 2. Action Potentials
VI. Effect of Anaesthetic VII. Mechanism of Action
C. Muscle Spindles D. Human Muscles. . . . .
I. Evoked Contractions II. Tremor
1. Unwanted Effect of Sympathomimetic Bronchodilators 2. Parkinsonian Tremor. . . . 3. Some Other Types of Tremor ....... .
III. Therapy of Spasticity . . . .. ....... . IV. Therapy of Hyperkalaemic Familial Periodic Paralysis
E. Effects on Chronically Denervated Muscles I. Fibrillation . . . . . . . . . .
II. Membrane Potential . . . . . . . F. Actions on Neuromuscular Transmission.
I. Endplate Potential and Miniature Endplate Potentials . II. Mechanisms of Action. . .
G. Effects on Fatigued Muscles . . H. Summary of Effects of Adrenaline
IX
36 37 37 37 37 38 38 38 39 39
39
47
48 49 52 56 61 62 62 64 66 67 71
73 73 74 74 76 78 80 81 81 81 88 90 94 97 99
103
x Contents
I. Effects Unrelated to Adrenergic Mechanisms I. Adrenergic Neurone Blocking Drugs
II. Beta-Adrenoceptor Blocking Drugs
103 105 106 107 108
1. Plasma Membrane 2. Sarcoplasmic Reticulum
References 109
CHAPTER 3
Systemic Pharmacology of Adrenergic Agonists and Antagonists: Effects on the Digestive System. G. BURNSTOCK and H. WONG. With 1 Figure
A. Introduction ........... . 129 B. Alpha- and Beta-Adrenoceptor Agonists 130
I. Effect on Motility. . . . . . . . . 130 1. Introduction. . . . . . . . . 130 2. Effect on Non-Sphincteric Smooth Muscle 130 3. Effect on Sphincteric Smooth Muscle . . 131 4. Effect on Acetylcholine Release from Enteric Neurones 131 5. Effect on Noradrenaline Release from Adrenergic Neurones 133 6. Mechanism of Action . . . . . . . . 133
II. Effect on Gastro-Intestinal Vasculature . . . . . 134 III. Effect on Gastric and Intestinal Secretion . . . . 135
1. Action of Alpha- and Beta-Adrenoceptor Agonists 135 2. Mechanism of Action 136
IV. Effect on Absorption. . . . . . . 138 V. Summary. . . . . . . . . . . . 138
C. Adrenergic Transmitter Releasing Agents 139 I. Introduction . . . . . . 139
II. Effect on Motility . . . 139 III. Effect on Gastric Secretion 140 IV. Summary . . . . . . . 140
D. Alpha- and Beta-Adrenoceptor Antagonists 140 I. Introduction . . . . 140
II. Effect on Motility . . . . 141 III. Effect on Vasculature. . . 142 IV. Effect on Gastric Secretion 142
1. Alpha-Adrenoceptor Antagonists 142 2. Beta-Adrenoceptor Antagonists. 143
V. Summary . . . . . . . . . . . 143 E. Adrenergic Neurone Blocking Agents and False Transmitters 144
I. Introduction ..... 144 II. Effect on Motility 145
III. Effect on Gastric Secretion 146 IV. Summary 146
References . 147
Contents
CHAPTER 4
Effects of Adrenergic Activators and Inhibitors on the Endocrine System. D.E. POTTER. With 6 Figures
XI
A. Introduction . . . . . . . . . . . . . . . . . . . . . . . . 161 B. Embryologic Relationship of the Neural and Endocrine Systems. . 162 C. Role of Catecholamines in Modulating the Function of the Endocrine
System. . . . . . . . . . . . . . . . . . . . . . . . . . .. 163 I. Mediators of Catecholamine-Induced Modulation of the Endocrine
System ........................... 163 II. Adrenergic Drugs Used to Examine Hormone Secretion and Action 164
1. Neutral Amino Acids . . . . 164 2. Enzyme Inhibitors . . . . . 165 3. Inhibitors of Neuronal Uptake 166 4. Receptor Agonists 166 5. Receptor Antagonists . . . . 167 6. Neurotoxins . . . . . . . . 167 7. Inhibitors of Monoamine Storage and Release 167
D. Effects of Adrenergic Agents on the Endocrine System in Laboratory Animals and Man. . . . . . . . . . 167
I. Adrenergic Drugs and the Pituitary 167 1. Anterior Pituitary. . . . . . 167 2. Posterior Pituitary . . . . . . 180
II. Adrenergic Drugs and the Pineal . 181 III. Adrenergic Drugs and the Thyroid and Parathyroid 181
1. Thyroxine and Triiodothyronine . . . . . 182 2. Thyrocalcitonin and Parathyroid Hormone 185
IV. Adrenergic Drugs and the Gut . . 186 V. Adrenergic Drugs and the Pancreas 187
1. Insulin . . . 188 2. Glucagon . . . . . . . . . 191 3. Somatostatin. . . . . . . . 194
VI. Adrenergic Drugs and the Kidney 194 1. Renin-Angiotensin 195 2. Erythropoietin 196 3. Prostaglandins 197
E. Concluding Remarks 198
References 198
CHAPTER 5
Systemic Pharmacology of Adrenergic Activators and Inhibitors: Effects on the Genital System. M. SAS and L. KovAcs. With 7 Figures
A. Introduction . . . . . . . . . . . . . . . . . . . . . . . . 213 B. Effect of Beta-Sympathomimetics on the Myometrium in Pregnancy. 213
I. Connection Between the Structure and Effect of Beta-Sympathomimetics ................. 214
XII Contents
II. Mechanism of Action . . . . . . . . . . . . . . . . . 216 III. Metabolism and Pharmacokinetics . . . . . . . . . . . 217
C. Effect of Beta-Sympathomimetics on the Non-Pregnant Uterus . 218 D. Effect of Beta-Sympathomimetics on the Fallopian Tubes. . . . 219 E. Administration of Beta-Sympathomimetic Drugs in Obstetrics. . 219
I. Clinical Studies. . . . . . . . . . 219 II. Drugs Applied in Clinical Practice . . 220
III. Indications . 220 IV. Contra-Indications . 221 V. Methods .... . 221
VI. Effectiveness . . . . 221 F. Maternal Side-Effects of To co lysis Carried out With Beta-Symp~thomimetics
I. Cardiac Effects . . . . . . . 222 II. Metabolic Effects .... . 224
1. Carbohydrate Metabolism . 224 2. Lipid Metabolism . 225 3. Blood Gases and Acid-Base Balance . 225 4. Electrolytes . . . . . . . . . . . . 226 5. Thrombocyte Function . . . . . . . 227
G. Therapy of the Side-Effects of Beta-Sympathomimetic Treatment . . 2'27 I. Beta-Receptor Blockers . . . . . . . . . . . . . . . . . 227
II. Calcium Antagonists. . . . . . . . . . . . . . . . . . . 228 H. Foetal Effects of Tocolysis Carried out With Beta-Sympathomimetics . 229
I. Diaplacental Penetration ...... . 229 II. Effect on the Utero-Placental Circulation . 230
III. Effect on the Foetal Heart . . . . . . . 232 IV. Myocardium Lesion and Tocolysis. . . . 234 V. The Effect of Beta-Sympathomimetics on Foetal Pulmonary
Maturation ..................... . 234 VI. Effect on Newborns of Beta-Sympathomimetic Treatment of Pregnant
Women .236
References ............................. 236
CHAPTER 6
Effects of Adrenergic Activators and Inhibitors on Kidney Function. H. OSSWALD and J. GREVEN. With 6 Figures
A. Introduction . . . . . . . . . . . . . . . 243 B. Renal Hemodynamics . . . . . . . . . . . 243
I. Effects of Alpha-Adrenergic Activators . . 243 1. Adrenaline and Noradrenaline. . . . 243 2. Other Alpha-Adrenergic Activators. . 247 3. Factors that Influence Renal Hemodynamic Response to Vasoconstrictive Catecholamines . . . . 247
II. Effects of Alpha-Adrenergic Inhibitors . . 249 III. Effects of Dopamine . . . . . . . . 251 IV. Effects of Beta-Adrenergic Activators . . 252
Contents
V. Effects of Beta-Adrenergic Inhibitors . . . . VI. Use of Catecholamines in Renal Angiography
VII. Conclusion . . . . . . . . . . . . . . . C. Renin Release . . . . . . . . . . . . . . . .
I. Evidence for Neural Control of Renin Release II. Effects of Beta-Adrenergic Activators and Inhibitors
III. Effects of Dopamine. . . . . . . . . . . . . . IV. Effects of Alpha-Adrenergic Activators and Inhibitors V. Conclusion . . . . . . . . . . .
D. Tubular Electrolyte and Water Transport . I. Effects of Beta-Adrenergic Activators
1. Evidence for Direct Tubular Effects 2. Evidence for Renal Effects Mediated Through Changes in Release
XIII
· 253 .254 .254 · 255 · 255 .256 · 258 · 258 · 259 · 261 · 261 · 261
of Antidiuretic Hormone. . . . . . . . 265 II. Effects of Beta-Adrenergic Inhibitors . 266
III. Effects of Alpha-Adrenergic Activators. . 267 IV. Effects of Alpha-Adrenergic Inhibitors . . 268
E. Kidney Intermediary Metabolism . . . . . . 269 I. Effects of Adrenergic Activators and Inhibitors on Kidney cAMP
Content and Its Relation to Renal Gluconeogenesis . . II. Miscellaneous Effects . . . . . . . . . . . . . . .
F. Summary of Effects of Catecholamines on Kidney Function
References
CHAPTER 7
Effects of the Adrenergic Activators and Inhibitors on the Urinary Tract. J. HANNAPPEL. With 6 Figures
· 269 · 270 · 271
· 271
A. The Upper Urinary Tract . . . . . . . . . 289 I. Morphology of the Upper Urinary Tract . 289
1. Anatomy. . . . . . . . . . . . . . 289 2. Histology. . . . . . . . . . . . . . 289
II. Functional Studies in the Upper Urinary Tract . 291 1. Pharmacologic Studies in Isolated Calyx and Renal Pelvis Preparations . . . . . . . . . . . . . .. . . . . . . . 291 2. Pharmacologic Studies in Isolated Ureter Preparations . . 294 3. Pharmacologic Studies in Isolated Pyeloureter Preparations . 299 4. In Vivo Studies in the Pyeloureteral System . 300
B. The Lower Urinary Tract . . . . . . . . . 301 I. Morphology of the Lower Urinary Tract . 301
1. Anatomy. . . . . . . . . . . . . . 301 2. Histology . . . . . . . . . . . . . 302
II. Functional Studies in the Lower Urinary Tract . 303 1. Pharmacologic Studies in Isolated Bladder Dome and Body
Preparations . . . . . . . . . . . . . . . . . . . . . 303 2. Pharmacologic Studies in Isolated Bladder Neck and Urethra
Preparations . . . . . . . . . . . . . . . . . . . .. . 308
XIV Contents
3. In Vivo Studies in Bladder Dome and Body · 308 4. In Vivo Studies in Bladder Neck and Urethra · 309
References · 312
CHAPTER 8
Miscellaneous Effects: Effects of Adrenergic Activators and Inhibitors on the Eye. A. KAHAN. With 2 Figures
A. Introduction . . . . . . . . . . . . . . . . . . . . . I. Targets of Adrenergic Agents in the Eye and Its Adnexa
1. Adrenergic Effects on Outflow of Aqueous Humor . 2. Adrenergic Effects on Aqueous Humor Secretion . . 3. Intraocular Smooth Muscles as Targets of Adrenergic Agents 4. Retinal Targets of Adrenergic Drugs . . . 5. Targets of Adrenergic Agents in the Cornea 6. Targets of Adrenergic Agents of the Lens . 7. Targets of Adrenergic Agents in the Orbita .
II. Adrenergic Interactions Between the Eye and the Organism 1. Retinal Light Stimulation and the Circadian Rhythm . 2. Ocular Targets of Melatonin and of Its Antagonist MSH
B. Adrenergic Alpha- and Beta-Receptor Activators I. Adrenergic Receptors . . . . .
II. Adrenergic Receptor Stimulators 1. Norepinephrine . . . . 2. Epinephrine . . . . . . . . 3. Beta-Receptor Stimulators . . 4. Systemic Administration of Adrenergic Receptor Stimulators 5. Administration of Catecholamine Precursors . . . . . . .
· 319 · 319 · 321 · 321 · 322 .322 · 323 · 323 .324 · 324 · 324 .325 · 326 · 326
327 328 328 328 329 329
6. Factors Determining the Different Effects of Adrenergic Receptor Stimulators in the Eye . . . . . . . . 330
C. Adrenergic Transmitter Releasing Agents. . . . . . . . I. Agents Increasing the Stores of Transmitters . . . .
II. Agents Inhibiting Re-Uptake into the Storing Vesicles III. Simple or Hydroxylated Phenylalkylamines . . . IV. Clonidine . . . . . . . . . . . . . . . . .
· 331 332 332 333 333
D. Adrenergic Alpha- and Beta-Receptor Blocking Agents 333 I. General Considerations . . . . . . . . . 333
II. Effects of Alpha-Receptor Blocking Agents 334 III. Effects of Beta-Receptor Blocking Agents. . 335
1. Synopsis of Their Different Effects. . . . 335 2. Betal- and BetarReceptor Blocking Agents 335 3. Betal-Receptor Blocking Agents . . 336 4. Beta2-Receptor Blocking Agents . . . . . 336
IV. Dopaminergic Receptor Blocking Agents . . . 336 E. Adrenergic Nerve-End Inhibitors, Neural Transmitter Depleting Agents and
False Transmitters . . . . . . . . . . . . . . . . . . . . . . . . 336
Contents xv
I. General Considerations . . . . . . . . . . . . . . . . . . . . 336 II. Effects of Adrenergic Nerve-End Inhibitors on the Eye . . . . . . . 337
III. Effects of Adrenergic Transmitter Depleting Procedures and Agents on the Eye . . . . . . 338
IV. False Transmitters. . 338 F. Summary . 339 References .... . . . . 340
CHAPTER 9
Effects of Adrenergic Activators and Inhibitors on the Sweat Glands. D. ROBERTSHAW. With 4 Figures A. Classification of Sweat Glands B. Apocrine Glands .
I. Perissodactyla . . 1. Equidae .... 2. Rhinocerotidae .
II. Artiodactyla . 1. Camelidae . 2. Bovidae . 3. Suidae ..
III. Carnivora . 1. Canidae.
IV. Marsupialia. V. Primates. .
1. Prosimii . 2. Anthropoidae
C. Eccrine Glands I. Felidae .
II. Muridae . III. Primates .
1. Anthropoidae D. Pathological Considerations E. Conclusion.
References
Sect~on V: Kinetics, Biotransformation, Toxic Effects and Clinical Implications
CHAPTER 1 Kinetics and Biotransformation of Adrenergic Activators and Inhibitors: Adrenergic Alpha- and Beta-Receptor Activators. K. H. RAHN. With 7 Figures
345 346 346 346 347 348 348 348 351 351 351 351 352 352 352 352 352 353 353 353 357 358
. 359
A. Alpha-Receptor Activators . 365 I. Etilephrine . . . 365
1. Metabolism . 365 2. Kinetics. . . 365
XVI
II. Phenylephrine 1. Metabolism 2. Kinetics. .
B. Beta-Receptor Activators. I. Isoprenaline . . . .
1. Biotransformation 2. Kinetics. . . . .
II. Orciprenaline. . . . 1. Biotransformation 2. Kinetics. . . . .
III. Salbutamol .... 1. Biotransformation 2. Kinetics ... .
IV. Terbutaline ... . 1. Biotransformation 2. Kinetics ....
V. Fenoterol . . . . . 1. Biotransformation 2. Kinetics
References
CHAPTER 2
Kinetics and Biotransformation of Adrenergic Activators and Inhibitors: Adrenergic Transmitter Releasing Agents. H.A.J. STRUYKER-BounmR. With 3 Figures
A. Tyramine . . . . . . . . . . . . I. Introduction ....... .
II. Endogenous Tissue Distribution . III. Pharmacokinetics IV. Biotransformation
1. Introduction 2. Beta-C-Hydroxylation 3. Deamination .... 4. Ring-Hydroxylation
B. Amphetamine and Related Compounds I. Introduction ...... .
II. Pharmacokinetics .... . 1. Absorption and Distribution 2. Excretion . . .
III. Biotransformation .... . 1. Introduction .... . 2. Aromatic Para-Hydroxylation 3. Beta-C-Hydroxylation 4. N-Dealkylation and Deamination
Contents
...
366 366 366 367 367 367 369 370 371 371 372 372 374 375 376 376 377 378 378
380
· 385 · 385 · 385 · 386 · 387 · 387 · 388 · 389 · 389 · 389 · 389 · 391 · 391 · 394 .395 .395 .397 .398 .399
Contents
C. Ephedrine and Related Compounds I. Introduction ...... .
II. Pharmacokinetics .... . 1. Absorption and Tissue Distribution 2. Excretion . . . . . . . . .
III. Biotransformation ..... . D. Phentermine and Related Compounds
I. Introduction ...... . II. Pharmacokinetics .... .
1. Absorption and Distribution 2. Excretion . . .
III. Biotransformation E. Fenfluramine
I. Introduction II. Pharmacokinetics
1. Absorption and Distribution 2. Excretion ...
III. Biotransformation
References
CHAPTER 3
Kinetics and Biotransformation of Adrenergic Inhibitors. A.J. SMITH and G. T. TUCKER. With 32 Figures
Introduction ....... . Criteria for Selection of Drugs Dermitions . . .
I. Methyldopa II. Clonidine .
III. 6-Hydroxydopamine IV. Reserpine V. Bethanidine .
VI. Debrisoquine VII. Guanethidine
VIII. Guanoxan XI. Phenoxybenzamine X. Phentolamine
XI. Prazosin XII. Priscoline . .
XIII. Labetalol . . Beta-Adrenoceptor Blocking Agents
I. Acebutolol II. Alprenolol
III. Atenolol IV. Bufuralol V. Bunolol
XVII
402 402 402 402 403 404 404 404 405 405 405 406 407 407 407 407 408 408
409
.417
.417
. 418
.418
.422
.424
.426
.429
.431
.434
.437
.437
.439
.440
.442
.443
.445
.445
.448
.451
.453
.454
XVIII
VI. Dichloroisoprenaline VII. Metoprolol
VIII. Oxprenolol IX. Pindolol X. Practolol
XI. Pronethalol XII. Propranolol
XIII. S otal 01 XIV. Timolol XV. Tolamolol
XVI. Toliprolol Summary
References
CHAPTER 4
Contents
.456
.456
.459
.461
.464
.467
.469
.479
.480
.482
.484
.487
· 488
Toxic. Effects of Adrenergic Nerve-End Inhibitors, Neural Transmitter Depleting Agents and False Transmitters. P. JUUL
A. Introduction ....... . B. Adrenergic Nerve-End Inhibitors
I. General Toxicity. . . II. Cardiovascular System
III. Respiratory System. IV. Blood ...... . V. Liver ....... .
VI. Gastrointestinal System. VII. Genitourinary System. .
VIII. Central Nervous System IX. Peripheral Nervous System X. Other Adverse Reactions
XI. Effects on Foetus . . . . XII. Drug Interactions . . . .
C. Neural Transmitter-Depleting Agents I. General Toxicity. . .
II. Cardiovascular Effects III. Respiratory System. IV. Blood ...... . V. Liver ...... .
VI. Gastrointestinal System. VII. Genitourinary System. .
VIII. Central Nervous System IX. Peripheral Nervous System X. Other Adverse Reactions
XI. Effects on Foetus XII. Drug Interactions . . .
505 507 508 509 512 512 512 512
· 513 · 515 · 515 · 518 · 518 · 518
· 519 520 521 522 522 522 522 523 524 525 526
· 526 · 527
Contents
D. False Transmitters. . . . . I. General Effects. . . .
II. Cardiovascular System III. Respiratory System IV. Blood ...... . V. Liver ...... .
VI. Gastrointestinal System. VII. Genitourinary System .
VIII. Central Nervous System IX. Peripheral Nervous System X. Other Adverse Reactions
XI. Effects on Foetus XII. Drug Interactions
References
CHAPTER 5
Clinical Features of Adrenergic Agonists and Antagonists. B.N.C. PRICHARD, C.W.I. OWENS, and J. TUCKMAN
A. Alpha- and Beta-Adrenoceptor Agonists I. Introduction. . .
II. Mode of Action . 1. Non-Selective . 2. Alpha-Selective 3. BetarSelective
III. Clinical Uses . . 1. Cardiovascular Medicine . 2. Obstetric Medicine. . 3. Respiratory Medicine 4. Psychiatry
IV. The Future B. Clonidine . . . .
I. Mode of Action II. Haemodynamic and Renal Effects
III. Clinical Use IV. Side-Effects . .
C. Alpha-Methyldopa . I. Mode of Action
II. Cardiovascular Effects III. Clinical Use .... IV. Side-Effects . . . . .
D. Adrenergic Neuron Inhibiting Drugs (ANIDs) I. Mode of Action . . .
II. Haemodynamic Effects . . . III. Clinical Use ...... . IV. Side-Effects and Precautions .
IXX
· 527 · 528 · 528 · 529 · 530 · 531 · 532 · 533 · 533 · 534 · 534 · 534 · 535
· 535
559 559 559 559 566 566 569 569 574 578 592 592 593 593 596 598 598
· 601 · 601 · 602 · 603 .604 .605 · 605 .607 .609 .610
xx
E. Alpha-Receptor Inhibitory Drugs . . . . . . . . . I. Hypertension .............. .
II. Heart Failure Following Myocardial Infarction. III. Asthma ....... .
F. Beta-Adrenergic Inhibitory Drugs I. Hypertension . . .
1. Introduction . . . . . 2. Mode of Action .... 3. Classification and Clinical Evaluation 4. Response of Blood Pressure to Physiological Stimuli During
Treatment ........... . 5. Use in Combination With Other Drugs 6. Selection of Patients for Treatment 7. Pressure Response 8. Conclusion
II. Angina Pectoris . . 1. Introduction . . 2. Mode of Action . 3. Effect ..... 4. Comparison of Adrenergic Blocking Drugs 5. Beta-Blocking Drugs and Other Anti-Anginal Agents 6. Withdrawal 7. Regulation of Dose . 8. Value ...... .
III. Cardiovascular Disease 1. Acute Myocardial Infarction 2. Long-Term Cardioprotective Effect 3. Vasculoprotective Effect . 4. Blood ........ . 5. Arrhythmias . . . . . . 6. Congenital Heart Disease . 7. Fallot's Tetralogy 8. Other Cardiovascular Uses
IV. Hyperthyroidism V. Tremor ....
VI. Psychotropic Uses 1. Anxiety ... 2. Drug Dependence 3. Psychosis 4. Migraine
VII. Glaucoma VIII. Side-Effects
IX. Conclusion
References
Author Index
Subject Index
Contents
.611
.611
.618
.619
.619
.620
.620
.620
.627
. 631
.632
.634
.634
.634
.635
.635
.635
.637
.640
.641
.641
.642
.643
.644
.644
.645
.645
.646
.646
.648
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.650
.650
.650
.651
.651
.652
.652
.653
.655
.656
.699
. 817
Contents Part I: Activators and Inhibitors
Section I: General Considerations
CHAPTER 1 Chemistry of Alpha- and Beta-Adrenoceptor Agonists and Antagonists. D.K.PHILLIPS
CHAPTER 2 Sympathomimetic Amine-Induced Responses of Effector Organs Subserved by Alpha-, Beta1-, and Beta2-Adrenoceptors. A ARNOLD
CHAPTER 3 Evaluation of Adrenergic Alpha- and Beta-Receptor Activators and Adrenergic Alphaand Beta-Receptor Blocking Agents. P. N. PATIL and R.R.RuFFOLO, JR. With 9 Figures
CHAPTER 4
Evaluation of Agents That Release or Modify Release of Adrenergic Transmitter. lM. ARMSTRONG and AF. GREEN
CHAPTER 5 Catecholamine Receptors on Nerve Terminals. M.J. RAND, W. MCCULLOCH, and D.F. STORY. With 10 Figures
CHAPTER 6
Adrenergic Agents, Calcium Ions, and Cyclic N ucleotides in the Control of Cell Proliferation. J.F. WHITFIELD. With 26 Figures
CHAPTER 7 Effects on the Metabolism. S. ELLIS
Section II: Effects on the Autonomic and on the Central Nervous System
A. Presynaptic Receptors in the Autonomic Nervous System. J. S. GILLESPIE
B. Adrenergic Activators and Inhibitors on the Central Nervous System. A PHILIPPU
CHAPTER 1
Regulation of Monoamine Synthesis and Utilization by Receptors. N.-E. ANDEN. With 9 Figures
XXII Contents of Part I
CHAPTER 2
Interactions of Opiates and Endorphins With Cerebral Catecholamines. J. BLAsIG and A. HERZ
CHAPTER 3
Behavioural Pharmacology Reflecting Catecholamine Neurotransmission. U. UNGERSTEDT. With 11 Figures
CHAPTER 4 Regulation of the Arterial Blood Pressure. A. PHILIPPU. With 4 Figures
CHAPTER 5
Catecholamines and the Regulation of Body Temperature. R.D. MYERS. With 5 Figures
CHAPTER 6
Regulation of Food Intake. J. F. MARSHALL. With 2 Figures
CHAPTER 7
Regulation of Water Intake. D.K. MEYER and G. HERTTING
Section III: Effects on the Cardiovascular System
CHAPTER 1
Effect of Adrenergic Activators and Inhibitors on the Electrical Activity of the Heart. L. SZEKERES and J. Gy. P APP
CHAPTER 2
Effects of Beta- and A1pha-Adrenoceptor Activators and Adrenergic Transmitter Releasing Agents on the Mechanical Activity of the Heart. H. SCHOLZ. With 8 Figures
CHAPTER 3
Effects of Adrenergic Activators and Inhibitors on the Coronary Circulation. J.R. PARRATT. With 22 Figures
CHAPTER 4
Effects on Myocardial Metabolism. L. WILL-SAHAB and E. G. KRAUSE. With 4 Figures
CHAPTER 5
Effects on the General Hemodynamics and Peripheral Circulation. H. VAPAATALO and P. SAYNAVALAMMI. With 5 Figures
Author Index
Subject Index
