Adrenergic Activators and Inhibitors

of Part II.- Section IV: Effects on Organ Systems Other Than the Nervous and the Cardiovascular System.- 1 Systemic Pharmacology of Adrenergic Activators and Inhibitors: Effects on the Respiratory System.- A. Introduction.- B. Epinephrine: A Unique Example of Direct Activator of Alpha- and Beta-Adrenoceptors.- I. Alpha- and Beta-Receptors in the Respiratory System.- 1. Upper Respiratory Tract.- 2. Lower Respiratory Tract.- 3. Pulmonary Circulation.- 4. Bronchial Circulation.- 5. Ventilation - Perfusion Relationship.- II. Antiasthmatic Use and Airway Resistance.- 1. Classic Physiologic Concept.- 2. Recent Biochemical Concepts.- III. Adverse Effects on the Pulmonary Circulation.- 1. Pulmonary Arterial Hypertension.- 2. Acute Pulmonary Edema.- IV. Tachyphylaxis and Status Asthmaticus.- V. Epinephrine as Neurohumoral Transmitter of the Airways.- C. Direct Activator of Alpha-Receptors.- I. Norepinephrine.- 1. Pulmonary Vasoconstriction and Pulmonary Edema.- 2. Uptake of Norepinephrine in the Pulmonary Circulation.- II. Dopamine.- III. Phenylephrine.- IV. Methoxamine.- V. Nasal Decongestants.- D. Direct Activators of Beta-Receptors.- I. Isoproterenol.- 1. Antiasthmatic Use and Airway Resistance.- 2. Paradoxical Bronchospasm.- 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 Phenylpropanolamine 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.- 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.- 2 Effects of Adrenergic Activators and Inhibitors on the Skeletal Muscles.- 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.- I. Effects Unrelated to Adrenergic Mechanisms.- I. Adrenergic Neurone Blocking Drugs.- II. Beta-Adrenoceptor Blocking Drugs.- 1. Plasma Membrane.- 2. Sarcoplasmic Reticulum.- References.- 3 Systemic Pharmacology of Adrenergic Agonists and Antagonists: Effects on the Digestive System.- A. Introduction.- B. Alpha- and Beta-Adrenoceptor Agonists.- I. Effect on Motility.- 1. Introduction.- 2. Effect on Non-Sphincteric Smooth Muscle.- 3. Effect on Sphincteric Smooth Muscle.- 4. Effect on Acetylcholine Release from Enteric Neurones.- 5. Effect on Noradrenaline Release from Adrenergic Neurones.- 6. Mechanism of Action.- II. Effect on Gastro-Intestinal Vasculature.- III. Effect on Gastric and Intestinal Secretion.- 1. Action of Alpha-and Beta-Adrenoceptor Agonists.- 2. Mechanism of Action.- IV. Effect on Absorption.- V. Summary.- C. Adrenergic Transmitter Releasing Agents.- I. Introduction.- II. Effect on Motility.- III. Effect on Gastric Secretion.- IV. Summary.- D. Alpha-and Beta-Adrenoceptor Antagonists.- I. Introduction.- II. Effect on Motility.- III. Effect on Vasculature.- IV. Effect on Gastric Secretion.- 1. Alpha-Adrenoceptor Antagonists.- 2. Beta-Adrenoceptor Antagonists.- V. Summary.- E. Adrenergic Neurone Blocking Agents and False Transmitters.- I. Introduction.- II. Effect on Motility.- III. Effect on Gastric Secretion.- IV. Summary.- References.- 4 Effects of Adrenergic Activators and Inhibitors on the Endocrine System.- A. Introduction.- B. Embryologic Relationship of the Neural and Endocrine Systems.- C. Role of Catecholamines in Modulating the Function of the Endocrine System.- I. Mediators of Catecholamine-Induced Modulation of the Endocrine System.- II. Adrenergic Drugs Used to Examine Hormone Secretion and Action.- 1. Neutral Amino Acids.- 2. Enzyme Inhibitors.- 3. Inhibitors of Neuronal Uptake.- 4. Receptor Agonists.- 5. Receptor Antagonists.- 6. Neurotoxins.- 7. Inhibitors of Monoamine Storage and Release.- D. Effects of Adrenergic Agents on the Endocrine System in Laboratory Animals and Man.- I. Adrenergic Drugs and the Pituitary.- 1. Anterior Pituitary.- 2. Posterior Pituitary.- II. Adrenergic Drugs and the Pineal.- III. Adrenergic Drugs and the Thyroid and Parathyroid.- 1. Thyroxine and Triiodothyronine.- 2. Thyrocalcitonin and Parathyroid Hormone.- IV. Adrenergic Drugs and the Gut.- V. Adrenergic Drugs and the Pancreas.- 1. Insulin.- 2. Glucagon.- 3. Somatostatin.- VI. Adrenergic Drugs and the Kidney.- 1. Renin-Angiotensin.- 2. Erythropoietin.- 3. Prostaglandins.- E. Concluding Remarks.- References.- 5 Systemic Pharmacology of Adrenergic Activators and Inhibitors: Effects on the Genital System.- A. Introduction.- B. Effect of Beta-Sympathomimetics on the Myometrium in Pregnancy.- I. Connection Between the Structure and Effect of Beta-Sympathomimetics.- II. Mechanism of Action.- III. Metabolism and Pharmacokinetics.- C. Effect of Beta-Sympathomimetics on the Non-Pregnant Uterus.- D. Effect of Beta-Sympathomimetics on the Fallopian Tubes.- E. Administration of Beta-Sympathomimetic Drugs in Obstetrics.- I. Clinical Studies.- II. Drugs Applied in Clinical Practice.- III. Indications.- IV. Contra-Indications.- V. Methods.- VI. Effectiveness.- F. Maternal Side-Effects of Tocolysis Carried out With Beta-Sympathomimetics.- I. Cardiac Effects.- II. Metabolic Effects.- 1. Carbohydrate Metabolism.- 2. Lipid Metabolism.- 3. Blood Gases and Acid-Base Balance.- 4. Electrolytes.- 5. Thrombocyte Function.- G. Therapy of the Side-Effects of Beta-Sympathomimetic Treatment.- I. Beta-Receptor Blockers.- II. Calcium Antagonists.- H. Foetal Effects of Tocolysis Carried out With Beta-Sympathomimetics.- I. Diaplacental Penetration.- II. Effect on the Utero-Placental Circulation.- III. Effect on the Foetal Heart.- IV. Myocardium Lesion and Tocolysis.- V. The Effect of Beta-Sympathomimetics on Foetal Pulmonary Maturation.- VI. Effect on Newborns of Beta-Sympathomimetic Treatment of Pregnant Women.- References.- 6 Effects of Adrenergic Activators and Inhibitors on Kidney Function.- A. Introduction.- B. Renal Hemodynamics.- I. Effects of Alpha-Adrenergic Activators.- 1. Adrenaline and Noradrenaline.- 2. Other Alpha-Adrenergic Activators.- 3. Factors that Influence Renal Hemodynamic Response to Vasoconstrictive Catecholamines.- II. Effects of Alpha-Adrenergic Inhibitors.- III. Effects of Dopamine.- IV. Effects of Beta-Adrenergic Activators.- 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 of Antidiuretic Hormone.- II. Effects of Beta-Adrenergic Inhibitors.- III. Effects of Alpha-Adrenergic Activators.- IV. Effects of Alpha-Adrenergic Inhibitors.- E. Kidney Intermediary Metabolism.- 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.- 7 Effects of the Adrenergic Activators and Inhibitors on the Urinary Tract.- A. The Upper Urinary Tract.- I. Morphology of the Upper Urinary Tract.- 1. Anatomy.- 2. Histology.- II. Functional Studies in the Upper Urinary Tract.- 1. Pharmacologic Studies in Isolated Calyx and Renal Pelvis Preparations.- 2. Pharmacologic Studies in Isolated Ureter Preparations.- 3. Pharmacologic Studies in Isolated Pyeloureter Preparations.- 4. In Vivo Studies in the Pyeloureteral System.- B. The Lower Urinary Tract.- I. Morphology of the Lower Urinary Tract.- 1. Anatomy.- 2. Histology.- II. Functional Studies in the Lower Urinary Tract.- 1. Pharmacologic Studies in Isolated Bladder Dome and Body Preparations.- 2. Pharmacologic Studies in Isolated Bladder Neck and Urethra Preparations.- 3. In Vivo Studies in Bladder Dome and Body.- 4. In Vivo Studies in Bladder Neck and Urethra.- References.- 8 Miscellaneous Effects: Effects of Adrenergic Activators and Inhibitors on the Eye.- 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.- 6. Factors Determining the Different Effects of Adrenergic Receptor Stimulators in the Eye.- 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.- D. Adrenergic Alpha- and Beta-Receptor Blocking Agents.- I. General Considerations.- II. Effects of Alpha-Receptor Blocking Agents.- III. Effects of Beta-Receptor Blocking Agents.- 1. Synopsis of Their Different Effects.- 2. Betax- and Beta2-Receptor Blocking Agents.- 3. Betax-Receptor Blocking Agents.- 4. Beta2-Receptor Blocking Agents.- IV. Dopaminergic Receptor Blocking Agents.- E. Adrenergic Nerve-End Inhibitors, Neural Transmitter Depleting Agents and False Transmitters.- I. General Considerations.- II. Effects of Adrenergic Nerve-End Inhibitors on the Eye.- III. Effects of Adrenergic Transmitter Depleting Procedures and Agents on the Eye.- IV. False Transmitters.- F. Summary.- References.- 9 Effects of Adrenergic Activators and Inhibitors on the Sweat Glands.- 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.- Section V: Kinetics, Biotransformation, Toxic Effects and Clinical Implications.- 1 Kinetics and Biotransformation of Adrenergic Activators and Inhibitors: Adrenergic Alpha- and Beta-Receptor Activators.- A. Alpha-Receptor Activators.- I. Etilephrine.- 1. Metabolism.- 2. Kinetics.- 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.- 2 Kinetics and Biotransformation of Adrenergic Activators and Inhibitors: Adrenergic Transmitter Releasing Agents.- 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.- 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.- 3 Kinetics and Biotransformation of Adrenergic Inhibitors.- Criteria for Selection of Drugs.- Definitions.- 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.- VI. Dichloroisoprenaline.- VII. Metoprolol.- VIII. Oxprenolol.- IX. Pindolol.- X. Practolol.- XI. Pronethalol.- XII. Propranolol.- XIII. Sotalol.- XIV. Timolol.- XV. Tolamolol.- XVI. Toliprolol.- Summary.- References.- 4 Toxic Effects of Adrenergic Nerve-End Inhibitors, Neural Transmitter Depleting Agents and False Transmitters.- 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.- 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.- 5 Clinical Features of Adrenergic Agonists and Antagonists.- A. Alpha- and Beta-Adrenoceptor Agonists.- I. Introduction.- II. Mode of Action.- 1. Non-Selective.- 2. Alpha-Selective.- 3. Beta2-Selective.- 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.- 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.