Modern Inhalation Anesthetics, Softcover reprint of the original 1st ed. 1972 Handbook of Experimental Pharmacology Series, Vol. 30

With contributions by numerous experts

Section 1..- Foreword and Commentary.- Section 2..- The Chemistry of Modern Inhalation Anesthetics.- I. Introduction.- II. Halothane.- A. Synthesis.- 1. ICI Process.- 2. Hoechst Process.- 3. Miscellaneous Processes.- 4. Synthesis of Optically Active Halothane.- 5. Synthesis of Isotopically Labeled Halothane.- B. Chemical Reactions of Halothane.- 1. Thermal Decomposition.- 2. Reactions with Metals.- 3. Reaction with Base.- 4. Photochemical Reactions.- 5. Halothane Azeotrope.- III. Methoxyflurane.- A. Synthesis.- B. Synthesis of Isotopically Labeled Methoxyflurane.- C. Chemical Reactions of Methoxyflurane.- 1. Thermal Decomposition.- 2. Reactions with Metals.- 3. Reaction with Bases.- 4. Reaction with Acids.- 5. Photochemical Reactions.- IV. Fluroxene.- A. Synthesis.- 1. Air Reduction Process.- 2. Miscellaneous Processes.- B. Chemical Reactions of Fluroxene.- Fluroxene Azeotropes.- V. Teflurane.- A. Synthesis.- B. Chemical Properties.- 1. Reaction with Base.- 2. Photochemical Stability.- VI. Roflurane.- VII. Flammability.- VIII. Foaming in Halogenated Anesthetics.- References.- Section 3.0 Clinical Monographs.- 3.1 Halothane.- I. Development of Halothane and Early Clinical Trials.- II. Physical and Chemical Properties of Halothane.- III. Methods of Assaying Halothane Concentration.- IV. Methods of Administration: Anesthetic Circuits and Vaporizers.- A. Anesthetic Circuits.- B. Vaporizers.- V. Uptake and Distribution of Halothane — Clinical Considerations.- VI. Anesthetic Requirement of Halothane.- VII. Effects on Physiological Systems.- A. Nervous System.- B. Cerebral Circulation and Metabolism.- C. Respiratory System.- D. Circulatory System.- E. Liver.- F. Other Systems.- VIII. Clinical Considerations.- A. Specific Applications.- B. Miscellaneous After-effects.- IX. Concluding Remarks.- References.- 3.2 Methoxyflurane and Teflurane.- I. Pre-Anesthetic Medication.- II. Techniques of Administration.- A. Open Drop Technique.- B. Semi-Closed System.- C. Closed System.- D. Non-Rebreathing System.- E. Penthrane Analgizer.- III. Other Drugs Used in Conjunction with Methoxyflurane.- IV. Methoxyflurane and Muscle Relaxants.- V. Induction Techniques.- VI. Types of Surgery Suitable for Methoxyflurane Anesthesia.- VII. The Use of Methoxyflurane for Obstetrical Analgesia and Anesthesia.- VIII. Contraindications and Precautions.- IX. Summary and Critique.- X. Teflurane.- XI. Chemical and Physical Properties.- XII. Pharmacology.- XIII. Miscellaneous Findings.- XIV. Clinical Use of Teflurane.- XV. Summary and Conclusions.- References.- 3.3. Fluroxene.- I. Flammability.- II. Azeotrope.- III. Methods of Estimation.- IV. Bio-transformation.- V. Cardiovascular Effects.- VI. Central Nervous System Effects.- VII. Respiratory Effects.- VIII. Gastro-intestinal, Hepatic, and Renal Effects.- IX. Clinical Considerations.- X. Applications.- XI. Conclusion.- References.- Section 4.0. Comparative Action on Vital Systems of Man.- 4.1. Central Nervous System.- A. Stages and Planes of Anesthesia.- B. Clinical Observations.- C. Anesthetic Agents.- 1. Ethers — Diethyl Ether (Ether).- 2. Halogenated Agents.- 3. Other Anesthetics.- Summary.- References.- 4.2. Autonomic Nervous System.- I. Introduction.- II. Afferent Nervous System.- 1. Baroreceptor Effects.- 2. Chemoreceptor Effects.- III. Central Nervous System.- IV. Peripheral Nervous System.- 1. Preganglionic Effects.- 2. Ganglionic Effects.- 3. Nerve Ending.- V. Effector Sites.- VI. Biochemistry.- VII. Concluding Remarks.- VIII. Summary.- References.- 4.3. Circulatory Effects of Modern Inhalation Anesthetic Agents.- I. Introduction.- A. Hemodynamics.- B. Regional Blood Flow.- C. Cardiac Arrhythmias.- D. Catecholamines.- E. Myocardial Function.- II. Halothane.- A. Hemodynamics.- 1. Cardiac Output.- a) Extra-Anesthetic Factors.- b) Adaptation.- c) Effects of Induction.- d) Oxygen Consumption.- e) Hemorrhage.- f) Halothane-Ether Azeotrope.- 2. Arterial Pressure.- a) Extra-Anesthetic Factors.- b) Adaptation.- c) Effects of Induction.- d) Halothane-Ether Azeotrope.- 3. Heart Rate.- a) Extra-Anesthetic Factors.- b) Adaptation.- c) Induction.- d) Mechanism.- e) Halothane-Ether Azeotrope.- 4. Stroke Volume.- a) Adaptation.- b) Induction.- 5. Total Peripheral Resistance.- 6. Central Venous Pressure.- B. Regional Blood Flow.- 1. Pulmonary Circulation.- 2. Coronary Blood Flow.- 3. Renal Circulation.- 4. Splanchnic Circulation.- 5. Cerebral Circulation.- 6. Peripheral (Limb) Circulation.- 7. Microcirculation.- C. Myocardial Function.- D. Arrhythmias.- 1. Incidence and Types.- 2. Hemodynamic Effect of Atrial Arrhythmias.- 3. Effect of CO2.- 4. Administration of Epinephrine.- 5. Injection of Other Cardiovascular-active Agents.- 6. Adrenergic Block.- 7. Mechanism of Arrhythmias.- E. Catecholamines.- 1. Plasma and Tissue Catecholamine Levels.- 2. Norepinephrine Release and Reuptake.- 3. Response to Catecholamines.- 4. Adrenergic Blockade.- F. Blood Volume.- G. Blood Viscosity.- III. Methoxyflurane.- A. Hemodynamics.- 1. Cardiac Output.- 2. Arterial Pressure.- a) Extra-Anesthetic Factors.- 3. Heart Rate.- a) Extra-Anesthetic Factors.- 4. Stroke Volume.- 5. Total Peripheral Resistance.- 6. Central Venous (Right Atrial) Pressure.- B. Regional Circulation.- 1. Pulmonary Circulation.- 2. Coronary Blood Flow.- 3. Renal Blood Flow.- 4. Peripheral (Limb) Flow.- 5. Microcirculation.- C. Myocardial Function.- D. Arrhythmias.- 1. Incidence and Types.- 2. Effect of Increased C02.- 3. Administration of Epinephrine and Other Agents.- E. Catecholamines.- 1. Plasma Levels.- 2. Response to Norepinephrine; Disposition of Norepinephrine.- 3. Response to Adrenergic Blockade.- F. Miscellaneous Effects.- IV. Fluroxene.- A. Hemodynamics.- B. Regional Circulation.- C. Myocardial Function.- D. Arrhythmias.- V. Teflurane.- A. Hemodynamics.- B. Arrhythmias.- VI. Halopropane.- A. Hemodynamics.- B. Arrhythmias.- C. Catecholamines.- D. Miscellaneous Effects.- VII. Nitrous Oxide.- A. Hemodynamics.- B. Regional Circulation.- C. Catecholamines.- D. Myocardial Contractility.- VIII. Miscellaneous Agents.- References.- 4.4. Liver. C. Trey (see page 502).- 4.5. General Anesthesia and the Kidney.- Indirect Circulatory Effects.- Sympathetic Nervous System.- Endocrine System.- Direct Effects of Anesthetics on Renal Function.- Summary of Anesthetic Effects on Renal Function.- Nephrotoxicity.- Summary.- References.- 4.6. Respiratory System.- I. Physiologic Changes During Anesthesia.- II. Depth of Anesthesia.- III. Resting Ventilation.- IV. Ventilatory Response.- V. Other Drugs.- VI. Surgical Stimulation.- VII. Recovery.- Summary.- References.- 4.7. Metabolic Effects of Anesthetics.- I. Direct Effects.- II. Indirect Effects.- III. In Vivo Changes.- Summary.- References.- 4.8. Endocrine System.- Summary.- References.- 4.9. The Action of Inhalation Anesthetics on the Gastrointestinal Tract.- I. Introduction.- A. Potential Spectrum of Gastrointestinal Activity.- II. Esophagus.- A. Physiology.- 1. Pharyngoesophageal Sphincter.- 2. Esophagus.- 3. Gastroesophageal Sphincter.- B. Pathophysiology.- 1. Nausea, Retching and Emesis.- 2. Regurgitation.- 3. Eructation.- 4. Clinical Considerations.- C. Pharmacology.- D. Special Clinical Considerations.- III. Gastric Emptying.- A. Physiology.- B. Pharmacology.- IV. Secretion.- A. Salivary Secretion.- B. Gastric Secretion.- V. Absorption.- VI. Motility.- A. Physiology.- B. Preanesthetic Medication.- C. Pharmacology.- 1. Gastric and Intestinal Contractile Activity.- 2. Gastrointestinal Transit.- VII. Gas.- Summary.- References.- Section 5.0. Absorption, Distribution and Excretion.- 5.1. Kinetics.- A. A Simple Analogue.- B. Quantitation of the Analogue.- C. Comparison with Experiment.- D. The General Pattern of Distribution.- E. The Effects of Different Inspired Tensions.- F. The Effects of Different Solubilities.- G. The Approach to Equilibrium for Specific Agents.- H. The Use of “Overpressure”.- J. The Effects of Changes of Ventilation and Circulation.- K. Elimination during Recovery.- L. The Effects of Processes not Represented by the Simple Analogue.- References.- 5.2. Biotransformation.- I. Introduction.- II. Chloroform.- III. Diethyl Ether.- IV. Halothane.- V. Methoxyflurane.- VI. Trichloroethylene.- VII. Fluroxene.- VIII. Other Anesthetics.- IX. Enzyme Systems.- X. Implications of Metabolism.- References.- Section 6.0. Mechanism of Anesthesia.- 6.1. Molecular Aspects.- References.- 6.2. Neurophysiological Aspects.- I. Experimental Work on the Cat.- A. Halothane.- 1. The EEG Recording.- 2. The Arousal Response.- 3. Evoked Potentials.- a) Along the Specific Primary Pathways.- b) Along the Non-specific Pathways.- 4. Effect of Halothane on the Recruiting Response.- 5. After-discharges.- 6. Effect of Halothane on the Metrazol (Pentylene Tetrazol) Threshold.- 7. Reactions to Dental Stimulation.- B. Methoxyflurane.- 1. The EEG Recording.- 2. Reticular Arousal Response.- 3. Evoked Potentials.- a) Changes in the Evoked Potentials along the Specific Primary Pathway under the Effect of this Drug are seen as.- b) Non-specific Pathways.- 4. Effect of Methoxyflurane on the Recruiting Response.- 5. Effects on the After-discharges and the Metrazol (Pentylene Tetrazol) Threshold.- 6. Responses to Dental Stimulation.- II. Primate Investigations.- A. Halothane.- a) Before the Drug.- b) Effects of Inhaling 0.5% Halothane.- c) Effects of 1% Halothane.- d) Effects of 2% Halothane.- e) After Stopping Inhalation of Halothane.- B. Methoxyflurane.- a) Before Anesthesia.- b) Inhalation of 0.25% of Methoxyflurane.- c) Inhalation of 0.5% Methoxyflurane.- Conclusions.- References.- 6.3. Effects of Anesthetics on Metabolism of Brain.- I. Introduction.- II. Oxygen and Oxidations.- A. Physiological Considerations.- B. Anesthesia.- C. Non-Volatile Anesthetics.- D. Volatile Anesthetics.- E. In Vitro Studies.- III. Glucose.- A. Glucose Uptake during Narcosis.- B. Brain Level of Glucose.- C. Glycogen Levels.- D. Effects on Glucose Metabolism in Sympathetic Ganglia and Perfused Brain.- IV. High Energy Phosphates.- V. Amino Acid and Protein Metabolism.- VI. Phospholipids.- VII. Acetylcholine.- A. Surface Release.- B. Brain Content.- C. Enzyme-Related Studies.- References.- Section 7..- Exploratory and Newer Compounds.- I. Aim.- II. History.- 1. Chemical Structure.- 2. Purity.- 3. Flammability.- 4. Chemical Inertness.- Chronological List of Some Key References in the Development of Fluorinated Anesthetics.- Patent List of Fluorinated Anesthetics.- References.- Section 8..- Comparative Aspects of Anesthesia in Animals.- I. Inhalation Anesthetics.- II. Tracheal Intubation.- III. Complications and Species Differences of Tracheal Intubation.- IV. Systems for Veterinary Anesthesia.- V. Intravenous Anesthetic Agents.- VI. Non-Barbiturate Injectable Drugs.- Urethan.- VII. Preanesthetic Medication and Drugs for Restraint.- A. Narcotic-Analgesics.- B. Neuroleptanalgesia.- C. Atropine Sulfate.- D. Tranquilizers.- E. Cyclohexamines (Dissociogenic Agents).- F. Rompun.- References.- Section 9..- Toxicity of Impurities.- I. Hydrocarbons.- II. Ethers.- III. Halogenated Compounds.- IV. Nitrous Oxide.- References.- Section 10.0.- Interaction of Drugs.- I. Chemical Reactions.- II. Transport Phenomena.- III. Interaction at Receptor Site.- IV. Interaction at Several Sites.- V. Altered Drug Metabolism.- VI. Effects of Temperature.- VII. Patient Factors Affecting Drug Action.- References.- 4.4. The Liver.- I. Clinical and Biochemical Assessment of Liver Function.- II. The Diagnostic Approach to Liver Disease.- III. Systemic Effects of Liver Failure.- IV. The Treatment of Patients with Fulminant Hepatic Failure before and during Anesthesia.- V. Post-Operative Acute Hepatic Failure.- VI. Toxic and Drug Injuries to the Liver.- VII. Viral Hepatitis.- VIII. Chronic Hepatitis.- IX. Alcoholic-Associated Liver Disease.- X. Anesthesia for Patients with Liver Disease.- References.- Author Index.