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Book Details
Abstract
Pharmacology and physiology are the foundation of every anesthesia provider’s training and clinical competency. Pharmacology and Physiology for Anesthesia: Foundations and Clinical Application, 2nd Edition, delivers the information you need in pharmacology, physiology, and molecular-cellular biology, keeping you current with contemporary training and practice. This thoroughly updated edition is your one-stop, comprehensive overview of physiology, and rational anesthetic drug selection and administration, perfect for study, review, and successful practice.
- Contains new chapters on Special Populations (anesthetic pharmacology in obesity, geriatrics, and pediatrics), Oral and Non-IV Opioids, Thermoregulation, Physiology and Pharmacology of Obstetric Anesthesia, Chemotherapeutic and Immunosuppresive Drugs, and Surgical Infection and Antimicrobial Drugs.
- Incorporates entirely new sections on Physics, Anatomy, and Imaging.
- Includes new information on consciousness and cognition, pharmacodynamics, the immune system, and anti-inflammatory drugs.
- Features user-friendly tables, figures, and algorithms (including 100 new illustrations), all presented in full color and designed to help explain complex concepts.
- Helps you understand the molecular mechanism of drug actions and identify key drug interactions that may complicate anesthesia with dedicated sections on these areas.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | cover | ||
| Inside Front Cover | ifc1 | ||
| Pharmacology and Physiology for Anesthesia | i | ||
| Copyright Page | iv | ||
| Dedication | v | ||
| Contributors | vii | ||
| Preface to the Second Edition | xiii | ||
| Excerpts from the Preface to the First Edition | xv | ||
| Table Of Contents | xvii | ||
| Second Half title page | xix | ||
| I Basic Principles of Pharmacology | 1 | ||
| 1 Mechanisms of Drug Action | 2 | ||
| Abstract | 2.e1 | ||
| Keywords | 2.e1 | ||
| Chapter Outline | 2 | ||
| The Receptor Concept | 2 | ||
| Historical Beginnings | 2 | ||
| Modern Development | 3 | ||
| Pharmacodynamics | 3 | ||
| Drug Binding | 3 | ||
| From Drug Binding to Physiologic Effect | 4 | ||
| Efficacy | 5 | ||
| Full Agonists, Partial Agonists, and Inverse Agonists | 6 | ||
| Antagonism | 6 | ||
| Allosteric Drug Interactions | 8 | ||
| Multiple Binding Sites on the Same Receptor Protein | 8 | ||
| Allosteric Binding Sites | 8 | ||
| Pharmacogenetics | 9 | ||
| Drug Discovery | 10 | ||
| Structure-Activity Relationship | 10 | ||
| Identification of Drug Targets | 10 | ||
| Purification of Receptors | 10 | ||
| Drug Targets | 11 | ||
| Cell Signaling | 12 | ||
| Emerging Developments | 14 | ||
| Pharmacophore Modeling | 14 | ||
| Phenotype-Based Drug Discovery | 14 | ||
| Novel Antidotes | 17 | ||
| Key Points | 17 | ||
| Key References | 18 | ||
| References | 18 | ||
| 2 Pharmacokinetic and Pharmacodynamic Principles for Intravenous Anesthetics | 20 | ||
| Abstract | 20.e1 | ||
| Keywords | 20.e1 | ||
| Chapter Outline | 20 | ||
| Historical Perspective | 20 | ||
| Unique Aspects of Anesthetic Pharmacology | 21 | ||
| Anesthesiology Compared With Other Disciplines | 21 | ||
| A Surfing Analogy as a Simple Conceptual Framework | 21 | ||
| Clinical Pharmacology | 22 | ||
| Posology | 22 | ||
| General Schema | 23 | ||
| Pharmacokinetics | 24 | ||
| Pharmacodynamics | 24 | ||
| The Biophase | 25 | ||
| Drug Interactions | 25 | ||
| Pharmacologic Modeling | 26 | ||
| PK-PD Models as Versions of Pharmacologic Reality | 26 | ||
| PK-PD Model Building Methods | 26 | ||
| Limitations in Building & Applying PK-PD Models | 28 | ||
| Early Model Misspecification | 28 | ||
| Stereochemistry | 28 | ||
| Active Metabolites | 29 | ||
| Variability | 29 | ||
| Pharmacologic Simulation | 29 | ||
| Unimportance of Individual PK-PD Model Parameters | 29 | ||
| Importance of PK-PD Model Simulation | 30 | ||
| PK-PD Model Simulation and Anesthesia Posology | 31 | ||
| Bolus Front-End and Back-End Kinetics | 31 | ||
| Infusion Front-End Kinetics | 31 | ||
| Infusion Back-End Kinetics | 32 | ||
| Influence of Dose on Bolus Onset and Offset of Effect | 32 | ||
| Influence of Loading Dose on Infusion Front-End and Back-End Kinetics | 34 | ||
| Influence of Special Populations | 34 | ||
| Influence of a Second Drug on Effect | 35 | ||
| PK-PD Models and Technology | 35 | ||
| Target-Controlled Infusion | 35 | ||
| Emerging Developments | 37 | ||
| PK-PD Advisory Displays | 37 | ||
| Propofol Measurement in Expired Gas | 39 | ||
| Allometric Scaling in Pharmacokinetics | 39 | ||
| Key Points | 39 | ||
| Key References | 40 | ||
| References | 40 | ||
| 3 Pharmacokinetics of Inhaled Anesthetics | 44 | ||
| Abstract | 44.e1 | ||
| Keywords | 44.e1 | ||
| Chapter Outline | 44 | ||
| Historical Perspective | 44 | ||
| Classes of Inhaled Anesthetics | 44 | ||
| Physical Properties | 45 | ||
| Measuring Anesthetic Potency as MAC | 46 | ||
| Monitoring Inhaled Anesthetic Delivery | 48 | ||
| Differences Between Inhaled and Intravenous Anesthetic Delivery | 48 | ||
| Agent Analysis | 48 | ||
| Monitoring Neurophysiologic Effect | 49 | ||
| Metabolism and Degradation | 49 | ||
| Metabolism | 49 | ||
| Chemical Degradation | 49 | ||
| Carbon Monoxide Production | 50 | ||
| Uptake and Distribution | 50 | ||
| General Principles | 50 | ||
| Determinants of Wash-In | 51 | ||
| Special Factors | 51 | ||
| Tissue Uptake | 51 | ||
| Recovery and Elimination | 52 | ||
| Nitrous Oxide: Concentration Effect, Second Gas Effect, Diffusion Hypoxia, and Effects on Closed Gas Spaces | 53 | ||
| Gas Delivery Systems | 54 | ||
| Reaction of CO2 With Barium Hydroxide Lime (Baralyme, Obsolete) | 56 | ||
| Reaction of CO2 With Lithium Hydroxide (in Current Use) | 56 | ||
| Low-Flow Anesthesia | 57 | ||
| Pharmacoeconomic Considerations | 57 | ||
| Emerging Developments | 57 | ||
| Intravenous Delivery of Volatile Anesthetics | 57 | ||
| Volatile Anesthetics in the Intensive Care Unit | 57 | ||
| Key Points | 58 | ||
| Physics: Liquids, Vapors, Gases, and the Gas Laws | 60 | ||
| Outline | 60 | ||
| Background | 60 | ||
| Liquids, Gases, and Vapors | 60 | ||
| Liquefaction and Vaporization | 60 | ||
| Gas Laws | 62 | ||
| Humidity | 64 | ||
| Gas Conditions | 65 | ||
| References | 65 | ||
| Physics: Monitoring Gas Concentrations | 66 | ||
| Outline | 66 | ||
| Background | 66 | ||
| Calibration and Preparation Before Use | 66 | ||
| Monitoring Methods | 66 | ||
| Sidestream | 66 | ||
| Mainstream | 67 | ||
| Technologies | 67 | ||
| Infrared Absorption | 67 | ||
| Paramagnetic Oxygen Sensor | 68 | ||
| Electrochemical Oxygen Sensor | 68 | ||
| Mass Spectrometry | 69 | ||
| Raman Scatter Analysis | 69 | ||
| References | 69 | ||
| Key References | 58 | ||
| References | 58 | ||
| 4 Drug Metabolism and Pharmacogenetics | 70 | ||
| Abstract | 70.e1 | ||
| Keywords | 70.e1 | ||
| Chapter Outline | 70 | ||
| Evolutionary Perspective | 70 | ||
| Pharmacogenetics, Pharmacogenomics, and Variability in Drug Responses | 70 | ||
| Pharmacokinetic Considerations | 70 | ||
| Classification of Drug Metabolism Reactions | 70 | ||
| Phase I Metabolism | 71 | ||
| Phase II Metabolism | 71 | ||
| Phase I Enzymes | 72 | ||
| Cytochrome P450 | 72 | ||
| Flavin-Containing Monooxidases | 74 | ||
| Amine Oxidases, Including Monoamine Oxidase | 76 | ||
| Esterases, Including Butyrylcholinesterase (Pseudocholinesterase) | 77 | ||
| Phase II Enzymes | 77 | ||
| Sites of Drug Metabolism | 78 | ||
| Liver | 79 | ||
| Intestinal Mucosa | 80 | ||
| Lung | 80 | ||
| Blood | 80 | ||
| Pharmacogenomics and Drugs Commonly Used in Anesthesia (Table 4.15) | 81 | ||
| Neuromuscular Blockers | 81 | ||
| Butyrylcholinesterase Deficiency | 81 | ||
| Increased Butyrylcholinesterase Activity | 81 | ||
| Opioids | 82 | ||
| Pharmacokinetic Alterations | 82 | ||
| Opioid Absorption and Distribution | 82 | ||
| Opioid Metabolism | 82 | ||
| Pharmacodynamic Alterations | 83 | ||
| Opioid Receptors | 83 | ||
| Intravenous Anesthetics | 83 | ||
| Pharmacokinetic Alterations | 83 | ||
| II Nervous System | 144 | ||
| 8 Central Nervous System Physiology | 145 | ||
| Abstract | 145.e1 | ||
| Keywords | 145.e1 | ||
| Chapter Outline | 145 | ||
| Historical Perspective | 145 | ||
| Glia | 146 | ||
| CSF, Interstitial Fluid, and the Glymphatic System | 146 | ||
| The Neuron | 148 | ||
| Basic Structure | 148 | ||
| Excitability | 148 | ||
| Communication | 153 | ||
| Membrane Time Constant | 153 | ||
| Action Potential | 154 | ||
| Synapses | 154 | ||
| Transmitter Release and Action | 154 | ||
| Plasticity | 156 | ||
| Transmitters and Receptors | 157 | ||
| Neuronology | 159 | ||
| The Brain: Structure Determines Function | 159 | ||
| Structure | 159 | ||
| Spinal Cord | 162 | ||
| Function | 163 | ||
| Default Mode Network | 163 | ||
| Brain Rhythms | 163 | ||
| Emerging Developments | 164 | ||
| Probing the Brain | 164 | ||
| Optogenetics and Pharmacogenetics | 165 | ||
| Key Points | 166 | ||
| Physics: Basic Electronics and Electrical Hazards | 170 | ||
| Outline | 170 | ||
| Background | 170 | ||
| Basic Electrical Concepts | 170 | ||
| Simple Circuits | 170 | ||
| Electrical Circuit Elements | 171 | ||
| Electrical Hazards | 172 | ||
| Reference | 173 | ||
| Key References | 167 | ||
| References | 167 | ||
| 9 Central Nervous System Physiology | 174 | ||
| Abstract | 174.e1 | ||
| Keywords | 174.e1 | ||
| Chapter Outline | 174 | ||
| Cerebrovascular Anatomy | 174 | ||
| Vascular Architecture | 174 | ||
| Arteries and Arterioles | 174 | ||
| Venous Circulation | 174 | ||
| Anterior Circulation | 175 | ||
| Posterior Circulation | 175 | ||
| Regulation of Cerebral Blood Flow | 175 | ||
| Chemical Regulation of Cerebral Blood Flow | 176 | ||
| Cerebral Metabolic Rate | 176 | ||
| Functional State | 177 | ||
| Anesthetic Agents | 177 | ||
| Temperature | 177 | ||
| Paco2 | 177 | ||
| Pao2 | 177 | ||
| Myogenic Regulation (Autoregulation) of Cerebral Blood Flow | 178 | ||
| Neurogenic Regulation of Cerebral Blood Flow | 178 | ||
| Viscosity Effects on Cerebral Blood Flow | 179 | ||
| Vasoactive Agents | 180 | ||
| Systemic Vasodilators | 180 | ||
| Adrenergic Receptor Agonists/Antagonists | 180 | ||
| α1-Receptor Agonists | 181 | ||
| β-Receptor Agonists | 181 | ||
| β-Receptor Blockers | 181 | ||
| Dopamine | 181 | ||
| Intravenous Anesthetics | 181 | ||
| Volatile Anesthetics | 181 | ||
| Age | 181 | ||
| Cerebral Spinal Fluid Dynamics | 181 | ||
| Production | 181 | ||
| Circulation | 181 | ||
| Function | 182 | ||
| Blood-Brain Barrier | 182 | ||
| Pathophysiology of Cerebral Ischemia | 182 | ||
| Critical CBF Thresholds | 182 | ||
| Energy Failure and Excitotoxicity | 183 | ||
| The Nature of Neuronal Death | 184 | ||
| Timing of Neuronal Death | 184 | ||
| Key Points | 185 | ||
| Anatomy and Imaging: The Nervous System | 188 | ||
| Key References | 185 | ||
| References | 185 | ||
| 10 Pharmacology of Intravenous Anesthetics | 193 | ||
| Abstract | 193.e1 | ||
| Keywords | 193.e1 | ||
| Chapter Outline | 193 | ||
| History of Intravenous Anesthesia | 193 | ||
| General Anesthesia by Intravenous Agents | 193 | ||
| Intravenous Anesthesia Mechanisms and Theory | 194 | ||
| Pharmacologic Targets of Intravenous Anesthetics in the Central Nervous System | 194 | ||
| GABAA Receptors | 194 | ||
| GABAA Insights From Mutagenic Studies | 195 | ||
| N-Methyl-d-Aspartate Receptors | 197 | ||
| Other Molecular Targets | 198 | ||
| Individual Agents | 198 | ||
| Barbiturates | 198 | ||
| Benzodiazepines | 200 | ||
| Etomidate | 201 | ||
| Propofol | 203 | ||
| Pharmacology | 203 | ||
| Formulation and Preparation | 203 | ||
| Metabolism, Redistribution, Clearance, and Elimination | 204 | ||
| Advantages and Disadvantages of Propofol as an Induction Agent | 205 | ||
| Clinical Features of Anesthesia Maintenance With Propofol | 205 | ||
| Fospropofol | 206 | ||
| Ketamine | 206 | ||
| Dexmedetomidine | 207 | ||
| Emerging Developments | 209 | ||
| High-Tech Delivery Systems | 209 | ||
| Novel Sedatives | 209 | ||
| Reversal of General Anesthesia | 210 | ||
| Non-Anesthesia Uses of Intravenous Anesthetics | 210 | ||
| Key Points | 210 | ||
| Key References | 210 | ||
| References | 211 | ||
| 11 Pharmacology of Inhaled Anesthetics | 217 | ||
| Abstract | 217.e1 | ||
| Keywords | 217.e1 | ||
| Chapter Outline | 217 | ||
| Historical Perspective | 217 | ||
| Discovery of Inhaled Anesthetics | 217 | ||
| Development of Modern Inhaled Anesthetics | 218 | ||
| Structure-Activity Relationships | 218 | ||
| Meyer-Overton Correlation | 218 | ||
| Stereoselectivity | 219 | ||
| Mechanisms of Action | 220 | ||
| From Lipid-Based to Protein-Based Mechanisms | 220 | ||
| Diversity of Molecular Targets | 220 | ||
| Multiple Behavioral Endpoints | 220 | ||
| Molecular and Cellular Sites of Action | 221 | ||
| Drug Class Effects | 224 | ||
| Nonanesthetic Effects | 225 | ||
| Bronchodilation | 225 | ||
| Neuromuscular Effects | 225 | ||
| Analgesia and Neuroprotection | 225 | ||
| Adverse Effects | 225 | ||
| Respiratory Depression | 225 | ||
| Cardiovascular Depression | 225 | ||
| Cardiac Dysrhythmias | 226 | ||
| Neurophysiologic Effects | 226 | ||
| Immunomodulatory Effects | 226 | ||
| Hepatotoxicity | 226 | ||
| Nephrotoxicity | 227 | ||
| Malignant Hyperthermia | 227 | ||
| Postoperative Nausea and Vomiting | 227 | ||
| Metabolic Effects | 227 | ||
| Unique Features of Individual Agents | 227 | ||
| Agents With Prominent GABAA Receptor Activity | 227 | ||
| Halothane, Enflurane, Methoxyflurane | 227 | ||
| Isoflurane | 227 | ||
| Sevoflurane | 228 | ||
| Desflurane | 228 | ||
| Ether and Chloroform | 228 | ||
| Agents With Prominent NMDA Receptor Activity | 228 | ||
| Nitrous Oxide | 228 | ||
| Xenon | 228 | ||
| Cyclopropane | 228 | ||
| Environmental Considerations | 228 | ||
| Drug Interactions | 228 | ||
| Reduction in MAC by Anesthetic Adjuvants | 228 | ||
| MAC Additivity | 228 | ||
| Synergy With Opioid-Induced Respiratory Depression | 229 | ||
| Factors Influencing MAC | 229 | ||
| Age | 229 | ||
| Temperature | 229 | ||
| Pharmacogenetic Effects on Potency | 229 | ||
| Common Clinical Indications and Considerations | 230 | ||
| Induction and Maintenance of Anesthesia | 230 | ||
| Neuroanesthesia and Neuromonitoring | 230 | ||
| Cardiac Anesthesia | 230 | ||
| Pediatric Anesthesia | 230 | ||
| Obstetric Anesthesia | 230 | ||
| Ambulatory Anesthesia | 230 | ||
| Thoracic Anesthesia | 231 | ||
| Emerging Developments | 231 | ||
| Developmental Neurotoxicity | 231 | ||
| Anesthesia and Neurodegenerative Disease | 232 | ||
| Neuroinflammation and Cognitive Dysfunction | 232 | ||
| Inhaled Anesthetic Sensitivity: Triple Low | 233 | ||
| Anesthetic Preconditioning | 233 | ||
| Immunomodulation and Cancer | 233 | ||
| Closed-Loop Anesthetic Delivery | 233 | ||
| Accelerated Emergence | 234 | ||
| Key Points | 235 | ||
| Key References | 235 | ||
| References | 235 | ||
| 12 Drugs for Neuropsychiatric Disorders | 241 | ||
| Chapter Outline | 241 | ||
| Historical Perspective | 241 | ||
| Antidepressant Drugs | 242 | ||
| Tricyclic Antidepressants | 242 | ||
| History | 242 | ||
| Basic Pharmacology | 242 | ||
| Structure-Activity | 242 | ||
| Mechanism | 242 | ||
| Metabolism | 243 | ||
| Clinical Pharmacology | 244 | ||
| Pharmacokinetics | 244 | ||
| Pharmacodynamics | 244 | ||
| Therapeutic Effects. | 244 | ||
| Adverse Effects. | 244 | ||
| Drug Interactions | 244 | ||
| Selective Serotonin Reuptake Inhibitors | 245 | ||
| History | 245 | ||
| Basic Pharmacology | 245 | ||
| Structure-Activity | 245 | ||
| Mechanism | 245 | ||
| Metabolism | 245 | ||
| Clinical Pharmacology | 246 | ||
| Pharmacokinetics | 246 | ||
| Pharmacodynamics | 246 | ||
| Therapeutic Effects. | 246 | ||
| Adverse Effects. | 247 | ||
| Drug Interactions | 247 | ||
| Monoamine Oxidase Inhibitors | 247 | ||
| Basic Pharmacology | 247 | ||
| Clinical Pharmacology | 247 | ||
| Adverse Effects, Dietary Interactions, and Drug Interactions | 248 | ||
| Dietary Interactions | 248 | ||
| Drug Interactions | 248 | ||
| Atypical Antidepressants | 248 | ||
| Anxiolytic Drugs | 248 | ||
| Benzodiazepines | 248 | ||
| History | 248 | ||
| Basic Pharmacology | 248 | ||
| Structure-Activity | 248 | ||
| Mechanism | 248 | ||
| Metabolism | 248 | ||
| Clinical Pharmacology | 250 | ||
| Pharmacokinetics | 250 | ||
| Pharmacodynamics | 250 | ||
| Therapeutic Effects. | 250 | ||
| Adverse Effects. | 250 | ||
| Drug Interactions | 251 | ||
| Antipsychotic Drugs | 251 | ||
| First-Generation (Typical) Antipsychotics | 251 | ||
| Pharmacology | 251 | ||
| Side Effects | 251 | ||
| Extrapyramidal Side Effects | 251 | ||
| Neuroleptic Malignant Syndrome | 254 | ||
| Other Side Effects | 254 | ||
| Second-Generation (Atypical) Antipsychotics | 254 | ||
| Individual Agents | 254 | ||
| Clozapine (Clozaril) | 254 | ||
| Olanzapine (Zyprexa) | 255 | ||
| Quetiapine (Seroquel) | 255 | ||
| Aripiprazole (Abilify) | 255 | ||
| Risperidone (Risperdal) | 256 | ||
| Mood Stabilizer Drugs | 256 | ||
| Lithium | 256 | ||
| History | 256 | ||
| Basic Pharmacology | 256 | ||
| Structure-Activity. | 256 | ||
| Mechanism | 256 | ||
| Metabolism | 256 | ||
| Clinical Pharmacology | 256 | ||
| Pharmacokinetics | 256 | ||
| Pharmacodynamics | 256 | ||
| Therapeutic Effects | 256 | ||
| Adverse Effects. | 256 | ||
| Drug Interactions | 257 | ||
| Anticonvulsant Mood Stabilizers | 257 | ||
| Individual Agents | 257 | ||
| Valproate (Depakote) | 257 | ||
| Carbamazepine (Tegretol) | 257 | ||
| Lamotrigine (Lamictal) | 257 | ||
| Psychostimulants | 258 | ||
| Pharmacologic Treatment of Parkinson Disease | 258 | ||
| Levodopa | 258 | ||
| History | 258 | ||
| Basic Pharmacology | 258 | ||
| Structure-Activity | 258 | ||
| Mechanism | 258 | ||
| Metabolism | 258 | ||
| Clinical Pharmacology | 258 | ||
| Pharmacokinetics | 258 | ||
| Pharmacodynamics | 258 | ||
| Therapeutic Effects. | 258 | ||
| Adverse Effects. | 259 | ||
| Dopamine Agonists | 259 | ||
| History | 259 | ||
| Basic Pharmacology | 260 | ||
| Structure-Activity | 260 | ||
| Mechanism | 260 | ||
| Metabolism | 260 | ||
| Clinical Pharmacology | 260 | ||
| Pharmacokinetics | 260 | ||
| Pharmacodynamics | 260 | ||
| Therapeutic Effects. | 260 | ||
| Adverse Effects. | 260 | ||
| MAO-B Inhibitors | 260 | ||
| Pharmacologic Treatment of Myasthenia Gravis | 260 | ||
| Anticholinesterases | 260 | ||
| History | 260 | ||
| III Cardiovascular System | 455 | ||
| 23 Cardiovascular Physiology | 456 | ||
| Abstract | 456.e1 | ||
| Keywords | 456.e1 | ||
| Chapter Outline | 456 | ||
| Historical Perspective | 456 | ||
| Cardiac Excitation | 456 | ||
| General Concepts | 456 | ||
| The Action Potential | 458 | ||
| Fast Response Tissue | 458 | ||
| Phase 0—Rapid Depolarization | 458 | ||
| Phase 1—Early Repolarization | 458 | ||
| Phase 2—Plateau | 459 | ||
| Phase 3—Final Repolarization | 459 | ||
| Phase 4—Resting Membrane Potential | 459 | ||
| Slow Response Tissue | 459 | ||
| Phase 4—Slow Spontaneous Depolarization | 459 | ||
| Phase 0—Depolarization | 459 | ||
| Impulse Propagation and Conduction | 459 | ||
| Excitation-Contraction Coupling | 460 | ||
| Membrane Depolarization and Activator Calcium | 460 | ||
| Modulation of Excitation-Contraction Coupling | 463 | ||
| Autoregulation of Mechanical Function: Frequency and Length Dependence | 463 | ||
| Frequency Dependence | 463 | ||
| Length Dependence | 464 | ||
| Vascular Regulation | 464 | ||
| Principles and Caveats | 464 | ||
| Vascular Smooth Muscle Structure | 464 | ||
| Modulation of Vascular Smooth Muscle Tone | 465 | ||
| Mechanisms of Vasoconstriction | 466 | ||
| Mechanisms of Vasodilation | 467 | ||
| Vasoregulation Signaling Pathways | 468 | ||
| Regulation of [Ca2+]i | 468 | ||
| Vasodilation: The G-Protein–cAMP Pathway | 468 | ||
| Vasodilation: Nitric Oxide−cGMP Pathway | 468 | ||
| Vasoconstriction: PLC-Phosphatidylinositol Pathway | 468 | ||
| Regulation of Myofilament Ca2+ Sensitivity | 468 | ||
| Regulation of Vascular Smooth Muscle by the Endothelium | 468 | ||
| Endothelium-Derived Relaxing Factors | 468 | ||
| Nitric Oxide | 468 | ||
| Prostacyclin | 469 | ||
| Endothelium-Derived Hyperpolarizing Factor | 469 | ||
| Endothelium-Derived Contracting Factors | 469 | ||
| Endothelin I | 469 | ||
| Cyclooxygenase Products | 469 | ||
| Examples of Local, Autonomic, and Humoral Regulation of Vascular Smooth Muscle | 469 | ||
| Local Regulation | 469 | ||
| Autonomic Regulation | 469 | ||
| Adrenergic | 469 | ||
| Cholinergic | 469 | ||
| Humoral | 469 | ||
| Emerging Developments | 470 | ||
| Proteomics to Advance Cardiac Physiology | 470 | ||
| Key Points | 470 | ||
| Key References | 471 | ||
| References | 471 | ||
| 24 Cardiovascular Physiology | 473 | ||
| Abstract | 473.e1 | ||
| Keywords | 473.e1 | ||
| Chapter Outline | 473 | ||
| Cardiac Physiology | 473 | ||
| Basic Cardiac Anatomy | 473 | ||
| Determinants and Control of Cardiac Output | 474 | ||
| Heart Rate | 474 | ||
| Stroke Volume | 474 | ||
| Preload | 474 | ||
| Contractility | 475 | ||
| Afterload | 475 | ||
| The Cardiac Cycle | 475 | ||
| Indices of Cardiac Function | 477 | ||
| Calculation of Cardiac Output Using the Thermodilution Method | 477 | ||
| Cardiac Function Curves With the Pulmonary Artery Catheter | 477 | ||
| Cardiac Function Using the Transpulmonary Thermodilution Method | 477 | ||
| Isovolumic Contraction Index | 478 | ||
| Ejection Phase Index | 479 | ||
| Ventricular Pressure-Volume Loop: End-Systolic Pressure-Volume Relations | 479 | ||
| Hemodynamics and Systemic Vascular Control | 481 | ||
| Pressure Changes in Systemic and Pulmonary Circulations | 481 | ||
| Determinants of Blood Flow: Poiseuille’s Law | 481 | ||
| Blood Viscosity | 482 | ||
| Turbulent Flow | 482 | ||
| Major Vessel Types: Structure and Function | 483 | ||
| Factors Influencing the Balancing Between Capillary Filtration and Absorption | 483 | ||
| Major Cardiovascular Reflexes | 485 | ||
| Arterial Baroreceptor Reflex | 485 | ||
| Bezold-Jarisch Reflex | 485 | ||
| Bainbridge Reflex | 488 | ||
| Tissue Oxygen Transport | 488 | ||
| General Concepts | 488 | ||
| Oxygen Transport in the Blood | 488 | ||
| Characteristic Values for Parameters of Oxygen Delivery | 490 | ||
| Diffusion of Oxygen to Tissues: Capillary to Cell Oxygen Delivery | 490 | ||
| Measurement of Oxygen Consumption | 491 | ||
| Critical Oxygen Delivery | 492 | ||
| Determinants of Myocardial Oxygen Supply and Demand | 492 | ||
| Control of Coronary Blood Flow | 492 | ||
| Coronary Flow Reserve | 493 | ||
| Myocardial Oxygen Demand | 494 | ||
| Impaired Myocardial Oxygen Balance: Mechanisms of Myocardial Ischemia | 494 | ||
| Emerging Developments | 495 | ||
| Noninvasive Perioperative Monitoring | 495 | ||
| Key Points | 495 | ||
| Anatomy and Imaging: The Cardiovascular System | 500 | ||
| A. The Aortic Arch in an Idealized Anatomic Drawing | 505 | ||
| B. Arteries of the Upper Extremity in an Idealized Anatomic Drawing | 505 | ||
| C. Relationships of the Subclavian Vessels, Scalene Muscles, and Brachial Plexus Visualized in an Idealized Anatomic Drawing and by Ultrasonography | 505 | ||
| D. The Profunda Artery as Visualized in an Anatomic Dissection and by Ultrasonogaphy | 505 | ||
| E. the Brachial Artery as Visualized in an Anatomic Dissection and by Ultrasonography | 509 | ||
| F. The Ulnar and Radial Arteries as Visualized in an Anatomic Dissection and by Ultrasonography | 509 | ||
| References | 509 | ||
| Physics: Fluid Dynamics | 510 | ||
| Outline | 510 | ||
| Background | 510 | ||
| Fluid Flow | 510 | ||
| Volumetric Flow | 510 | ||
| Mass Flow | 510 | ||
| Viscosity | 511 | ||
| Types and Properties of Flow | 511 | ||
| Laminar Flow | 511 | ||
| Turbulent Flow | 512 | ||
| Convection | 512 | ||
| Bernoulli’s Law | 512 | ||
| Flow Meters | 512 | ||
| Differential Pressure Sensors | 512 | ||
| Rotameters | 512 | ||
| Vane Anemometers | 513 | ||
| Hot-Wire Anemometers | 513 | ||
| Ultrasonic Anemometers | 513 | ||
| Physics: Invasive and Noninvasive Blood Pressure Measurement | 514 | ||
| Outline | 514 | ||
| Background | 514 | ||
| Noninvasive Blood Pressure Measurement | 514 | ||
| Palpation and Oscillometric Method | 514 | ||
| Korotkoff Sounds | 514 | ||
| Continuous, Invasive Blood Pressure Monitoring | 515 | ||
| Resonant or Natural Frequency | 516 | ||
| Damping | 517 | ||
| Fast-Flush Test | 517 | ||
| Morphology of the Arterial Waveform | 518 | ||
| Leveling and Zeroing | 519 | ||
| References | 519 | ||
| Key References | 497 | ||
| References | 497 | ||
| 25 Vasopressors and Inotropes | 520 | ||
| Abstract | 520.e1 | ||
| Keywords | 520.e1 | ||
| Chapter Outline | 520 | ||
| Historical Perspective | 520 | ||
| Structure-Activity Relationships | 521 | ||
| Mechanisms | 522 | ||
| Metabolism/Pharmacokinetics | 523 | ||
| Pharmacodynamics and Drug Interactions | 523 | ||
| Pharmacogenetics | 523 | ||
| Individual Drugs | 525 | ||
| Epinephrine | 525 | ||
| Isoproterenol | 526 | ||
| Norepinephrine | 526 | ||
| Dopamine | 526 | ||
| Dobutamine | 527 | ||
| Milrinone | 527 | ||
| Phenylephrine | 528 | ||
| Vasopressin | 528 | ||
| Ephedrine | 529 | ||
| Digoxin | 529 | ||
| Rational Drug Selection | 529 | ||
| Septic Shock | 529 | ||
| Cardiac Arrest | 529 | ||
| Mild, Intraoperative Hypotension | 529 | ||
| Hypotension in the Parturient | 529 | ||
| Right Heart Failure | 530 | ||
| Postbypass Hypotension | 530 | ||
| Emerging Developments | 531 | ||
| Key Points | 531 | ||
| Key References | 531 | ||
| References | 532 | ||
| 26 Antihypertensive Drugs and Vasodilators | 535 | ||
| Abstract | 535.e1 | ||
| Keywords | 535.e1 | ||
| Chapter Outline | 535 | ||
| Historical Perspective | 536 | ||
| Sites and Mechanisms of Antihypertensive and Vasodilator Drugs | 537 | ||
| Basic Pharmacology and Mechanisms of Action of Individual Drug Classes | 538 | ||
| Calcium Channel Blockers | 538 | ||
| β Blockers | 538 | ||
| Action of β Blockers at Adrenergic Receptors | 539 | ||
| Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Antagonists | 539 | ||
| Diuretics | 540 | ||
| Centrally Acting Agents | 540 | ||
| α2 Adrenoreceptor Agonists | 541 | ||
| α1 Adrenoreceptor Antagonists | 541 | ||
| Nitrovasodilators | 541 | ||
| Other Vasodilators | 542 | ||
| Pharmacokinetics, Pharmacodynamics, and Adverse Effects | 543 | ||
| Calcium Channel Blockers | 543 | ||
| Adverse Drug Interactions | 544 | ||
| Newer Calcium Channel Blockers | 544 | ||
| β Blockers | 544 | ||
| Antihypertensive Effect of β Blockers | 545 | ||
| Newer β Blockers | 545 | ||
| Adverse Effects of β Blockers | 545 | ||
| Angiotensin-Converting Enzyme Inhibitors | 546 | ||
| Angiotensin II Receptor Antagonists | 546 | ||
| Adverse Effects and Drug Interactions | 546 | ||
| Diuretics | 546 | ||
| Adverse Effects and Drug Interactions | 547 | ||
| α2 Adrenoreceptor Agonists | 547 | ||
| α1 Adrenoreceptor Antagonists | 547 | ||
| Phentolamine and Phenoxybenzamine | 547 | ||
| Vasodilators | 547 | ||
| Hydralazine | 547 | ||
| Nicorandil | 548 | ||
| Minoxidil | 548 | ||
| Nitrates | 548 | ||
| Phosphodiesterase Inhibitors | 548 | ||
| Pharmacotherapy of Hypertension | 548 | ||
| Hypertension and Anesthesia | 549 | ||
| Pulmonary Vasodilators | 549 | ||
| Phosphodiesterase Inhibitors | 550 | ||
| Novel Pulmonary Vasodilators | 550 | ||
| Emerging Developments | 550 | ||
| New Management Guidelines for Hypertension | 550 | ||
| Direct Renin Inhibitors | 551 | ||
| Natriuretic Peptides | 551 | ||
| Endothelin and Endothelin Blockade | 551 | ||
| Key Points | 552 | ||
| Key References | 553 | ||
| References | 553 | ||
| 27 Antiarrhythmic Drugs | 556 | ||
| Abstract | 556.e1 | ||
| Chapter Outline | 556 | ||
| Historical Perspective | 556 | ||
| Basic Pharmacology | 557 | ||
| Singh-Vaughan Williams Classification of Antiarrhythmic Drugs | 557 | ||
| Sodium Channels and Class I Antiarrhythmic Drugs | 557 | ||
| β Receptors and Class II Antiarrhythmics | 560 | ||
| Potassium Channels and Class III Antiarrhythmic Drugs | 560 | ||
| Calcium Channels and Class IV Antiarrhythmics | 563 | ||
| Clinical Pharmacology | 564 | ||
| Categories of Arrhythmogenic Mechanisms | 564 | ||
| Automaticity | 564 | ||
| Triggered | 564 | ||
| Conduction | 564 | ||
| Clinical Application | 565 | ||
| Class I—Sodium Channel Blockers | 565 | ||
| Class Ia Nav Channel Blockers | 565 | ||
| Class Ib Nav Channel Blockers | 566 | ||
| Class Ic Nav Channel Blockers | 566 | ||
| Class II—β Blockers | 567 | ||
| Class III—Potassium Channel Blockers | 567 | ||
| Class IV—Calcium Channel Blockers | 568 | ||
| Emerging Developments | 569 | ||
| Molecular Genetics of Arrhythmias | 569 | ||
| Long QT Syndrome | 569 | ||
| Short QT Syndrome | 570 | ||
| Brugada Syndrome | 570 | ||
| Other Inherited Arrhythmia Syndromes | 570 | ||
| hERG Drug Interactions | 570 | ||
| Gene Therapy Guided by Molecular Genetics of Inherited Arrhythmias | 571 | ||
| Key Points | 571 | ||
| Key References | 572 | ||
| References | 572 | ||
| 28 Cardiopulmonary Resuscitation | 575 | ||
| Abstract | 575.e1 | ||
| Keywords | 575.e1 | ||
| Chapter Outline | 575 | ||
| Historical Perspective | 575 | ||
| Oxygen Delivery, Consumption, and the Margin of Error | 575 | ||
| Compensated Hypovolemia and Supply-Dependent Oxygen Consumption | 576 | ||
| Early Goal-Directed Therapy | 576 | ||
| Cardiopulmonary Resuscitation | 577 | ||
| Compression and Decompression | 577 | ||
| Ventilation and Blood Flow During CPR | 577 | ||
| CPR and Intracranial Pressure | 578 | ||
| Optimizing Chest Compression/Decompression | 579 | ||
| Automated Chest Compression Devices | 580 | ||
| Targeted Temperature Management After Resuscitation | 581 | ||
| Emerging Developments | 582 | ||
| Extracorporeal Life Support for Refractory Cardiac Arrest | 582 | ||
| Key Points | 583 | ||
| Key References | 583 | ||
| References | 583 | ||
| IV Pulmonary System | 585 | ||
| 29 Pulmonary Physiology | 586 | ||
| Abstract | 586.e1 | ||
| Keywords: | 586.e1 | ||
| Chapter Outline | 586 | ||
| Pulmonary Ventilation | 586 | ||
| Muscles of Ventilation | 586 | ||
| The Airway | 587 | ||
| Cellular Physiology | 587 | ||
| Neural Control | 587 | ||
| Humoral Control | 587 | ||
| Physical and Chemical Effects | 587 | ||
| Local Cellular Mechanisms | 588 | ||
| Molecular Physiology | 588 | ||
| Bronchodilator Pathway | 589 | ||
| Bronchoconstrictor Pathway | 589 | ||
| Bronchoconstriction in Airway Disease | 589 | ||
| Oxygenation | 590 | ||
| Ventilation and Perfusion Relationships | 590 | ||
| Distribution of Ventilation | 590 | ||
| Distribution of Perfusion | 590 | ||
| Ventilation in Relation to Perfusion | 591 | ||
| Shunt | 591 | ||
| Effects of General Anesthesia | 591 | ||
| Active Control of Pulmonary Vascular Resistance | 592 | ||
| Hypoxic Pulmonary Vasoconstriction | 592 | ||
| Cellular Physiology of Hypoxic Pulmonary Vasoconstriction | 592 | ||
| Molecular Physiology | 592 | ||
| Control of Breathing | 593 | ||
| Respiratory Center | 593 | ||
| Central Pattern Generation | 593 | ||
| Connections to the Respiratory Center | 593 | ||
| Molecular Physiology | 594 | ||
| Chemical Control of Ventilation | 594 | ||
| Central Chemoreceptors | 594 | ||
| Peripheral Chemoreceptors | 594 | ||
| Molecular Physiology | 595 | ||
| Ventilatory Response to Sustained Hypoxia | 595 | ||
| Emerging Developments | 595 | ||
| Carbon Dioxide Oscillations and Control of Ventilation | 595 | ||
| Asthma Phenotypes and Targeted Therapies | 596 | ||
| Remodeling of Airways | 596 | ||
| Key Points | 597 | ||
| Anatomy and Imaging: The Thoracic Wall, Intercostal Space, and Thorax | 599 | ||
| Physics: Blood Gas Measurement | 603 | ||
| Outline | 603 | ||
| Background | 603 | ||
| Blood Gas Measurement Instrumentation | 603 | ||
| Measurement of Oxygen Tension: Clarke (Polarographic) Oxygen Electrode | 603 | ||
| Measurement of pH: Glass Electrode | 603 | ||
| Measurement of pCO2: the Severinghaus Electrode | 604 | ||
| Sampling for Blood Gas Analysis | 605 | ||
| References | 605 | ||
| Physics: Regulators, Medical Gas Cylinders, and Pressure Measurement of Gases | 606 | ||
| Outline | 606 | ||
| Background | 606 | ||
| Medical Gas Cylinders | 606 | ||
| Medical Gas Cylinder Safety | 606 | ||
| Estimating the Remaining Volume | 606 | ||
| Pressure Measurement and Regulation of Gases | 607 | ||
| References | 608 | ||
| Physics: Pulse Oximetry | 609 | ||
| Outline | 609 | ||
| Background | 609 | ||
| Pulse Oximetry Probe | 609 | ||
| Principle | 609 | ||
| Limitations of Pulse Oximetry | 610 | ||
| References | 612 | ||
| Key References | 597 | ||
| References | 597 | ||
| 30 Pulmonary Pharmacology | 613 | ||
| Abstract | 613.e1 | ||
| Keywords | 613.e1 | ||
| Chapter Outline | 613 | ||
| β2-Adrenoceptor Agonists | 614 | ||
| Structure-Activity | 614 | ||
| Mechanism and Metabolism | 614 | ||
| Clinical Pharmacology | 615 | ||
| Pharmacokinetics, Pharmacodynamics, and Therapeutic Effects | 615 | ||
| Adverse Effects | 615 | ||
| Drug Interactions | 616 | ||
| Clinical Application | 616 | ||
| Common Applications | 616 | ||
| Rationale Drug Selection and Administration | 616 | ||
| Anticholinergics | 616 | ||
| Structure-Activity | 616 | ||
| Mechanism and Metabolism | 616 | ||
| Clinical Pharmacology | 616 | ||
| Pharmacokinetics, Pharmacodynamics, and Therapeutic Effects | 616 | ||
| Adverse Effects | 616 | ||
| Clinical Application | 617 | ||
| Common Applications | 617 | ||
| Inhaled Corticosteroids | 619 | ||
| Structure-Activity | 619 | ||
| Mechanism and Metabolism | 619 | ||
| Clinical Pharmacology | 619 | ||
| Pharmacokinetics, Pharmacodynamics, and Therapeutic Effects (Table 30.2) | 619 | ||
| Adverse Effects | 620 | ||
| Drug Interactions | 620 | ||
| Clinical Application | 620 | ||
| Common Applications | 620 | ||
| Methylxanthines and Phosphodiesterase Inhibitors | 620 | ||
| Structure-Activity | 620 | ||
| Mechanism and Metabolism | 620 | ||
| Clinical Pharmacology | 621 | ||
| Pharmacokinetics, Pharmacodynamics, and Therapeutic Effects | 621 | ||
| Adverse Effects | 621 | ||
| Drug Interactions | 621 | ||
| Special Populations | 621 | ||
| Clinical Application | 621 | ||
| Common Applications | 621 | ||
| Leukotriene Receptor Inhibitors and 5-Lipoxygenase Inhibitors | 621 | ||
| Structure-Activity | 621 | ||
| Mechanism | 621 | ||
| Clinical Pharmacology | 622 | ||
| Pharmacokinetics, Pharmacodynamics, and Metabolism | 622 | ||
| Drug Interactions | 622 | ||
| Clinical Application | 622 | ||
| Common Applications | 622 | ||
| Monoclonal Antibodies | 622 | ||
| Structure-Activity | 622 | ||
| Mechanism and Metabolism | 622 | ||
| Clinical Pharmacology | 623 | ||
| Pharmacokinetics, Pharmacodynamics, and Therapeutic Effects | 623 | ||
| Adverse Effects | 623 | ||
| V Gastrointestinal and Endocrine Systems | 629 | ||
| 31 Liver and Gastrointestinal Physiology | 630 | ||
| Chapter Outline | 630 | ||
| Liver | 630 | ||
| Anatomy | 630 | ||
| Blood Supply | 631 | ||
| Liver Function | 631 | ||
| Storage | 631 | ||
| Filtering and Cleansing | 632 | ||
| Metabolism of Nutrients | 632 | ||
| Synthesis of Coagulation Factors | 632 | ||
| Bile Secretion | 632 | ||
| Bilirubin and Jaundice | 632 | ||
| Liver Regeneration | 632 | ||
| Portal Hypertension | 633 | ||
| Hepatic Drug Metabolism and Excretion | 633 | ||
| Anesthetic Pharmacology and the Liver | 634 | ||
| Liver Disease: Etiologies and Severity | 634 | ||
| Cirrhosis and Perioperative Risk: Nonhepatic Surgery | 634 | ||
| Hepatic Surgery | 635 | ||
| Gastrointestinal Tract | 635 | ||
| Anatomy | 635 | ||
| Properties of the Gastrointestinal Tract | 635 | ||
| Respiration and Pharyngeal Swallowing | 635 | ||
| Lower Esophageal Sphincter | 635 | ||
| Neural Control | 636 | ||
| Enteric Nervous System | 636 | ||
| Parasympathetic Stimulation | 636 | ||
| Sympathetic Stimulation | 636 | ||
| Hormonal Control | 636 | ||
| Splanchnic Circulation | 636 | ||
| Stomach Emptying | 636 | ||
| Enterogastric Nervous Reflex | 636 | ||
| Secretory Functions | 637 | ||
| Autonomic Stimulation | 637 | ||
| Gastric Secretions | 637 | ||
| Pancreatic Digestive Enzymes | 638 | ||
| Bicarbonate | 638 | ||
| Absorption of Nutrients | 638 | ||
| Glucose | 638 | ||
| Fats | 638 | ||
| Gastrointestinal Disorders | 638 | ||
| Anesthetic Pharmacology and the Gastrointestinal Tract | 640 | ||
| Emerging Developments | 640 | ||
| Tissue Engineering | 640 | ||
| Key Points | 642 | ||
| Key References | 642 | ||
| References | 642 | ||
| 32 Liver and Gastrointestinal Pharmacology | 645 | ||
| Abstract | 645.e1 | ||
| Keywords | 645.e1 | ||
| Chapter Outline | 645 | ||
| Liver Pharmacology | 645 | ||
| Cytochrome P450 Enzymes | 645 | ||
| Hepatic Extraction | 645 | ||
| Plasma Protein Binding | 647 | ||
| Anesthetic Drugs and the Liver | 647 | ||
| Anesthetic Agents and Hepatic Blood Flow | 647 | ||
| Metabolism of Volatile Anesthetics and Hepatotoxicity | 647 | ||
| Metabolism of Intravenous Anesthetic Agents | 647 | ||
| Hepatobiliary Metabolism and Elimination of Neuromuscular Blockers | 648 | ||
| Gastrointestinal Pharmacology | 648 | ||
| Basic Principles | 648 | ||
| Gastric Acid–Suppressing Medications | 648 | ||
| Drugs to Reduce Portal Venous Pressure | 649 | ||
| Opioids and the Gastrointestinal System | 650 | ||
| Sphincter of Oddi Spasm | 651 | ||
| Statins | 651 | ||
| Other Treatments for Dyslipidemia | 651 | ||
| Hepatitis C Treatment | 651 | ||
| Emerging Developments | 651 | ||
| Suppression of Gastric Acid Secretion | 651 | ||
| Direct-Acting Antivirals for Hepatitis C Treatment | 652 | ||
| PCSK9 Inhibitors for Dyslipidemia | 652 | ||
| Obeticholic Acid | 652 | ||
| Key Points | 652 | ||
| Key References | 653 | ||
| References | 653 | ||
| 33 Nutritional and Metabolic Therapy | 657 | ||
| Abstract | 657.e1 | ||
| Keywords | 657.e1 | ||
| Chapter Outline | 657 | ||
| Fasting in the Perioperative Period | 657 | ||
| Benefits of Early Enteral Feeding | 658 | ||
| Timing of Nutrient Delivery | 658 | ||
| Pharmaconutrition-Immunonutrition | 659 | ||
| Specific Nutrients | 660 | ||
| Glutamine | 660 | ||
| Clinical Outcome Studies Using Glutamine | 661 | ||
| Arginine | 661 | ||
| Clinical Outcome Studies Using Arginine | 662 | ||
| Recommendations Regarding Delivery of Arginine | 663 | ||
| Omega-3 Fatty Acids | 663 | ||
| Clinical Outcome Studies Using 20 and 22 Carbon Omega-3 Fatty Acids | 664 | ||
| Recommendations Regarding Delivery of Omega-3 Fatty Acids | 664 | ||
| Timing of Delivery of Nutrients as Pharmacologic Agents | 665 | ||
| Use of Protocols Enhance Safe Delivery of Nutrients | 665 | ||
| Emerging Developments | 665 | ||
| New Malnutrition Definitions and Other Nutrients | 665 | ||
| Probiotics | 666 | ||
| Conclusion | 666 | ||
| Key Points | 667 | ||
| Key References | 667 | ||
| References | 667 | ||
| 34 Pharmacology of Postoperative Nausea and Vomiting | 671 | ||
| Abstract | 671.e1 | ||
| Keywords | 671.e1 | ||
| Chapter Outline | 671 | ||
| Historical Perspective | 671 | ||
| Mechanisms of Nausea and Vomiting | 672 | ||
| Serotonin Receptor Antagonists | 673 | ||
| Ondansetron | 673 | ||
| Granisetron and Dolasetron | 673 | ||
| Palonosetron | 676 | ||
| Dopamine Receptor Antagonists | 678 | ||
| Droperidol | 678 | ||
| Haloperidol | 679 | ||
| Metoclopramide | 679 | ||
| Corticosteroids | 679 | ||
| NK1 Receptor Antagonists | 680 | ||
| Aprepitant | 681 | ||
| Scopolamine | 682 | ||
| H1-Receptor Antagonists | 683 | ||
| Dimenhydrinate and Diphenhydramine | 683 | ||
| Promethazine | 684 | ||
| GABA Receptor Agonists | 684 | ||
| Propofol | 684 | ||
| Benzodiazepines | 685 | ||
| Opioid Receptor Antagonists | 685 | ||
| Naloxone | 685 | ||
| Alvimopan | 686 | ||
| Cannabinoids | 687 | ||
| Risk-Based Prophylaxis | 687 | ||
| Enhanced Recovery After Surgery | 687 | ||
| Multimodal Therapy | 687 | ||
| Emerging Developments | 688 | ||
| Novel Antiemetic Drugs | 688 | ||
| Postdischarge Nausea and Vomiting | 688 | ||
| Key Points | 689 | ||
| Key References | 689 | ||
| References | 690 | ||
| 35 Endocrine Physiology | 693 | ||
| Abstract | 693.e1 | ||
| Keywords | 693.e1 | ||
| Chapter Outline | 693 | ||
| Pituitary Physiology | 693 | ||
| Anterior Pituitary | 693 | ||
| Hyperpituitarism and Anterior Lobe Tumors | 694 | ||
| Gigantism and Acromegaly | 694 | ||
| Cushing Disease | 694 | ||
| Prolactinomas | 695 | ||
| Posterior Pituitary | 695 | ||
| Diabetes Insipidus and Syndrome of Inappropriate Antidiuretic Hormone | 695 | ||
| Parathyroid Physiology | 696 | ||
| Primary Hyperparathyroidism | 697 | ||
| Multiple Endocrine Neoplasia | 697 | ||
| Secondary Hyperparathyroidism | 697 | ||
| Hypoparathyroidism | 697 | ||
| Thyroid Physiology | 698 | ||
| Hypothyroidism | 698 | ||
| Hyperthyroidism | 699 | ||
| Thyroiditis | 699 | ||
| Adrenal Gland Physiology | 700 | ||
| Adrenal Cortex Physiology | 700 | ||
| Cushing Syndrome | 700 | ||
| Glucocorticoid Deficiency | 701 | ||
| Hyperaldosteronism | 701 | ||
| Hypoaldosteronism | 701 | ||
| Adrenal Medulla Physiology | 702 | ||
| Pheochromocytoma | 702 | ||
| Pancreas Physiology | 703 | ||
| Diabetes Mellitus | 704 | ||
| Emerging Developments | 704 | ||
| Key Points | 705 | ||
| Key References | 706 | ||
| References | 706 | ||
| 36 Endocrine Pharmacology | 708 | ||
| Abstract | 708.e1 | ||
| Keywords | 708.e1 | ||
| Chapter Outline | 708 | ||
| Drugs to Treat Disorders of the Endocrine Pancreas | 709 | ||
| Insulin | 709 | ||
| Basic Pharmacology | 709 | ||
| Clinical Pharmacology | 709 | ||
| Individual Insulin Preparations | 710 | ||
| Regular Insulin | 710 | ||
| Rapidly Acting Insulin Analogues | 711 | ||
| Intermediate-Acting Insulin | 711 | ||
| Long-Acting Insulins | 711 | ||
| Inhaled Insulin | 711 | ||
| Clinical Application | 711 | ||
| Oral Hypoglycemic Agents: Sulfonylureas, Biguanides, Thiazolidinediones | 712 | ||
| Basic Pharmacology | 712 | ||
| VI Immunity and Infection | 752 | ||
| 38 Chemotherapy, Immunosuppression, and Anesthesia | 753 | ||
| Abstract | 753.e1 | ||
| Keywords | 753.e1 | ||
| Chapter Outline | 753 | ||
| Chemotherapy | 753 | ||
| Drugs That Cause DNA/RNA Damage | 754 | ||
| Alkylating Agents | 754 | ||
| Antimetabolites | 754 | ||
| Antineoplastic Antibiotics | 754 | ||
| Topoisomerase Inhibitors | 757 | ||
| Drugs That Suppress Proliferation: Microtubule-Binding Agents | 758 | ||
| Molecular Therapies, Growth Inhibitors, and Targeted Therapies | 759 | ||
| Monoclonal Antibodies | 762 | ||
| Antimetastasis Therapy | 764 | ||
| Immunotherapy | 764 | ||
| How Anesthetics Might Affect Cancer | 765 | ||
| Opioids | 765 | ||
| Volatile Anesthetics | 765 | ||
| Propofol | 765 | ||
| Local Anesthetics | 766 | ||
| Other Factors | 766 | ||
| Key Points | 766 | ||
| Key References | 767 | ||
| References | 767 | ||
| 39 Infection, Antimicrobial Drugs, and Anesthesia | 769 | ||
| Abstract | 769.e1 | ||
| Keywords | 769.e1 | ||
| Chapter Outline | 769 | ||
| Historical Perspective | 769 | ||
| Introduction | 769 | ||
| Surgical Antibiotic Prophylaxis | 770 | ||
| Clinical Pharmacology of Common Perioperative Antimicrobial Agents | 772 | ||
| Beta-Lactam Antibiotics | 772 | ||
| Penicillins | 772 | ||
| Cephalosporins | 772 | ||
| Monobactams (Aztreonam) | 772 | ||
| Carbapenems (Doripenem, Ertapenem, Imipenem, and Meropenem) | 772 | ||
| Aminoglycosides (Including Streptomycin, Neomycin, Kanamycin, Amikacin, Gentamicin, and Tobramycin) | 772 | ||
| Fluoroquinolones | 773 | ||
| Vancomycin | 773 | ||
| Clindamycin | 773 | ||
| Metronidazole | 773 | ||
| Amphotericin B | 773 | ||
| Selection of Antimicrobial Agents for SSI Prevention | 773 | ||
| Dosing and Administration of Prophylactic Antibiotics | 774 | ||
| Clostridium Difficile Infection | 774 | ||
| Cost Containment | 776 | ||
| Summary | 776 | ||
| Emerging Developments | 776 | ||
| Key Points | 777 | ||
| Key References | 778 | ||
| References | 778 | ||
| VII Fluid, Electrolyte, and Hematologic Homeostasis | 781 | ||
| 40 Renal Physiology | 782 | ||
| Abstract | 782.e1 | ||
| Keywords | 782.e1 | ||
| Chapter Outline | 782 | ||
| Renal Blood Flow and Glomerular Filtration Rate | 782 | ||
| Renal Blood Flow | 782 | ||
| Renal Clearance | 782 | ||
| Renal Plasma Flow | 783 | ||
| Glomerular Filtration Rate | 783 | ||
| Age-Related Renal Changes | 783 | ||
| The Nephron | 784 | ||
| Water and the Kidney | 784 | ||
| Salt and the Kidney | 784 | ||
| Potassium and the Kidney | 785 | ||
| Toxin and Metabolite Excretion | 787 | ||
| Acid–Base Balance | 787 | ||
| Renal Hormone Production | 787 | ||
| Defining Renal Failure | 787 | ||
| Risk of Perioperative Acute Kidney Injury | 788 | ||
| Acute Kidney Injury in Surgical Patients | 788 | ||
| Assessment and Management of Acute Kidney Injury | 789 | ||
| Preoperative Approach | 789 | ||
| Intraoperative Management of Renal Function | 789 | ||
| Anesthetic Drugs and Impaired Renal Function | 790 | ||
| Common Perioperative Medications That Impair Renal Function | 790 | ||
| Perioperative Renal Replacement Therapy | 790 | ||
| Hepatorenal Syndrome | 791 | ||
| Emerging Developments | 791 | ||
| Prevention and Biomarkers for Acute Kidney Injury | 791 | ||
| Key Points | 792 | ||
| Key References | 792 | ||
| References | 793 | ||
| 41 Intravascular Volume Replacement Therapy | 795 | ||
| Abstract | 795.e1 | ||
| Key words | 795.e1 | ||
| Chapter Outline | 795 | ||
| Historical Perspective | 795 | ||
| Conventional Concepts | 796 | ||
| Body Water | 796 | ||
| Measurement of Body Fluid Spaces | 796 | ||
| Maintenance Requirements for Water, Sodium, and Potassium | 796 | ||
| Interstitium | 797 | ||
| Third Space | 798 | ||
| Fluid Shifts and Losses During Surgery, and Their Replacement | 799 | ||
| Conventional Indices of Resuscitation | 799 | ||
| Response to Fluid Challenge | 800 | ||
| Static Measurements of Intravascular Volume | 800 | ||
| Pulmonary Artery Occlusion Pressure | 800 | ||
| Transesophageal Echocardiography | 800 | ||
| Intrathoracic Blood Volume Index and Global End-Diastolic Volume Index | 800 | ||
| Stroke Volume Variation and Pulse Pressure Variation | 800 | ||
| Esophageal Doppler Catheter | 801 | ||
| Passive Leg Raising Test | 801 | ||
| Oxygen Delivery and the Microcirculation | 801 | ||
| Body Fluid Dynamics (Modeling Fluid Therapy) | 801 | ||
| Plasma Volume Expansion | 802 | ||
| Volume Kinetics for Infusion Fluids | 803 | ||
| Estimation of Volume Kinetic Parameters | 805 | ||
| Population Kinetics for Infusion Fluids | 805 | ||
| Pharmacodynamics of Infusion Fluids | 805 | ||
| Guiding Principles and Clinical Implications | 806 | ||
| Crystalloids | 806 | ||
| Colloids | 807 | ||
| Sepsis and Critical Illness | 809 | ||
| Clinical Fluid Therapy Guidelines | 809 | ||
| Basal Requirements and Rehydration | 809 | ||
| Day Surgery Cases: Minor Surgery | 809 | ||
| Surgery Performed With Spinal or Epidural Block | 809 | ||
| Gastrointestinal Surgery | 809 | ||
| Emerging Developments | 809 | ||
| Key Points | 810 | ||
| Key References | 810 | ||
| References | 810 | ||
| 42 Electrolytes and Diuretics | 814 | ||
| Abstract | 814.e1 | ||
| Keywords | 814.e1 | ||
| Chapter Outline | 814 | ||
| Electrolytes | 814 | ||
| Sodium | 814 | ||
| Physiologic Role | 814 | ||
| Hyponatremia | 814 | ||
| Hypernatremia | 818 | ||
| Potassium | 820 | ||
| Physiologic Role | 820 | ||
| Hypokalemia | 820 | ||
| Hyperkalemia | 821 | ||
| Calcium | 822 | ||
| Physiologic Role | 822 | ||
| Hypocalcemia | 823 | ||
| Hypercalcemia | 825 | ||
| Phosphate | 826 | ||
| Physiologic Role | 826 | ||
| Hypophosphatemia | 826 | ||
| Hyperphosphatemia | 827 | ||
| Magnesium | 827 | ||
| Physiologic Role | 827 | ||
| Hypomagnesemia | 827 | ||
| Hypermagnesemia | 828 | ||
| Diuretics | 828 | ||
| Proximal Convoluted Tubule–Carbonic Anhydrase Inhibitors | 829 | ||
| Ascending Loop of Henle: Loop Diuretics | 829 | ||
| Thiazides | 830 | ||
| Potassium-Sparing Diuretics | 830 | ||
| Osmotic Diuretics | 830 | ||
| Diuretics in Heart Failure | 830 | ||
| Adverse Effects of Diuretics | 831 | ||
| Volume Depletion | 831 | ||
| Azotemia | 831 | ||
| Hypokalemia | 831 | ||
| Hyponatremia | 831 | ||
| Emerging Developments | 832 | ||
| Key Points | 832 | ||
| Key References | 832 | ||
| References | 833 | ||
| VIII Blood and Hemostasis | 836 | ||
| 43 Blood and Coagulation | 837 | ||
| Abstract | 837.e1 | ||
| Keywords | 837.e1 | ||
| Chapter Outline | 837 | ||
| Normal Hemostatic Mechanisms | 837 | ||
| Hypercoagulability | 838 | ||
| Inherited Risk Factors | 838 | ||
| Increased Procoagulant Effects | 838 | ||
| Reduction of Natural Anticoagulant Factors | 838 | ||
| Fibrinolysis Modulation | 839 | ||
| Other Inherited Conditions | 840 | ||
| Acquired Risk Factors | 840 | ||
| Disease States Associated With Hypercoagulability | 841 | ||
| Heparin-Induced Thrombocytopenia | 841 | ||
| Hypocoagulability: Perioperative Bleeding | 842 | ||
| Risk Factors for Bleeding | 842 | ||
| Patient-Related Causes of Bleeding | 842 | ||
| Common Inherited Hemostatic Disorders | 842 | ||
| Physician-Related Factors | 843 | ||
| Procedure-Related Factors | 843 | ||
| Pharmacologic Factors | 843 | ||
| Disorders of Hemostasis: Disseminated Intravascular Coagulation | 843 | ||
| Thrombocytopenia | 843 | ||
| Coagulopathy | 843 | ||
| Fibrinogen Consumption | 843 | ||
| Reductions in Coagulation Inhibitors | 844 | ||
| Fibrinolysis Indicators | 844 | ||
| Hemostatic Testing | 844 | ||
| Point-of-Care Coagulation Testing | 844 | ||
| Transfusion Algorithms and Massive Transfusion | 845 | ||
| Blood Conservation | 845 | ||
| Key Points | 846 | ||
| Key References | 846 | ||
| References | 847 | ||
| 44 Transfusion and Coagulation Therapy | 849 | ||
| Chapter Outline | 849 | ||
| Hemoglobin and Volume Replacement Therapies | 849 | ||
| Historical Aspects of Transfusion | 849 | ||
| Packed Red Blood Cells | 850 | ||
| Clinical Uses | 850 | ||
| Side Effects | 850 | ||
| Erythropoietin | 851 | ||
| Side Effects | 851 | ||
| Blood Substitutes | 851 | ||
| Albumin | 851 | ||
| Synthetic Colloids | 852 | ||
| Hemostatic Interventions and Coagulation Therapies | 852 | ||
| Platelet Concentrates | 852 | ||
| Clinical Uses | 853 | ||
| Side Effects | 854 | ||
| Plasma | 855 | ||
| Solvent-Detergent (S/D) Plasma | 855 | ||
| Lyophilized Plasma | 855 | ||
| Clinical Uses | 856 | ||
| Side Effects | 856 | ||
| Cryoprecipitate | 857 | ||
| Clinical Uses | 857 | ||
| Side Effects | 857 | ||
| Fibrinogen Concentrate | 858 | ||
| Clinical Use | 858 | ||
| Index | 895 | ||
| A | 895 | ||
| B | 898 | ||
| C | 899 | ||
| D | 902 | ||
| E | 903 | ||
| F | 904 | ||
| G | 904 | ||
| H | 905 | ||
| I | 907 | ||
| J | 908 | ||
| K | 908 | ||
| L | 909 | ||
| M | 910 | ||
| N | 911 | ||
| O | 913 | ||
| P | 914 | ||
| Q | 917 | ||
| R | 917 | ||
| S | 918 | ||
| T | 919 | ||
| U | 921 | ||
| V | 921 | ||
| W | 922 | ||
| X | 922 | ||
| Z | 922 | ||
| Inside Back Cover | ibc1 |