Additional Information
Book Details
Abstract
Better understand the complexities of pharmacology and physiology relevant to your practice with the brand-new medical reference book, Pharmacology and Physiology for Anesthesia. Drs. Hugh Hemmings and Talmage Egan provide the clinical insights you need to effectively administer anesthesia, ensuring patient safety and the most optimal outcomes.
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Consult this title on your favorite e-reader, conduct rapid searches, and adjust font sizes for optimal readability.
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Access comprehensive, continually updated research on the physiology of organ systems and clinical topics in the pharmacology of anesthetic drugs.
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Quickly and easily reference the information you need through user-friendly tables, figures, and algorithms, all presented in lavish full color throughout.
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Understand the molecular mechanism of drug actions and identify key drug interactions that may complicate anesthesia with dedicated sections on these key areas.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front cover | cover | ||
| Pharmacology and Physiology for Anesthesia | i | ||
| Copyright page | iv | ||
| Dedication | v | ||
| Preface | vii | ||
| Contributing Authors | ix | ||
| Table of Contents | xiii | ||
| Expert Consult page | IFC2 | ||
| I Basic Principles of Pharmacology | 1 | ||
| 1 Mechanisms of Drug Action | 3 | ||
| The Receptor Concept | 3 | ||
| Historical Beginnings | 3 | ||
| Modern Development | 4 | ||
| Pharmacodynamics | 4 | ||
| Drug Binding | 4 | ||
| From Drug Binding to Physiologic Effect | 5 | ||
| Efficacy | 6 | ||
| Full Agonists, Partial Agonists, and Inverse Agonists | 7 | ||
| Antagonism | 8 | ||
| Allosteric Drug Interactions | 9 | ||
| Multiple Binding Sites on the Same Receptor Protein | 9 | ||
| Allosteric Binding Sites | 10 | ||
| Pharmacogenetics | 10 | ||
| Drug Discovery | 11 | ||
| Structure-Activity Relationship | 11 | ||
| Identification of Drug Targets | 12 | ||
| Purification of Receptors | 12 | ||
| Drug Targets | 12 | ||
| Cell Signaling | 13 | ||
| Emerging Developments | 16 | ||
| Pharmacophore Modeling | 16 | ||
| Phenotype-Based Drug Discovery | 17 | ||
| Key Points | 17 | ||
| Key References | 17 | ||
| References | 18 | ||
| 2 Pharmacokinetic and Pharmacodynamic Principles for Intravenous Anesthetics | 20 | ||
| Historical Perspective | 20 | ||
| Unique Aspects of Anesthetic Pharmacology | 21 | ||
| Anesthesiology versus Other Disciplines | 21 | ||
| A Surfing Analogy as a Simple Conceptual Framework | 21 | ||
| Clinical Pharmacology | 22 | ||
| Posology | 22 | ||
| General Schema | 22 | ||
| Pharmacokinetics | 24 | ||
| Pharmacodynamics | 24 | ||
| The Biophase | 24 | ||
| Drug Interactions | 25 | ||
| Pharmacologic Modeling | 26 | ||
| PK-PD Models as Versions of Pharmacologic Reality | 26 | ||
| PK-PD Model Building Methods | 26 | ||
| Limitations in Building and 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- 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- 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 | 36 | ||
| PK-PD Advisory Displays | 36 | ||
| Propofol Measurement in Expired Gas | 38 | ||
| Key Points | 39 | ||
| Key References | 40 | ||
| References | 40 | ||
| 3 Pharmacokinetics of Inhaled Anesthetics | 43 | ||
| Historical Perspective | 43 | ||
| Classes of Inhaled Anesthetics | 43 | ||
| Physical Properties | 44 | ||
| Measuring Potency (MAC) | 45 | ||
| Monitoring Drug Delivery | 47 | ||
| Differences Between Inhalational and Intravenous Anesthetic Delivery | 47 | ||
| Agent Analysis | 47 | ||
| Monitoring Neurophysiologic Effect | 48 | ||
| Metabolism and Degradation | 48 | ||
| Metabolism | 48 | ||
| Chemical Degradation | 48 | ||
| Carbon Monoxide Production | 48 | ||
| Uptake and Distribution | 49 | ||
| General Principles | 49 | ||
| Determinants of Wash-in | 49 | ||
| Special Factors | 50 | ||
| Tissue Uptake | 50 | ||
| Recovery and Elimination | 51 | ||
| Nitrous Oxide: Concentration Effect, Second Gas Effect, Diffusion Hypoxia, and Effects on Closed Gas Spaces | 51 | ||
| Gas Delivery Systems | 53 | ||
| Reaction of carbon dioxide with barium hydroxide lime (Baralyme, obsolete) | 53 | ||
| Reaction of carbon dioxide with soda lime (in current use) | 53 | ||
| Low Flow Anesthesia | 53 | ||
| Pharmacoeconomic Considerations | 53 | ||
| Emerging Developments | 55 | ||
| Intravenous Delivery of Volatile Anesthetics | 55 | ||
| Key Points | 55 | ||
| Key References | 56 | ||
| References | 56 | ||
| 4 Drug Metabolism and Pharmacogenetics | 58 | ||
| Basics of Genetics | 58 | ||
| Chromosomes, Genes, and Alleles | 58 | ||
| Genotype and Phenotype | 59 | ||
| Genetic Mutations | 60 | ||
| Pharmacogenetic Approach | 60 | ||
| History of Pharmacogenetics | 61 | ||
| Pharmacogenetics and Drug Metabolism | 62 | ||
| Phase I Drug Metabolism | 62 | ||
| Cytochrome 450 Enzyme Family | 62 | ||
| Flavin-Containing Monooxygenase Enzymes | 64 | ||
| Phase II Drug Metabolism | 64 | ||
| Pharmacogenetics of Anesthetic Drugs | 64 | ||
| Opioids | 64 | ||
| Inhalation and Intravenous Anesthetic Agents | 65 | ||
| Nonsteroidal Antiinflammatory Drugs | 65 | ||
| Emerging Developments | 65 | ||
| Key Points | 65 | ||
| Key References | 66 | ||
| References | 67 | ||
| 5 Pharmacodynamic Drug Interactions | 70 | ||
| History | 70 | ||
| Study of Drug Interactions | 71 | ||
| Terminology | 71 | ||
| Shift in Dose-Response Curve | 71 | ||
| Isobolograms | 73 | ||
| Response Surface Models | 73 | ||
| Trial Design | 74 | ||
| Pharmacologic Basis of Drug Interactions | 76 | ||
| Understanding Drug Interactions Among Commonly Used Anesthetic Drugs | 76 | ||
| Inhaled Anesthetics and Opioids | 76 | ||
| Inhaled Anesthetics and Other Agents | 78 | ||
| Propofol | 78 | ||
| Propofol and Midazolam | 79 | ||
| Propofol and Opioids | 80 | ||
| Propofol and Inhaled Anesthetics | 81 | ||
| Midazolam and Opioids | 81 | ||
| Ketamine and Midazolam or Propofol | 82 | ||
| Emerging Developments | 82 | ||
| Key Points | 84 | ||
| Key References | 84 | ||
| References | 84 | ||
| 6 Adverse Drug Reactions | 86 | ||
| Definition and Incidence | 86 | ||
| Drug Administration Errors | 87 | ||
| Types of Adverse Drug Reactions | 88 | ||
| A—Augmented—Dose Related | 88 | ||
| B—Bizarre—Drug Idiosyncrasy, Not Dose Related | 88 | ||
| Acetylator Status | 89 | ||
| Cytochrome P450 Variants | 89 | ||
| Plasma Cholinesterase Variants | 89 | ||
| Glucose-6-Phosphate Dehydrogenase Deficiency | 89 | ||
| The Porphyrias | 90 | ||
| Malignant Hyperthermia | 90 | ||
| Allergic Drug Reactions | 91 | ||
| C—Chronic—Direct Organ Damage: Dose Related and Time Related | 93 | ||
| D—Delayed—Time Related | 94 | ||
| E—End of Use—Withdrawal | 95 | ||
| F—Drug Failure | 95 | ||
| Emerging Developments | 96 | ||
| Key Points | 97 | ||
| Key References | 98 | ||
| References | 98 | ||
| II Nervous System | 101 | ||
| 7 Central Nervous System Physiology: | 103 | ||
| Historical Perspective | 103 | ||
| Glia | 104 | ||
| Neuron | 104 | ||
| Basic Structure | 105 | ||
| Excitability | 105 | ||
| Communication | 108 | ||
| Changes in Membrane Potential | 108 | ||
| Membrane Time Constant and Passive Propagation | 109 | ||
| Action Potential | 110 | ||
| Synapse | 110 | ||
| Transmitter Release and Action | 112 | ||
| Plasticity | 113 | ||
| Transmitters and Receptors | 114 | ||
| Neuronology | 115 | ||
| The Brain: Structure Determines Function | 115 | ||
| Structure | 115 | ||
| Spinal Cord | 119 | ||
| Function | 119 | ||
| Default Mode Network | 120 | ||
| Brain Rhythms | 120 | ||
| Key Points | 121 | ||
| Key References | 121 | ||
| References | 121 | ||
| 8 Central Nervous System Physiology: | 123 | ||
| Cerebrovascular Anatomy | 123 | ||
| Vascular Architecture | 123 | ||
| Arteries and arterioles | 123 | ||
| Venous circulation | 124 | ||
| Anterior circulation | 124 | ||
| Posterior circulation | 124 | ||
| Regulation of Cerebral Blood Flow | 124 | ||
| Chemical Regulation of Cerebral Blood Flow | 125 | ||
| Cerebral metabolic rate | 125 | ||
| Functional state | 125 | ||
| Anesthetic agents | 125 | ||
| Temperature | 125 | ||
| PaCO2 | 126 | ||
| PaO2 | 126 | ||
| Myogenic Regulation (Autoregulation) of Cerebral Blood Flow | 126 | ||
| Neurogenic Regulation of Cerebral Blood Flow | 128 | ||
| Viscosity Effects on Cerebral Blood Flow | 128 | ||
| Vasoactive Agents | 128 | ||
| Systemic vasodilators | 129 | ||
| Catecholamine agonists/antagonists | 129 | ||
| α1-Receptor agonists | 129 | ||
| β-Receptor agonists | 129 | ||
| β Receptor blockers | 129 | ||
| Dopamine | 129 | ||
| Intravenous anesthetics. | 129 | ||
| Inhaled anesthetics | 129 | ||
| Age | 130 | ||
| Cerebral Spinal Fluid Dynamics | 130 | ||
| Production | 130 | ||
| Circulation | 130 | ||
| Function | 130 | ||
| Blood-Brain Barrier | 130 | ||
| Pathophysiology of Cerebral Ischemia | 131 | ||
| Critical CBF Thresholds | 131 | ||
| Energy Failure and Excitotoxicity | 131 | ||
| Nature of Neuronal Death | 132 | ||
| Timing of Neuronal Death | 132 | ||
| Key Points | 133 | ||
| Key References | 133 | ||
| References | 133 | ||
| 9 Intravenous Anesthetics | 137 | ||
| History of Intravenous Anesthesia | 137 | ||
| General Anesthesia by Intravenous Agents | 137 | ||
| Intravenous Anesthesia Mechanisms and Theory | 138 | ||
| Pharmacologic Targets of Intravenous Anesthetics in the Central Nervous System | 139 | ||
| GABAA Receptors | 139 | ||
| GABAA Insights from Mutagenic Studies | 139 | ||
| N-Methyl-d-Aspartate Receptors | 140 | ||
| Other Molecular Targets | 142 | ||
| Individual Agents | 142 | ||
| Barbiturates | 142 | ||
| Benzodiazepines | 144 | ||
| Etomidate | 146 | ||
| Propofol | 146 | ||
| Ketamine | 149 | ||
| Dexmedetomidine | 151 | ||
| Emerging Developments | 152 | ||
| High-Tech Delivery Systems | 152 | ||
| Novel Sedatives | 152 | ||
| Novel Applications of Existing Sedatives | 153 | ||
| Reversal of General Anesthesia | 153 | ||
| Key Points | 154 | ||
| Key References | 154 | ||
| References | 154 | ||
| 10 Pharmacology of Inhaled Anesthetics | 159 | ||
| Historical Perspective | 159 | ||
| Discovery of Inhaled Anesthetics | 159 | ||
| Development of Modern Inhaled Anesthetics | 160 | ||
| Structure-Activity Relationships | 161 | ||
| Meyer-Overton Correlation | 161 | ||
| Stereoselectivity | 161 | ||
| Mechanisms of Action | 162 | ||
| From Lipid to Protein-Based Mechanisms | 162 | ||
| Diversity of Molecular Targets | 162 | ||
| Multiple Behavioral Endpoints | 162 | ||
| Molecular and Cellular Sites of Action | 163 | ||
| Drug Class Effects | 165 | ||
| Nonanesthetic Effects | 166 | ||
| Bronchodilation | 166 | ||
| Neuromuscular Effects | 166 | ||
| Analgesia and Neuroprotection | 166 | ||
| Adverse Effects | 166 | ||
| Respiratory Depression | 166 | ||
| Cardiovascular Depression | 167 | ||
| Cardiac Dysrhythmias | 167 | ||
| Neurophysiologic Effects | 167 | ||
| Mutagenic and Immunomodulatory Effects | 167 | ||
| Hepatotoxicity | 168 | ||
| Nephrotoxicity | 168 | ||
| Malignant Hyperthermia | 168 | ||
| Postoperative Nausea and Vomiting | 169 | ||
| Metabolic Effects | 169 | ||
| Unique Features of Individual Agents | 169 | ||
| Agents with Prominent GABAA Receptor Activity | 169 | ||
| Halothane, Enflurane, Methoxyflurane | 169 | ||
| Isoflurane | 169 | ||
| Sevoflurane | 169 | ||
| Desflurane | 169 | ||
| Ether and Chloroform | 169 | ||
| Agents with Prominent NMDA Receptor Activity | 169 | ||
| Nitrous Oxide | 169 | ||
| Xenon | 170 | ||
| Cyclopropane | 170 | ||
| Environmental Considerations | 170 | ||
| Drug Interactions | 170 | ||
| Reduction in MAC by Anesthetic Adjuvants | 170 | ||
| MAC Additivity | 170 | ||
| Synergy with Opioid-Induced Respiratory Depression | 170 | ||
| Factors Influencing MAC | 170 | ||
| Age | 170 | ||
| Temperature | 170 | ||
| Pharmacogenetic Effects on Potency | 171 | ||
| Common Clinical Indications and Considerations | 171 | ||
| Induction and Maintenance of Anesthesia | 171 | ||
| Neuroanesthesia and Neuromonitoring | 171 | ||
| Cardiac Anesthesia | 172 | ||
| Pediatric Anesthesia | 172 | ||
| Obstetric Anesthesia | 172 | ||
| Ambulatory Anesthesia | 172 | ||
| Thoracic Anesthesia | 172 | ||
| Emerging Developments | 172 | ||
| Developmental Neurotoxicity | 172 | ||
| Anesthesia and Neurodegenerative Disease | 173 | ||
| Neuroinflammation and Cognitive Dysfunction | 174 | ||
| Anesthetic Preconditioning | 174 | ||
| Immunomodulation and Cancer | 174 | ||
| Key Points | 174 | ||
| Key References | 175 | ||
| References | 175 | ||
| 11 Drugs for Neuropsychiatric Disorders | 180 | ||
| Historical Perspective | 180 | ||
| Antidepressant Drugs | 181 | ||
| Tricyclic Antidepressants | 181 | ||
| History | 181 | ||
| Basic Pharmacology | 181 | ||
| Structure-activity | 181 | ||
| Mechanism | 181 | ||
| Metabolism | 182 | ||
| Clinical Pharmacology | 182 | ||
| Pharmacokinetics | 182 | ||
| Pharmacodynamics | 182 | ||
| Therapeutic effects. | 182 | ||
| Adverse Effects | 182 | ||
| Drug Interactions | 182 | ||
| Selective Serotonin Reuptake Inhibitors | 183 | ||
| History | 183 | ||
| Basic Pharmacology | 183 | ||
| Structure-Activity | 183 | ||
| Mechanism | 183 | ||
| Metabolism | 184 | ||
| Clinical Pharmacology | 184 | ||
| Pharmacokinetics | 184 | ||
| Pharmacodynamics | 184 | ||
| Therapeutic effects. | 184 | ||
| Adverse effects. | 185 | ||
| III Cardiovascular and Pulmonary Systems | 349 | ||
| 20 Cardiovascular Physiology: | 351 | ||
| Historical Perspective | 351 | ||
| Cardiac Excitation | 351 | ||
| General Concepts | 351 | ||
| The Action Potential | 353 | ||
| Fast Response Tissue | 353 | ||
| Phase 0—Rapid Depolarization | 353 | ||
| Phase 1—Early Repolarization | 353 | ||
| Phase 2—Plateau | 353 | ||
| Phase 3—Final Repolarization | 353 | ||
| Phase 4—Resting Membrane Potential | 353 | ||
| Slow Response Tissue | 353 | ||
| Phase 4—Slow Spontaneous Depolarization | 353 | ||
| Phase 0—Depolarization | 353 | ||
| Impulse Propagation and Conduction | 354 | ||
| Excitation-Contraction Coupling | 355 | ||
| Membrane Depolarization and Activator Calcium | 355 | ||
| Modulation of Excitation-Contraction Coupling | 356 | ||
| Autoregulation of Mechanical Function: Frequency and Length Dependence | 357 | ||
| Frequency Dependence | 357 | ||
| Length Dependence | 357 | ||
| Vascular Regulation | 358 | ||
| Principles and Caveats | 358 | ||
| Vascular Smooth Muscle Structure | 358 | ||
| Modulation of Vascular Smooth Muscle Tone | 359 | ||
| Mechanisms of Vasoconstriction | 359 | ||
| Mechanisms of Vasodilation | 360 | ||
| Vasoregulation Signaling Pathways | 361 | ||
| Regulation of [Ca2+]i | 361 | ||
| Vasodilation: The G Protein-cAMP Pathway | 361 | ||
| Vasodilation: Nitric Oxide-cGMP Pathway | 361 | ||
| Vasoconstriction: PLC-Phosphatidylinositol Pathway | 361 | ||
| Regulation of Myofilament Ca2+ Sensitivity | 361 | ||
| Regulation of Vascular Smooth Muscle by the Endothelium | 361 | ||
| Endothelium-Derived Relaxing Factors | 362 | ||
| Nitric Oxide (NO) | 362 | ||
| Prostacyclin (PGI2) | 362 | ||
| Endothelium-Derived Hyperpolarizing Factor (EDHF) | 362 | ||
| Endothelium-Derived Contracting Factors | 362 | ||
| Endothelin I (ET-1) | 362 | ||
| Cyclooxygenase Products | 362 | ||
| Examples of Local, Autonomic, and Humoral Regulation of Vascular Smooth Muscle | 362 | ||
| Local Regulation | 362 | ||
| Autonomic Regulation | 362 | ||
| Adrenergic | 362 | ||
| Cholinergic | 362 | ||
| Humoral | 362 | ||
| Key Points | 363 | ||
| Key References | 363 | ||
| References | 364 | ||
| 21 Cardiovascular Physiology: | 366 | ||
| Cardiac Physiology | 366 | ||
| Basic Cardiac Anatomy | 366 | ||
| Control of Cardiac Output | 367 | ||
| The Cardiac Cycle | 369 | ||
| Indices of Cardiac Function | 371 | ||
| Cardiac Function Curves with the Pulmonary Artery Catheter | 371 | ||
| Isovolumic Contraction Index | 371 | ||
| Ejection Phase Index | 371 | ||
| Ventricular Pressure-Volume Loop: End Systolic Pressure Volume Relations | 371 | ||
| Hemodynamics and Systemic Vascular Control | 373 | ||
| Pressure Changes in Systemic and Pulmonary Circulations | 373 | ||
| Determinants of Blood Flow: Poiseuille’s Law | 373 | ||
| Blood Viscosity | 374 | ||
| Turbulent Flow | 375 | ||
| Major Vessel Types: Structure and Function | 375 | ||
| Factors Influencing the Balance Between Capillary Filtration and Absorption | 376 | ||
| Major Cardiovascular Reflexes | 376 | ||
| Arterial Baroreceptor Reflex | 376 | ||
| Bezold-Jarisch Reflex | 376 | ||
| Bainbridge Reflex | 377 | ||
| Tissue Oxygen Transport | 377 | ||
| General Concepts | 377 | ||
| Oxygen Transport in the Blood | 378 | ||
| Oxygen Supply and Consumption | 379 | ||
| Diffusion of Oxygen to Tissues: Capillary to Cell Oxygen Delivery | 380 | ||
| Oxygen Consumption | 382 | ||
| Critical Oxygen Delivery | 382 | ||
| Determinants of Myocardial Oxygen Supply and Demand | 383 | ||
| Control of Coronary Blood Flow | 383 | ||
| Coronary Flow Reserve | 384 | ||
| Myocardial Oxygen Demand | 384 | ||
| Impaired Myocardial Oxygen Balance: Mechanisms of Myocardial Ischemia | 385 | ||
| Emerging Developments | 385 | ||
| Key Points | 386 | ||
| Key References | 387 | ||
| References | 387 | ||
| 22 Vasopressors and Inotropes | 390 | ||
| Historical Perspective | 390 | ||
| Structure-Activity Relationships | 391 | ||
| Mechanisms | 391 | ||
| Metabolism and Pharmacokinetics | 393 | ||
| Pharmacodynamics and Drug Interactions | 393 | ||
| Pharmacogenetics | 394 | ||
| Individual Drugs | 395 | ||
| Epinephrine | 395 | ||
| Isoproterenol | 396 | ||
| Norepinephrine | 396 | ||
| Dopamine | 396 | ||
| Dobutamine | 397 | ||
| Milrinone | 397 | ||
| Phenylephrine | 398 | ||
| Vasopressin | 398 | ||
| Ephedrine | 399 | ||
| Digoxin | 399 | ||
| Rational Drug Selection | 399 | ||
| Septic Shock | 400 | ||
| Cardiac Arrest | 400 | ||
| Mild, Intraoperative Hypotension | 400 | ||
| Hypotension in the Parturient | 400 | ||
| Right Heart Failure | 400 | ||
| Post-Bypass Hypotension | 400 | ||
| Emerging Developments | 400 | ||
| Key Points | 401 | ||
| Key References | 402 | ||
| References | 402 | ||
| 23 Antihypertensive Drugs and Vasodilators | 405 | ||
| Historical Perspective | 406 | ||
| Sites and Mechanisms of Antihypertensive and Vasodilator Drugs | 407 | ||
| Basic Pharmacology and Mechanisms of Action of Individual Drug Classes | 407 | ||
| Calcium Channel Blockers | 407 | ||
| β Blockers | 408 | ||
| Action of β Blockers at the Adrenergic Receptor | 408 | ||
| Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Antagonists | 409 | ||
| Diuretics | 410 | ||
| Centrally Acting Agents | 410 | ||
| α2-Adrenoreceptor Agonists | 411 | ||
| α-Adrenoreceptor Antagonists | 411 | ||
| Nitrovasodilators | 411 | ||
| Other Vasodilator | 412 | ||
| Pharmacokinetics, Pharmacodynamics, and Adverse Effects | 413 | ||
| Calcium Channel Blockers | 413 | ||
| Adverse Drug Interactions | 414 | ||
| New Calcium Channel Blockers | 414 | ||
| β Blockers | 414 | ||
| Antihypertensive Effect of β Blockers | 415 | ||
| New β Blockers | 415 | ||
| Adverse Effects of β Blockers | 415 | ||
| Angiotensin-Converting Enzyme Inhibitors | 416 | ||
| Angiotensin II Receptor Antagonists | 416 | ||
| Adverse Effects and Drug Interactions | 416 | ||
| Diuretics | 417 | ||
| Adverse Effects and Drug Interactions | 417 | ||
| α2-Adrenoreceptor Agonists | 417 | ||
| α-Adrenoreceptor Antagonists | 417 | ||
| Phentolamine and Phenoxybenzamine | 417 | ||
| Vasodilators | 418 | ||
| Hydralazine | 418 | ||
| Nicorandil | 418 | ||
| Minoxidil | 418 | ||
| Nitrates | 418 | ||
| Phosphodiesterase Inhibitors | 419 | ||
| Pharmacotherapy of Hypertension | 419 | ||
| Hypertension and Anesthesia | 419 | ||
| Pulmonary Vasodilators | 420 | ||
| Phosphodiesterase Inhibitors. | 421 | ||
| Novel Pulmonary Vasodilators. | 421 | ||
| Emerging Developments | 421 | ||
| Direct Renin Inhibitors | 421 | ||
| Natriuretic Peptides | 421 | ||
| Endothelin and Endothelin Blockade | 421 | ||
| Key Points | 422 | ||
| Key References | 423 | ||
| References | 423 | ||
| 24 Antiarrhythmic Drugs | 426 | ||
| Historical Perspective | 426 | ||
| Basic Pharmacology | 427 | ||
| Singh-Vaughan Williams Classification of Antiarrhythmic Drugs | 427 | ||
| Sodium Channels and Class I Antiarrhythmic Drugs | 429 | ||
| β Receptors and Class II Antiarrhythmics | 430 | ||
| Potassium Channels and Class III Antiarrhythmic Drugs | 431 | ||
| Calcium Channels and Class IV Antiarrhythmics | 433 | ||
| Clinical Pharmacology | 433 | ||
| Categories of Arrhythmogenic Mechanisms | 433 | ||
| Automaticity | 433 | ||
| Triggered | 433 | ||
| Conduction | 434 | ||
| Clinical Application | 435 | ||
| Class I—Sodium Channel Blockers | 435 | ||
| Class Ia Nav Channel Blockers | 435 | ||
| Class Ib Nav Channel Blockers | 436 | ||
| Class Ic Nav Channel Blockers | 437 | ||
| Class II—β Blockers | 437 | ||
| Class III—Potassium Channel Blockers | 437 | ||
| Class IV—Calcium Channel Blockers | 439 | ||
| Emerging Developments | 439 | ||
| Molecular Genetics of Arrhythmias | 439 | ||
| Long QT Syndrome | 439 | ||
| Short QT Syndrome | 440 | ||
| Brugada Syndrome | 440 | ||
| Other Inherited Arrhythmia Syndromes | 440 | ||
| hERG Drug Interactions | 441 | ||
| Gene Therapy Guided by Molecular Genetics of Inherited Arrhythmias | 441 | ||
| Key Points | 442 | ||
| Key References | 442 | ||
| References | 442 | ||
| 25 Pulmonary Physiology | 445 | ||
| Pulmonary Ventilation | 445 | ||
| Muscles of Ventilation | 445 | ||
| Control of Airway Diameter | 446 | ||
| Cellular Physiology | 446 | ||
| Neural Control | 446 | ||
| Humoral Control | 447 | ||
| Physical and Chemical Effects | 447 | ||
| Local Cellular Mechanisms | 447 | ||
| Molecular Physiology | 447 | ||
| Bronchodilator Pathway | 447 | ||
| Bronchoconstrictor Pathway | 448 | ||
| Bronchoconstriction in Airway Disease | 448 | ||
| Oxygenation | 449 | ||
| Ventilation and Perfusion Relationships | 449 | ||
| Distribution of Ventilation | 449 | ||
| Distribution of Perfusion | 450 | ||
| Ventilation in Relation to Perfusion | 450 | ||
| Shunt | 450 | ||
| Effects of General Anesthesia | 451 | ||
| Pulmonary Vascular Resistance | 451 | ||
| Hypoxic Pulmonary Vasoconstriction | 451 | ||
| Cellular Physiology of Hypoxic Pulmonary Vasoconstriction | 451 | ||
| Molecular Physiology | 452 | ||
| Control of Breathing | 452 | ||
| Respiratory Center | 452 | ||
| Central Pattern Generation | 452 | ||
| Connections to the Respiratory Center | 453 | ||
| Molecular Physiology | 453 | ||
| Chemical Control of Ventilation | 453 | ||
| Central Chemoreceptors | 454 | ||
| Peripheral Chemoreceptors | 454 | ||
| Molecular Physiology | 455 | ||
| Ventilatory Response to Sustained Hypoxia | 455 | ||
| Emerging Developments | 455 | ||
| Remodeling of Airways | 455 | ||
| Iron and Hypoxic Pulmonary Vasoconstriction | 455 | ||
| CO2 Oscillations and Control of Ventilation | 456 | ||
| Key Points | 456 | ||
| Key References | 456 | ||
| References | 456 | ||
| 26 Pulmonary Pharmacology | 458 | ||
| β2-Adrenoceptor Agonists | 459 | ||
| Structure-Activity | 459 | ||
| Mechanism and Metabolism | 459 | ||
| Clinical Pharmacology | 459 | ||
| Pharmacokinetics, Pharmacodynamics, and Therapeutic Effects | 459 | ||
| Adverse Effects | 461 | ||
| Drug Interactions | 461 | ||
| Clinical Application | 461 | ||
| Common Applications | 461 | ||
| Rationale for Drug Selection and Administration | 461 | ||
| Anticholinergics | 461 | ||
| Structure-Activity | 461 | ||
| Mechanism and Metabolism | 462 | ||
| Clinical Pharmacology | 462 | ||
| Pharmacokinetics, Pharmacodynamics, and Therapeutic Effects | 462 | ||
| Adverse Effects | 462 | ||
| Clinical Application | 462 | ||
| Inhaled Steroids | 463 | ||
| Structure-Activity | 463 | ||
| Mechanism and Metabolism | 463 | ||
| Clinical Pharmacology | 464 | ||
| Pharmacokinetics, Pharmacodynamics, and Therapeutic Effects | 464 | ||
| Adverse Effects | 464 | ||
| Drug Interactions | 464 | ||
| Clinical Application | 465 | ||
| Methylxanthines and Phosphodiesterase Inhibitors | 465 | ||
| Structure-Activity | 465 | ||
| Mechanism and Metabolism | 465 | ||
| Clinical Pharmacology | 465 | ||
| Pharmacokinetics, Pharmacodynamics, and Therapeutic Effects | 465 | ||
| Adverse Effects | 466 | ||
| IV Gastrointestinal and Endocrine Systems | 473 | ||
| 27 Liver and Gastrointestinal Physiology | 475 | ||
| Liver | 475 | ||
| Anatomy | 475 | ||
| Blood Supply | 476 | ||
| Liver Function | 476 | ||
| Storage | 476 | ||
| Filtering and Cleansing | 477 | ||
| Metabolism of Nutrients | 477 | ||
| Synthesis of Coagulation Factors | 477 | ||
| Bile Secretion | 477 | ||
| Bilirubin and Jaundice | 477 | ||
| Liver Regeneration | 478 | ||
| Portal Hypertension | 478 | ||
| Hepatic Drug Metabolism and Excretion | 479 | ||
| Anesthetic Pharmacology and the Liver | 479 | ||
| Etiology and Severity of Liver Disease | 479 | ||
| Hepatic Surgery | 479 | ||
| Gastrointestinal Tract | 480 | ||
| Anatomy | 480 | ||
| Properties of the Gastrointestinal Tract | 480 | ||
| Respiration and Pharyngeal Swallowing | 480 | ||
| Lower Esophageal Sphincter | 480 | ||
| Neural Control | 481 | ||
| Enteric Nervous System | 481 | ||
| Parasympathetic Stimulation | 481 | ||
| Sympathetic Stimulation | 481 | ||
| Hormonal Control | 481 | ||
| Splanchnic Circulation | 481 | ||
| Stomach Emptying | 481 | ||
| Enterogastric Nervous Reflex | 481 | ||
| Secretory Functions | 481 | ||
| Autonomic Stimulation | 482 | ||
| Gastric Secretions | 482 | ||
| Pancreatic Digestive Enzymes | 482 | ||
| Bicarbonate Ions | 483 | ||
| Absorption of Nutrients | 483 | ||
| Glucose | 483 | ||
| Fats | 483 | ||
| Gastrointestinal Disorders | 483 | ||
| Anesthetic Pharmacology and the Gastrointestinal Tract | 485 | ||
| Key Points | 485 | ||
| Key References | 485 | ||
| References | 486 | ||
| 28 Nutritional and Metabolic Therapy | 487 | ||
| Fasting in the Perioperative Period | 487 | ||
| Benefits of Early Enteral Feeding | 488 | ||
| Timing of Nutrient Delivery | 488 | ||
| Gastrointestinal Dysfunction | 489 | ||
| Nutrition and Metabolism in the Critically Ill | 491 | ||
| Specific Nutrients | 492 | ||
| Glutamine | 492 | ||
| Clinical Outcome Studies Using Glutamine | 492 | ||
| Delivery of Glutamine | 493 | ||
| Arginine | 493 | ||
| Clinical Outcome Studies Using Arginine | 493 | ||
| DELIVERY OF ARGININE | 495 | ||
| Omega-3 Fatty Acids | 495 | ||
| Clinical Outcome Studies Using 20 and 22 Carbon Omega-3 Fatty Acids | 496 | ||
| Delivery of Omega-3 Fatty Acids | 496 | ||
| Timing of Delivery of Nutrients as Pharmacologic Agents | 496 | ||
| Emerging Developments | 497 | ||
| New Protocols and Malnutrition Definitions | 497 | ||
| Additional Metabolically Active Nutrients | 497 | ||
| Future Studies | 498 | ||
| Key Points | 498 | ||
| Key References | 498 | ||
| References | 499 | ||
| 29 Pharmacology of Postoperative Nausea and Vomiting | 503 | ||
| Historical Perspective | 503 | ||
| Mechanisms of Nausea and Vomiting | 504 | ||
| Serotonin Receptor Antagonists | 505 | ||
| Ondansetron | 505 | ||
| Granisetron and Dolasetron | 505 | ||
| Palonosetron | 508 | ||
| Dopamine Receptor Antagonists | 509 | ||
| Droperidol | 509 | ||
| Haloperidol | 510 | ||
| Metoclopramide | 510 | ||
| Corticosteroids | 511 | ||
| NK1 Receptor Antagonists | 512 | ||
| Aprepitant | 512 | ||
| Anticholinergic Drugs | 512 | ||
| Scopolamine | 513 | ||
| H1 Receptor Antagonists | 514 | ||
| Dimenhydrinate and Diphenhydramine | 514 | ||
| Promethazine | 515 | ||
| GABA Receptor Agonists | 515 | ||
| Propofol | 515 | ||
| Benzodiazepines | 516 | ||
| Opioid Receptor Antagonists | 516 | ||
| Alvimopan | 516 | ||
| Risk-Based Prophylaxis and Multimodal Therapy | 517 | ||
| Emerging Developments | 518 | ||
| Novel Antiemetic Drugs | 518 | ||
| Postdischarge Nausea and Vomiting | 518 | ||
| Key Points | 519 | ||
| Key References | 519 | ||
| References | 520 | ||
| 30 Endocrine Physiology | 523 | ||
| Pituitary Physiology | 523 | ||
| Anterior Pituitary | 523 | ||
| Hyperpituitarism and Anterior Lobe Tumors | 524 | ||
| Gigantism and Acromegaly | 524 | ||
| Cushing Disease | 525 | ||
| Prolactinomas | 525 | ||
| Posterior Pituitary | 525 | ||
| Diabetes Insipidus and Syndrome of Inappropriate Antidiuretic Hormone | 526 | ||
| Parathyroid Physiology | 526 | ||
| Primary Hyperparathyroidism | 527 | ||
| Multiple Endocrine Neoplasia | 527 | ||
| Secondary Hyperparathyroidism | 527 | ||
| Hypoparathyroidism | 527 | ||
| Thyroid Physiology | 528 | ||
| Hypothyroidism | 529 | ||
| Hyperthyroidism | 529 | ||
| Thyroiditis | 529 | ||
| Adrenal Gland Physiology | 530 | ||
| Adrenal Cortex Physiology | 530 | ||
| Cushing Syndrome | 530 | ||
| Glucocorticoid Deficiency | 531 | ||
| Hyperaldosteronism | 531 | ||
| Hypoaldosteronism | 531 | ||
| Adrenal Medulla Physiology | 531 | ||
| Pheochromocytoma | 532 | ||
| Pancreas Physiology | 532 | ||
| Diabetes Mellitus | 533 | ||
| Key Points | 534 | ||
| Key References | 535 | ||
| References | 535 | ||
| 31 Endocrine Pharmacology | 536 | ||
| Drugs to Treat Disorders of the Endocrine Pancreas | 536 | ||
| Insulin | 536 | ||
| Basic Pharmacology | 536 | ||
| Clinical Pharmacology | 537 | ||
| Individual Insulin Preparations | 538 | ||
| Regular Insulin | 538 | ||
| Rapidly Acting Insulin Analogues | 538 | ||
| Intermediate-Acting Insulin | 538 | ||
| Long-Acting Insulins | 538 | ||
| Inhaled Insulin | 538 | ||
| Clinical Application | 539 | ||
| Oral Hypoglycemic Agents: Sulfonylureas, Biguanides, Thiazolidinediones | 539 | ||
| Basic Pharmacology | 539 | ||
| Sulfonylureas | 539 | ||
| Biguanides | 539 | ||
| V Fluid, Electrolyte, and Hematologic Homeostasis | 559 | ||
| 32 Renal Physiology | 561 | ||
| Renal Blood Flow and Glomerular Filtration Rate | 561 | ||
| Renal Blood Flow | 561 | ||
| Renal Clearance | 562 | ||
| Renal Plasma Flow | 562 | ||
| Glomerular Filtration Rate | 562 | ||
| Age-Related Renal Changes | 563 | ||
| The Nephron | 563 | ||
| Water and the Kidney | 563 | ||
| Salt and the Kidney | 563 | ||
| Potassium and the Kidney | 564 | ||
| Toxin and Metabolite Excretion | 564 | ||
| Acid-Base Balance | 565 | ||
| Renal Hormone Production | 565 | ||
| Defining Renal Failure | 566 | ||
| Risk of Perioperative Acute Kidney Injury | 567 | ||
| Acute Kidney Injury in Surgical Patients | 567 | ||
| Assessment and Management of Acute Kidney Injury | 568 | ||
| Preoperative Approach | 568 | ||
| Intraoperative Management of Renal Function | 568 | ||
| Anesthetic Drugs and Impaired Renal Function | 569 | ||
| Common Perioperative Medications That Impair Renal Function | 569 | ||
| Renal Replacement Therapy during and after Surgery | 569 | ||
| Hepatorenal Syndrome | 570 | ||
| Emerging Developments | 570 | ||
| Prevention and Biomarkers for Acute Kidney Injury | 570 | ||
| Key Points | 571 | ||
| Key References | 571 | ||
| References | 572 | ||
| 33 Intravascular Volume Replacement Therapy | 574 | ||
| Historical Perspective | 574 | ||
| Conventional Concepts | 575 | ||
| Body Water | 575 | ||
| Measurement of Body Fluid Spaces | 575 | ||
| Maintenance Requirements for Water, Sodium, and Potassium | 575 | ||
| Interstitium | 576 | ||
| Third Space | 577 | ||
| Fluid Shifts and Losses During Surgery, and Their Replacement | 578 | ||
| Clinical Assessment of Intravascular Volume in Critically Ill Patients | 579 | ||
| Conventional Indices of Resuscitation | 579 | ||
| Urinary Output and Clinical Signs of Hypovolemia | 579 | ||
| Response to Fluid Challenge | 579 | ||
| Static Measurements of Intravascular Volume | 580 | ||
| Central Venous Pressure | 580 | ||
| Pulmonary Artery Occlusion Pressure | 580 | ||
| Transesophageal Echocardiography | 580 | ||
| Intrathoracic Blood Volume Index and Global End-Diastolic Volume Index | 580 | ||
| Stroke Volume Variation and Pulse Pressure Variation | 580 | ||
| Esophageal Doppler Catheter | 580 | ||
| Near Infrared Spectroscopy | 581 | ||
| Body Fluid Dynamics (Modeling Fluid Therapy) | 581 | ||
| Computing Intravascular Expansion from an Endogenous Marker—Hemoglobin | 581 | ||
| Plasma Volume Expansion | 582 | ||
| Volume Kinetics for Infusion Fluids | 583 | ||
| Estimation of Volume Kinetic Parameters | 584 | ||
| Population Kinetics for Infusion Fluids | 585 | ||
| Pharmacodynamics of Infusion Fluids | 585 | ||
| Guiding Principles and Clinical Recommendations | 585 | ||
| Crystalloids | 585 | ||
| Normal Saline | 585 | ||
| Hypertonic Saline | 586 | ||
| Ringer’s Solutions | 586 | ||
| Glucose Solutions | 586 | ||
| Colloids | 587 | ||
| Albumin | 588 | ||
| Dextran-Containing Solutions | 588 | ||
| Hetastarch | 588 | ||
| Gelatin | 588 | ||
| Summary | 588 | ||
| Clinical Fluid Therapy Guidelines | 588 | ||
| Basal Requirements and Rehydration | 588 | ||
| Day Surgery Cases: Minor Surgery | 589 | ||
| Surgery Under Spinal or Epidural Block | 589 | ||
| Gastrointestinal Surgery | 589 | ||
| Emerging Developments | 589 | ||
| Key Points | 589 | ||
| Key References | 589 | ||
| References | 590 | ||
| 34 Electrolytes and Diuretics | 593 | ||
| Electrolytes | 593 | ||
| Sodium | 593 | ||
| Physiologic Role | 593 | ||
| Hyponatremia | 594 | ||
| Hypernatremia | 597 | ||
| Potassium | 599 | ||
| Physiologic Role | 599 | ||
| Hypokalemia | 600 | ||
| Hyperkalemia | 601 | ||
| Calcium | 602 | ||
| Physiologic Role | 602 | ||
| Hypocalcemia | 603 | ||
| Hypercalcemia | 604 | ||
| Phosphate | 605 | ||
| Physiologic Role | 605 | ||
| Hypophosphatemia | 605 | ||
| Hyperphosphatemia | 606 | ||
| Magnesium | 606 | ||
| Physiologic Role | 606 | ||
| Hypomagnesemia | 607 | ||
| Hypermagnesemia | 608 | ||
| Diuretics | 608 | ||
| Proximal Convoluted Tubule—Carbonic Anhydrase Inhibitors | 609 | ||
| Ascending Loop of Henle—Loop Diuretics | 609 | ||
| Distal Convoluted Tubule—Thiazides | 609 | ||
| Collecting Ducts—Potassium Sparing Diuretics | 610 | ||
| Osmotic Diuretics | 610 | ||
| Diuretics in Heart Failure | 610 | ||
| Adverse Effects of Diuretics | 610 | ||
| Volume Depletion | 610 | ||
| Azotemia | 610 | ||
| Hypokalemia | 610 | ||
| Hyponatremia | 610 | ||
| Emerging Developments | 611 | ||
| Key Points | 611 | ||
| Key References | 612 | ||
| References | 612 | ||
| 35 Blood and Coagulation | 615 | ||
| Normal Hemostatic Mechanisms | 615 | ||
| Hypercoagulability | 616 | ||
| Inherited Risk Factors | 616 | ||
| Increased Procoagulant Effects | 616 | ||
| Reduction of Natural Anticoagulant Factors | 617 | ||
| Fibrinolysis Modulation | 618 | ||
| Other Inherited Conditions | 618 | ||
| Acquired Risk Factors | 618 | ||
| Disease States Associated with Hypercoagulability | 618 | ||
| Heparin-Induced Thrombocytopenia | 618 | ||
| Pathogenesis and Frequency | 618 | ||
| Diagnosis | 620 | ||
| Treatment | 620 | ||
| Hypocoagulability: Perioperative Bleeding | 620 | ||
| Risk Factors for Bleeding | 620 | ||
| Patient-Related Causes of Bleeding | 620 | ||
| Common Inherited Hemostatic Disorders | 621 | ||
| Physician-Related Factors | 621 | ||
| Procedure-Related Factors | 621 | ||
| Pharmacologic Factors | 621 | ||
| Disorders of Hemostasis: Disseminated Intravascular Coagulation | 622 | ||
| Thrombocytopenia | 622 | ||
| Coagulopathy | 622 | ||
| Fibrinogen Consumption | 622 | ||
| Reductions in Coagulation Inhibitors | 622 | ||
| Fibrinolysis Indicators | 622 | ||
| Hemostatic Testing | 622 | ||
| Point-of-Care Coagulation Testing | 623 | ||
| Transfusion Algorithms | 623 | ||
| Blood Conservation | 624 | ||
| Massive Transfusion | 624 | ||
| Key Points | 625 | ||
| Key References | 625 | ||
| References | 625 | ||
| 36 Transfusion and Coagulation Therapy | 628 | ||
| Historical Considerations | 628 | ||
| Hemoglobin and PLATELET Replacement | 629 | ||
| Packed Red Blood Cells | 629 | ||
| Clinical Uses | 629 | ||
| Index | 669 | ||
| A | 669 | ||
| B | 671 | ||
| C | 672 | ||
| D | 674 | ||
| E | 676 | ||
| F | 676 | ||
| G | 677 | ||
| H | 678 | ||
| I | 679 | ||
| J | 680 | ||
| K | 680 | ||
| L | 680 | ||
| M | 681 | ||
| N | 682 | ||
| O | 684 | ||
| P | 684 | ||
| Q | 686 | ||
| R | 686 | ||
| S | 687 | ||
| T | 688 | ||
| U | 689 | ||
| V | 689 | ||
| W | 690 | ||
| X | 690 | ||
| Z | 690 | ||
| Clinical Key | IBC1 |