Principles of drug action : the basis of pharmacology

목차 (Table of Contents)

• CONTENTS
• CHAPTER 1 Molecular Mechanisms of Drug Action = 1
• RECEPTORS = 1
• BINDING FORCES IN THE DRUG-RECEPTOR INTERACTION = 2
• Bond Types = 2
• Drug-Receptor Interaction as Resultant of the Several Bond Types = 18
• The Ionization of Drugs = 19
• STRUCTURE-ACTIVITY RELATIONSHIPS AND THE CONFORMATION OF THE RECEPTOR SURFACE = 22
• Methods of Studying Receptors = 22
• Acetylcholine and Congeners = 23
• The Polym6thylene Bismethonium Series = 27
• The Narcotic Analgesics = 33
• Congeners of the Adrenal Glucocorticoid Hormones = 36
• Congeners of the Pituitary Polypeptide Hormones = 39
• Cycloserine and the Inhibition of Bacterial Cell Wall Synthesis = 42
• Antibacterial Sulfonamides = 43
• CHARACTERIZATION OF DRUG-RECEPTOR INTERACTIONS = 47
• Model Interactions = 47
• Special Techniques for Studying Drug- Receptor Interactions = 57
• RECEPTOR ISOLATION = 66
• Steroid Hormone Receptors = 66
• Acetylcholine Receptor = 73
• Insulin Receptor = 80
• CONSEQUENCES OF DRUG RECEPTOR INTERACTION : ANALYSIS OF THE GRADED DOSE-RESPONSE RELATIONSHIP = 82
• Application of the Law of Mass Action : The Occupancy Assumption = 82
• The Log Dose-Response Curve = 89
• Alternatives to the Occupancy Assumption = 96
• DRUG ACTIONS THAT ARE NOT MEDIATED DIRECTLY BY RECEPTORS = 111
• Nonspecific Effects and Membrane Perturbations = 112
• Interaction of Drug with Small Molecule or Ion = 116
• Incorporation of Drug into a Macromolecule = 117
• CHAPTER 2 The Absorption, Distribution, and Elimination of Drugs = 129
• INTRODUCTION = 129
• DRUG ABSORPTION : ROUTES OF ADMINISTRATION = 131
• Intravascular Administration = 131
• Intramuscular Administration = 134
• Subcutaneous Administration = 134
• Absorption of Drugs Through the Skin = 136
• Inhalation of Drugs = 138
• Administration of Drugs by the Enteral Route = 143
• Methods of Modifying Drug Delivery = 149
• DRUG DISTRIBUTION = 154
• Apparent Volumes of Distribution = 154
• The Binding of Drugs to Plasma Proteins = 158
• Passage of Drugs Across Biologic Membranes = 164
• Passage of Drugs into the Central Nervous System = 184
• Passage of Drugs Across the Placenta = 198
• DRUG ELIMINATION : THE MAJOR ROUTES = 210
• Renal Excretion of Drugs = 210
• Extracorporeal Dialysis = 216
• Biliary Excretion of Drugs = 217
• CHAPTER 3 Drug Metabolism = 227
• INTRODUCTION = 227
• METHODS OF STUDYING DRUG METABOLISM = 230
• Separation of Metabolites = 230
• Detection, Identification, and Quantitative Estimation of Metabolites = 236
• CHEMICAL PATHWAYS OF DRUG METABOLISM = 242
• The Liver Microsomal Drug-Metabolizing System = 242
• Drug Oxidations That Are Not Mediated by the Liver Microsomal System = 251
• Reduction = 256
• Hydrolysis = 257
• Addition（Conjugation）Reactions = 258
• INHIBITION OF DRUG METABOLISM = 267
• SKF 525A = 267
• Disulfiram = 268
• Monoamine Oxidase Inhibitors = 7
• Xanthine Oxidase Inhibitors = 272
• STIMULATION AND DEPRESSION OF DRUG METABOLISM = 273
• SPECIES DIFFERENCES AND GENETIC VARIATION IN DRUG METABOLISM = 283
• EFFECTS OF AGE UPON DRUG METABOLISM = 289
• CHAPTER 4 The Time Course of Drug Action = 301
• RATE OF DRUG ABSORPTION = 301
• RATE OF DRUG ELIMINATION = 304
• ZERO-ORDER ABSORPTION, FIRST-ORDER ELIMINATION : THE PLATEAU PRINCIPLE = 311
• Derivation of the Principle and Its Application to Constant Infusions = 311
• Dosage Regimens = 318
• Drug Accumulation and Toxicity = 326
• Kinetics of Changes in Enzyme Levels = 329
• FIRST-ORDER ABSORPTION, FIRST-ORDER ELIMINATION KINETICS OF DRUG LEVELS AFTER SINGLE DOSES = 333
• KINETICS OF THE UPTAKE AND DISTRIBUTION OF DRUGS ADMINISTERED BY INHALATION = 338
• Introduction = 338
• Equilibrium in Clinical Anesthesia = 340
• Rate of Equilibration of Blood and Body Water = 341
• Influence of Body Fat = 350
• Speed of Induction and Recovery in Clinical Anesthesia 4 = 351
• CHAPTER 5 Drug Toxicity = 357
• INTRODUCTION = 357
• ENVIRONMENTAL TOXICITY = 359
• Pesticides = 360
• Air Pollution = 364
• Lead = 368
• Mercury = 372
• Food Additives = 374
• THE EVALUATION OF DRUG TOXICITY IN LOWER ANIMALS ANDIN MAN = 376
• TREATMENT OF TOXICITY = 394
• Principles of Nonspecific Therapy = 394
• Principles of Antidotal Treatment = 400
• Mechanism 1. Antidote Complexes with Poison, Rendering it Inert = 400
• Mechanism 2. Antidote Accelerates Metabolic Conversion of Poison to Nontoxic Product = 411
• Mechanism 3. Antidote Blocks Metabolic ForrTfation of Poison from Less Toxic Precursor = 412
• Mechanism 4. Antidote Specifically Accelerates Excretion of Poison = 415
• Mechanism 5. Antidote Competes with Poison for Essential Receptors = 416
• Mechanism 6. Antidote Blocks Receptors that are Responsible for Toxic Effect = 422
• Mechanism 7. Antidote Restores Normal Function by Repairing or Bypassing Effect of Poison = 423
• CHAPTER 6 Pharmacogenetics and Drug Idiosyncrasy = 437
• INTRODUCTION = 437
• DRUG TOXICITY DUE TO IMPAIRED DRUG METABOLISM = 444
• Succinylcholine Hydrolysis = 444
• Hereditary Methemoglobinemia = 450
• Slow Metabolism of Isoniazid = 452
• INCREASED SENSITIVITY TO DRUG = 454
• Abnormal Hemoglobins = 454
• NOVEL DRUG EFFECT = 455
• Primaquine Sensitivity = 455
• Malignant Hyperthermia = 462
• Hepatic Porphyria = 463
• DECREASED RESPONSIVENESS TO DRUG = 467
• Coumarin Resistance = 467
• Vitamin,D-Resistant Rickets = 469
• Inability to Taste Phenylthiourea = 470
• Juvenile Pernicious Anemia = 473
• Resistance to Succinylcholine = 474
• Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency = 474
• Racial Differences in Drug Response = 475
• ABNORMAL DISTRIBUTION OF DRUG = 476
• Copper （Wilson's Disease） = 476
• Iron（Primary Hemochromatosis） = 477
• Increased or Decreased Thyroxine-Binding Globulin = 479
• DIFFERENCES IN USE OF AND RESPONSE TO PSYCHOTROPIC DRUGS = 481
• CHAPTER 7 Drug Allergy = 489
• INTRODUCTION = 489
• IMMUNOLOGIC BASIS OF DRUG ALLERGY = 491
• The Immunoglobulins = 491
• Covalently Bonded Drug-Protein Conjugates = 493
• DRUG ALLERGY IN MAN = 499
• Manifestations of Drug Allergy = 500
• Frequency of Allergic Reactions to Drugs = 503
• Tests for Predicting Drug Allergies = 508
• Desensitization = 511
• Management of Drug Allergies = 511
• CHAPTER 8 Drug Resistance = 517
• ORIGIN OF ACQUIRED DRUG RESISTANCE = 517
• The Mutation-Selection Mechanism = 517
• Evidence for the Mutational Origins of Drug Resistance = 518
• Patterns of Emergence and Spread of Drug Resistance = 521
• BIOCHEMICAL MECHANISMS OF DRUG RESISTANCE = 525
• Mechanism 1. Decreased Intracellular Drug Level = 525
• Mechanism 2. Increased Destruction of Drug = 529
• Mechanism 3. Decreased Conversion of Drug to a More Active Compound = 534
• Mechanism 4. Increased Concentration of Metabolite Antagonizing the Drug Action = 538
• Mechanism 5. Altered Amount of Target Enzyme = 538
• Mechanism 6. Decreased Requirement for Product of Drug- Sensitive Enzyme（Hypothetical） = 540
• Mechanism 7. Enhanced Biochemical Mechanisms for Bypassing or Repairing the Drug-Sensitive Reaction = 540
• Mechanism 8. De&eased Affinity of Receptor for Drug = 542
• ANTIBACTERIAL AGENTS THAT INHIBIT PROTEIN SYNTHESIS = 552
• SELECTION OF DRUG-RESISTANT CELLS IN ANIMALS AND MAN = 560
• CHAPTER 9 Drug Tolerance and Physical Dependence = 569
• TOLERANCE BY INDIRECT MECHANISMS = 569
• Reduction of the Ambient Drug Concentration （Metabolic Tolerance） = 570
• Homeostatic Adjustments Antagonizing the Drug Action = 572
• TOLERANCE AT THE CELLULAR SITES OF DRUG ACTION = 574
• Acute Tolerance （Tachyphylaxis） = 575
• Tolerance and Physical Dependence in the Central Nervous System = 586
• CHAPTER 10 Chemical Mutagenesis = 623
• MOLEC IULAR BASIS OF MUTATION = 623
• BASE PAIR TRANSFORMATIONS = 630
• FRAME SHIFT MUTATIONS = 639
• METAPHASE POISONING （SPINDLE INACTIVATION） = 648
• CHEMICAL MUTAGENESIS IN ANIMALS AND MAN = 650
• The Human Germ Line = 650
• Some Common I\Aethods of Testing Mutagenicity in Animals = 654
• Evaluation of the Hazards of Chemical Mutagens in Man = 656
• CHAPTER 11 Chemical Carcinogenesis = 667
• MECHANISM OF ACTION OF CHEMICAL CARCINOGENS = 667
• Methods of Experimentation = 667
• Initiation and Promotion = 670
• Carcinogonesis and Mulagenesis = 673
• THE PRINCIPAL GROUPS OF CHEMICAL CARCINOGENS = 679
• Polycyclic Hydrocarbons = 679
• Amines = 682
• Alkylating Agents = 687
• Alkylation and Arylation in the Carcinogenic Process = 690
• CARCINOGENIC HAZARDS IN THE HUMAN ENVIRONMENT = 690
• Epidemic Outbreaks of Cancer = 690
• Smoking and Lung Cancer = 692
• The Problem of Eliminating and Excluding Carcinogens from the Environment = 696
• CHAPTER 12 Chemical Teratogenesis = 703
• EXPERIMENTAL TERATOGENESIS = 704
• Methods = 704
• Selectivity of Action in Teratogenesis = 705
• Genetic Influences = 706
• Sensitive Periods = 708
• Specificity and Variety of Teratogens = 710
• TERATOGENESIS IN MAN = 714
• Congenital Malformations in Human Populations = 714
• Accidental Human Exposure to Teratogens = 716
• Lessons of the Thalidomide Catastrophe = 718
• CHAPTER 13 Drug Development = 729
• INTRODUCTION = 729
• QUALITATIVE AND QUANTITATIVE ESTIMATION OF DRUG ACTION = 731
• Screening = 732
• Bioassay = 737
• METHODS OF DEVELOPING NEW DRUGS = 741
• Purification of Drugs from Natural Sources = 741
• Modification of Chemical Structure = 750
• Synthesis of New Drugs = 762
• CHAPTER 14 Drug Evaluation in Man = 779
• THE CLINICAL TRIAL = 779
• Introduction = 779
• Placebo Controls and Concurrent Comparisons = 780
• Randomization = 783
• Blind Designs = 785
• Two Trials With Antihistamines : An Illustrative Contrast = 787
• Sequential Trials = 790
• Critical Appraisal of Reports on Clinical Trials = 795
• Ethics of Human Experimentation = 797
• USE AND MISUSE OF DRUGS = 801
• Legal Controls Over Drug Availability = 801
• Self-medication, Prescribing Practices, and latrogenic Disease = 806
• Drug Nomenclature and Prices = 810
• MONITORING OF DRUG USE = 813
• Large-scale Surveillance = 813
• Drug Plasma Levels = 817
• DRUG INTERACTIONS = 819
• Absorption = 819
• Distribution = 821
• Drug Interaction at Receptor Sites = 824
• Metabolism = 824
• Excretion = 825
• Clinical Significance of Drug Interactions = 826
• INDEX = 833