Principles of drug action: the basis of pharmacology
Gespeichert in:
| Späterer Titel: | Principles of drug action |
|---|---|
| Hauptverfasser: | , , |
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
New York [u.a.]
Hoeber Med. Div., Harper & Row
1969
|
| Ausgabe: | Reprint. with corr. |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | XII, 884 S. Ill., graph. Darst. |
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Datensatz im Suchindex
| _version_ | 1804117249964900352 |
|---|---|
| adam_text | With 476 Illustrations
OF DRUG ACTION
THEBASISOFPHARMACOLOGY
Avram Goldstein, M D
PROFESSOR OF PHARMACOLOGY
Lewis Aronow, Ph D
ASSOCIATE PROFESSOR OF PHARMACOLOGY
Sumner M Kalman, M D
PROFESSOR OF PHARMACOLOGY
STANFORD UNIVERSITY SCHOOL OF MEDICINE
PALO ALTO, CALIFORNIA
Hoeber Medical Division
Harper amp; Row, Publishers, New York, Evanston, and London
CONTENTS
PREFACE xiii
CHAPTER 1 MOLECULAR MECHANISMS OF DRUG ACTION 1
Receptors 1
Binding Forces in the Drug-Receptor Interaction 3
Bond Types 3
Drug-Receptor Interaction as Resultant of the Several Bond Types 25
The Ionization of Drugs 25
Structure-Activity Relationships and the Conformation of the Receptor Surface 30
Methods of Studying Receptors 30
Drug-Protein Interactions as Models of Drug-Receptor Interactions 34
Acetylcholine and Congeners 40
The Polymethylene Bis-Methonium Series 44
The Morphinelike A nalgesics 50
Congeners of the Adrenal Glucocorticoid Hormones 56
Congeners of the Pituitary Polypeptide Hormones 59
Cycloserine and the Inhibition of Bacteria! Cell M all Synthesis 63
Antibacterial Sulfonamides 66
Consequences of Drug-Receptor Interactions: Analysis of the Graded Dose-
Response Relationship 70
Application of the Law of Mass A ction 70
The Double-Reciprocal Plot 72
The Log Dosd-Response Curve 77
Anomalous Antagonisms and Their Interpretation 88
Other Ways of Interpreting the Log Dose-Respon, e Relationship 94
Drug Actions that are not Mediated Directly by Receptors 99
CHAPTER 2 THE ABSORPTION, DISTRIBUTION, AND
ELIMINATION OF DRUGS 106
Introduction 106
Drug Absorption: Routes of Administration 108
Intravascular Administration 108
Intramuscular Administration 111
Subcutaneous A dministration 111
Absorption of Drugs through the Skin 114
Inhalation of Drugs 115
Administration of Drugs by the Enteral Route 119
Drug Distribution 130
Apparent Volumes of Distribution 130
The Binding of Drugs to Plasma Proteins 136
Passage of Drugs across Biologic Membranes 145
v
CONTENTS
PREFACE xiii
CHAPTER 1 MOLECULAR MECHANISMS OF DRUG ACTION 1
Receptors 1
Binding Forces in the Drug-Receptor Interaction 3
Bond Types 3
Drug-Receptor Interaction as Resultant of the Several Bond Types 25
The Ionization of Drugs 25
Structure-Activity Relationships and the Conformation of the Receptor Surface 30
Methods of Studying Receptors 30
Drug-Protein Interactions as Models of Drug-Receptor Interactions 34
Acetylcholine and Congeners 40
The Poly methylene Bis-Methonium Series 44
The Morphinelike Analgesics 50
Congeners of the Adrenal Glucocorticoid Hormones 56
Congeners of the Pituitary Polypeptide Hormones 59
Cycloserine and the Inhibition of Bacterial Cell U all Synthesis 63
Antibacterial Sulfonamides 66
Consequences of Drug-Receptor Interactions: Analysis of the Graded Dose-
Response Relationship 70
Application of the Law of Mass Action 70
The Double-Reciprocal Plot 72
The Log Dose-Response Curve 77
Anomalous Antagonisms and Their Interpretation 88
Other Ways of Interpreting the Log Dose-Respon se Relationship 94
Drug Actions that are not Mediated Directly by Receptors 99
CHAPTER 2 THE ABSORPTION, DISTRIBUTION, AND
ELIMINATION OF DRUGS 106
Introduction 106
Drug Absorption: Routes of Administration 108
Intravascular Administration 108
Intramuscular Administration 111
Subcutaneous Administration 111
Absorption of Drugs through the Skin 114
Inhalation of Drugs 115
Administration of Drugs by the Enteral Route 119
Drug Distribution 130
Apparent Volumes of Distribution 130
The Binding of Drugs to Plasma Proteins 136
Passage of Drugs across Biologic Membranes 145
v
Passage of Drugs into the Central Nervous System 160
Passage of Drugs across the Placenta 179
Drug Elimination: The Major Routes 194
Renal Excretion of Drugs 194
Extracorporeal Dialysis 202
Biliary Excretion of Drugs 203
CHAPTER 3 DRUG METABOLISM 206
Introduction 206
Methods of Studying Drug Metabolism 210
Separation of Metabolites 211
Quantitative Estimation of Metabolites 216
Chemical Pathways of Drug Metabolism 218
The Liver Microsomal Drug-Metabolizing System 218
Drug Oxidations that are not Mediated by the I Aver Microsomal System 232
Reduction 236
Hydrolysis 237
Synthetic (Conjugation) Reactions 238
Inhibition of Drug Metabolism 249
SKF525A- 249
Disulfiram 253
Monoamine Oxidase Inhibitors 257
Stimulation and Depression of Drug Metabolism 259
t
Species Differences and Genetic Variation in Drug Metabolism 266
Effects of Age upon Drug Metabolism 274
CHAPTER 4 THE TIME COURSE OF DRUG ACTION 280
Rate of Drug Absorption 280
Rate of Drug Elimination 283
Zero-Order Absorption, First-Order Elimination: The Plateau Principle 292
Derivation of the Principle and Its A pplication to Constant Infusions 292
Dosage Regimens 300
Drug Accumulation and Toxicity 309
Kinetics of Changes in Enzyme Levels 313
First-Order Absorption, First-Order Elimination: Kinetics of Drug Levels
after Single Doses 317
Kinetics of the Uptake and Distribution of Drugs Administered by Inhalation:
An Application of the Plateau Principle to Anesthetic Gases 323
Introduction 323
Equilibrium in Clinical Anesthesia 327
Rate of Equilibration of Blood and Body Water 329
Contents vii
Influence of Body Fat 337
Speed of Induction and Recovery in Clinical Anesthesia 339
CHAPTER 5 DRUG TOXICITY 343
Introduction 343
The Evaluation of Drug Toxicity in Lower Animals and in Man 350
Treatment of Toxicity 377
Principles of Nonspecific Therapy 377
Principles of Antidotal Treatment 384
CHAPTER 6 DRUG IDIOSYNCRASY AND PHARMACOGENETICS 429
Introduction 429
Abnormally Prolonged Drug Effect 434
Succinylcholine Hydrolysis 434
Hereditary Methemoglobinemia 441
Slow Metabolism of Isoniazid 443
Increased Sensitivity to Drug 444
Abnormal Hemoglobins 444
Novel Drug Effect 444
Primaquine Sensitivity 444
Porphyria 453
Decreased Responsiveness to Drug 457
Coumarin Resistance 457
Vitamin D-Resistant Rickets 460
Inability to Taste Phenylthiourea 461
Juvenile Pernicious Anemia 465
Resistance to Succinylcholine 465
Atropine Resistance (Rabbits) 466
Insulin Resistance {Mice) 467
Racial Differences in Drug Response 467
Abnormal Distribution of Drug 467
Copper ( Wilson s Disease) 467
Iron (Primary Hemochromatosis) 469
Increased or Decreased Thyroxine-Binding Globulin 472
Differences in Use of and Response to Psychotropic Drugs 474
CHAPTER 7 DRUG ALLERGY 476
Introduction 476
Immunologic Basis of Drug Allergy 479
Covalently Bonded Drug-Protein Conjugates 47 )
Affinity Labeling 489
viii Contents
Drug Allergy in Man 490
Manifestations of Drug Allergy 491
Frequency of Allergic Reactions to Drugs 495
Tests for Predicting Drug A llergies 503
Desensitization 505
Management of Drug A llergies 506
CHAPTER 8 DRUG RESISTANCE 508
Origin of Acquired Drug Resistance 508
The Mutation-Selection Mechanism 508
Evidence for the Mutational Origins of Drug Resistance 509
Patterns of Emergence and Spread of Drug Resistance 513
Biochemical Mechanisms of Drug Resistance 518
Mechanism 1 Decreased Intracellular Drug l evel 518
Mechanism 2 Increased Destruction of Drug 523
Mechanism 3 Decreased Conversion of Drug to a More Active
Compound 526
Mechanism 4 Increased Concentration of Metabolite Antagonizing the Drug
Action 530
Mechanism 5 Increased Amount of Target Enzyme 530
Mechanism 6 Decreased Requirement for Product of Drug-Sensitive
Enzyme (Hypothetical) 533
Mechanism 7 Alternative Metabolic Pathway Bypassing the Drug-Sensitive
Reaction (Hypothetical) 534
Mechanis^n 8 Decreased Relative Affinity of Enzyme for Drug Compared
with Substrate 534
Streptomycin Dependence 545
Protein Synthesis and the Genetic Code 545
Disturbance of Translation by Streptomycin 549
Phenotypic Suppression and the Misreading Hypothesis 552
Selection of Drug-Resistant Cells in Animals and Man 554
CHAPTER 9 DRUG TOLERANCE AND PHYSICAL DEPENDENCE 558
Tolerance by Indirect Mechanisms 558
Reduction of the Effective Drug Concentration 559
Homeostatic Adjustments Antagonizing the Drug Action 561
Tolerance at the Cellular Sites of Drug Action 564
Acute Tolerance (Tachyphylaxis) 565
Tolerance and Physical Dependence in the Central Nervous System 578
CHAPTER 10 CHEMICAL MUTAGENESIS 618
Introduction 618
Base Pair Transformations 628
Contents ix
Frame Shift Mutations 640
Chromosome Breakage 647
Metaphase Poisoning (Spindle Inactivation) 653
Chemical Mutagenesis in Animals and Man 657
The Human Germ Line 657
Some Common Methods of Testing Mutagenicity in Animals 660
Evaluation of the Hazards of Chemical Mutagens in Man 663
CHAPTER II CHEMICAL CARCINOGENESIS 669
Mechanism of Action of Chemical Carcinogens 670
Methods of Experimentation 670
Initiation and Promotion 673
Cancer as a Genetic Abnormality of Somatic Cells 677
Molecular Interactions of Carcinogens with Cell Constituents 680
The Principal Groups of Chemical Carcinogens 685
Polycyclic Hydrocarbons 685
Amines 689
Alkylating Agents 698
Alkylation and Arylation in the Carcinogenic Process 701
Carcinogenic Hazards in the Human Environment 702
Epidemic Outbreaks of Cancer 702
Smoking and Lung Cancer 704
The Problem of Eliminating and Excluding Carcinogens from the En-ft
vironment 708
CHAPTER 12 CHEMICAL TERATOGENESIS 711
Experimental Teratogenesis 713
Methods 713
Selectivity of Action in Teratogenesis 713
Genetic Influences 715
Sensitive Periods 717
Specificity and Variety of Teratogens 720
Teratogenesis in Man 724
Congenital Malformations in Human Populations 724
Accidental Human Exposure to Teratogens 726
Lessons of the Thalidomide Catastrophe 729
CHAPTER 13 DRUG DEVELOPMENT 735
Introduction 735
Qualitative and Quantitative Estimation of Drug Action 738
Screening 739
Bioassay 746
X Contents
Methods of Developing New Drugs 751
Purification of Drugs from Natural Sources 751
Modification of Chemical Structure 763
Synthesis of New Drugs 777
CHAPTER 14 THE SELECTION OF DRUGS FOR CLINICAL USE 792
Steps Leading to the Clinical Trial 792
Drug Evaluation in Man: The Clinical Trial 794
Placebo Controls and Concurrent Comparisons 794
Randomization 799
Blind Designs 801
Two Trials with Antihistamines: An Illustrative Contrast 803
Sequential Trials 808
Critical Appraisal of Reports on Clinical Trials 814
Ethics of Human Experimentation 815
Use and Misuse of Drugs 819
Legal Controls over Drug Availability 819
Self-Medication and Iatrogenic Disease 825
Drug Nomenclature and Drug Prices 827
Sources of Information about Drugs 831
Official Compendiums 832
Unofficial Compendiums 834
Critical Evaluations 835
Advertising and Promotion 838
APPENDIX I PRINCIPLES OF PRESCRIBING 841
APPENDIX II LIST OF ABBREVIATIONS AND SYMBOLS 847
INDEX 849
|
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| indexdate | 2024-07-09T15:51:25Z |
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| spelling | Goldstein, Avram Verfasser aut Principles of drug action the basis of pharmacology Avram Goldstein ; Lewis Aronow ; Sumner M. Kalman Reprint. with corr. New York [u.a.] Hoeber Med. Div., Harper & Row 1969 XII, 884 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Pharmakologie (DE-588)4045687-0 gnd rswk-swf Pharmakodynamik (DE-588)4174134-1 gnd rswk-swf 1\p (DE-588)4123623-3 Lehrbuch gnd-content Pharmakologie (DE-588)4045687-0 s DE-604 Pharmakodynamik (DE-588)4174134-1 s 2\p DE-604 Aronow, Lewis Verfasser aut Kalman, Sumner M. 20. Jh. Verfasser (DE-588)172203422 aut Später u.d.T. Principles of drug action (DE-604)BV004548398 HEBIS Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=001852198&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk 2\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk |
| spellingShingle | Goldstein, Avram Aronow, Lewis Kalman, Sumner M. 20. Jh Principles of drug action the basis of pharmacology Pharmakologie (DE-588)4045687-0 gnd Pharmakodynamik (DE-588)4174134-1 gnd |
| subject_GND | (DE-588)4045687-0 (DE-588)4174134-1 (DE-588)4123623-3 |
| title | Principles of drug action the basis of pharmacology |
| title_auth | Principles of drug action the basis of pharmacology |
| title_exact_search | Principles of drug action the basis of pharmacology |
| title_full | Principles of drug action the basis of pharmacology Avram Goldstein ; Lewis Aronow ; Sumner M. Kalman |
| title_fullStr | Principles of drug action the basis of pharmacology Avram Goldstein ; Lewis Aronow ; Sumner M. Kalman |
| title_full_unstemmed | Principles of drug action the basis of pharmacology Avram Goldstein ; Lewis Aronow ; Sumner M. Kalman |
| title_new | Principles of drug action |
| title_short | Principles of drug action |
| title_sort | principles of drug action the basis of pharmacology |
| title_sub | the basis of pharmacology |
| topic | Pharmakologie (DE-588)4045687-0 gnd Pharmakodynamik (DE-588)4174134-1 gnd |
| topic_facet | Pharmakologie Pharmakodynamik Lehrbuch |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=001852198&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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