Pharmacology (eBook)

Front Cover 1
Pharmacology: Principles and Practice 4
Copyright Page 5
Dedication 6
Contents 8
Contributors 10
Preface 12
Chapter 1: History of Pharmacology-From Antiquity to the Twentieth Century 14
1.1. What Is Pharmacology? 14
1.2. What Is the Position of Pharmacology in the Field of Therapeutics? 15
1.3. The Beginnings of Pharmacology 15
1.4. Pharmacology of the Greco-Roman Era 16
1.5. Pharmacology and the Middle Ages 16
1.6. Pharmacology and the Renaissance 17
1.7. Pharmacology and the Baroque Period 18
1.8. The Birth of Modern Pharmacology 18
References 20
Chapter 2: Dosage Forms and Their Routes of Administration 22
2.1. Introduction 22
2.2. Therapeutic Ramifications in Selecting the Appropriate Dosage Forms 23
2.3. Routes of Drug Administration 27
Review Questions 42
References 42
Chapter 3: Membranes and Drug Action 44
3.1. Introduction 44
3.2. What Is a Membrane? 45
3.3. The Membrane Environment 58
3.4. Role of Drug Polarity 60
3.5. Crossing the Membrane 62
3.6. The Membrane as a Drug Target 65
3.7. Drug Transporters 69
3.8. Key Points and Conclusion 70
Review Questions 71
References 73
Chapter 4: Ligand-Receptor Binding and Tissue Response 76
4.1. Introduction 76
4.2. Dose-Response Curves 76
4.3. Receptors 77
4.4. Affinity 77
4.5. Efficacy 78
4.6. Antagonism 81
4.7. Constitutive Receptor Activity 85
4.8. Extended Ternary Complex Model 85
4.9. Conclusions 86
Review Questions 87
References 87
Chapter 5: Hormesis and Pharmacology 88
5.1. Introduction 88
5.2. Hormesis 94
5.3. Selected Issues 106
5.4. Adaptive Response, Preconditioning and Autoprotection: How These Concepts Relate to Hormesis 108
5.5. Implementing Hormesis into Pharmacology and Toxicology 108
5.6. Remaining Issues 111
5.7. Summary and Conclusion 112
Review Questions 112
References 113
References for Figure 5.3. 115
Chapter 6: Signal Transduction and Second Messengers 116
6.1. Receptor Communication 116
6.2. Receptor/Second Messenger Crosstalk 123
6.3. Signal Transduction Targets for Drug Discovery 124
Review Questions 124
References and Further Reading 124
Chapter 7: Drug Distribution 126
7.1. Introduction 126
7.2. Biological Membranes 127
7.3. Factors Influencing Drug Distribution 135
7.4. Pharmacokinetic/Pharmacodynamic distribution properties 137
7.5. Specific Tissue Barriers 138
7.6. Summary 140
References 141
Chapter 8: Drug Metabolism 144
8.1. Introduction 144
8.2. Drug Metabolizing Enzymes 150
8.3. Conclusions and Key Points 181
Review Questions 183
References 183
Chapter 9: Drug Excretion 188
9.1. Introduction 188
9.2. Overview of Membrane Transporters Involved in Drug Excretion 189
9.3. Renal Drug Excretion 194
9.4. Hepatobiliary Excretion 201
9.5. Other Routes of Drug Excretion 207
9.6. Drug Excretion: Issues to Consider 209
9.7. Conclusions and Future Perspectives 210
Review Questions 210
References 210
Chapter 10: Pharmacokinetic Modeling 214
10.1. Introduction 215
10.2. Chemical Transport 219
10.3. Absorption 224
10.4. Distribution 226
10.5. Elimination (Metabolism and Excretion) 229
10.6. Organization of Single-Dose Pharmacokinetic Model Information 233
10.7. One-Compartment Bolus IV Injection (Instantaneous Absorption) Model 234
10.8. One-Compartment IV Infusion (Zero-Order Absorption) Model 240
10.9. One-Compartment First-Order Absorption Model 246
10.10. Two-Compartment Bolus IV Injection (Instantaneous Absorption) Model 253
10.11. Two-Compartment IV Infusion (Zero-Order Absorption) Model 261
10.12. Two-Compartment First-Order Absorption Model 266
10.13. Generalized Multicompartment Models 273
10.14. Multiple Dosing Models 277
10.15. Advanced Pharmacokinetic Modeling Topics 284
10.16. Summary of Key Points 289
Review Questions 290
Acknowledgements 290
References 290
Chapter 11: Bioanalytical Tools for Drug Analysis 292
11.1. Introduction 292
11.2. Small Molecule Chemical Bioanalysis 293
11.3. Theoretical Fundamentals of Chromatography 297
11.4. Analytical Separations in Practice 303
11.5. Key Points and Conclusions 314
Review Questions 314
References 315
Chapter 12: Drug-Drug Interactions with an Emphasis on Drug Metabolism and Transport 316
12.1. Introduction 316
12.2. DDIs Associated With Altered Drug Metabolism 320
12.3. Drug Transporters and DDIs 330
12.4. DDIs Associated with Protein Binding 333
12.5. Conclusions and Key Points 335
Review Questions 337
References 337
Chapter 13: Adverse Drug Reactions 340
13.1. Introduction 340
13.2. Type A ADRs 340
13.3. Examples of Type A ADRs 344
13.4. Avoiding Type A ADRs 345
13.5. Pharmacovigilance and ADR 346
13.6. Type B ADRs 347
13.7. Summary 362
Review Questions 362
References 362
Chapter 14: Risk Assessment 366
14.1. History 366
14.2. Hazard Identification 367
14.3. Dose Response Assessment 368
14.4. Exposure Assessment 369
14.5. Risk Characterization 370
14.6. Radiological Risk Assessments 377
14.7. Risk Management 378
14.8. Risk Communication 380
Review Questions 380
References 381
Chapter 15: Drug Resistance 384
15.1. Introduction 384
15.2. Cancer Cell Drug Resistance 384
15.3. Drug Resistance in Infectious Diseases 392
15.4. Summary 398
Review Questions 398
Chapter 16: Ion Channels 400
16.1. Introduction 400
16.2. Ion Channel Structure and Function: Basic Principles and Mechanisms 404
16.3. Ion Channel Pharmacology: Principles and Mechanisms 409
16.4. Ion Channel Groups: Functional Implications and Pharmacological Modulators 411
16.5. Methods for the Study of Ion Channels 427
16.6. Ion Channels and Disease 433
16.7. Ion Channels as Drug Targets 434
16.8. Key Points and Conclusions 437
Acknowledgments 437
Review Questions 437
Glossary 438
Abbreviations 438
References 439
Chapter 17: Targeting the Cell Cycle to Kill Cancer Cells 442
17.1. Introduction 442
17.2. The Cell Cycle 443
17.3. Cell Cycle Checkpoints 445
17.4. Mitotic Kinases as Targets of New Chemotherapeutics 455
17.5. Conclusions 460
Review Questions 460
References 461
Chapter 18: Programmed Cell Death 468
18.1. Introduction 468
18.2. Mechanism and Regulation of PCD 469
18.3. Apoptosis in Health and Disease 478
18.4. Therapeutic Strategies for Targeting Apoptosis 480
18.5. Key Points and Conclusions 486
Review Questions 486
Acknowledgements 486
Key References and Further Reading 486
Chapter 19: Drug Discovery 488
19.1. Introduction 488
19.2. Underlying Principles 498
19.3. Drug Discovery Case Studies 545
19.4. Summary 567
Review 568
References 571
Web Databases or General Information Starting-Points 573
Chapter 20: Genomics and Proteomics in Drug Design and Discovery 574
20.1. Introduction 574
20.2. Genomics and Proteomics 574
20.3. Major Technological Platforms of Genomics and Proteomics 576
20.4. Current Achievements and Potential Application of Genomics and Proteomics in Drug Design and Discovery 578
20.5. Conclusion and Future Prospects 582
Review Questions 582
Acknowledgements 582
References 583
Chapter 21: The Future of Pharmacology 588
21.1. Introduction 588
21.2. The Problem 588
21.3. Strategies for Searching for Future Drugs 589
21.4. Tools for Searching for Future Drugs 590
21.5. The Drugs of the Future 591
References 592
Index 594