About Author
Dr. James Scot is physician and dedicated his career to bridging the gap between molecular mechanisms and patient care. Born in Edinburgh, Scotland, Dr. James completed his medical degree and a Ph.D. in Cellular Biochemistry at the University of Oxford. He later moved to the United States, completing his residency at Massachusetts General Hospital and a fellowship in Clinical Pharmacology at Harvard Medical School. Dr. Scot's fascination with pharmacology began during his early laboratory days, where he spent hours studying how single-point mutations in the G-protein coupled receptors of cardiac myocytes completely altered drug efficacy. This led to his foundational realization that rote memorization of drug names is an ineffective way to learn medicine. Instead, a student or clinician must intimately understand the underlying biochemistry, physiology, and pathophysiology of the affected organ systems. Driven by this pedagogical philosophy, Dr. Scot pioneered an integrated, systems-based approach to pharmacology education. In his textbook, he crafts every chapter around a clinical vignette, a real-world patient presenting a therapeutic challenge. By deconstructing the disease's pathophysiology and examining molecular and cellular targets, he teaches students how to logically select medications, predict adverse effects, and design rational pharmacotherapy regimens. Now serving as the Chief of Clinical Pharmacology at an internationally renowned medical center in London, Dr. Scot continues to merge groundbreaking research with medical education. When he is not writing, treating patients, or speaking at global conferences, he enjoys mentoring young researchers and trekking through the Scottish Highlands.
Table of Content
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Preface
1. PERSPECTIVES OF PHARMACOLOGY OVER THE PAST 100 YEARS
1.1 Introduction
1.2 The Emergence of Pharmacology in Germany: Rudolf Buchheim
1.3 The Spread of Pharmacology
1.4 Pharmacology Through 100 Years and a Future Perspective
1.5 Conclusions
2. EMERGENT CONCEPTS OF RECEPTOR PHARMACOLOGY
2.1 Introduction
2.2 Shots in the Dark: Null Methods in Pharmacology
2.3 Recombinant Systems Redefine Receptor Pharmacology
2.4 Binding Gives Way to Functional Experiments
2.5 Understanding Agonism: The Black/Leff Operational Model
2.6 The Shift from Orthosteric to Allosteric Drug Action
2.7 The Move from Parsimonious Models to Dynamic Models of
Receptor Conformation
2.8 Allosteric Probe Dependence: Biased Receptor Signaling
2.9 Structure: Receptors Show Themselves
2.10 Genetics and Computer Science Impact Pharmacology
2.11 Conclusion
3. THE EVOLVING LANDSCAPE OF CANCER THERAPEUTICS
3.1 Biology of Cancer
3.2 Introduction
3.3 Clinical Trials in Oncology
3.4 Rationally Designed Therapies
3.5 Nuclear Medicine Therapies
3.6 Pharmacogenetics, Pharmacogenomics and Patient Selection for Treatment
3.7 Resistance Mechanisms
3.8 Cancer Drug Discovery and Preclinical Development
3.9 Current Issues in the Development of Drugs in Oncology
3.10 Conclusion and Future Perspectives
4. MONOCLONAL ANTIBODIES: PAST, PRESENT AND FUTURE
4.1 Introduction
4.2 Background
4.3 Monoclonal Antibody Structure Function and Production
4.4 Pharmacokinetics
4.5 Development
4. 6 Monoclonal Antibodies for the Treatment of Inflammatory Conditions
4.7 Monoclonal Antibodies for the Treatment of Solid Tumours
4.8 Adverse Effects and Limitations of Monoclonal Antibodies
4.9 The Future
5. 100 YEARS OF DRUG DELIVERY TO THE LUNGS
5.1 The History of Therapeutic Aerosols: From the Ancient Time to Present
5.2 Current Inhalation Delivery Systems
5.3 Advances in Aerosol Science
5.4 Looking to the Future
5.5 Conclusions
6. ION CHANNEL PHARMACOLOGY FOR PAIN MODULATION
6.1 General Introduction
6.2 Calcium Channels
6.3 Transient Receptor Potential (TRP) Channels
6.4 AcidSensing Family of Ion Channels (ASICs)
6.5 PIEZO Channels
6.6 Purinergic P2X3 Ion Channels
7. EXPLOITING THE DIVERSITY OF ION CHANNELS
7.1 Introduction
7.2 K+ Channels
7.3 Sodium Channels
7.4 Chloride Channels
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8. GENETICALLY ENCODED FLUORESCENT CALCIUM AND VOLTAGE
INDICATORS
8.1 Introduction
8.2 Calcium Versus Voltage Imaging
8.3 Advantages of Genetically Encoding Indicators
8.4 Key Features of Genetically Encoded Calcium and Voltage Indicators
8.5 Currently Available Indicators
8.6 Applications
8.7 Outlook
9. MECHANISTIC IMAGE-BASED MODELLING: CONCEPTS AND APPLICATIONS
9.1 Introduction
9.2 Mathematical Description of Spatially Resolved Systems
9.3 Mechanistic Image-Based Modelling Approach: Concepts and
Examples from Developmental Biology
9.4 Image-based Modelling for Biomedical Applications
9. 5 Image-based Modelling in Drug Discovery and Development
9.6 Outlook
10. PHARMACOMETABONOMICS: THE PREDICTION OF
DRUG EFFECTS USING METABOLIC PROFILING
10.1 Introduction
10.2 Discovery of Pharmacometabonomics
10.3 Recent Developments in Pharmacometabonomics and the
Delivery of Personalised Medicine
10.4 Conclusions
11. THE MICROBIOME AND ITS POTENTIAL FOR PHARMACOLOGY
11.1 Introduction
11.2 What Is the Human Microbiome and What Impacts It?
11.3 What Diseases and Biological Processes Is the Human
Microbiome Linked to?
11.4 How Do We Find Out About the Microbiome and Metabolome?
11.5 How Do Drugs Affect the Microbiome?
11.6 How Does the Microbiome Affect Drug Metabolism or Activity?
11.7 How Can Drugs Be Isolated from the Microbiome?
11.8 Conclusions
12. HARNESSING HUMAN MICROPHYSIOLOGY SYSTEMS
12.1 Introduction
12.2 QSP Involves Iterative Application of Experimental and Computational Models
12.3 Human Organ Microphysiology Systems (MPS) Complement
Animal Models of Disease and ADMETox
12.4 Summary and Conclusions
13. THE FUTURE OF CLINICAL TRIAL DESIGN
13.1 Introduction
13.2 Historical Overview of Clinical Trial Design
13.3 Increasing Complexity and Obstructions to Clinical Trials
13.4 Event-Based Versus Value-Based Endpoint Trials
13. 5 Areas of Opportunity for Value-Based Trials
13. 6 The Road Towards New Clinical Endpoints
13.7 Movement Towards Monocenter Studies
13.8 Technology Allows Home-Based Trials
13.9 Electronic Patient-Reported Outcomes (ePROs)
Represent Value for Study Participants
13.10 Frequent Measurements May Allow for Precision and
Personalized Medicine
13.11 Validation of New Endpoints
13.12 Hype, Hope, and the Drawbacks of Continuous Innovation
13.13 HomeBased Sampling of Alternative Matrices
13.14 Integration of ValueBased Endpoints in the Clinical Trial of the Future
Bibliography
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