About the Author viii Chapter 1: Introduction 1 Chapter 2: Definition and Scope of Pharmacology 3 Chapter 3: Movement of Drugs to and from Sites of Action 5 3.1 Physicochemical Factors in the Transfer of Drugs Across Membranes 6 3.2 Active, Carrier-Mediated Transport 7 3.3 Weak Electrolytes and Influence of pH 7 3.4 Absorption of Drugs 13 3.5 Bioavailability and Bioequivalence 15 3.6 Distribution of Drugs 15 Chapter 4: Biotransformation of Drugs 19 4.1 Consequences of Drug Metabolism 20 4.
2 Enzymatic Biotransformation Reactions 20 4.3 Metabolizing Systems in the Smooth Endoplasmic Reticulum ("Microsomal" Fraction of Cell Homogenates) 21 Chapter 5: Excretion of Drugs 26 Chapter 6: Clinical Pharmacokinetics 28 6.1 Introduction 28 6.2 Pharmacokinetic Parameters and Variables 29 6.3 A Simple Pharmacokinetic Model 35 6.4 A "Dose-Dependent" (or "Non-Linear") Pharmacokinetic Model 47 6.5 Intermittent Oral Dosing 52 6.6 Pharmacokinetics of Single Doses 54 6.
7 Recapitulation of Equations (These are the "Need-to-Know" Equations for Pharmacokinetics) 55 Chapter 7: Pharmacodynamics I: Determining Effects in Intact Organisms; Dose-Response Relationships in Patients 56 7.1 Graded Responses: Plots of Dose (Dosage) Versus Intensity of Effect 56 7.2 Therapeutic Index and Therapeutic Window 58 Chapter 8: Pharmacodynamics II: Determining Sites and Mechanisms of Action of Drugs 60 8.1 Introduction 60 8.2 Specificity of Drugs 62 8.3 Nature of Drug Receptors: Molecules that Combine with the Drug and Mediate its Actions 63 Chapter 9: Pharmacodynamics III: Quantitative Analysis of Drug-Receptor Interactions 64 9.1 The "Simple Occupancy Model" 65 9.2 "Competitive" or "Surmountable" Antagonists 68 9.
3 "Noncompetitive" or "Insurmountable" Antagonists 71 9.4 Irreversible Antagonists 73 9.5 Partial Agonists 73 9.6 The Allosteric Model for Drug-Receptor Interaction 77 9.7 "Spare Receptors" 81 9.8 Displacement of the Activation Curve to the Right of the Binding Curve: Fractional Occupancy Threshold 86 9.9 Review: The Use of the Dose-Response Curve to Characterize Drugs and Receptors 87 Chapter 10: Biological Receptor-Effector Mechanisms 90 10.1 Receptor Identification and Classification 90 10.
2 Location of Receptors 92 10.3 Second Messengers: The Intracellular Language 92 10.4 Signaling Networks of Protein Kinases and Transcription Factors 93 10.5 Importance of Second Messengers in Pharmacology 94 10.6 Receptor Structure and Proximal Effector Systems 94 10.7 G-Protein Coupled Receptors 96 10.8 The G-Protein Activation Cycle 96 10.9 The G-Proteins Provide Amplification, Diffusion, and Integration of Signals 99 10.
10 Signaling Homeostasis and Receptor Metabolism 100 10.11 Diseases Resulting From Receptor Malfunction 102 Chapter 11: Testing and Evaluation of New Drugs 103 Chapter 12: Further Study in Pharmacology 105 Index 107.