Pharmacology of Peptic Ulcer Disease

In this book the pathophysiology, diagnosis, and therapy of most aspects of peptic ulcer disease are examined in detail. Covered are the pharmacology of the parietal cell and the latest hypotheses for the development of acid-peptic disease including epidermal growth factor, gastrin and other peptide hormones, fatty acids and prostaglandins, helicobacter pylori, and gastric acid hypersecretion including Zollinger-Ellison syndrome. The book also deals with the newer antisecretory medication such as omeprazole with a review of H2-receptor antagonists. Rounding off the subject are chapters on gastroesophageal reflux disease, upper GI endoscopy, and videoendoscopy including digital imaging. This volume addresses a wide range of physicians who are interested in all aspects of acid-peptic disease. What distinguishes this volume from others is the timely update on a number of important issues pertaining to acid-peptic disease. Not only does it review a number of topics that are of great interest at the present time, but it introduces a vast amount of new unpublished data.

Inhalt
1 Pharmacology of the Parietal Cell.- A. Introduction.- B. Anatomy of Gastric Mucosa.- C. Secretion by the Stomach.- I. General.- II. Secretion and Absorption by Surface Epithelial Cells.- D. Gastric Barrier.- E. Agents Thought to Affect Gastric Barrier function.- I. Sucralfate.- II. Prostaglandins.- III. Bismuth Compounds.- F. Ion Transport by the Parietal Cell.- I. Apical Surface.- II. Basal Lateral Surface.- III. Stimulation of Acid Secretion.- IV. Mechanism of Parietal Cell Stimulation.- G. Receptor Antagonists.- I. Muscarinic Antagonists.- II. H2 Antagonists.- H. Mechanism of Gastric Proton Pump.- I. Transport by ATPase.- II. Reaction Cycle.- III. Structure of Gastric H+, K+-ATPase.- J. Inhibitors of H+, K+-ATPase.- I. Omeprazole.- 1. Effects on Acid Secretion.- 2. Duration of Action.- 3. Mechanism of Action.- II Reversible H+, K+-ATPase Inhibitors.- III. Clinical Use of Pump Inhibitors.- References.- 2 Epidermal Growth Factor.- A. Introduction.- B. Perspective on Growth Factors.- C. Perspective on Mucosal Disease.- D. EGF Structure.- E. Structure-Activity Relationships.- F. Biological Effects.- G. Gastrointestinal Activity.- I. Developmental Effects of EGF.- II. Gastric Acid Secretion.- III. Trophic Effects.- H. Conclusion.- References.- 3 Gastrin and Other Peptide Hormones.- A. Introduction.- B. The Molecular Heterogeneity of Gastrin.- C. Gastrin Release.- D. Autonomic Control of Gastrin Release.- E. Bombesin-Like Peptides.- F. Somatostatin.- G. Mechanism of Gastrin-Induced Gastric Acid Secretion.- H. Gastrin and Peptic Ulcer Disease.- J. Hypergastrinemic Syndromes.- K. Conclusion.- References.- 4 The Role of Essential Fatty Acids in Gastric and Duodenal Protection and Ulcer Therapy.- A. Cytoprotection and Prostaglandins.- I. Definition of Cytoprotection.- II. Mucosal Sites of Cytoprotection.- 1. Protection of the Mucosal Microvasculature.- 2. Direct Protection of Gastric Mucosal Cells.- III. Metabolism of Natural and Synthetic Prostaglandins.- B. Arachidonic Acid Cascade and Prostaglandin Synthesis by Gastric and Duodenal Mucosa.- I. Arachidonic Acid Cascade.- II. Sources of Arachidonic Acid from Mucosal Pools.- III. Control of Mucosal Prostaglandin Synthesis.- C. Dietary Sources of Arachidonic and Linoleic Acids.- I. Food Sources.- II. Absorption of Dietary Essential Fatty Acids.- III. Distribution of Absorbed Essential Fatty Acids Between Organs.- IV. The Requirement for Detergents for the Intestinal or Gastric Absorption of Essential Fatty Acids.- D. Gastric Mucosal Synthesis of Endogenous Prostanoids from Dietary Essential Fatty Acids.- I. The Requirement for Detergents for Absorption of Dietary Essential Fatty Acids into the Gastric Mucosa.- II. The Requirement for Direct Gastric Mucosal Contact with Solubilized Essential Fatty Acids for Mucosal Protection.- III. Generation of Prostanoids by the Gastric Mucosa from Solubilized Essential Fatty Acids.- E. Gastric Mucosal Protection by Solubilized Essential Fatty Acids.- I. Angiogenic Effect of Essential Fatty Acids.- F. Dietary Intake of Essential Fatty Acids.- I. Animal Studies.- II. Human Intake of Dietary Essential Fatty Acids and Its Relationship to Peptic Ulcer Disease.- G. Potential Therapeutic Advantages of Dietary Essential Fatty Acids Over the Synthetic Prostaglandins.- I. Effect of Short-Term Treatment with Dietary Essential Fatty Acids on the Human Gastric Mucosa.- H. Summary and Conclusion.- References.- 5 Helicobacter pylori.- A. Introduction.- B. Clinical Relevance of Helicobacter pylori.- I. Frequency in the General Population and Association with Chronic Gastritis and Peptic Ulcer Disease.- II. Causation.- 1. Chronic Gastritis.- 2. Peptic Ulcer Disease.- C. Attempts to Eradicate Helicobacter pylori.- I. Natural History.- II. Eradication of Helicobacter pylori Infections.- III. Methods to Confirm Eradication of Helicobacter pylori Infections.- IV. Bismuth Salts.- V. Antimicrobials as Monotherapy.- VI. Drug Combinations.- 1. Triple Drug Combinations.- 2. Double Drug Combinations.- VII. Toxicity of Antimicrobials and Bismuth Salts.- VIII. Experimental Therapeutic Approaches.- D. Eradication of Helicobacter pylori and Peptic Ulcer Disease.- I. Effect on Gastritis.- II. Effect on Healing of Duodenal Ulcers.- III. Effect on Relapse Rates of Duodenal Ulcers.- IV. Effect on Relapse Rates of Gastric Ulcers.- E. Whom to Treat and What to Expect?.- F. Summary and Conclusions.- References.- 6 Development of a New Gastric Antisecretory Drug for Clinical Use.- A. General Considerations.- B. Etiology and Pathophysiology of Peptic Ulcer.- C. Scope for Pharmacological Intervention.- D. Clinical Development of a New Antisecretory Drug for Peptic Ulcer.- I. Phase I.- II. Phase II.- III. Phase III.- IV. Phase IV.- References.- 7 Therapeutic use of Omeprazole in Man: Pharmacology, Efficacy, Toxicity, and Comparison with H2 Receptor Antagonists.- A. Introduction.- B. Pharmacology.- I. General.- II. Plasma Concentrations.- III. Inhibition of Acid Secretion.- IV. Other Actions of Omeprazole.- 1. Effect on Secretion of Intrinsic Factor and Vitamin B12 Absorption.- 2. Effect on Pepsin.- 3. Effects on Motility.- 4. Effects on Gastric Endocrine function.- C. Therapeutic Trials in Acid-Peptic Diseases.- I. Overview.- II. DuodenalUlcer.- 1. Effect of Different Doses of Omeprazole.- 2. Comparative Studies of Omeprazole and H2 Receptor Antagonists.- 3. Relapse After Stopping Omeprazole Therapy.- 4. Omeprazole Treatment for Ulcers Resistant to H2 Receptor Antagonists.- III. Gastric Ulcer.- 1. Noncomparative Studies of Omeprazole.- 2. Comparative Studies of Omeprazole and Ranitidine.- 3. Relapse After Stopping Omeprazole Therapy.- 4. Omeprazole Treatment for Ulcers Resistant to H2 Receptor Antagonists.- IV. Reflux Esophagitis.- 1. Effect of Different Doses of Omeprazole.- 2. Comparative Studies of Omeprazole and H2 Receptor Antagonists.- 3. Relapse After Stopping Omeprazole Therapy.- 4. Omeprazole Treatment for Reflux Esophagitis Resistant to H2 Receptor Antagonists.- V. Zollinger-Ellison Syndrome.- VI. Side-Effects and Toxicity.- D. Probable Role of Omeprazole in Acid-Peptic Diseases.- References.- 8 Hypothesis of Peptic Ulcer: A Modern Classification of a Multifactorial Disease.- A. Introduction.- B. Histopathology of Peptic Ulcer.- I. Ulcer Histology.- II. Gastritis Definitions.- 1. Endoscopic Gastritis.- 2. Histologic Gastritis.- C. Schwarz's Balance.- I. Mucosal Defenses.- 1. Measurement of the Barrier.- 2. The Mucus Gel and pH Gradient.- 3. Mucosal Healing.- 4. Mucosal Bloodflow.- 5. Other Mechanisms of Defense.- II. Aggressive Factors.- 1. Hydrogen Ion.- 2. Aspartic Proteinases.- 3. Bile Acids.- 4. Oxygen Free Radicals.- III. Risk Factors as Modifiers of Mucosal Defense.- 1. Blood Groups.- 2. Tobacco Use.- IV. Regulation of Mucosal Defenses: Prostaglandins and Epidermal Growth Factor.- 1. Role of Prostaglandins in Mucos…