Mononitrates : International Symposium on Mononitrates Montreux, Suisse, June 14-16, 1984

The nitrates have remarkable clinical effects that have stood the test of time in the management of ischemic heart disease. What is unusual about this class of com­ pounds is that, after many years of clinical use, we are still exploring new avenues as to the vascular mechanisms of their effect, their applications in treating other clini­ cal conditions, and the development of products with more favorable pharmacoki­ netic properties. This volume represents the proceedings of a symposium held June 14-16, 1984, in Montreux. The papers were selected to explore the current state of knowledge re­ garding the mechanisms of action, pharmacokinetics, and clinical efficacy of ni­ trates. Particular attention has been given to newer studies utilizing the 5-mononi­ trate metabolite of isosorbide dinitrate, a drug whose pharmacokinetic properties may make it an important new agent in the treatment of angina and congestive heart failure. One of the benefits of an international meeting of experts sharing their views on an internationally used group of drugs is that differences in concepts and clinical practice become apparent and can be discussed. The Montreux forum made it clear that clinicians in North and South America and Europe have diverging views on how the nitrates should be used. Front Matter....Pages I-XI Preface....Pages 1-2 Introductory Remarks on the Development of Isosorbide-5-Mononitrate....Pages 3-4 Front Matter....Pages 5-5 Nitrates: Mechanism of Vasodilation....Pages 7-16 Effect of Different Vasodilators on Epicardial Coronary Arteries....Pages 17-22 Effects of Isosorbide-5-Mononitrate on Hemodynamic Parameters and on Regional Myocardial Ischemia in Conscious Dogs....Pages 23-33 Isosorbide-5-Mononitrate Increases Cyclic Guanosine Monophosphate Concentration in Rat Aorta in Vitro and in Vivo....Pages 34-38 Activation of Counter-Regulatory Mechanisms on Administration of Equipotent Doses of Different Types of Vasodilators to Conscious Dogs....Pages 39-44 Differences in the Metabolism of Isosorbide-5-Mononitrate and Isosorbide Dinitrate and Their Consequences for Toxicologic Findings....Pages 45-49 Front Matter....Pages 51-51 Pharmacokinetics of ISDN, Sustained-Release ISDN, and IS-5-MN....Pages 53-66 Vascular Pharmacokinetics of Nitrates....Pages 67-72 Effect of Glyceryl Trinitrate, Isosorbide-5-Mononitrate, and Propranolol on Apparent Liver Blood Flow....Pages 73-77 Kinetics of IS-5-MN and Its Glucuronide in Patients with Renal Failure....Pages 78-85 Pharmacokinetics of IS-5-MN after Oral and Intravenous Administration in Patients with Hepatic Failure....Pages 86-91 Front Matter....Pages 93-93 Nitrate Tolerance: Animal Experiments and Clinical Studies in Heart Failure....Pages 95-100 Development and Disappearance of Tolerance to Organic Nitrates in Conscious Dogs....Pages 101-106 Tolerance and Rebound Phenomena in Nitrate Therapy....Pages 107-123 Tolerance to the Antiischemic Effect of Isosorbide Dinitrate during Continuous but not during Intermittent Oral Therapy....Pages 124-129 Clinical Relevance of Nitrate Tolerance....Pages 130-146 A Double-Blind Cross-Over Study on the Effectiveness and Possible Development of Tolerance during Long-Term Therapy with Isosorbide-5-Mononitrate or Isosorbide Dinitrate Slow-Release in Coronary Artery Disease....Pages 147-153 Nitrate Tolerance in Angina Pectoris....Pages 154-170 Front Matter....Pages 93-93 Comparison of the Hemodynamic Effects of Various Doses of Isosorbide-5-Mononitrate Following Single-Dose and Long-Term Administration in Patients with Coronary Heart Disease....Pages 171-187 Slow-Release Isosorbide-5-Mononitrate for the Treatment of Angina Pectoris: Duration of Effects....Pages 188-189 Front Matter....Pages 191-191 The Mechanism of Nitrates in the Relief of Rest Angina....Pages 193-200 Beneficial Effects of Isosorbide-5-Mononitrate on Exercise Performance in Patients with Chronic Stable Angina Pectoris....Pages 201-214 Comparison of Changes on Exercise-Induced Ischemia After a Single Oral Dose of IS-5-MN and ISDN....Pages 215-220 Double-Blind, Randomized Crossover Study on the Coronary Therapeutic Efficacy and Tolerance of IS-5-MN (ISMO 20) in Comparison with IS-5-MN + Metipranolol (ISMO-DISORAT 20/5) and Placebo....Pages 221-229 The Efficacy of IS-5-MN in Patients with Ischemic Heart Disease: A Pilot Study....Pages 230-234 Efficacy of Isosorbide-5-Mononitrate in the Prevention of Induced Attacks of Vasospastic Angina: Preliminary Results....Pages 235-244 Double-Blind-Comparison of the Effects of Nifedipine and Isosorbide-5-mononitrate on the Circulatory Response to Exercise, Exercise Tolerance, and ST-Segment Depression in Patients with Ischemic Heart Disease....Pages 245-253 Clinical Importance of the Coronary Steal Phenomenon: Are the Coronary Steal Phenomenon after Dipyridamole and the Antianginal Efficacy of Isosorbide Dinitrate or Nifedipine Related to Coronary Anatomy?....Pages 254-264 Effect of Nitroglycerin Patches on Hemodynamic and Exercise Parameters in Patients with Coronary Artery Disease compared with IS-5-MN and Placebo....Pages 265-269 Double-Blind, Cross-Over Study on the Antianginal Efficacy of IS-5-MN and ISDN s.r., a Multicenter Trial....Pages 270-276 Hemodynamic Effects of Isosorbide-5-Mononitrate in Patients with Coronary Artery Disease, at Rest and Under Exercise....Pages 277-287 The Effects of Isosorbide-5-Mononitrate on Left Ventricular Function Assessed by Systolic Time Intervals....Pages 288-291 Assessment of Changes in Left Ventricular Performance Induced by Nitrates at Rest Using an ECG-Gated Scintillation Probe Device....Pages 292-296 Front Matter....Pages 297-297 Nitrate Therapy of Congestive Heart Failure....Pages 299-305 Efficacy of IS-5-MN (ISMO 20) in Patients with Coronary Artery Disease and Impaired Left-Ventricular Function....Pages 306-310 Hemodynamic Effects of IS-5-MN in Patients with Congestive Heart Failure....Pages 311-315 Back Matter....Pages 317-320