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…mehr
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.
Preface.- Introductory Remarks on the Development of Isosorbide-5-Mononitrate.- Vasodilation with Nitrates.- Nitrates: Mechanism of Vasodilation.- Effect of Different Vasodilators on Epicardial Coronary Arteries.- Effects of Isosorbide-5-Mononitrate on Hemodynamic Parameters and on Regional Myocardial Ischemia in Conscious Dogs.- Isosorbide-5-Mononitrate Increases Cyclic Guanosine Monophosphate Concentration in Rat Aorta in Vitro and in Vivo.- Activation of Counter-Regulatory Mechanisms on Administration of Equipotent Doses of Different Types of Vasodilators to Conscious Dogs.- Differences in the Metabolism of Isosorbide-5-Mononitrate and Isosorbide Dinitrate and Their Consequences for Toxicologic Findings.- Clinical Pharmacology.- Pharmacokinetics of ISDN, Sustained-Release ISDN, and IS-5-MN.- Vascular Pharmacokinetics of Nitrates.- Effect of Glyceryl Trinitrate, Isosorbide-5-Mononitrate, and Propranolol on Apparent Liver Blood Flow.- Kinetics of IS-5-MN and Its Glucuronide in Patients with Renal Failure.- Pharmacokinetics of IS-5-MN after Oral and Intravenous Administration in Patients with Hepatic Failure.- Tolerance to Nitrates.- Nitrate Tolerance: Animal Experiments And Clinical Studies in Heart Failure.- Development and Disappearance of Tolerance to Organic Nitrates in Conscious Dogs.- Tolerance and Rebound Phenomena in Nitrate Therapy.- Tolerance to the Antiischemic Effect of Isosorbide Dinitrate during Continuous but not during Intermittent Oral Therapy.- Clinical Relevance of Nitrate Tolerance.- 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.- Nitrate Tolerance in Angina Pectoris.- 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.- Slow-Release IS-5-MN for the Treatment of Angina Pectoris: Duration of Effects.- Nitrates in Coronary Insufficiency.- The Mechanism of Nitrates in the Relief of Rest Angina.- Beneficial Effects of Isosorbide-5-Mononitrate on Exercise Performance in Patients with Chronic Stable Angina Pectoris.- Comparison of Changes on Exercise-Induced Ischemia After a Single Oral Dose of IS-5-MN and ISDN.- Double-Blind, Randomized Cross-Over 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.- The Efficacy of IS-5-MN in Patients with Ischemic Heart Disease: A Pilot Study.- Efficacy of Isosorbide-5-Mononitrate in the Prevention of Induced Attacks of Vasospastic Angina: Preliminary Results.- 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.- Clinical Importance of the Coronary Steal Phenomenon: Are the Coronary Steal Phenomenon after Dipyridamole and the Antianginal Efficacy of Isosorbide Dinitrate of Nifedipine Related to Coronary Anatomy?.- Effect of Nitroglycerin Patches on Hemodynamic and Exercise Parameters in Patients with Coronary Artery Disease Compared with IS-5-MN and Placebo.- Double-Blind, Cross-Over Study on the Antianginal Efficacy of IS-5-MN and ISDN s.r., a Multicenter Trial.- Hemodynamic Effects of Isosorbide-5-Mononitrate in Patients with Coronary Artery Disease, at Rest and Under Exercise.- The Effects of Isosorbide-5-Mononitrate on Left Ventricular FunctionAssessed by Systolic Time Intervals.- Assessment of Changes in Left Ventricular Performance Induced by Nitrates at Rest Using an ECG-Gated Scintillation Probe Device.- Nitrates in Heart Failure.- Nitrate Therapy of Congestive Heart Failure.- Efficacy of IS-5-MN (ISMO 20) in Patients with Coronary Artery Disease and Impaired Left-Ventricular Function.- Hemodynamic Effects of IS-5-MN in Patients with Congestive Heart Failure.
Preface.- Introductory Remarks on the Development of Isosorbide-5-Mononitrate.- Vasodilation with Nitrates.- Nitrates: Mechanism of Vasodilation.- Effect of Different Vasodilators on Epicardial Coronary Arteries.- Effects of Isosorbide-5-Mononitrate on Hemodynamic Parameters and on Regional Myocardial Ischemia in Conscious Dogs.- Isosorbide-5-Mononitrate Increases Cyclic Guanosine Monophosphate Concentration in Rat Aorta in Vitro and in Vivo.- Activation of Counter-Regulatory Mechanisms on Administration of Equipotent Doses of Different Types of Vasodilators to Conscious Dogs.- Differences in the Metabolism of Isosorbide-5-Mononitrate and Isosorbide Dinitrate and Their Consequences for Toxicologic Findings.- Clinical Pharmacology.- Pharmacokinetics of ISDN, Sustained-Release ISDN, and IS-5-MN.- Vascular Pharmacokinetics of Nitrates.- Effect of Glyceryl Trinitrate, Isosorbide-5-Mononitrate, and Propranolol on Apparent Liver Blood Flow.- Kinetics of IS-5-MN and Its Glucuronide in Patients with Renal Failure.- Pharmacokinetics of IS-5-MN after Oral and Intravenous Administration in Patients with Hepatic Failure.- Tolerance to Nitrates.- Nitrate Tolerance: Animal Experiments And Clinical Studies in Heart Failure.- Development and Disappearance of Tolerance to Organic Nitrates in Conscious Dogs.- Tolerance and Rebound Phenomena in Nitrate Therapy.- Tolerance to the Antiischemic Effect of Isosorbide Dinitrate during Continuous but not during Intermittent Oral Therapy.- Clinical Relevance of Nitrate Tolerance.- 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.- Nitrate Tolerance in Angina Pectoris.- 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.- Slow-Release IS-5-MN for the Treatment of Angina Pectoris: Duration of Effects.- Nitrates in Coronary Insufficiency.- The Mechanism of Nitrates in the Relief of Rest Angina.- Beneficial Effects of Isosorbide-5-Mononitrate on Exercise Performance in Patients with Chronic Stable Angina Pectoris.- Comparison of Changes on Exercise-Induced Ischemia After a Single Oral Dose of IS-5-MN and ISDN.- Double-Blind, Randomized Cross-Over 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.- The Efficacy of IS-5-MN in Patients with Ischemic Heart Disease: A Pilot Study.- Efficacy of Isosorbide-5-Mononitrate in the Prevention of Induced Attacks of Vasospastic Angina: Preliminary Results.- 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.- Clinical Importance of the Coronary Steal Phenomenon: Are the Coronary Steal Phenomenon after Dipyridamole and the Antianginal Efficacy of Isosorbide Dinitrate of Nifedipine Related to Coronary Anatomy?.- Effect of Nitroglycerin Patches on Hemodynamic and Exercise Parameters in Patients with Coronary Artery Disease Compared with IS-5-MN and Placebo.- Double-Blind, Cross-Over Study on the Antianginal Efficacy of IS-5-MN and ISDN s.r., a Multicenter Trial.- Hemodynamic Effects of Isosorbide-5-Mononitrate in Patients with Coronary Artery Disease, at Rest and Under Exercise.- The Effects of Isosorbide-5-Mononitrate on Left Ventricular FunctionAssessed by Systolic Time Intervals.- Assessment of Changes in Left Ventricular Performance Induced by Nitrates at Rest Using an ECG-Gated Scintillation Probe Device.- Nitrates in Heart Failure.- Nitrate Therapy of Congestive Heart Failure.- Efficacy of IS-5-MN (ISMO 20) in Patients with Coronary Artery Disease and Impaired Left-Ventricular Function.- Hemodynamic Effects of IS-5-MN in Patients with Congestive Heart Failure.
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