Although nitroglycerin is one of the oldest drugs in cardiology the problem of tolerance is a scientific challenge of today. The proceedings of this symposium highlight the most re- cent questions related to this topic. Apparently, partial tolerance, or rather partial decrease in sensitivity, can arise during nitrate therapy. Probably this is the consequence of a partial readjustment of the vascular system. This readjustment refers particularly to the arterial system, i.e., to the hypoten- sive effect of nitrates in the standing position. A similar effect on the venous side is not present. On the other hand, the results assembled in this volume confirm the experience of many decades that long-term antianginal therapy with nitrates remains effective even when high doses are applied. Thus partial tolerance which also occurs after other vasodilators such as prazosin, does not imply tolerance against antianginal effectiveness. From the information available to- day it is reasonable to treat patients with angina pectoris acutely as well as chronically with nitrates in individually adjusted doses. Frankfurt, November 1982 M. Kaltenbach v Contents Foreword...VSession 1-Pharmacology Tolerance from the Pharmacokinetic and Pharmacodynamic Viewpoints N. Rietbrock, A. Lassmann, B. G. Woodcock ...3 Does Tolerance Develop During Long-Acting Nitrate Therapy? A Critical Review J. Abrams ...13 Pharmacokinetics of Isosorbide Dinitrate During Tolerance Development Ho-Leung Fung ...25 Discussion ...29 ...Session II - Hemodynamics Lack of Tolerance Development to the Hemodynamic Effects of Nitrates in Patients with Chronic Congestive Heart Failure Joseph A. Franciosa ...35 Discussion ...41 ...

Although nitroglycerin is one of the oldest drugs in cardiology the problem of tolerance is a scientific challenge of today. The proceedings of this symposium highlight the most re- cent questions related to this topic. Apparently, partial tolerance, or rather partial decrease in sensitivity, can arise during nitrate therapy. Probably this is the consequence of a partial readjustment of the vascular system. This readjustment refers particularly to the arterial system, i.e., to the hypoten- sive effect of nitrates in the standing position. A similar effect on the venous side is not present. On the other hand, the results assembled in this volume confirm the experience of many decades that long-term antianginal therapy with nitrates remains effective even when high doses are applied. Thus partial tolerance which also occurs after other vasodilators such as prazosin, does not imply tolerance against antianginal effectiveness. From the information available to- day it is reasonable to treat patients with angina pectoris acutely as well as chronically with nitrates in individually adjusted doses. Frankfurt, November 1982 M. Kaltenbach v Contents Foreword...VSession 1-Pharmacology Tolerance from the Pharmacokinetic and Pharmacodynamic Viewpoints N. Rietbrock, A. Lassmann, B. G. Woodcock ...3 Does Tolerance Develop During Long-Acting Nitrate Therapy? A Critical Review J. Abrams ...13 Pharmacokinetics of Isosorbide Dinitrate During Tolerance Development Ho-Leung Fung ...25 Discussion ...29 ...Session II - Hemodynamics Lack of Tolerance Development to the Hemodynamic Effects of Nitrates in Patients with Chronic Congestive Heart Failure Joseph A. Franciosa ...35 Discussion ...41 ...