Nitroglycerin and other organic nitrates have been used for over a century in the treatment of angina pectoris. Millions of patients, throughout the world, have placed nitroglycerin tablets under the tongue and have experienced rapid and dramatic relief from the chest pain that frequently occurs as a manifestation of disease of the coronary arteries. The empirical observation of the safe use of nitrates for tile alleviation of the symptoms of angina have led to their widespread medical acceptance. The use of organic nitrates preceded any knowledge of their mechanism of action or their ultimate metabolic fate. Thus, more simply stated, although sub lingual nitrates helped the patients, little was known concerning what these drugs do to the body or what the body does to the drugs. A substantial number of investigators have focused on these questions especially during the last two decades. We now have considerably more insight into the pathways of degradation of organic nitrates and the relationship of the metabolic processes to the biological action of these agents. Similarly, considerable effort has been expended in understanding the mechanism of action of these agents directly on vascular smooth muscle and on cardiac work and performance. Finally, there is a more substantive understanding of the physiology of the coronary circulation as well as the" pathophysiologic manifestations of myocardial disease.

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 ... V Session 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 ...

No detailed description available for "120 Years of Nitrate Therapy - Prepared for the Next Millenium".

Nitrates remain among the most commonly used therapeutic agents in cardiology. That they can re lieve pain in angina pectoris has been known at least since 1867, when Lauder Brunton described their clinical use. Now, almost 130 years later, we are constantly learning more about their optimal use in anginal syndromes. For example, there is no doubt that nitrate tolerance occurs, but equally no doubt that certain drug dosages help to attenuate such toler ance. Thus, our understanding of nitrate tolerance has been taken further by the advent of new nitrate preparations and by studies at a basic science level. The current intense interest in nitrates has been rekindled by the growing emphasis on the role of the endothelium in the production of nitric oxide, a basic cardiovascular regulator. If nitric oxide is vasodilator and protects the vascular endothelium, then nitrates should also have similar properties. Hence this book starts off with the role of the endothelium and ni trates in vasodilation. Next, the mechanisms of ac tion of nitrates are considered with emphasis on the role of cyclic GMP. The chief limitation to the use of nitrates lies in nitrate tolerance. After carefully looking at all the evidence, the authors of the third chapter conclude that the mechanism is likely to be multifactorial. The mechanism responsible for the tolerance still remains unknown. In vitro tolerance may be due to enhanced production of vascular superoxide [1].

Nitrite and Nitrate in Human Health and Disease delivers a comprehensive review of nitrite and nitrate biology, from basic biochemistry to the complex physiology and metabolism of these two naturally occurring molecules in the human body. Well-organized and well referenced chapters cover the rich history of nitrite and nitrate, sources of exposure, and the physiological effects when consumed through foods containing nitrite and nitrate. The chapters are written by leading experts, all of whom share their research and perspectives in order to help define the context for benefits vs. any potential risks associated with nitrite and nitrate use, either through dietary ingestion or therapeutic dosing. This diverse collection of authors includes vascular biologists, physiologists, physicians, epidemiologists, cancer biologists, registered dieticians, chemists, and public health experts from five countries in both academia and government. Nitrite and Nitrate in Human Health and Disease provides a balanced view of nitric oxide biochemistry, and nitrite and nitrate biochemistry in physiology and in the food sciences.

A one-of-a-kind guide specifically for rehabilitation specialists! A leader in pharmacology and rehabilitation, Charles Ciccone, PT, PhD offers a concise, easy-to-access resource that delivers the drug information rehabilitation specialists need to know. Organized alphabetically by generic name, over 800 drug monographs offer the most up-to-date information on drug indications, therapeutic effects, potential adverse reactions, and much more! A list of implications for physical therapy at the end of each monograph helps you provide the best possible care for your patients. It’s the perfect companion to Pharmacology in Rehabilitation, 4th Edition!