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Titlebook: Nitrates III; Cardiovascular Effec P. R. Lichtlen,H.-J. Engel,H. J. C. Swan (Director Conference proceedings 1981 Springer-Verlag Berlin He

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书目名称Nitrates III
副标题Cardiovascular Effec
编辑P. R. Lichtlen,H.-J. Engel,H. J. C. Swan (Director
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图书封面Titlebook: Nitrates III; Cardiovascular Effec P. R. Lichtlen,H.-J. Engel,H. J. C. Swan (Director Conference proceedings 1981 Springer-Verlag Berlin He
描述Pharmacological and clinical research on nitrates continues to be of growing interest in many centers. This is surprising in view of the fact that their favorable effects in angina pectoris were described by Brunton and by Murrell in the Lancet more than 100 years ago. As expected, a host of new information has been collected since the two previous symposia on nitrates held in Stockholm in 1975 and Berlin in 1978. New insights were gained into the pharmacology, pharmacokinetics and pharmacodynamics of nitrates, as well as into their clinical effects in acute and chronic ischemic heart diseases and in severe congestive heart failure. Relatively little progress, however, was observed in research into the basic action of nitrates. Although most investigators agree that intracellular sequestration of calcium is probably the main mechanism by which nitrates lead to the reduction of vascular smooth muscle tone, the exact site of their action still remains undefined. In contrast, dose-dependent differences in venous and arteriolar tone have long been clearly established. Treatment was again in the main stream of discussion. The question of tolerance following long-term administration was
出版日期Conference proceedings 1981
关键词Herz-Kreislauf-System; Nitrat; Nitrates; angina pectoris; calcium; circulation; clinical research; heart; ki
版次1
doihttps://doi.org/10.1007/978-3-642-68085-4
isbn_softcover978-3-642-68087-8
isbn_ebook978-3-642-68085-4
copyrightSpringer-Verlag Berlin Heidelberg 1981
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Comparative Haemodynamic and Pharmacokinetic Investigations After Oral Isosorbide-2-mononitrate and The metabolites isosorbide-2-mononitrate (IS-2-MN) and 5-mononitrate (IS-5-MN) are demonstrable in the plasma for several hours at concentrations which are but slowly decreasing, in contrast to those measured after oral isosorbide dinitrate, (ISDN) [2].
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Newer Methods of Administration of Nitrates to Man to Give a More Predictable Therapeutic ResponseIsosorbide dinitrate (ISDN) given orally is extensively metabolised by “first pass” metabolism, less than 3% appearing unchanged in the blood using this route. However, the two mononitrate metabolites are active and thus probably contribute significantly to the observed effects when ISDN is given orally.
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Induction and Inhibition of Organic Nitrate MetabolismOrganic nitrate vasodilators, such as glyceryl trinitrate (GTN) or isosorbide dinitrate (ISDN), are denitrated by the glutathione (GSH) S-transferases (EC 2.5.1.18) according to the general scheme [3]:RONO.+GSH→RHO+HNO.+GSSG.
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978-3-642-68087-8Springer-Verlag Berlin Heidelberg 1981
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Fate of Isosorbide Mononitrates in Manegimen, the duration of action, and the relationship between plasma concentration and effect are still under discussion. In an attempt to solve some of these problems, a pharmacologic and/or therapeutic role for the nitrated metabolites of substances such as glyceryl trinitrate and isosorbide dinitrate has been postulated.
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