By Prof. Dr. J. C. Skou (auth.), Prof. Dr. Erland Erdmann, Prof. Dr. K. Greef, Prof. Dr. J. C. Skou (eds.)
The bicentenary of William Withering's now recognized clinical file entitled "An Account of the Foxglove and a few of its clinical makes use of" has given us the social gathering to investigate the state-of-the-art. Cardiac glycosides in 1985 are thought of tobe the foundation for scientific therapy of myocardial failure, including diuretics and vasodilators within the extra serious circumstances. however, the debate as to their unique position within the therapy of middle failure with sinus rhythm hasn't ever ceased. even if cardiac glycosides are of unquestionable price in tachycardia brought on by atrial traumatic inflammation or atrial flutter, the power use of those medicines in sinus rhythm isn't really typically authorized. the advance of tolerance has been mentioned. it truly is of curiosity that Withering hirnself wrote: "-let it (foxglove) be endured until eventually it both acts at the kidneys, the tummy, the heart beat, or the bowels; Iet or not it's stopped upon the 1st visual appeal of any of those results, and that i will continue that the sufferer won't be afflicted by its exhibition, nor the practitioner be disillusioned in any average expectation. " In West Germany on my own, greater than 3 million sufferers (about five% of the complete inhabitants) are continuously taking cardiac glycosides. those medications are the main prescribed medicaments in lots of nations. hence, we thought of it helpful and essential to evaluate in a serious manner latest wisdom concerning the foxglove; to document new findings and to judge outdated Statements.
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Extra resources for Cardiac Glycosides 1785–1985: Biochemistry — Pharmacology — Clinical Relevance
In: Blümchen G (ed) Beiträge zur Geschichte der Kardiologie. Rodenbirken p 193ff Grosse-Brockhoff F (1980) Herzbehandlung mit dem 'Fingerhut' einst und jetzt. Vorträge der Natur-, Ingenieur- und Wirtschaftswiss. Klasse, Rheinisch-Westf Akad Wiss N 293: Opladen Hornolle A-E (1845) Memoire sur Ja digitale pourpree. J pharm chim 3 ser 7: 57-83 Issekutz B (1971) Die Geschichte der Arzneimittelforschung. Akademiai Kiad6 Budapest p 251 ff Jung LM (1985) Therapeutic Use of Digitalis until the Time of William Withering.
Endogenaus ligands for the glycoside binding site on Na+ ,K+A TPase have been sought by many investigators. Lipids or their derivatives appear to play some roJe in modifying Na+ ,K+ -ATPase activity. These compounds, however, do not bind to the enzyme at the glycoside binding site. Convincing evidence has not been available to indicate the presence of a true digitalis-like principle. These aspects are discussed elsewhere in this book. Drug-induced alterations of sodium pump activity A current popular hypothesis for the mechanism of the positive inotropic action of digitalis glycosides is as follows.
Elevation of [Na+]; and its effect on Na+Jca2+ exchange The above discussion indicates that a modest sodium pump inhibition or an increase in Na + influx rate slightly elevates [Na+]; . This increase has been proposed to elevate intracellular Ca 2+during diastole , to increase the Ca 2+ loading of the sarcoplasmic reticulum , and to increase Ca 2 + release during membrane excitation. This indirect mechanism, rather than a direct augmentation of Ca 2 + influx in exchange for elevated [Na+]; during membrane excitation, appears tobe supported by the following Observations.