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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 9 (1976), S. 345-354 
    ISSN: 1432-1041
    Keywords: 3H-digitoxin ; metabolism ; spironolactone ; enzyme induction ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of spironolactone on the metabolism of intravenously administered3H-digitoxin (80 µCi) was investigated in eight patients. In three of them the labelled glycoside was given on a second occasion after spironolactone treatment had been discontinued for at least 65 days. Of total urinary radioactivity 79 % was unaltered drug and 12 % consisted of water soluble compounds. No digitoxigenin or digoxigenin and only trace amounts (〈2 %) of digoxin and the bis- and monoglycosides of digoxigenin were found. After spironolactone total urinary radioactivity was unchanged but the fraction eliminated as unchanged digitoxin fell from 79 to 66 % and the water soluble compounds increased from 12 to 26 % (p〈0.05). In addition spironolactone caused a 20 % reduction in the half-life of serum radioactivity (p〈0.01) and a 16 % reduction in the volume of distribution (p〈0.05). Induction of hepatic enzymes by spironolactone is proposed to explain the alteration in the metabolism of digitoxin in man. Both the altered metabolic pattern and the reduction in the volume of distribution appear to contribute to the reduction in half-life.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Clinical and experimental medicine 154 (1971), S. 165-176 
    ISSN: 1591-9528
    Keywords: Blood-pH ; resp. Acidosis ; Cardiovascular Drugs ; Blut-pH ; resp. Acidose ; kreislaufaktive Pharmaka
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Elektrisch gereizte Vorhofpräparate des Meerschweinchens wurden in einem Tyrodebad suspendiert, dessen pH durch Begasung mit verschiedenen CO2-Konzentrationen auf 7,0, 7,4 bzw. 7,8 eingestellt wurde. Kontraktionskraft und maximale Kontraktionsgeschwindigkeit der Vorhöfe wurden durch diese pH-Änderungen nicht beeinflußt. Der positiv inotrope Effekt von Tyramin, Isoproterenol und Calcium war bei pH 7,0 abgeschwächt, bei pH 7,8 verstärkt. An narkotisierten Katzen wurde durch Beatmung mit 10 bzw. 20% CO2 eine respiratorische Acidose mit pH-Werten von 7,15 bzw. 7,0 erzeugt. Dabei traten eine mäßige Zunahme der Herzfrequenz, der maximalen Druckanstiegsgeschwindigkeit (dp/dtmax) und des systolischen Femoralisdruckes ein. Die Wirkung aller untersuchten Pharmaka war in Acidose abgeschwächt, wobei sich aber folgende quantitative und qualitative Unterschiede ergaben: 1. Die blutdrucksenkende Wirkung des Isoproterenols und die blutdrucksteigernde Wirkung des Noradrenalins waren stärker abgeschwächt als ihre positiv inotrope Wirkung am Herzen. 2. Die pressorische Wirkung des Angiotensins und Noradrenalins war weniger beeinträchtigt als die des Naphazolins. 3. Die blutdrucksenkende Wirkung des Acetylcholins war im Gegensatz zu der des Isoproterenols weniger abgeschwächt.
    Notes: Summary Experiments were performed on guinea pigs isolated atria which were stimulated electrically. If the pH of the tyrode solution was changed by variation of pCO2 no alteration of force of contraction and maximal velocity of contraction (dT/dtmax.) occured. The inotropic effects of tyramine, isoproterenol and calcium were diminished at pH 7.0 and increased at pH 7.8. During respiratory acidosis (pH 7.0) anaesthetized cats showed a small increase in heart rate, left ventricular dp/dtmax. and arterial blood pressure. The effects of all tested drugs were diminished in acidosis, whereby the following qualitative and quantitative differences appeared: 1. The depressive effect of isoproterenol and the stimulating effect of norepinephrine on arterial blood pressure were much more diminished than the positive inotropic effect of these drugs. 2. The effect of angiotensin and norepinephrine on arterial blood pressure was less affected than that of naphazoline. 3. The effect of acetylcholine on arterial blood pressure was scarcely diminished in contrast to that of isoproterenol.
    Type of Medium: Electronic Resource
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