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  • 1990-1994
  • 1970-1974  (5)
  • Cardiac Glycosides  (3)
  • Aldosterone Antagonists  (1)
  • Glibenclamide  (1)
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Material
Years
  • 1990-1994
  • 1970-1974  (5)
Year
Keywords
  • 1
    Electronic Resource
    Electronic Resource
    Extrarenal actions of aldosterone antagonists in guinea pigs (1973)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 279 (1973), S. 9-18 
    Details
    ISSN: 1432-1912
    Keywords: Aldosterone Antagonists ; β-Methyl-Digoxin ; Guinea Pigs ; Potassium ; Cardiac Toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of aldosterone antagonists on the cardiotoxicity of β-methyl-digoxin in guinea pigs were investigated in vivo and in vitro. 1. Three days of pretreatment with spironolactone influenced neither plasma concentrations, urinary output and tissue distribution of radioactivity after intravenous injection of β-methyl-digoxin nor the pattern of lipid soluble metabolites in the urine. 2. Spironolactone injected intraduodenally 1 h before the infusion of β-methyl-digoxin decreased the cardiotoxicity of the latter if hypokalemia was reduced or prevented by giving 0.4–1.0 mEq/kg KCl 1 h before β-methyl-digoxin. 3. Three days of pretreatment with canrenoate-K decreased the cardiotoxicity of β-methyl-digoxin in vivo without the administration of KCl. 4. Isolated hearts from guinea pigs pretreated with canrenoate-K for 3 days tolerated the perfusion with toxic concentrations of β-methyl-digoxin better than those from controls although the rate of potassium extrusion from the heart was not decreased. 5. The addition of canrenone to the fluid perfusing isolated hearts decreased the potassium extrusion produced by and the toxicity of β-methyl-digoxin. The results suggest that the decreased glycoside toxicity is due to the stimulation of inward transport of potassium by aldosterone-antagonists described in the preceding paper.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00502063
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    β-Methyl-digoxin (1974)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 282 (1974), S. 9-14 
    Details
    ISSN: 1432-1912
    Keywords: Cardiac Glycosides ; Distribution ; Guinea Pigs ; Protein Binding ; Therapeutic Ratio
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In guinea pigs under urethane anaesthesia the concentrations of radioactivity in the plasma, the liver and the heart and the protein binding of radioactivity were measured 1 h after the intravenous injection of 0.2 μmoles/kg β-methyldigoxin or digoxin. The distribution coefficients were calculated between the concentrations in the plasma water and the tissues. Apart from a slightly higher distribution coefficient for β-methyl-digoxin than for digoxin between liver and plasma water there was no significant difference between the two glycosides. In guinea pigs under barbital anaesthesia, cardiac failure was produced by additional doses of barbital-Na. Bemegride was given to counteract the effects of barbital on the vasomotor centre. β-Methyl-digoxin and digoxin were infused until cardiac arrest. For each animal the doses were calculated which led to an increase in cardiac performance by 50 g · cm/sec, arrhythmia, ventricular fibrillation or cardiac arrest. The therapeutic range was calculated from the doses producing arrhythmias and those increasing cardiac performance by 50 g · cm/sec (“therapeutic” dose). There was no difference between the “therapeutic” and toxic doses and the therapeutic ratios of β-methyl-digoxin and digoxin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00647399
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Ursachen der Potenzierung der hypoglykämischen Wirkung von Sulfonylharnstoff-Derivaten durch Medikamente (1971)
    Springer
    European journal of clinical pharmacology 4 (1971), S. 32-37 
    Details
    ISSN: 1432-1041
    Keywords: Glibenclamide ; pharmacokinetics ; metabolism ; potentiation of hypoglycemic action ; phenylbutazone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Description / Table of Contents: Summary Metabolically healthy subjects were given an intravenous injection of 1,13 mg14C-labelled glibenclamide (HB 419). The plasma level, renal elimination of the radioactivity and metabolism of the substance were investigated. Two minutes after administration the HB 419 is virtually present only in the blood and at the end of the distribution period mostly in the extracellular space. 53% of the radioactivity is excreted via the kidneys in the form of metabolites. If glibenclamide is administrated in the same way to the same subjects after pretreatment with phenylbutazone there are no differences in the course of the plasma levels or the rate of elimination from the blood. There is, however, a significant difference in the excretion of the radioactivity in the urine. In the presence of phenylbutazone significantly less HB 419 metabolite is excreted renally. In view of the known alternative route of elimination it is suggested that the amount not excreted in the urine is in compensation eliminated via the bile. There was no difference in the metabolism of glibenclamide between the control and phenylbutazone treated groups. The potentiation by phenylbutazone of HB 419 action, and probably also that of other antidiabetic sulphonylureas, must therefore be due predominantly to other causes (Communication III).
    Notes: Zusammenfassung Stoffwechselgesunde Versuchspersonen erhielten14C-markiertes Glibenclamid in einer Dosis von 1.13 mg/Vpn i.v. gespritzt. Plasmaspiegelverläufe, renale Elimination der Radioaktivität und die Metabolisierung der Substanz wurden untersucht. Zwei Minuten nach der Applikation ist HB 419 praktisch nur im Blutund nach Abschluß der Verteilung weitgehend im Extracellulärraum vorhanden. 53% der Radioaktivität werden über die Nieren in Form von Metaboliten ausgeschieden. Wird den gleichen Probanden nach Prämedikation mit Phenylbutazon Glibenclamid in gleicher Weise verabfolgt, ergibt sich kein Unterschied hinsichtlich der Plasmaspiegelverläufe und der Eliminationsgeschwindigkeit aus dem Blut. Ein signifikanter Unterschied besteht jedoch in der Ausscheidung der Radioaktivität in den Harn (26.3%). In Gegenwart von Phenylbutazon wird ein signifikant geringerer Anteil von HB 419-Metaboliten renal eliminiert. Aufgrund des bekannten zweiten Ausscheidungsweges wird vermutet, daß der fehlende Anteil kompensatorisch über die Galle eliminiert wird. Die Metabolisierung von Glibenclamid weist keine Differenzen zwischen Phenylbutazon-und Kontroll-Gruppe auf. Die Wirkungspotenzierung von HB 419 — wahrscheinlich auch diejenige anderer antidiabetisch wirksamer Sulfonylharnstoffe — durch Phenylbutazon dürfte demnach überweigend andere Ursachen haben. (Mitteilung III).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00568896
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  • 4
    Electronic Resource
    Electronic Resource
    β-Methyl-digoxin (1973)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 279 (1973), S. 211-226 
    Details
    ISSN: 1432-1912
    Keywords: Cardiac Glycosides ; Brain ; Behaviour ; Distribution ; Protein Binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats and mice were injected with 3H-labelled β-methyldigoxin, digoxin or digitoxin i.p. Four hours later, the concentrations of radioactivity were measured in the plasma and in skeletal muscle or in the brain. Protein binding in the plasma was determined and the concentration of radioactivity in the plasma water was calculated. By dividing the injected dose or the concentration in the tissue by that in the plasma water, distribution coefficients (DCs) were calculated for the whole body, skeletal muscle and brain. Some extra-cardiac effects of the three glycosides were quantified and the concentrations that may be expected in plasma water, skeletal muscle and brain after the administration of equiactive doses were calculated. 1. The DC of the injected dose was lower for β-methyl-digoxin than for digoxin and digitoxin. This difference cannot be explained by a slow elimination of β-methyl-digoxin suggesting that it has a low distribution volume in these species. 2. In rats, the DC between skeletal muscle and plasma water decreased in the order digitoxin 〉 digoxin ≫ β-methyl-digoxin. 3. In mice and rats, the DC between brain and plasma water decreased in the order digitoxin ≫ β-methyl-digoxin 〉 digoxin. 4. Protein binding decreased in the order digitoxin ≫ digoxin 〉 β-methyldigoxin. 5. In rats, the doses producing an equal increase in potassium excretion decreased in the order digitoxin 〉 digoxin 〉 β-methyl-digoxin. On the other hand, the concentrations of radioactivity in the plasma water correlated with these doses decreased in the order β-methyl-digoxin 〉 digitoxin ≫ digoxin. There was no significant difference between the intracellular concentrations of digoxin and β-methyl-digoxin in skeletal muscle. 6. In mice, there was no clear correlation between inhibition of spontaneous motility or righting reflexes on the rotating rod and the concentrations of radioactivity in the plasma water or in the brain. β-Methyl-digoxin is moee lipophilic than digoxin but it penetrates less into skeletal muscle. It is as lipophilic as digitoxin, but it penetrates less into the brain of rats and mice. This shows that penetration of the cell membrane by cardiac glycosides does not solely depend on lipid solubility.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00500601
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  • 5
    Electronic Resource
    Electronic Resource
    β-Methyl-digoxin (1974)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 286 (1974), S. 195-210 
    Details
    ISSN: 1432-1912
    Keywords: Cats ; Cardiac Glycosides ; Inotropic Action ; Distribution ; Protein Binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The tissue distribution and the positive inotropic effect of α- and β-methyl-digoxin, digoxin, and digitoxin were investigated in cats under pentobarbital anaesthesia, the emetic effect of β-methyl-digoxin and digoxin in unanaesthetized animals. 1. The distribution volume calculated by dividing the injected dose by the concentration in the plasma water after 60 min decreased in the order digitoxin 〉 β-methyl-digoxin ≥ α-methyl-digoxin 〉 digoxin. 2. The distribution coefficients between tissue and plasma water decreased for all glycosides in the order kidney 〉 liver 〉 heart 〉 diaphragm 〉 erythrocytes 〉 perirenal fat 〉 brain. 3. α-Methyl-digoxin and digoxin were metabolized to a larger extent than were β-methyl-digoxin and digitoxin. 4. 200 nmoles/kg digoxin produced arrhythmias, whereas equimolar doses of the other glycosides were well tolerated. 5. Except for α-methyl-digoxin, there was a close relation between the increase in dp/dt max and the concentration in the plasma water 60 min after the injection. The differences in the equieffective doses of β-methyl-digoxin, digoxin, and digitoxin can therefore be explained by the differences in tissue distribution. 6. Although higher concentrations of β-methyl-digoxin than of digoxin were found in the brain, there was no difference in the central activity of the two glycosides.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00501612
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    Paper (German National Licenses)
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