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  • 2000-2004
  • 1995-1999
  • 1970-1974  (3)
  • Guinea Pigs  (2)
  • Cardiac Output  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 279 (1973), S. 9-18 
    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
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 282 (1974), S. 9-14 
    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
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 272 (1972), S. 32-45 
    ISSN: 1432-1912
    Keywords: Cardioglycoside ; Labelled Compound ; Absorption ; Cardiac Output ; Guinea-Pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glycosides were injected into a ligated loop of the small intestine of guinea-pigs under urethane anaesthesia. From the residual radioactivity in the intestinal loop at various times after the injection the amount absorbed was determined and from that the rate of absorption, assuming exponential absorption. β-Methyl-digoxin was absorbed more rapidly than digoxin and its derivatives β-acetyl-digoxin and lanatoside C but slower than digitoxin. β-Methyl-digoxin was much better absorbed from a suspension than from a solution; this caused the difference from digitoxin to disappear to a large extent. The high rate of absorption of β-methyl-digoxin in humans is probably explicable in this way. The rate of absorption of β-methyl-digoxin was independent of the dose until the appearance of arrhythmias; it decreased with progressing intoxication. Absorption was delayed when cardiac output was decreased by barbital anaesthesia. The amount absorbed at the onset of arrhythmias can be calculated from the injected dose, the rate of absorption and the time. For β-methyl-digoxin and digoxin it corresponded to the effective doses determined by intravenous infusion and to the cardiotoxicity after intraduodenal injection. The cardiotoxicity of β-acetyl-digoxin and digitoxin was less than that expected from the amounts absorbed suggesting metabolic inactivation during absorption. The relative enteral activity is not only determined by the absorption but also by the rate of elimination. The rate at which the material should leave the intestine in order to maintain arrhythmia was calculated. It was considerably greater for digitoxin than for β-methyl-digoxin or digoxin.
    Type of Medium: Electronic Resource
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