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  • 1970-1974  (3)
  • Cardioglycoside  (2)
  • Inotropic Action  (1)
  • 1
    Electronic Resource
    Electronic Resource
    β-Methyl-digoxin (1972)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 272 (1972), S. 32-45 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00498792
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    β-Methyl-digoxin (1972)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 272 (1972), S. 46-64 
    Details
    ISSN: 1432-1912
    Keywords: Cardioglycoside ; Labelled Compound ; Drug Metabolism ; Pharmacokinetics ; Absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary β-Methyl-digoxin was much more resistant to enzymatic degradation than digoxin, β-acetyl-digoxin and digitoxin. Only in the bile was an appreciable percentage of the radioactivity attributable to a hydrophilic metabolite. The distribution volume of β-methyl-digoxin increased with time, but was independent of the dose and of the mode of administration. The blood levels during i. v. infusion and after i. d. injection can be used for calculating the speed of absorption during the first 20 min only. The correlations between blood levels and pharmacodynamic activity were investigated by varying the dose injected intraduodenally or the speed of i. v. infusion. Although the effective doses were constant, the blood levels expected at the onset of arrhythmias decreased with decreasing speed of administration. Signs of acute tolerance were observed when the experiment lasted for more than 30 min. In the heart, the equilibrium between blood and tissue levels of radioactivity was reached sooner than in the rest of the body. Whereas maximal blood levels were observed about 30 min after oral administration in man, they continued to rise for at least 60 min after i.d. injection in guineapigs. This confirms earlier observations that β-methyl-digoxin is absorbed more rapidly in man than in guinea-pigs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00498793
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    Paper (German National Licenses)
    Fulltext
  • 3
    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
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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