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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 32 (1987), S. 309-311 
    ISSN: 1432-1041
    Keywords: digoxin ; verapamil ; cirrhosis ; drug interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of a single low dose of verapamil (80 mg) on the serum levels of digoxin (single dose of 0.5 mg) was studied in 6 patients with hepatic cirrhosis and in 6 healthy volunteer controls. In the cirrhotic patients verapamil increased the peak serum level and the total AUC of digoxin by 98% and 32%, respectively. There was an associated 23% decrease in the renal digoxin clearance. In normal subjects only marginal alterations in digoxin kinetics were observed following verapamil administration. The results indicate that cirrhosis magnifies the influence of verapamil on digoxin kinetics.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Journal of medicinal chemistry 36 (1993), S. 2475-2484 
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 336 (1987), S. 445-452 
    ISSN: 1432-1912
    Keywords: PGI2 ; Guinea-pig ileum ; Procaine ; Quercetin ; FCCP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the guinea-pig terminal ileum a maximally effective concentration of prostacyclin (PGI2) (1 μol/l) induced contractions that were partially resistant to tetrodotoxin (TTX) 0.1 μmol/l, to low temperature (20°C) and to atropine (30 nmol/l). Half maximum contractions evoked by PGI2 (20 nmol/l) were abolished by TTX and by low temperature, which did not modify the response to exogenous acetylcholine (ACh), as well as by atropine. Procaine (5–500 μol/l) caused a concentration-dependent inhibition of contractions induced by PGI2 (20 nmol/l and 1 μmol/l) and by equieffective concentrations of ACh (20 nmol/l and 0.4 μol/l, respectively). The order of magnitude for this inhibition was ACh 20 nmol/l = PGI2 20 nmol/l 〉 PGI21 μmol/l 〉 ACh 0.4 μmol/l. In preparations exposed to TTX or to low temperature procaine (50 μmol/l) did not affect the residual response to PGI2 (1 μmol/l). Quercetin (1 and 5 μol/l) inhibited the effect of PGI2 and, at higher concentrations, it also caused partial depression of the responses to ACh. Quercetin did not alter TTX-resistant and low temperature-resistant contractions induced by PGI2 1 μmol/l. Carbonyl cyanide-trifluoromethoxyphenyl hydrazone (FCCP) (0.1–1 μol/l) reduced the effect of PGI2 and of ACh to approximately the same extent and inhibited the residual response to PGI2 1 μmol/l in preparations treated with TTX or expressed to low temperature. The present results show that PGI2, besides acting on cholinergic neurons, also exerts a direct effect on smooth muscle cells and FCCP can be used to block this effect. In contrast procaine and quercetin selectively inhibit the ACh-mediated component of PGI2 action.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 330 (1985), S. 222-226 
    ISSN: 1432-1912
    Keywords: 6-Thiocaffeine ; 6-Thiotheophylline ; Xanthines ; Inotropic and chronotropic effects ; Cyclic AMP phosphodiesterase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Cardiac effects of thio-xanthine derivatives, S-caffeine and S-theophylline, were studied on isolated guinea-pig atria and on partially purified cardiac cAMP phosphodiesterase enzymes. Theophylline and caffeine were taken as reference compounds. 2. On electrically driven left atria S-caffeine (0.01–1 mmol/l) decreased contractile tension in a concentration dependent manner. On spontaneously beating atria, the same concentrations of S-caffeine showed negative inotropic as well as negative chronotropic effects. 3. On electrically driven left atria, S-theophylline (0.01–1 mmol/l) increased heart contractile tension but, at higher concentrations, a reversal of the stimulating effect was observed. 4. Both S-caffeine and S-theophylline inhibited bovine heart cAMP phosphodiesterase activity to a comparable extent. Their inhibitory potencies were about three and nine times higher than those of theophylline or caffeine but consistently lower than that of IBMX. 5. The results show that the replacement of O with S in the methylxanthine molecule drastically modifies the effects induced by the drugs on cardiac function without changing those on cAMP phosphodiesterase.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Cardiovascular drugs and therapy 4 (1990), S. 509-513 
    ISSN: 1573-7241
    Keywords: guinea-pig atria ; milrinone ; ATP ; adenosine ; inotropism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In spontaneously beating atria from reserpinetreated guinea pigs, milrinone (1–100 μg/ml) induced a positive inotropic and chronotropic effect but was ineffective in preparations preincubated with adenosine deaminase (1 U/ml). Both in spontaneously beating and in electrically driven atria, ATP and adenosine evoked a dual effect: a first negative phase characterized by a reduction in contractile force, followed by a positive phase of increased inotropism. In these preparations milrinone inhibited the early negative influence exerted by purine compounds and amplified the following positive phase. These data suggest that the positive inotropic and chronotropic effect of milrinone may originate from its interference with endogenous purines.
    Type of Medium: Electronic Resource
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