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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 55 (1977), S. 759-761 
    ISSN: 1432-1440
    Keywords: Allopurinol ; Phenprocoumon ; Arzneimittelwechselwirkungen ; Orale Antikoagulantien ; Allopurinol ; Phenprocoumon ; Drug interaction ; Oral anticoagulants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Conditions in two patients on long-term phenprocoumon (Marcumar®) treatment are reported who had signs of phenprocoumon overdosage when given simultaneously allopurinol. The determination of phenprocoumon plasma concentrations in one patient showed that phenprocoumon accumulates for several weeks during treatment with allopurinol. Signs of phenprocoumon overdosage thus can appear long time after starting allopurinol treatment.
    Notes: Zusammenfassung Wir berichten über zwei Patienten, bei denen während einer Dauertherapie mit Phenprocoumon (Marcumar®) nach Gabe von Allopurinol Zeichen der Phenprocoumonüberdosierung auftraten. Messungen der Phenprocoumonplasmakonzentration bei einem der Patienten zeigte, daß Phenprocoumon während gleichzeitiger Behandlung mit Allopurinol über mehrere Wochen kumulierte. Zeichen einer Phenprocoumonüberdosierung können demnach lange Zeit nach Beginn einer gleichzeitigen Behandlung mit Allopurinol auftreten.
    Type of Medium: Electronic Resource
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 277 (1973), S. 107-112 
    ISSN: 1432-1912
    Keywords: Dibutyryl Cyclic AMP ; Adrenaline ; Heart ; Contractile Force ; 45Ca Uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of dibutyryl cyclic AMP (DB-AMP; 10−3M) and adrenaline (2.2×10−6 M) on contractile force, 45Ca uptake, and total myocardial Ca concentration were investigated in electrically driven left auricles isolated from rat hearts. The experiments were performed at an extracellular Ca concentration of 0.45 mM and at low frequency of stimulation (15 beats/min). 45Ca exposure was 5 min. Under the conditions used, both drugs increased contractile force and enhanced 45Ca uptake (expressed as relative specific activity) by about 30% (DB-AMP) and 40% (adrenaline), respectively. Thus, the results provide evidence that the effects of adrenaline on 45Ca uptake in mammalian cardiac muscle can be mimicked by DB-AMP.
    Type of Medium: Electronic Resource
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  • 13
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography B: Biomedical Sciences and Applications 223 (1981), S. 238-242 
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 14
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Clinica Chimica Acta 128 (1983), S. 125-132 
    ISSN: 0009-8981
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 15
    ISSN: 1432-0428
    Keywords: Keywords Diabetes mellitus, endothelium, nitric oxide, tetrahydrobiopterin, endothelium-dependent vasodilation, acetylcholine, NG-monomethyl-l-arginine.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Tetrahydrobiopterin is an essential cofactor of nitric oxide synthase, and its deficiency decreases nitric oxide bioactivity. Our aim was to find whether supplementation of tetrahydrobiopterin could improve endothelial dysfunction in diabetic patients.¶Methods. Forearm blood flow responses to the endothelium-dependent vasodilator acetylcholine (0.75– 3.0 μg · 100 ml–1· min–1) and to the endothelium-independent vasodilator sodium nitroprusside (0.1–1.0 μg · 100 ml–1· min–1) before and during concomitant intra-arterial infusion of tetrahydrobiopterin (500 μg/min) were measured by venous occlusion plethysmography in 12 control subjects and 23 patients with Type II (non-insulin-dependent) diabetes mellitus.¶Results. In control subjects, tetrahydrobiopterin had no effect on the dose-response curves to acetylcholine and sodium nitroprusside. In contrast, in diabetic patients, the attenuated endothelium-dependent vasodilation to acetylcholine was considerably improved by concomitant treatment with tetrahydrobiopterin, whereas the endothelium-independent vasodilation was not affected. This beneficial effect of tetrahydrobiopterin in diabetic patients could be completely blocked by N G-monomethyl-l-arginine.¶Conclusion/interpretation. These findings suggest the possibility that endothelial dysfunction in Type II diabetes might be related to decreased availability of tetrahydrobiopterin. [Diabetologia (2000) 43: 1435–1438]
    Type of Medium: Electronic Resource
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 20 (1981), S. 147-155 
    ISSN: 1432-1041
    Keywords: azapropazone ; cirrhosis ; renal failure ; non-steroidal anti-inflammatory drug ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of azapropazone 600 mg i.v. was investigated in 6 healthy subjects, 13 patients with cirrhosis and 8 patients with renal failure. In healthy subjects the elimination half-life was 12.2±2.1 h (mean ± SD), the volume of distribution 10.6±3.31 and the total clearance was 597±135 ml·h−1. Renal clearance accounted for about 62% of the total clearance. The free fraction of azapropazone in the plasma was 0.0045±0.0006. The patients with cirrhosis were divided into Group I with modest and Group II with severe impairment of liver function. In Group I the total clearance of azapropazone was not significantly different from that in healthy subjects. There was a 2.5-fold increase in its free fraction in plasma, and a reduction in the free drug clearance to about half that in healthy subjects. In Group II patients total clearance was reduced to about 20% of normal. This was partly due to reduced non-renal clearance but mainly to impaired renal clearance of azapropazone. The diminished renal clearance was considered at least in part to represent a drug-induced impairment of renal function, as there was a concomitant reduction in creatinine clearance. The free fraction of azapropazone in the plasma was markedly enhanced (〉0.02), and simultaneously, free drug clearance was drastically reduced, to about 2% of that in healthy subjects. In patients with renal failure the total clearance was diminished, depending on the degree of impairment of kidney function. Anephric patients were estimated to have about one third of the total clearance in normal subjects. The free fraction of azapropazone in the plasma was increased in 4 of the 8 patients. It is concluded that patients with cirrhosis and modest impairment of liver function may require about half the normal dose of azapropazone, since free drug clearance is reduced by about 50%. Patients with severe impairment of liver function are expected to be highly susceptible to dose-related side effects, since the pronounced increase in the free fraction in plasma and the decreases in renal and non-renal clearance lead to marked reduction in free drug clearance and so to accumulation of free drug in the body. In patients with renal failure the dose of azapropazone should be reduced according to the degree of impairment of kidney function and plasma protein binding of the drug.
    Type of Medium: Electronic Resource
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 10 (1976), S. 349-356 
    ISSN: 1432-1041
    Keywords: Dicoumarol ; coumarin ; anticoagulants ; tolbutamide ; drug interactions ; anticoagulant action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of repeated administration of tolbutamide on the elimination and anticoagulant action of a single oral dose of dicoumarol 600 mg was studied in four healthy male subjects using a crossover design. In all subjects the plasma concentration of dicoumarol in the postabsorptive phase was lower during concomitant tolbutamide treatment. However, the subjects differed with respect to the elimination kinetics of dicoumarol and the effect of tolbutamide on some of the measured pharmacokinetic paramaters. In two subjects dicoumarol was eliminated by apparent first-order kinetics. Tolbutamide led to a pronounced increase in the elimination rate and a shift in the plasma concentration-response relationship towards a lower concentration of dicoumarol. The total hypoprothrombinaemic effect per dose of dicoumarol was not affected. The decline in the dicoumarol concentration in plasma in the other two subjects was concentration-dependent. Apparent first-order kinetics were observed only at plasma concentrations below 10 mg/L. Tolbutamide treatment did not markedly affect the slope of the terminal portion of the plasma concentration vs. time curve, but diminished the area under the total curve. The plasma concentration-response relationship of dicoumarol was not affected by tolbutamide, but there was a small decrease in the area under the anticoagulant effect vs. time curve. The plateau level of tolbutamide in plasma increased considerably in all subjects after administration of one dose of dicoumarol. Thus, simultaneous administration of tolbutamide and dicoumarol to man often causes no changes in the anticoagulant activity of dicoumarol, but this is due not to lack of interaction of the drugs but to the complexity of their interactions, involving processes that may counteract each other.
    Type of Medium: Electronic Resource
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 18 (1980), S. 461-465 
    ISSN: 1432-1041
    Keywords: antiarrhythmic drugs ; lorcainide ; haemodynamic effects ; i.v. dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The cardiovascular effects of a single i.v. dose (2 mg/kg over 5 min) of lorcainide were studied in 14 patients with heart disease. In the haemodynamic part of the study (6 patients), the aortic and pulmonary systolic, diastolic and mean pressures, left ventricular systolic and end-diastolic pressures, cardiac output and the rate of rise of left ventricular pressure were measured before and for 30 min after administration of the drug. Lorcainide produced a slight and short-lasting decrease in the aortic and pulmonary systolic pressures, and all other pressure values remained unchanged. The cardiac output and systemic vascular resistance were not altered by lorcainide. It consistently depressed the rate of rise of left ventricular pressure (maximum mean decrease 19%). In the angiographic part of the study (8 patients), the ejection fraction and the mean velocity of circumferential fiber shortening were measured before and 5 min after lorcainide. In all but one patient, lorcainide decreased the ejection fraction (mean decrease 11.6%), and the mean velocity of circumferential fiber shortening was uniformly diminished by lorcainide (mean decrease 29.7%). Thus, lorcainide moderately impaired myocardial performance in patients with normal and reduced left ventricular function without producing hypotensive side effects.
    Type of Medium: Electronic Resource
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 54 (1998), S. 95-96 
    ISSN: 1432-1041
    Keywords: Keywords Digoxin ; Amiodorone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 20
    ISSN: 1432-1041
    Keywords: Key words Mibefradil; refractory periods ; electro physiology ; atrioventricular node ; calcium antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective : This multicenter, double-blind, placebo-controlled, parallel-group study was designed to assess the acute effects of intravenous mibefradil on the electrophysiologic characteristics of the human heart. Methods : Seventy-one patients referred for routine electrophysiologic testing were randomized to receive one of three intravenous treatments: placebo $n=23$ , 15 mg mibefradil in 15 min followed by 25 mg in 60 min (group 1, $n=24$ ), or 35 mg mibefradil in 15 min followed by 45 mg in 60 min (group 2, $n=24$ ). Electrophysiologic evaluations were performed prior to study drug administration and 30 min after the start of the infusion. Plasma samples were obtained at the start of the infusion and after 15, 75, and 105 min. Results : Sinus node recovery time decreased significantly in Group 1 patients (−103 ms). Corrected sinus node recovery time in group 2 patients was 68.7 ms $(P=0.053)$ . Compared to placebo, mibefradil produced mild but significant slowing of conduction in group 2 patients as manifested by an increase in the AH interval of 6.7 ms. Atrioventricular (AV) nodal refractoriness was increased, as indicated by a prolongation of the Wenckebach point in patients in both group 1 (32.1 ms) and group 2 (32.5 ms), compared to placebo. All adverse events were classified as mild to moderate and only one event (vasovagal attack) was considered to be treatment related. Conclusions : At plasma levels close to those found after chronic oral administration of 50 and 100 mg mibefradil, the higher dose produced an increase in corrected sinus node recovery time. Mibefradil also produced small but significant effects on AV nodal conduction and increased AV nodal refractoriness. Mibefradil had no effect on any other electrophysiologic parameter and was well tolerated.
    Type of Medium: Electronic Resource
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