Factors responsible for interindividual differences in the dose requirement of phenprocoumon

The total and unbound plasma concentrations of phenprocoumon and the prothrombin complex activity were determined in 51 patients on phenprocoumon. A 7-fold difference in the dosing rate (10-70 micrograms/kg/day) was required to maintain the prothrombin complex activity at 11-30% of normal. The variation in dosing requirement was mainly due to interindividual differences in the intrinsic clearance of phenprocoumon and only to a minor degree to differences in sensitivity to it. On average patients with myocardial infarction required only 2/3 of the daily dose of phenprocoumon of post cardiac surgery patients and patients with thrombosis and emboli. That difference appeared to be due to higher…

Isosorbide dinitrate: pharmacokinetics after intravenous administration.

Isosorbide dinitrate (ISDN) is an important organic nitrate found therapeutically useful in its sublingual and oral forms in various cardiovascular diseases such as angina pectoris (1) and congestive heart failure (2). Recently Distante et al. (3) showed that an intravenous infusion of this drug, at 0.021–0.083 mg/min is also effective in managing unstable angina. The availability of an intravenous dosage form of ISDN not only affords the opportunity to characterize the pharmacokinetics of this drug after this particular mode of therapy, but also gives the possibility of assessing the bio-availability of this drug after other (e.g., oral) routes of administration in patients. This latter po…

Intracardiac Cardioversion for Ablation of the Atrioventricular Conduction System in Patients with Drug Resistant Atrial Flutter

The technique of intracardiac cardioversion for the ablation of the atrioventricular conduction system was used in three male patients (65, 53 and 57 years of age) with atrial flutter unresponsive to medical management. In the first patient a DC current of 80 J was applied while the other patients required 300 and 400 J respectively. In the first patient a transient third degree AVblock was induced enabling the ventricular rate to be easily controlled with drugs. This patient died 5 months later of resistant congestive heart failure. Autopsy revealed no gross evidence of myocardial damage in the tricuspid valve area or in the interventricular septum. In the other two patients a permanent th…

Über den Einfluß von Mn++-Ionen auf die positiv inotrope Wirkung einiger Pharmaka an isolierten Meerschweinchenvorhöfen

�ber den Einflu� von Mangan-Ionen auf die positiv inotrope Wirkung von Adrenalin, Theophyllin und Digitoxigenin an isolierten Meerschweinchenvorh�fen

The influence of bivalent manganese ions (Mn++) on the positive inotropic effect of adrenaline, theophylline, and digitoxigenin was studied in isolated, electrically driven left guinea-pig auricles in phosphate-free Tyrode's solutions with different extracellular calcium concentrations ([Ca]e; 0.45; 1.8; 7.2 mM).

Prognostic significance of repetitive ventricular response in chronic coronary artery disease.

A prospective study was conducted in 267 patients with angiographically defined coronary artery disease without documented ventricular tachycardia to determine the prognostic significance of repetitive ventricular response (RVR) after programmed electrical stimulation (PES). The patients were classified inducible if RVR with 3 or more echo beats (RVR greater than or equal to 3) could be induced. 89 patients without previous myocardial infarction (MI), 61 survivors of MI occurring between 6 weeks and 3 months before and 117 patients who had survived longer than 3 months after MI were studied. A standardized stimulation protocol with single (S1S2) and double (S1S2S3) extrastimuli during ventr…

Possible coumarin-like mechanism of action for cephalosporins.

In three patients treated with cephalosporins (one patient with latamoxef, two patients with cefazedone) vitamin K1 was injected to investigate whether this was followed by an increase in vitamin K1 2,3-epoxide plasma concentrations as compared to controls. Such a rise in K1-epoxide concentrations in the plasma can be demonstrated following treatment with coumarins. This reflects an inhibition of the vitamin K1-epoxide reductase in the liver. Coumarins are thought to induce hypoprothrombinaemia by such a mechanism. In all three patients we found a considerable increase in the vitamin K1-epoxide plasma concentrations following injection of 10 mg vitamin K1, whereas in normal subjects only tr…