PubMed Health⌕ Search

Biomedical subjects

K Schenck-Gustafsson

Publications and source records attributed to K Schenck-Gustafsson.

At least 19 recordsLinked to original sources
PubMed1993

Positive effects of increased nurse support for male patients after acute myocardial infarction.

The effect of increased nurse support on patients below 70 years of age attending an out-patient clinic following acute myocardial infarction was evaluated. Patients who saw a nurse 14 days after discharge (n = 56) were compared to a control group (n = 47) who, following the ordinary routines, were first seen 8 weeks after discharge. Increased nurse support had positive effects on psychosocial variables such as depressive feelings, expected quality of life in the future, and satisfaction with contact with the staff. However, no effects were found on any of the cardiac variables. Patients in the intervention group showed a decrease in depressive feelings during the 8 weeks follow-up period, whereas there was an increase for the control group. The patients in the intervention group also tended to have a better belief in the future compared to the control group. Patients in the intervention group were more satisfied with the staff contact than were the control group.

Ambulatory Care↗
PubMed1992

Comparative class 1 electrophysiologic and anticholinergic effects of disopyramide and its main metabolite (mono-N-dealkylated disopyramide) in healthy humans.

During steady-state treatment with disopyramide, its main and active metabolite, mono-N-dealkylated disopyramide, was reported to reach concentrations that were equal to or higher than the parent drug in 25% of 70 evaluated patients. This metabolite has been found to have a more pronounced anticholinergic action than the parent drug on in vitro evaluation, but neither its anticholinergic nor its direct electrophysiologic effects on the human heart have been properly assessed. We therefore compared the acute electrophysiologic and anticholinergic effects (the standard being atropine, 0.04 mg/kg) of disopyramide and its main metabolite, given 2 mg/kg body weight intravenously to 10 healthy individuals in a double-blind, randomized, crossover design. The anticholinergic effect of these substances on sinus and atrioventricular node function was unexpectedly found to be of similar magnitude and more pronounced than previously thought (at least one-third the effects of the atropine dose). The class 1 electrophysiologic effects were as follows: intra-atrial and His-Purkinje conduction (the PA and the HV interval, respectively) was prolonged 33% (95% CI: 18-47%) and 27% (21-32%) by disopyramide, and 15% (10-19%) and 13% (10-17%), respectively, by the metabolite. Disopyramide also prolonged the QRS, JT, and QT intervals by 15% (9-21%), 10% (8-13%), and 10% (7-12%), respectively. The metabolite caused a 9% (7-12%) prolongation of the QRS interval (significantly less than disopyramide), but shortened repolarization (as reflected by the JT interval) by -7% (-2 to -11%; p < 0.01), which is similar to the acute effects of lidocaine 2 mg/kg body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Time-dependent variation in the cardiac conduction system assessed in young healthy individuals at weeks' interval: implications for clinical trials.

The time-dependent physiologic variations of the cardiac conduction system were evaluated at repeated invasive studies in 10 healthy individuals. Their mean age was 28 years (range 22 to 34) and they volunteered to undergo two electrophysiologic studies at intervals of 14 to 63 days (mean 25). The coefficients of variation, repeatability and reproducibility, which should be the preferred statistics when assessing the reproducibility of continuous variables, were calculated. The mean sinus cycle length had a high reproducibility, with coefficients of variation between 2% and 6%. The mean and maximal sinus node recovery times, however, varied considerably. The reproducibility was very high for ventricular depolarization and repolarization (QRS, JT, QT), with coefficients of variation between 2% and 6%. The coefficients of variation were below the acceptable 10% value for intraatrial conduction, atrioventricular (AV) node conduction, His-Purkinje conduction as well as the Wenckebach point; for the effective refractory period of the AV node, it was 12%. Repeat invasive electrophysiologic testing is a safe and reproducible method for evaluating and comparing cardioactive drug effects in healthy subjects. The same statistical analyses were applied to previously published studies on continuous electrophysiologic variables, which allowed comparisons among different groups of healthy and sick persons, as well as among different electrophysiologic variables and procedures. Furthermore, the minimal actual treatment differences that can be detected with a reasonable (80%) probability at a predetermined (5%) significance level using a crossover design were estimated for different electrophysiologic variables. These data will assist in the calculation of the necessary sample size for clinical trials and related purposes.

Adult↗
PubMed1991

Digoxin-verapamil interaction: reduction of biliary but not renal digoxin clearance in humans.

The interaction between digoxin and verapamil was studied in six patients (mean age +/- SD, 61 +/- 5 years) with chronic atrial fibrillation. The effects of adding verapamil (240 mg/day) on steady-state plasma concentrations and renal and biliary clearances of digoxin were studied in a crossover manner. The biliary clearance of digoxin was determined by a duodenal perfusion technique. Verapamil induced a 44% increase in steady-state plasma concentrations of digoxin, from 0.80 +/- 0.24 to 1.15 +/- 0.40 nmol/L (p less than 0.01). The biliary clearance of digoxin decreased by 43%, from 187 +/- 89 to 101 +/- 55 ml/min (p less than 0.05), in the presence of verapamil, whereas the renal clearance was unaffected (153 +/- 31 versus 173 +/- 51 ml/min; difference not significant). Our results indicate that the main inhibitory effect of verapamil on digoxin elimination is on the biliary route.

Bile↗
PubMed1987

Skeletal muscle binding and renal excretion of digoxin in man.

Ten healthy subjects were treated with three or four different doses of digoxin, 0.25 to 0.88 mg daily, in random order. Digoxin concentrations in serum (SDC) and skeletal muscle (SMDC) were determined as well as its renal clearance after 2 weeks of treatment with each dose. The mean ratio SMDC/SDC decreased non-significantly by about 20% from 33 +/- 15 at the lowest SDC interval (0.5-0.9 nmol/l) to 28 +/- 7 at the highest concentration interval (2.0-2.4 nmol/l). This is in accordance with findings from previous studies. No significant change was observed in the renal clearance of digoxin with increasing digoxin concentration, supporting the concept of first-order renal elimination of digoxin.

Adult↗
PubMed1987

Quinidine reduces biliary clearance of digoxin in man.

Quinidine is known to reduce the renal clearance of digoxin, but this effect does not completely explain the influence of quinidine on the total clearance of digoxin. We therefore studied the effect of quinidine administration on biliary clearance of digoxin in five patients with atrial fibrillation. Biliary clearance of digoxin under steady state conditions before and during treatment with quinidine was investigated using a duodenal-marker-perfusion technique. Quinidine caused an average 42% (range 21-65%, P less than 0.02) reduction of the measured biliary clearance of digoxin. We conclude that the biliary effect adds to the previously demonstrated inhibitory effect of quinidine on the renal clearance of digoxin and helps to explain the decrease in total clearance of the drug. This is the first demonstration in man of a pharmacokinetic drug interaction at the level of biliary excretion.

Aged↗
PubMed1985

Kinetics and dynamics of disopyramide and its dealkylated metabolite in healthy subjects.

The kinetics and dynamics of total and free (unbound) disopyramide (D) after dosing with D, 1.5 and 2 mg/kg iv, were compared with those of the dealkylated metabolite (MND) after dosing with MND, 0.5 and 1.5 mg/kg iv, in six healthy subjects. Dynamic parameters included ECG with measurement of the QT interval corrected for heart rate (QTc), systolic time intervals, vitamin C-stimulated saliva secretion, pupil size, and maximum accommodation capacity. Mean values of total clearance, apparent volume of distribution, and elimination t1/2 of MND were 5.9, 2.3, and 0.4 times those of total D, respectively. D significantly prolonged the QTc and systolic time intervals and induced transient inhibition of stimulated saliva secretion. In contrast, MND induced no substantial change in either the QTc or systolic time intervals, but did induce more persistent inhibition of salivary secretion. If anticholinergic potency is determined as the degree of inhibition of stimulated saliva flow per plasma concentration unit, MND was three times as potent as its parent when measured at maximum inhibition. There were no consistent drug effects on the ocular parameters. The effect of D on QTc correlated with both total and free plasma concentrations. Furthermore, its transient salivary inhibitory effect paralleled its initial rapid decline in plasma concentration. There was no relationship between the MND plasma concentration and its salivary inhibitory effect. We conclude that disopyramide significantly affected the QTc and systolic time intervals in healthy subjects, while MND in a similar dose had no such effects. MND more strongly inhibited stimulated saliva flow, indicating a more potent anticholinergic effect than D.

Adult↗
PubMed1984

Quinidine-induced changes in serum and skeletal muscle digoxin concentration; evidence of saturable binding of digoxin to skeletal muscle.

Eleven patients with atrial fibrillation on maintenance digoxin therapy were investigated by analysis of serum (SDC) and skeletal muscle (SMDC) digoxin concentrations before and 24 h and 2 weeks after starting quinidine treatment. After cardioversion the maintenance dose of digoxin was reduced in order to obtain the same steady-state SDC after 2 weeks, as before quinidine. SDC was increased by quinidine therapy from 1.56 to 2.40 nmol/l after 24 h. With the reduced digoxin dose SDC was 1.68 nmol/l after 2 weeks. The ratio SMDC/SDC decreased after 24 h of quinidine treatment from 35.4 to 29.0 (p less than 0.01). After 2 weeks of quinidine treatment with the reduced digoxin dose, the ratio had risen to 38.1, which did not differ significantly from the initial ratio. The present data suggest that the reduced skeletal muscle binding of digoxin during quinidine therapy is due to saturation of digoxin binding sites secondary to the increase in the total body load of digoxin at steady-state, and not to direct interference by quinidine with digoxin binding sites.

Aged↗
PubMed1983

Cardiac effects of treatment with quinidine and digoxin, alone and in combination.

Systolic time intervals (QS2-I and LVET-I) and echocardiographically determined ejection fraction and velocity of circumferential fiber shortening were recorded in 10 healthy volunteers as measures of inotropic effect during maintenance treatment with 4 consecutive drug regimens: (1) quinidine, 1,200 mg/day; (2) digoxin, average dose 0.31 mg/day; (3) the combination of (1) and (2); and (4) digoxin alone (average dose 0.65 mg/day) to provide the same steady-state serum concentration of digoxin as during the period with combination of digoxin and quinidine. The steady-state serum concentration of digoxin during the low-dose regimen increased from 0.72 +/- 0.15 (mean +/- standard deviation [SD]) to 1.63 +/- 0.28 nmol/liter when quinidine was added. With the high dose of digoxin alone, the serum digoxin level reached 1.68 +/- 0.50 nmol/liter. Skeletal muscle digoxin concentrations during these periods were 27.7 +/- 8.3, 48.7 +/- 16.2, and 51.6 +/- 23.6 nmol/kg of dry weight, respectively. The skeletal muscle to serum concentration ratio of digoxin decreased significantly during quinidine treatment. Systolic time intervals were significantly prolonged by quinidine alone and shortened by digoxin alone, the latter effect being dose-dependent. Subtracting the effect of quinidine itself, the induced increase in digoxin level caused a significant increase in inotropic effect. When these corrected values were compared with those attained during the period with the same steady-state digoxin concentration but in the absence of quinidine, no significant differences were found. Echocardiographically measured ejection fraction and velocity of circumferential fiber shortening showed trends for similar drug effects, as did the systolic time intervals. This study, performed under steady-state conditions, demonstrates that the quinidine-induced increase in steady-state serum digoxin concentration will, with due consideration to quinidine's own pharmacodynamic properties, be accompanied by increased cardiac effects. This indicates that quinidine is not interfering with active receptor sites in the heart for digoxin.

Adult↗
PubMed1982

Renal function and digoxin clearance during quinidine therapy.

To investigate further the handling of digoxin by the kidneys during quinidine therapy, clearances of digoxin, 51Cr-EDTA, PAH and endogenous creatinine were measured together with beta 2-microglobulin in the urine before and during quinidine therapy in 10 patients on maintenance digoxin therapy. Renal clearance of digoxin (corrected for 30% plasma binding) decreased on the average by 55% (137 +/- 73 to 73 +/- 25 ml/min, mean +/- SD). The steady state plasma concentration of digoxin increased more than twofold (1 . 0 +/- 0 . 34 to 2 . 5 +/- 0 . 79 nmol/L, mean +/- SD). The clearances of 51Cr-EDTA and PAH were not altered during quinidine therapy, indicating that neither glomerular filtration nor total renal blood flow changed when quinidine was added. The ratio of the renal clearance of unbound digoxin to that of the glomerular filtration rate was above one for all 10 patients before quinidine, indicating the involvement of tubular secretion in the renal elimination of digoxin. After the administration of quinidine this ratio decreased in all patients (from 1 . 51 +/- 0 . 30 to 0 . 83 +/- 0 . 38, mean +/- SD). Some patients had ratios well below one suggesting re-absorption of digoxin. Beta 2-microglobulin excretion was unchanged during treatment with quinidine. It is concluded that a significant portion of the renal elimination of digoxin in man results from tubular secretion and that this excretory mechanism is inhibited by quinidine.

Aged↗
PubMed1981

Pharmacokinetics of digoxin in patients subjected to the quinidine-digoxin interaction.

1 This study was designed to evaluate pharmacokinetically the digoxin-quinidine interaction in patients with atrial fibrillation. 2 Five patients on maintenance digoxin therapy were given [3H]-digoxin as a single i.v. dose before and during quinidine therapy and the elimination of [3H]-digoxin from plasma and excretion in urine were determined. 3 The mean steady state plasma concentration of digoxin increased from 0.7 to 1.3 nmol/l after quinidine administration. 4 The apparent volume of distribution of digoxin decreased on the average 38%. Renal clearance and the total body clearance of digoxin decreased 51 and 56% respectively (mean values). Also non renal clearance was reduced. The fraction of digoxin excreted unmetabolised in urine did not change during quinidine treatment. The mean elimination half life of digoxin increased from 49 to 72 h during quinidine. 5 In two patients the DC-shock did not cause a conversion to sinus rhythm. However, the quinidine induced changes in the pharmacokinetics of digoxin in these patients did not differ from the others. 6 Quinidine appears to decrease the amount of digoxin distributed to body tissue(s). In addition, the reduction of renal clearance of digoxin and the observed unchanged clearance of creatinine suggests an inhibition of the renal secretion of digoxin.

Adult↗