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Biomedical subjects

W Doering

Publications and source records attributed to W Doering.

At least 37 records · Page 2Linked to original sources
PubMed1983

Interaction between digoxin and calcium antagonists and antiarrhythmic drugs.

The influence of several calcium antagonists and antiarrhythmic drugs on digoxin kinetics and actions were investigated in 36 healthy men during digoxin steady state (0.375 mg/day). The subjects were randomly assigned to three subgroups and each group received placebo (control) and two of the following regimens (doses three times a day) in a randomized sequence for 2 wk each: verapamil (80 mg) and nifedipine (10 mg), verapamil (120 mg) and gallopamil (50 mg), or propafenone (150 mg) and quinidine (250 mg). Plasma digoxin concentration (PDC) rose during the cotreatments in the sequence: gallopamil (+16%) less than propafenone (+37%) less than nifedipine (+45%) less than verapamil (almost independent of dose, +69%) less than quinidine (+118%). These increases in PDC correlated closely to decreases in renal digoxin clearances. Renal creatinine clearance was virtually unaffected. The rise of PDC resulted in increased glycoside effects, as measured by the shortening of systolic time intervals and flattening of T wave. There was a linear correlation between PDC and changes in mean corrected electromechanical systole and T wave flattening. We conclude that, in addition to quinidine, other antiarrhythmic drugs and various calcium antagonists interact kinetically with digoxin and that the increasing PDCs are cardioactive.

Adult↗
PubMed1983

[Effect of tiaprofenic acid on serum digoxin concentration].

The effect of concomitant tiaprofenic acid (Surgam) administration (200 mg t.i.d.) on serum digoxin concentration (SDC) was evaluated in 12 healthy volunteers on digoxin maintenance treatment. During a 10-day coadministration period with tiaprofenic acid no significant increase in SDC was observed (0.97 +/- 0.24 vs. 1.12 +/- 0.21 ng/ml, p less than 0.05). Mean tiaprofenic acid concentration amounted to 2.85 +/- 1.94 micrograms/ml 14 h after last drug intake. The incidence of adverse reactions was minimal with gastrointestinal upset in one person. Tiaprofenic acid had no influence on red or white blood cell count. Thus, in contrast to various other nonsteroidal antiinflammatory drugs coadministration of tiaprofenic acid (600 mg daily) has no relevant influence on serum digoxin levels.

Adult↗
PubMed1983

The quinidine-digoxin interaction in patients with impaired renal function.

Quinidine has been reported to reduce clearance and the distribution volume of digoxin. Data are presented indicating that serum digoxin concentration (SDC) is increased throughout the coadministration of quinidine. This strongly suggests that the quinidine-induced reduction of digoxin clearance is the main mechanism underlying this drug interaction. It has been suggested that beside renal clearance quinidine also reduces non-renal clearance of digoxin. Direct evidence is provided by a study in patients with impaired renal function. Irrespective of the degree of renal impairment, quinidine increases SDC to about the same amount as found in patients with normal renal function. Since quinidine does not interfere with plasma protein binding of digoxin, this implies a decrease in non-renal clearance. In all patient groups the incidence of this drug interaction is rather high; however, pronounced interindividual differences occur as regards the extent of the increase in SDC. Regardless of the state of renal function careful monitoring of digitalized patients is mandatory once quinidine therapy is initiated. Since it may take a week or more until a new steady state is established in patients with impaired renal function, this period of close monitoring should be extended correspondingly.

Blood Proteins↗
PubMed1982

Quinidine-digoxin interaction: evidence for involvement of an extrarenal mechanism.

The influence of quinidine 750mg per day for one week on serum digoxin concentration (SDC) was evaluated in digitalized anuric patients on chronic haemodialysis. During quinidine administration the SDC increased markedly, from 0.84 +/- 0.37 to 1.58 +/- 0.72 ng/ml (p less than 0.01), a comparable effect ot that reported previously in patients with normal renal function. Neither in vitro nor in vivo did quinidine alter the serum protein binding of digoxin. The increase in SDC in anuric patients indicates a decrease in the extrarenal clearance of digoxin, which means that mechanisms other than of renal origin are also involved in the interaction of quinidine and digoxin. There was great interindividual variability in the extent of the quinidine-induced rise in SDC. Regardless of the state of renal function, careful monitoring of digitalized patients seems mandatory once quinidine treatment is initiated.

Anuria↗
PubMed1982

Quinidine-digoxin interaction: cardiac efficacy of elevated serum digoxin concentration.

Cardioactivity due to elevated serum digoxin concentration (SDC) after quinidine (Q) and digoxin (D) was evaluated in six healthy subjects by means of measurement of systolic time intervals (STIs). Each subject randomly received basic treatments with 0.2 mg D and placebo (PL1). Randomized coadministrations with Q (1 gm/day), sparteine (SP) (0.8 gm/day), and placebo (PL2) were given for 7-day periods. A steady-state dose of 0.4 mg D was added. Mean SDC increased from 0.48 ng/ml during 0.2 mg D + PL2 to 1.13 ng/ml on 0.2 mg D + Q (P less than 0.05); it was unchanged by SP. On 0.4 mg D there were further shortenings of STIs compared to those on 0.2 mg D + PL2. Q markedly prolonged STIs; the SP effects were similar but less pronounced. When given with Q or SP, the effect of D was obscured by opposing inotropic properties; consequently, despite increasing SDC, measureable STIs were unchanged. The true glycoside effect was determined by comparing the effects of the pure antiarrhythmic to those of the antiarrhythmic with D. These calculations showed that the glycoside effect of the elevated SDC during Q + D dosing was much the same as the effect of 0.4 mg D.

Adult↗
PubMed1982

Effects of i.v. prenalterol in patients with severe cardiac failure at rest and during exercise.

Prenalterol administration (150 micrograms/kg i.v.) exerted beneficial effects on resting and/or exercise cardiac performance in patients with congestive cardiomyopathy (n = 12) and 1 patient with hypertensive heart disease (= group I, n = 13), while the haemodynamic response in patients with severe coronary heart disease (n=3) or cor pulmonale (n = 1) was non-uniform. At rest mean right and left ventricular filling pressures decreased by 26 and 19% (p less than 0.02 and p less than 0.02), respectively, while stroke volume increased by 8% (p less than 0.05), cardiac index by 25% (p less than 0.01) and heart rate by 15% (p less than 0.005) 5 min after prenalterol administration in group I. During exercise there was no further increase in heart rate, while filling pressures decreased and cardiac index increased significantly compared to control exercise. This typical inotropic response to prenalterol was observed in fully digitalised patients. Maximal effects occurred about 15 min after i.v. administration.

Adrenergic beta-Agonists↗
PubMed1981

[Quinidine-digoxin interaction (author's transl)].

An additional dose of 500 mg of rapidly absorbed quinidine increased the digoxin concentration in serum after 3-5 hours by up to 46% and prolonged digoxin half life from 50 to 100 hours in six probands who were on chronic quinidine-digoxin medication. These effects were not elicited regularly in persons pretreated with digoxin only. The results show that quinidine both diminishes elimination and produces transient redistribution of digoxin. Chronic quinidine medication leads to protracted digoxin elimination resulting in marked prolongation of digoxin half life. This is the reason for persisting increase of digoxin concentration in serum. Estimation of serum digoxin levels should thus be done 8 hours after the last quinidine (and digoxin) medication at the earliest. On cessation of digoxin, as is done preparing for electric cardioversion, one should remember that digoxin elimination is clearly prolonged should quinidine treatment be continued.

Digoxin↗
PubMed1981

Quinidine-digoxin interaction: effect of quinidine on 86Rb-uptake of human erythrocytes.

Co-administration of quinidine results in a marked increase in serum digoxin concentration (SDC). The implication of this increase in SDC in regard to an increased digoxin effect on the heart is controversial. The 86Rb-erythrocyte-assay represents a perfect model to study whether quinidine interferes with digoxin at the Na-K-ATPase (the so called glycoside receptor) and thus presumably with the inotropic effect of the glycoside. The inhibitory effect of digoxin (0-150 ng/ml) on the 86Rb-uptake was measured in the absence and presence of quinidine in therapeutic or higher concentrations (0-60 microgram/ml). Addition of quinidine produced no effect on digoxin-induced inhibition of Na-K-ATPase activity. Together with our clinical observations these results strongly suggest that the increased SDC during concomitant quinidine therapy actually reflects an increased digoxin effect on the heart.

Digoxin↗
PubMed1979

Quinidine-digoxin interaction: Pharmacokinetics, underlying mechanism and clinical implications.

Administration of quinidine with digoxin increased serum digoxin concentrations in 79 patients and five volunteers. In 38 patients on a constant glycoside maintenance dose, the addition of quinidine to digoxin therapy resulted in a mean 2.5-fold increase (from 0.98 +/- 0.37 to 2.47 +/- 0.71 ng per milliliter, mean +/- 1 S.D.) (P less than 0.001). The addition of quinidine decreased renal glycoside clearance (from 91.6 +/- 27.8 to 40.6 +/- 15.8 ml per minute) (P less than 0.001). Unlike other investigations, our studies provided no evidence that quinidine displaced digoxin at specific cardiac binding sites. The elevated digoxin levels found during quinidine administration suggest a 30 to 50 per cent reduction of the digoxin dose. Adverse reactions to combined quinidine-digoxin therapy may be partly due to digitalis intoxication.

Adult↗
PubMed1978

[A questionnaire for early recognition of digitalis intoxication (author's transl)].

The diagnostically relevant data of 1164 patients under digitalis were stored in a computer and compared statistically for toxic and nontoxic patients. Resulting from this a questionnaire was developed in which each item was weighted according to its own diagnostic value. In a prospective study 77 suspected cases of digitalis intoxication were classified according to their scoring in the questionnaire. In 92% of the patients this classification was confirmed by the final diagnosis (after withdrawal of the glycoside). Mean score and mean serum digoxin concentration (SDC) of the toxic patients were significantly higher. There was a high consensus between the final diagnosis, the classification by the questionnaire and the SDC. The questionnaire proved to be a useful aid in the bedside diagnosis of digitalis intoxication.

Arrhythmias, Cardiac↗
PubMed1978

[The influence of quinidine on serum digoxin concentrations (author's transl)].

We were able to demonstrate a significant rise of serum digoxin concentrations (SDC) under simultaneous quinidine-glycoside therapy. The reason for this elevation is not yet known. In vitro studies under addition of quinidine showed no influence on the SDC-values measured by a tritium-labelled radioimmunoassay. The mean SDC of 18 patients under simultaneous quinidine therapy was 2.39 +/- 0.84 ng/ml (3.06 +/- 1.08 nmol/l) compared to a mean SDC of 1.23 +/- 0.74 ng/ml (1.57 +/- 0.95 nmol/l) of 11 patients without quinidine therapy (p less than 0.001). Both groups of patients received the same maintenance dose and showed no obvious impairment of renal function and no significant difference in mean body weight. Our results suggest that part of the great number of adverse reactions seen under a combined glycoside-quinidine therapy might be due to the elevated SDC-values. For these patients a low-normal glycoside maintenance dose and an early reduction of the quinidine dose is recommended.

Digoxin↗
PubMed1978

[A simplified radioimmunoassay for digoxin determination using a 125-j-labelled, solid-phase kit (author's transl)].

Our experience with a commercially available kit (Radioimmunoassay DIGOXIN, Boehringer, Mannheim) using (125J)-labelled digoxin and antibody-coated tubes is reported. This simplified method requires only two pepetting steps per sample and results can be obtained in 70 min. The intra- and interassay coefficient of variation ranged between 7% and 8%. The specific digoxin antibody gave no clinical relevant cross-reactions with spironolactone or prednisone (less than 0.0007%). Of the digoxin metabolites the aglucone digoxigenin showed 31% cross-reaction while the more important cardioactive metabolites digoxigenin-bis- and mono-digitoxide had the same binding affinity to the antibody as digoxin, beta-methyldigoxin and beta-acetyldigoxin. Cross-reaction with digitoxin was 6.8%. More than double-fold dilution of serum protein concentration showed little influence on the digoxin values measured. The results obtained by this new kit compare closely with those obtained by our tritium-labelled kit (r = 0.94, p less than 0.001). Therefore, the upper therapeutic limit of 1.9 ng/ml can be adopted for this method.

Antibodies↗