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PubMed1984

[Trial for digitalis withdrawal in hemodialysis patients].

The indication for digitalis treatment was investigated in a controlled and prospective study lasting 12 months in 110 patients on long-term haemodialysis. In ten patients, digitalis was needed because of tachyarrhythmia due to atrial fibrillation and in five because of recurrent pulmonary edema. In 57 patients receiving digitoxin, therapy was discontinued for 4 to 6 weeks, whereas 13 patients not yet treated with digitalis, received digitoxin for 4 weeks. Without digitoxin, trial fibrillation occurred in 4 patients, while no patient experienced atrial fibrillation with digitoxin (P = 0.002). In 13 patients, radiological findings (heart enlargement, pulmonary congestion) were better with digitoxin than without. Thus digitoxin appeared to be clearly indicated in 29% of the haemodialysed patients. Additionally, digitalis was indicated in 31 patients because of heart enlargement, pulmonary congestion and (or) previous pulmonary edema. Initially, 76% of the patients were receiving digitoxin, whereas, after the investigation, the rate was only 57% (P less than 0.001). The prospective frequency of clinically apparent digitoxin intoxication was low (3%) and so were the overall toxic plasma digitoxin levels (5%). Digitalis should be given deliberately but not restrictively to haemodialysis patients, since atrial fibrillation (13%) and heart failure (50%) are frequent and often concealed.

Adult↗
PubMed1995

Immunoreactivity of endogenous digitalis-like substances in cord blood sera studied with antidigitoxin monoclonal antibodies.

The presence of digitoxin-like immunoreactive substances, whose nature is yet unknown, has been demonstrated in the umbilical cord blood. We selected six antidigitoxin monoclonal antibodies (MAb) having different specificity profiles concerning digitoxin analogs and steroid hormones. These antibodies were tested in a digitoxin radioimmunoassay (RIA). With the help of this technique, we measured the concentrations of apparent digitoxin in the cord blood drawn either at birth or in utero from mothers not undergoing any digitalis treatment. In the cord blood of newborns, the concentrations of apparent digitoxin, measured by the two MAbs that have the highest cross-reactions with dehydroepiandrosterone (DHEA) (123A23 and 145A41), were two or three times higher than with the other antibodies. In the fetal cord blood, where the concentration of DHEA is five to seven times lower than that observed at birth, these antibodies revealed a threefold lower concentration of apparent digitoxin than that observed in blood drawn at birth. Furthermore, MAbs that had similar specificities towards digitoxin analogs and steroids showed different measurements of digitoxin-like concentrations. These observations suggest that digitoxin-like immunoreactive compounds detected by the RIA may constitute a group of different molecules, one of which would be the DHEA.

Antibodies, Monoclonal↗
PubMed1997

Digitoxinlike and digoxinlike immunoreactivitis in sera of patients with uremia and liver disease as measured by fluorescence polarization immunoassays: poor correlation between digitoxinlike and digoxinlike immunoreactivities.

Digoxinlike immunoreactive substances (DLIS) cross-react with antidigoxin antibodies and falsely elevante total digoxin levels. Cross-reactivity of DLIS with various immunoassays for digoxin has been extensively studied in the past. The digitoxin molecule differs from digoxin by having one extra hydroxyl group in the aglycone ring. Therefore, DLIS may also falsely elevate total digitoxin concentrations. However, in the past, limited studies have shown the presence of digitoxinlike immunoreactive substances (DTLIS) in cord blood and sera of neonates. We compared DLIS and DTLIS concentrations in sera of patients with uremia, liver disease, and hypoalbuminemia. We found measurable DLIS concentrations in 11 of 45 patients by the fluorescence polarization immunoassay (FPIA) for digoxin (range, 0.20-0.89 ng/ml digoxin equivalent). These patients did not receive any digoxin or digitoxin. Using the FPIA, we also found elevated DTLIS concentrations in 10 of these 45 patients (range, 2.88-21.24 ng/ml digitoxin equivalent). Given the narrow therapeutic range of digitoxin (15-30 ng/ml), this cross-reactivity is significant. Elevated concentrations of DTLIS in sera falsely elevated the measured concentrations of digitoxin (positive interference) when known amounts of digitoxin were added to such sera. Interestingly, we found a poor correlation between DLIS and DTLIS concentrations in sera of patients with liver disease and uremia (r = 0.58), with some patients having no measurable DLIS activity but measurable DTLIS activity and vice versa. Digoxin showed only 4-8% cross-reactivity against digitoxin antibody with a wide range of concentration. Some proposed DLIS compounds (nonesterified fatty acids, cholic acid, lysophospholipid, and DHEA-sulfate) did not show any cross-reactivity with the digitoxin assay at a concentrations much higher than the physiologic range. We conclude that DTLIS activity is present in patients with liver disease and uremia, and the correlation between DLIS activity and DTLIS activity is poor. Moreover, some proposed DLIS do not explain the DTLIS activity detected in serum.

Digitoxin↗
PubMedDate not supplied

Current status of cardiac glycoside drug interactions.

The effects of concomitant drug therapy on the absorption, distribution, and elimination of digoxin and digitoxin are reviewed. A number of agents can increase or decrease the absorption of digoxin and digitoxin from the gastrointestinal tract by altering GI motility, binding the drugs through physical adsorption, altering the properties of the intestinal wall, or altering the bacterial flora of the intestine. The steady-state serum concentrations of digoxin and digitoxin can be affected if the changes in absorption are of sufficient magnitude, and adjustments in digoxin or digitoxin dosage may be required. A reduction in digoxin and digitoxin protein binding has occurred during concomitant administration of heparin and cardiac glycosides. Since digitoxin is more highly protein bound than digoxin, interactions that involve changes in protein binding are of much greater clinical importance with digitoxin. A number of drugs increase or decrease the elimination of digoxin and digitoxin, and subtherapeutic or toxic concentrations of the cardiac glycosides often result. Drugs that induce hepatic microsomal enzymes can increase the elimination of digitoxin, which is eliminated mainly by hepatic biotransformation. Digoxin is eliminated mainly by renal excretion; renal clearance of digoxin may be increased by vasodilators and thyroid hormones and decreased by quinidine, verapamil, amiodarone, and potassium-sparing diuretics. The clinical importance of changes in serum concentrations of the cardiac glycosides that result from alterations in glycoside elimination requires further study, as does the importance of preliminary reports of interactions between cardiac glycosides and diazepam, captopril, and combination therapy with quinidine-pentobarbital or quinidine-rifampin. Because the cardiac glycosides have a narrow therapeutic range, patients receiving concomitant therapy with agents that might affect the absorption, distribution, or elimination of the cardiac glycosides should be monitored carefully for symptoms of digitalis toxicity or undertreatment.

Anti-Arrhythmia Agents↗