Disease relevance of Coramedan

• Use of cholestyramine resin in digitoxin toxicity [1].
• Development of myocardial hypertrophy was comparable in treated and untreated banded groups.These results demonstrate that a significant positive inotropic effect persists in both normal and nonfailing hypertrophied myocardium during chronic digitoxin administration [2].
• The neuroprotective potential of Na(+)/K(+)-ATPase is of particular interest because of its known "druggability"; indeed, Food and Drug Administration-approved, small-molecule compounds such as digitoxin and digoxin have been in clinical usage for congestive heart failure and arrhythmias for several decades [3].
• We therefore suggest that digitoxin, with its lengthy history of human use, deserves consideration as a candidate drug for suppressing IL-8-dependent lung inflammation in CF [4].
• Digitoxin mimics gene therapy with CFTR and suppresses hypersecretion of IL-8 from cystic fibrosis lung epithelial cells [4].

Psychiatry related information on Coramedan

• CONCLUSION: In contrast to digoxin, the effect of physical activity the serum concentration of digitoxin can be disregarded [5].
• A 65-year old woman with known history of reactive depression and failed suicide attempts ingested 7 mg digitoxin at 09.00 h [6].

High impact information on Coramedan

• Reversal of advanced digitoxin toxicity and modification of pharmacokinetics by specific antibodies and Fab fragments [7].
• The data suggest that the mechanism for this interaction is a reduction in elimination and not displacement of digitoxin from tissue binding sites [8].
• All other antiinflammatory effects of digitoxin on NF-kappaB and c-Jun N-terminal kinase pathways appear to follow from the blockade of this initial upstream signaling event [9].
• The Na,K-ATPase contains a binding site for cardiac glycosides, such as ouabain, digoxin, and digitoxin, which is highly conserved among species ranging from Drosophila to humans [10].
• Digitoxin also has effects on global gene expression in CF cells [4].

Chemical compound and disease context of Coramedan

• Induction of these liver microsomal enzymes decreases the toxicity of digitoxin by increasing its oxidative cleavage to digitoxigenin bis- and monodigitoxoside (dt2 and dt1) [11].
• The obligate anaerobe Eubacterium lentum inactivated the cardiac glycoside digitoxin by reducing the double bond in the lactone ring [12].
• Digitoxin therapy partially restores cardiac catecholamine and brain serotonin metabolism in congestive heart failure [13].
• 26 mongrel dogs were given a single dose of 0.03mg/kg tritium-labelled digoxin, beta-methyldigoxin, digitoxin or ouabain 2 hrs or 95 hrs following experimental coronary occlusion [14].
• The microbial transformation of digitoxin (I) by Streptomyces sp. yielded digoxin (III) as main product along with the by-products 7beta -hydroxydigitoxin (II) and 7beta -hydroxydigoxin (IV) [15].

Biological context of Coramedan

• The specific mechanism of digitoxin action is to block phosphorylation of the inhibitor of NF-kappa B (I kappa B alpha) [4].
• The bioavailability of digoxin is appreciably less than that of digitoxin, averaging about two-thirds to three-fourths of the equivalent dose given intravenously in the case of currently available tablet formulations [16].
• Plasma protein binding of digitoxin (PPB) was 95.0 +/- 1.1% in the patients and 96.7 +/- 0.6% in the healthy subjects (n.s [17].
• The differences in elimination kinetics of digitoxin and its metabolites of uremic patients and healthy subjects were not significant [18].
• The altered pattern of digitoxin metabolites is most consistent with uremia-induced changes in hydroxylation and hydrolysis [19].

Anatomical context of Coramedan

• The effect of chronic digitoxin administration on the contractile state of normal and nonfailing hypertrophied myocardium [2].
• We show here that digitoxin, at sub nM concentrations, can suppress hypersecretion of IL-8 from cultured CF lung epithelial cells [4].
• Digitoxin is nearly completely absorbed from the normal gastrointestinal tract and has a half-life averaging 5 to 6 days in patients receiving usual doses irrespective of renal function [16].
• However, dt2 formation was the major pathway of digitoxin metabolism catalyzed by human liver microsomes, although humans were much less active (approximately 2%) than rats in this regard [11].
• Chloroform extraction and thin-layer chromatography in plasma, urine and feces suggested no qualitative alteration in the metabolism of digitoxin [18].

Associations of Coramedan with other chemical compounds

• The kinetics of digitoxin and two of its metabolites, the bis- and monodigitoxosides of digitoxigenin, were determined in six normal subjects [20].
• Effect of heparin on digitoxin protein binding [21].
• In addition, the relative orders of potency of four cardiac glycosides in displacing [3H]ouabain from high affinity binding sites and inhibiting both 86Rb uptake and NE stimulation of NAT activity were the same (acetyldigitoxin greater than ouabain greater than digitoxin greater than strophanthidin) [22].
• Effects of quinidine on pharmacokinetics and pharmacodynamics of digitoxin achieving steady-state conditions [23].
• This fluoroimmunoassay for digitoxin in serum involves use of a sheep antiserum to digitoxin coupled to magnetizable solid-phase particles and fluorescein-labeled 3-O-succinyl digitoxigenin as tracer [24].

Gene context of Coramedan

• In vitro experiments were performed with cytosolic and microsomal fractions of human liver specimens in order to investigate which enzyme forms of sulfotransferase (ST) and UDP-glucurosyltransferase (GT) are involved in the metabolism of digitoxin (dt-3) and/or its cleavage products [25].
• Hydroxysteroid sulfotransferase and a specific UDP-glucuronosyltransferase are involved in the metabolism of digitoxin in man [25].
• In rats, cytochrome P450 (P450) IIIA enzymes are an important determinant of digitoxin toxicity [11].
• Based on this correlation, we correctly predicted that hamsters, which have the highest P450 IIIA activity, are extremely resistant to digitoxin toxicity [11].
• Species differences in the toxicity and cytochrome P450 IIIA-dependent metabolism of digitoxin [11].

Analytical, diagnostic and therapeutic context of Coramedan

• We interpret this result to suggest that digitoxin can also partially mimic the genomic consequences of gene therapy with CF transmembrane conductance regulator [4].
• Pharmacokinetics of digoxin and digitoxin in patients undergoing hemodialysis [26].
• Serum and urine digitoxin concentrations were determined by radioimmunoassay [27].
• To further examine the relationship between digitoxin toxicity and P450 IIIA activity, the pathways of digitoxin metabolism catalyzed by liver microsomes from nine mammalian species were examined by high performance liquid chromatography [11].
• Digitoxin in patients with hepatorenal insufficiency after repeated oral administration [17].

References