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PubMed1990

[Cardioactive contaminants and actual active ingredient content of various digitalis preparations].

To establish possible cardioactive impurities which have not been totally separated while isolating the compound from plant material several preparations containing digoxin (NOVODIGAL = beta-acetyldigoxin, LANITOP = beta-methyldigoxin and LANICOR = digoxin) were analyzed by HPLC-chromatography after careful extraction. Impurities were found (digoxigenin, digoxigenin-monodigitoxosid, digoxigenin-bisdigitoxosid) which on the one hand occur as natural lanatosid-derivates in digitalis leaves but on the other hand also are described as possible metabolites of digoxin in human organism. The experiments have shown that the results of studies in metabolization of digoxin without knowledge of purity of the substance applied have to be interpreted with care.

Digitalis Glycosides↗

PubMed1989

[Utilization of cardiac glycosides in Czechoslovakia--does it correspond to need?].

The data are given on the consumption of cardiac glycosides (CD) in the CSSR over the past 18 years (1970-1987). Consumption expressed in terms of defined daily doses (DDD) permitted to construct time series of the consumption of this group of pharmacotherapeutic agents as a whole as well as individual CG and to compare the data thus obtained with similar data from abroad. The results indicate that the consumption of CG as a whole culminated in Czechoslovakia in 1983 (27.6 DDD per a population of 1000 per day = 27.6 DDD/1000/d) and that there has been a slow decline ever since. Compared with foreign data, Czechoslovakia's quantitative consumption of CG is roughly between countries noted for traditionally high consumption (GDR 84.8 DDD/1000/d) and those with low consumption (Scandinavian countries with the exception of Sweden, about 10 DDD/1000/d). Unlike Czechoslovakia, however, all other countries with well established CG consumption have been exhibiting a relatively steep and lasting decline in CG consumption since the late 1970s. This reduction reflects modern trends of CG pharmacotherapy, especially stricted consideration of the uses as distinct from the risks of CG administration, as well as some of the recent efforts to terminate long-term CG treatment particularly in vaguely indicated cases. As for individual CG consumption, Czechoslovakia, similarly as other countries, has been favouring more rational prescription of oral digoxin at the expense of the oral form of lanatoside C, while parenteral digoxin has for all practical purposes become a substitute for strophantin.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Glycosides↗

PubMed1987

Electrophysiological mechanisms for the initiation and maintenance of ventricular fibrillation in nonischemic rabbit hearts.

Two series of experiments were carried out using isolated, perfused rabbit hearts to elucidate the mechanisms of initiation and maintenance of ventricular fibrillation in the absence of ischemia. In the first series, either single premature or rapid electrical stimulation induced ventricular fibrillation, during which the spread of excitation was studied by recording electrograms from the endocardial and epicardial surfaces of both ventricles. Left ventricular endocardial stimulation appeared to induce fibrillation most easily. Initiation of ventricular fibrillation was preceded by the spread of areas showing a conduction delay. In certain instances, excitation of the endocardial and subendocardial tissue was necessary for the maintenance of repetitive responses. Injury to the endocardial and subendocardial layers of a ventricle (or both ventricles) by formaldehyde perfusion made the initiation of fibrillation more difficult, although complete prevention of fibrillation required extensive injury with a significant reduction in the excitable myocardial mass. In the second series of experiments, sustained ventricular fibrillation was produced by rapid electrical stimulation and the effects of several antiarrhythmic agents or electrolytes were studied by recording transmembrane action potentials of subepicardial ventricular muscle fibers with microelectrodes. Quinidine, lidocaine, and high K+ concentration significantly decreased the frequency of cellular depolarization and terminated fibrillation in all the 14 hearts studied. These agents suppressed local responses and small action potentials, and made the action potentials more uniform. In 5 of the 14 hearts in these three groups, termination of fibrillation was followed by either transient or prolonged periods of regular ventricular tachycardia. High Mg2+ concentration and bretylium tosylate tended to hyperpolarize the cell membrane, but less markedly decreased the frequency of cellular discharge. Defibrillation was achieved in only two of the ten hearts in which these two interventions were tested. Lanatoside C shortened the action potential duration, sometimes increased the frequency of cellular depolarization, and tended to sustain fibrillatory movements. These observations suggest the role of numerous microreentry movements in both the initiation and maintenance of ventricular fibrillation, although unifocal, ectopic impulse formation may not be definitely ruled out as an initiating mechanism. The possible defibrillating effect of certain antiarrhythmic agents is suggested.

Animals↗

PubMedDate not supplied

[Sensitization to digoxin with demostration of reagini antibodies].

The author presents the case of a male patient, 60 years old, suffering a chronic obstructive bronchopneumopathy with cor pulmonale in a state of cardiorespiratory insuffiency. Without any personal or familial history of allergy, a few minutes after the ingestion of .5mg of Digoxin a picture occurs of urticaria, angioneurotic edema and asthmatic crisis that disappears with sympatheticomimetics. No other medication was used, previously or at the time. The existence of reaginic antibodies is made evident with positive reactions to Digoxin and C Lanatosid in a Leftwich passive transference test and cutaneous tests. No alteration was found in the number of platelets and leucocytes nor in the percentage of eosinophils within 24 hours after the anaphylactic accident. The oral provocation test with the excipient of the commercial preparation was negative; the tolerance to Methyl-Digoxin complete. The literature referring to sensitization to digitalis glycosides is reviewed and some consideration is given to its mechanism.

Antibodies↗

PubMed1983

[Electrocardiographic changes in the rat induced by digitalis glucosides].

Electrocardiographic changes induced by desacetil-lanatoside C and digitoxin, administered intravenously, have been studied in 25 anesthetized rats. No differences were observed between the actions of the two glucosides. Their negative chronotropic action can be effected with two mechanisms: one indirect, through vagal reflex, therefore immediate and, in general, brief; one direct, for direct action on the heart, which is gradual and long lasting. Their action on the a-v conduction is recorded by a rise in the duration of the P-Q tract, or, for higher doses, by blocking fenomena, which are brief and completely reversible. Signs of subendocardial damage are often observed, these too brief. The appearance of extrasystoles is rare.

Animals↗

PubMed1983

[Electrocardiographic changes in the rat induced by high doses of the coenzymatic forms of several vitamins of the B group].

No modification, neither immediate nor late, was observed after the intravenous injection of high doses of the coenzymatic forms of thiamine and pyridoxine. On the contrary, after the injection of high doses of the coenzyme A, a sudden, conspicuous and brief (20-25") diminution of heart rate was observed. Such a phenomenon was much more marked and longer if, before the coenzyme A, a digitalic compound (desacetil-lanatoside C or digitoxin) was administered.

Animals↗

PubMed1981

Synthesis and biological activity of digitoxigenin aminoesters.

A series of 3 beta-esters of digitoxigenin (3 beta-hydroxy-14 beta-hydroxy-5 beta-card-20(22)-enolide) with alpha-aminoacids, were synthesized and tested for inotropic activity on the guinea-pig isolated heart and by slow infusion in the cat in comparison with digitoxigenin, Lanatoside C and Strophantin K. Esterification of the 3 beta-hydroxy group of digitoxigenin with various amino acids led to compounds still retaining inotropic activity with low in vivo potency and short duration of action. The compounds are inactive when administered orally.

Animals↗

PubMed1980

[The treatment of digitalis poisoning with antibiotics (author's transl)].

Digitalis intoxication occurs frequently and proves fatal in 5-10% of all cases. Treatment is limited to symptomatic measures. Glycoside-specific antibodies offer a new way of treatment of digitalis intoxication. In our experiments with cats, they were found to be highly effective in reversing digoxin-induced arrhythmias. Specific antibodies have previously been employed in a patient with suicidal digoxin intoxication. We report a case of nonsuicidal Lanatosid-C intoxication treated with F(ab')2-fragments of digoxin-specific antibodies from the sheep. The treatment was successful and without side-effects. Serum concentration of free digoxin and total digoxin measured during and after treatment showed a decrease of free and a sharp raise in total digoxin. For clinical use, antibody fragments are superior to intact antibodies. Problems and possible indications concerning the treatment of digitalis intoxication with antibodies are briefly discussed.

Animals↗

PubMed1995

[When, why, and how to treat atrial fibrillation].

Treatment of atrial fibrillation aims to convert it to sinus rhythm and maintain this rhythm after conversion, to reduce ventricular frequency when fibrillation is not converted and to prevent systemic embolies. Conversion to sinus rhythm is achieved with electrical cardioversion or with intravenous antiarrhythmic drugs (Lanatoside C, amiodarone or beta blockers). The most useful drugs to maintain sinus rhythm are amiodarone, quinidine alone or associated to verapamil, sotalol and propafenone. The best drug used to control cardiac frequency in a rapid atrial fibrillation is digitalis. However, when there is a decrease in vagal tone and an increase in sympathetic activity, digitalis losses its effectiveness and a betablocker or a calcium blocker must be added. Electrical cardioversion is the treatment of choice for atrial fibrillation of Wolff Parkinson White syndrome. When there is a rapid, symptomatic and uncontrollable atrial fibrillation, electrical ablation of atrio-ventricular junction and the implantation of a definitive pacemaker is the treatment of choice. Lately, a new procedure has been devised, called of the labyrinth, that can re-establish sinus rhythm, atrial contraction and atrio ventricular conduction. The embolic risk of atrial fibrillation depends on its etiology and the decision to anticoagulate must balance the risks and benefits of this treatment.

Adult↗

PubMed1993

[Determination of cardenolides in Digitalis lanata by a solid-phase immunoenzyme method].

A competitive solid-phase EIA technique using high-affinity digoxin-specific monoclonal antibodies has been developed to determine cardenolides in Digitalis lanata. The test-system can detect digoxin and closely related compounds in concentration of 0.1 nmol/ml. The content of cardenolides, tested by ELISA, correlated well with the total content of digoxin, deslanoside C and lanatoside C as analysed by HPLC. The test-system is useful in estimating the productivity of large series and samples of tissue clones of Digitalis lanata.

Antibodies, Monoclonal↗

PubMed1964