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PubMed1978

Potassium-related cardiac arrhythmias and their treatment.

Severe abnormalities of potassium balance constitute medical emergencies. Symptoms of hypokalemia are vague between 3.5 and 3.0 mEq/liter. Clinical problems can occur with the plasma potassium value lower than 2.7 mEq/liter. Hypokalemia and digitalis glycosides share electrophysiologic actions. Hypokalemia is both synergistic and potentiating for digitalis. In the presence of a normal amount of digitalis, toxicity may be prompted by coexisting hypokalemia. Hyperkalemia does not threaten life until plasma potassium values are greater than 7.0 mEq/liter. The immediate suspicion and recognition of hypokalemia or hyperkalemia in various clinical situations is imperative. Once suspected, confirmation of the diagnosis should follow immediately. Probably the single most useful diagnostic aid is the electrocardiogram, especially in critical situations with hyperkalemia. Prompt intravenous infusion of a calcium preparation, sodium bicarbonate, glucose, and insulin will provide rapid relief from serious hyperkalemia. The appropriate administration of these readily available drugs may obviate an otherwise critical situation.

Arrhythmias, Cardiac↗
PubMed1992

Digitalis and neurohormonal abnormalities in heart failure and implications for therapy.

A pathophysiologic hallmark of heart failure is neurohormonal excitation, a prominent feature of which is activation of the sympathetic nervous system. Studies from our laboratories demonstrate that clinical heart failure is characterized by marked increases in efferent sympathetic neural outflow to muscle; the magnitude of this sympatho-excitation parallels the degree of cardiac dysfunction. Impairments of cardiopulmonary and arterial baroreflex sensory mechanisms appear to be responsible to a significant degree for this sympatho-excitation, consistent with findings in animal models of heart failure. Digitalis glycosides exert modest inotropic actions when administered to patients with heart failure. Digitalis also has potent autonomic effects that can potentiate impaired arterial and cardiopulmonary baroreflex mechanisms in experimental models of cardiac dysfunction. Acute digitalis administration to patients with moderate-to-severe heart failure produces profound and sustained sympatho-inhibition, which precedes any observed hemodynamic action of the agent. Further, acute digitalization of such patients rapidly normalizes impaired baroreflex-mediated mechanisms. Data now suggest that the mechanism of action of digitalis in humans is an acute potentiation of baroreceptor-mediated afferent regulation of sympathetic neural mechanisms. Prospective, randomized and controlled studies now are required to test the hypothesis that the acute effects of digitalis on autonomic mechanisms also are observed during chronic administration. In theory, the chronic sympatho-inhibitory action of digitalis, combined with its chronic potentiation of impaired baroreflex mechanisms, may offer beneficial effects independent of its inotropic actions in patients with heart failure.

Digitalis Glycosides↗
PubMed1975

Interaction of heart glycosides and phenobarbital.

One week's administration of phenobarbital does not affect the disappearance of a single dose of digitalis glycosides from the serum of man. The increase of bile flow and of liver weight produced by phenobarbital in the rat is not further enhanced by glycosides. In case of acute digitalization, the enzyme inducing effect of barbiturates has probably no clinical significance.

Adolescent↗
PubMed1977

[Changes in the end part of the ECG ventricular complex under the effect of digitalis preparations and their combination with metabolic preparations].

Analysis of the dynamics of changes in the end part of the ECG ventricular complex in 311 patients with rheumatic heart disease and stages IIA, IIB, and III circulatory insufficiency after treatment with preparations of digitalis and their combination with biologically active substances (orotic acid, vitamin B12, calcium pantothenate, ATP, methionine, inosi-F) is presented. When digitalis glycosides are used with preparations that have an effect on the nucleic acid synthesis and energy production, the "digitalis--induced" changes in the end part of the ECG ventricular complex are less marked while the clinical effect of treatment is more appreciable

Adenosine Triphosphate↗
PubMed1997

Ouabain-sensitive Na+,K(+)-ATPase activity in toad brain.

Toads of the genus Bufo are highly resistant to the toxic effects of digitalis glycosides, and the Na+,K(+)-ATPase of all toad tissues studied to date has been relatively insensitive to inhibition by digitalis and related compounds. In studies of brain microsomal preparations from two toad species, Bufo marinus and Bufo viridis, inhibition of ATPase activity and displacement of [3H]ouabain from Na+,K(+)-ATPase occurred over broad ranges of ouabain or bufalin concentrations, consistent with the possibility that more than one Na+,K(+)-ATPase isoform may be present in toad brain. The data could be fitted to one- or two-site models, both of which were consistent with the presence of Na+,K(+)-ATPase activity with high sensitivity to ouabain and bufalin. Ki (concentration capable of producing 50% inhibition of activity) values for ouabain in the one-site model were in the 0.2 to 3.7 microM range, whereas Ki1 values in the two-site model ranged from 0.085 to 0.85 microM, indicating that brain ATPase was at least three orders of magnitude more sensitive to ouabain than B. marinus bladder ATPase (Ki = 5940 microM). Ouabain was also an effective inhibitor of 86Rb+ uptake in B. marinus brain tissue slices (Ki = 3.1 microM in the one-site model; Ki1 = 0.03 microM in the two-site model). However, the relative contribution of the high ouabain-sensitivity site to the total activity was 17% in the transport assay as compared with 63% in the Na+,K(+)-ATPase enzymatic assay. We conclude that a highly ouabain-sensitive Na+,K(+)-ATPase activity is present and functional in toad brain but that its function may be partially inhibited in vivo.

Animals↗
PubMed1985

[Digitalis therapy: prescription frequency, serum concentrations and withdrawal trials].

The frequency of therapy with digitalis glycosides was determined in 4.143 patients on their first visit at a medical outpatient clinic. 508 (12.3%) patients said to take digitalis. Of 480 (94.5%) patients, a digoxin serum concentration was obtained. It was in 229 (47.7%) patients below, in 31 (6.5%) above, and in 220 (45.8%) within the therapeutic range (0.8-2.0 ng/ml). From the 251 patients with a serum digoxin concentration greater than or equal to 0.8 ng/ml, 220 (87.7%) were not included in a withdrawal trial on the basis of predetermined criteria, mainly because of cardiac diseases (52%). Digitalis therapy was withdrawn in 31 patients. 5 patients started to take the drug again on their own; they were considered drop-outs. In the remaining 26 patients, no symptoms of heart failure appeared during a 3-month observation period; in 2 patients, however, atrial fibrillation requiring intervention occurred. Our results confirm the frequent use of digitalis therapy in Germany, but also the frequent presence of subtherapeutic serum digoxin concentrations. Withdrawal should be considered in patients with a questionable indication for this therapy; the occasional occurrence of supraventricular arrhythmias, and not so much of heart failure, should be anticipated.

Aged↗