PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “DIGITALIS GLYCOSIDES”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 559 records · Page 31Linked to original sources
PubMed1991

Inotropic agents. Catecholamines, digoxin, amrinone.

Three broad categories of pharmacologic support that enhance myocardial contractility and modify organ blood flow are reviewed. Appropriate selection among these compounds will minimize the occurrence of adverse effects. The catecholamines increase cardiac work and myocardial oxygen demand. In the setting of a failing ventricle, the increase in oxygen requirement may be balanced by improved coronary blood flow. Problems associated with catecholamines include tachycardia, induction of dysrhythmias, and unsuitable vasoconstriction. Epinephrine and isoproterenol are most likely to increase heart rate excessively. Norepinephrine is most likely to be associated with poor tissue perfusion. Amrinone, a bipyridine, has a favorable effect on oxygen balance in the failing ventricle and is unlikely to produce tachycardia or dysrhythmias. Principal concerns are the potential for accumulation in the patient with multiple organ system failure and the lack of pharmacokinetic information in critically ill patients, including children. Thrombocytopenia may be a problem as well. Digitalis glycosides are venerable drugs. Acute and chronic toxicity are problems that the intensivist is called on to treat frequently. Therapy with digitalis Fab fragments is now routine for severe intoxications and should improve outcome.

Amrinone↗
PubMedDate not supplied

The fundamental mechanism of inotropic action of digitalis.

Evidence from several sources, including electrophysiologic studies and cation flux and content measurements, now allows a reasonably cohesive synthesis of the molecular and cellular events that lead from inhibition of the Na pump by digitalis to the enhancement of the generation of contractile force by cardiac muscle. It is generally agreed that Na pump inhibition, with consequent elevation in [Na+]i and [Ca2+]i, underlies both the therapeutic (positive inotropic) and toxic (arrhythmic) responses of the heart, and accounts for the well-known difficulty in separating therapeutic and toxic clinical effects of digitalis glycosides. In the intact patient or experimental animal, cardiac glycosides also exert effects that are mediated through neural pathways, and these can exert important influences on the integrated response to digitalis administration.

Calcium Channels↗
PubMed1976

[Investigations on the Stability of Proscillaridine, Proscillaridine-3'-methylether and Proscillaridine-4'-methylether in Artificial Gastric and Intestinal Fluids (author's transl)].

The stability of bufadienolides in artificial gastric and intestinal fluids was investigated at different pH-values as a function of incubation time using proscillaridine, proscillaridine-3'-methylether and proscillaridine-4'-methylether. These glycosides were completely stable on pH 3.0--8.5 during the investigated time interval of 1 h. At lower pH-values cleavage of the glycosidic bond occurred. At pH 1.0 73% of proscillaridine, 33% of proscillaridine-3'-methylether and 41% of proscillaridine-4'-methylether were decomposed. At pH 2.0 only about 10% decomposition of these compounds could be detected. These experiments show that the stability of proscillaridine in gastric juice is comparable with the stability of digitalis glycosides and digoxin derivatives. The stability of methylated proscillaridine derivatives in artificial digestion fluids, however, proved to be superior to any orally administered cardiac glycoside.

Administration, Oral↗
PubMed1984

[Physiopathology and clinical aspects of myocardial insufficiency].

Myocardial failure is caused by cardiac lesions (specific heart muscle diseases, heart valve disease etc.) and by extracardiac disease (arterial hypertension, endocrinopathies etc.). For the quantification of cardiac function, the relationship between cardiac size or systolic wall stress respectively and ventricular function is important. For diagnostics except for physical examination results mostly non-invasive techniques (chest x-ray, echocardiography, radionuclide ventriculography etc.) are used. Therapy of myocardial failure has to consider primarily the potentially treatable internistic main disease (blood pressure reduction in arterial hypertension, heart valve operations in heart valve diseases etc.). Symptomatically, except dietetic and physical measures, digitalis glycosides, diuretics, vasodilators and newer positively inotropic drugs are used.

Diagnosis, Differential↗
PubMed1984

Role of sympathetic nervous system in ischemia-induced reduction of digoxin tolerance in anesthetized cats.

Acute myocardial ischemia reduces tolerance of the heart to arrhythmogenic actions of digitalis glycosides. Because both ischemia and the glycoside produce profound changes in activity of the autonomic nervous system and because sympathetic discharge or catecholamines enhance toxic actions of the cardiac glycosides, the possibility that alterations in digitalis sensitivity of ischemic heart involve changes in sympathetic nerve activity was examined using alpha-chloralose-anesthetized cats. Left anterior descending coronary artery (LAD) was completely occluded by ligation and, 40 min later, a slow i.v. infusion of digoxin was started at a rate of 1 microgram/kg/min. LAD ligation alone did not produce arrhythmias in that condition, but shortened the time to onset of digoxin-induced arrhythmias and thereby reduced the amount of digoxin required to produce the toxic manifestation. Concomitantly, digoxin concentration in plasma and nonischemic areas of the heart were lower in LAD-ligated cats at the onset of arrhythmias than those in sham-operated cats. Myocardial digoxin content in the ischemic area of the LAD-occluded heart was lower than that in nonischemic areas of the same heart. At the onset of digoxin-induced arrhythmias, Na,K-adenosine triphosphatase activity of ischemic myocardium was significantly higher than that in the nonischemic area, reflecting a lower digoxin occupancy of the glycoside binding sites on the sodium pump. Spinal cord (C1) transection or propranolol treatment prolonged the time to arrhythmias in both control and LAD-ligated cats, but failed to abolish the effect of LAD ligation to augment digoxin toxicity. Bilateral vagotomy also did not alter the enhancement of digoxin toxicity caused by ligation of LAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1985

Digitalis: neurally mediated arrhythmogenic and coronary vasoconstrictor properties.

Studies of digitalis have revealed an appreciable role of the autonomic nervous system in the modulation of the cardiovascular toxicity of digitalis. Neuraxis transection experiments and studies using digitalis compounds that fail to enter the central nervous system suggest that centers located in the floor of the fourth cerebral ventricle play a substantial part in the neural arrhythmogenic effects of the digitalis glycosides. Electrical stimulation of the area postrema in partially digitalized animals, not otherwise manifesting ventricular arrhythmias, elicits ventricular tachycardia. Neuraxis transection experiments and studies with a charged digitalis derivative also suggest localization of the coronary vasoconstrictive properties of digitalis to the area postrema. The results suggest that this region of the brainstem is sensitive to a neurally active substance, digitalis, causing peripheral sympathetic effects of considerable consequence.

Adrenergic alpha-Antagonists↗
PubMed1978

[The heart in hypertension. V. Systolic and diastolic wall stress and degree of hypertrophy as determinants of diagnostic and therapeutical consequences (author's transl)].

The appropriateness of hypertrophy was analyzed in 64 patients with essential hypertension during diagnostic cardiac catheterization and left ventriculography. The degree of hypertrophy may be described by the relationships between peak systolic pressure, mass to volume ratio and peak systolic wall stress. The peak systolic wall stress represents an important determinant of the appropriateness of hypertrophy and has great influence on left ventricular function and myocardial energy demand. The hypertrophy in essential hypertension may be subdivided into 3 different types of hypertrophy: (a) inappropriate hypertrophy associated with increased mass-to-volume ratio and decreased systolic wall stress, (b) appropriate hypertrophy with normal systolic wall stress and (c) inappropriate hypertrophy with normal or decreased mass-to-volume ratio, however with significantly increased systolic wall stress. On the basis of the appropriateness or degree of left ventricular hypertrophy in essential hypertension the therapeutical consequences are being discussed with special reference to beta receptor blockade and digitalis glycosides.

Adrenergic beta-Antagonists↗
PubMed1984

Localization of neurally mediated arrhythmogenic and coronary vasoconstrictor properties of digitalis.

Studies of the cardiotoxicity of digitalis have revealed an appreciable role of the autonomic nervous system in modulating these toxicities. Neuraxis transection experiments and studies with digitalis compounds that fail to enter the central nervous system suggest that centers localized to the floor of the fourth cerebral ventricle play a substantial part in neural arrhythmogenic effects of the digitalis glycosides. Stimulation of the area postrema (AP) in animals partially digitalized, but not otherwise manifesting ventricular arrhythmias, elicits ventricular tachycardia. Neuraxis transection experiments and studies with a charged digitalis derivative also suggest localization of the coronary vasoconstrictive properties of digitalis to the AP. The results suggest that this region of the brain stem is sensitive to neurally active substances that cause peripheral sympathetic effects of considerable consequence.

Animals↗
PubMed1980

Digitalis metabolism and human liver alcohol dehydrogenase.

Human liver alcohol dehydrogenase (alcohol: NAD" oxidoreductase, EC 1.1.1.1) catalyzes the oxidation of the 3 beta-OH group of digitoxigenin, digoxigenin, and gitoxigenin to their 3-keto derivatives, which have been characterized by high performance liquid chromatography and mass spectrometry. These studies have identified human liver alcohol dehydrogenase as the unknown NAD(H)-dependent liver enzyme specific for the free hydroxyl group at C3 of the cardiac genins; this hydroxyl is the critical site of the genins' enzymatic oxidation and concomitant pharmacological inactivation in humans. Several kinetic approaches have demonstrated that ethanol and the pharmacologically active components of the digitalis glycosides are oxidized with closely similar kcat/Km values at the same site on human liver alcohol dehydrogenase, for which they compete. Human liver alcohol dehydrogenase thereby becomes an important biochemical link in the metabolism, pharmacology, and toxicology of ethanol and these glycosides, structurally unrelated agents that are both used widely. Both the competition of ethanol with these cardiac sterols and the narrow margin of safety in the therapeutic use of digitalis derivatives would seem to place at increased risk those individuals who receive digitalis and simultaneously consume large amounts of ethanol or whose alcohol dehydrogenase function is impaired.

Alcohol Oxidoreductases↗
PubMed1983

Observations on the biphasic nature of digitalis electrophysiological actions in the human right atrium.

Cardiac electrophysiological effects of a digitalis glycoside have been investigated by right atrial intracardiac stimulation and recording in 12 patients with paroxysmal supraventricular tachyarrhythmias. Measurements were made of atrial effective refractoriness by pacing together with programmed premature extrastimulation. Simultaneous recordings of atrial action potential duration from a site close to the sinoatrial node and from a more distal atrial site were made using an endocardial contact-injury potential technique. All subjects received methyldigoxin 10.0 micrograms X kg-1 intravenously, while half were also pretreated with atropine. A biphasic response to methyldigoxin was observed, with initial action potential prolongation, maximal at 20 min post-infusion, followed by significant action potential shortening which persisted to the end of the study period at 40 min. The initial phase, that of prolongation, was associated with smaller increases in atrial effective refractoriness and increased vulnerability to atrial tachyarrhythmia initiation. During the subsequent phase of action potential shortening, the gap between the termination of effective refractoriness and completion of action potential repolarisation was narrowed, coinciding with diminished vulnerability to tachyarrhythmias. Slight but significant atrioventricular conduction delay was apparent 30 to 40 min after glycoside infusion, indicating enhanced vagal activity during the phase of action potential shortening. Prior atropinisation reduced the magnitude of both early and late components of the biphasic action potential response to digitalis, supporting the proposition that both components are mediated via cardiac muscarinic receptors. Since vagal effects on the atrioventricular junction appeared during the later phase, it is suggested that initial action potential prolongation by digitalis may have been effected via local acetylcholine release, while subsequent action potential shortening may have been caused by a combination of vagally and locally mediated activity.

Action Potentials↗
PubMed1975

Digitalis toxicity: epidemiology and clinical use of serum concentration measurements.

Despite continuing advances in understanding of the basic pharmacology of the cardiac glycosides, digitalis intoxication remains a common clinical problem. Physician education programs and increasing use of serum or plasma concentration data have, however, been shown to be capable of substantially reducing the incidence of digitalis toxicity. Methodologic progress and availability of commercial radioimmunoassay kits have placed measurement of clinically relevant serum or plasma cardiac glycoside concentrations within the capability of most well equipped clinical laboratories. Extensive experience with serum digitalis levels now provides a basis for ongoing examination of the role of these measurements in clinical practice. Results of studies to date demonstrate that mean serum digoxin and digitoxin levels are significantly higher in patients with electrocardiographic evidence of toxicity compared with patients without such evidence. It must be emphasized, however, that because of overlap in serum digitalis levels between these two groups, sole dependence on these levels for established of a diagnosis of digitalis toxicity is not warranted. Multiple factors influence individual responses to cardiac glycosides, and serum concentration data must be interpreted in the over-all clinical context. Type and extent of underlying heart disease are important determinants of the clinical response to any given dose or concentration of cardiac glycoside. Knowledge of the serum digitalis concentration is likely to be helpful in the setting of suspected digitalis intoxication in the absence of an adequate history, or in the presence of fluctuating renal function, overt or suspected malabsorption, or uncertain bioavailability. More generally, such measurements may prove useful whenever an unanticipated response to digitalis is encountered, whether it be suspected toxicity or the absence of an expected therapeutic effect.

Creatinine↗
PubMed1975

Serum digitalis measurements in the assessment of digitalis resistance and sensitivity.

Antibodies to digitalis glycosides have been elicited in experimental animals and have been utilized in the development of rapid, sensitive, specific and convenient radioimmunoassay methods for the clinical measurement of digoxin and other cardiac glycosides in man. The use of these assay methods has supplemented earlier studies with radiolabeled digitalis preparations and has made it possible to obtain much new information concerning factors which may contribute to the well known patient to patient variability in digitalis dosage requirements and in sensitivity to the toxic effects of cardiac glycosides. In some patients with a poor clinical response to digitalis, the finding of a serum concentration which is relatively low for the dose prescribed may suggest that true digitalis resistance is not present and may raise questions of poor patient compliance, tablet inadequacies, intestinal malabsorption, increased metabolic degradation or hyperthyroidism; if the cause of the low serum level cannot be identified or corrected, serial serum measurements should enable safe and rational upward adjustment of dosage. In some patients with digitalis toxicity, the finding of a serum level which is relativity high for the dose prescribed may suggest that the patient is not sensitive to digitalis but rather is excreting it slowly; in such instances in elderly patients (with decreased glomerular filtration rates) and in patients with renal disease, serial digitalis measurements are useful adjuncts to clinical observation in determining optimal digitalis dosage schedules. A knowledge of serum digitalis concentrations should enable us to develop sound principles for a more rational approach to the clinical administration of cardiac glycosides, especially in patients with unusually high dosage requirements or with unusual sensitivity to relatively small doses of digitalis.

Animals↗
PubMed1995

Na,K-ATPase inhibitors from bovine hypothalamus and human plasma are different from ouabain: nanogram scale CD structural analysis.

The specific, high affinity binding of plant-derived digitalis glycosides by the mammalian sodium and potassium transporting adenosine triphosphatase (Na,K-ATPase, or sodium pump), a plasma membrane enzyme with critical physiological importance in mammalian tissues, has raised the possibility that a mammalian analog of digitalis might exist. We previously isolated and structurally characterized from bovine hypothalamus a novel isomer of the plant glycoside, ouabain, which differs structurally only in the attachment site and/or the stereochemistry of the steroid moiety [Tymiak et al. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 8189-8193]. Hamlyn and co-workers reported a molecule purified from human plasma which by mass spectrometry could not be distinguished from plant ouabain [Hamlyn et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 6259-6263]. Since rhamnoside cardiotonic steroids are not known as natural products from mammalian sources, it became important to compare these two pure isolates to determine if the same or structurally distinct compounds has been found. Our results indicate that the human and bovine Na,K-ATPase-inhibitors are identical, but different from plant ouabain. This supports the notion that the human sodium pump may be under specific physiological regulation by a mammalian analog of the digitalis glycosides.

Animals↗
PubMed1994

Digitalis in congestive heart failure.

The indications for digitalis glycosides in the treatment of congestive heart failure with sinusrhythm have been disputed since early in this century. In the last decade several well designed studies have been published that have established the effectiveness of digitalis in this condition. However, new groups of drugs have been introduced in the treatment of heart failure and have been compared with digitalis. Ibopamine appeared to be an effective alternative for digitalis in patients with heart failure of low NYHA class. Because of their proven favourable effect on patient survival, ACE inhibitors are replacing digitalis as first-line drug--after diuretics--in the treatment of congestive heart failure. In this review of the literature the present place of digitalis in the treatment of heart failure is discussed.

Angiotensin-Converting Enzyme Inhibitors↗