Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Digitalis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 181 records · Page 10Linked to original sources
PubMed2002

Hemodynamic and plasma atrial natriuretic peptide responses to acute digitalis therapy in patients with normal and impaired left ventricular function.

BACKGROUND: Digitalis has a long history in the treatment of heart failure but its effects on cardiac hemodynamics and neurohormonal modulation are not well characterized. AIMS: The purpose of this study was to evaluate the relationship between atrial natriuretic peptide (ANP) and the hemodynamic responses to acute digitalis administration in patients with normal and impaired left ventricular function (LVD). METHODS AND RESULTS: Thirty patients were enrolled in the study, 20 with LVD (LVEF=22+/-8%) and 10 control subjects (LVEF=77+/-10%). Hemodynamics and plasma ANP concentrations were measured supine and with leg elevation before and after digitalis. In patients with normal ventricular function, the hemodynamic stress of leg elevation in the pre-digitalis state resulted in significant (P<0.05) increases in PAWP and MPAP. Digitalis administration in the supine position produced reductions in heart rate, PAWP, MPAP and CI; SVR was increased. In LVD patients leg elevation further increased PAWP, RAP and MPAP. Digitalis in the supine position, however, reduced RAP, MPAP and PAWP and increased CI. These improved hemodynamics were preserved during the stress of leg elevation. Leg elevation following digitalis resulted in increased ANP concentrations despite decreased cardiac filling pressures. CONCLUSIONS: Acute digitalis administration results in hemodynamic improvement in LVD patients which may in part result from digitalis stimulated release of myocardial ANP under conditions of hemodynamic stress.

Adult↗
PubMed2001

[Two cases of digitalis toxicity with reversible and severe decrease of visual acuity].

BACKGROUND: We performed electrophysiologic tests on two patients with digitalis toxicity who first had photophobia and xanthopsia and revealed reversible reduced visual acuity and binocular central scotoma. CASES: The patients were a 72-year-old male and a 54-year-old male who had symptoms of digitalis toxicity. FINDINGS: The corrected visual acuity was severely decreased during digitalis toxicity, 0.02 oculus dexter (OD) and 0.1 oculus sinister (OS) in case 1 and 0.04 OD and 0.2 OS in case 2. But visual acuity recovered as the blood levels of digitalis decreased to the normal level and the corrected visual acuity was 0.7 OD and 0.8 OS in case 1 and 0.8 OD and 0.9 OS in case 2. We recorded 30 Hz-flicker electroretinogram (ERG), single flash ERG, photopic ERG, and scotopic ERG when digitalis blood levels were elevated and normal. Decreased amplitudes of 30 Hz-flicker ERG and photopic ERG suggested that photoreceptor function was disturbed at digitalis toxicity and cone dysfunction was more severely disturbed than rod dysfunction. CONCLUSION: 30 Hz-flicker ERG, as well as electrocardiogram and digitalis blood level, is a relatively convenient and useful measure of digitalis toxicity. It is necessary consiler toxicity when severe visual dysfunction is observed in patients with digitalis therapy.

Aged↗
PubMed1986

Bile salts as endogenous digitalis like factors.

Digitalis-like factors were assayed by radioimmunoassay of digoxin in 6 bile samples obtained from patients at autopsy and in plasma from three patients with combined hepatic and acute renal failure. None of the patients received digoxin. Digitalis like factor values in bile samples were 23 to 85 nmol digoxin equivalents/1. Bile salt concentrations ranged from 38-104 mmol/l in the bile and 28-184 mumol/l in the plasma of these subjects. Bile, plasma digitalis like factor extracts and bile salt standards (0.1-3 mM) showed concentration dependent displacement of [125I]-digoxin from digoxin antibody, inhibition of hog brain Na,K-ATPase and displacement of [3H]-ouabain from Na,K-ATPase. The concentration-displacement curves suggest that bile salts could account for 50-79% of the total digitalis like factors in the six bile samples and 2-7% in the plasma of the three patients. High performance liquid chromatographic fractionation of a bile sample showed digitalis like factor peaks co-eluating with standards of tauro- and glycocholate, tauro- and glycochenodeoxycholate and tauro- and glycodeoxycholate. These bile salt peaks accounted for 78% of the total digitalis like factors in all high performance liquid chromatographic peaks in bile, but only 7% of the total digitalis like factor activity in all high performance liquid chromatographic peaks in an extract of plasma from one of the patients with hepatic and renal failure. The bile salts appear to be examples of endogenous digitalis like compounds which do not act by simple competitive ligand binding to antidigoxin antibody and Na,K-ATPase. They make an important contribution to digitalis like factor activity in bile, but not in plasma.

Acute Kidney Injury↗
PubMed1995

Differentiation between isoforms of Na+/K+-transporting atpase from human and guinea-pig muscle through use of digitalis derivatives as analytical probes.

The aims of the study included: to explore the protein structure basis for the differences in digitalis sensitivity between isoforms of Na/K-ATPase from human and guinea-pig cardiac muscle; to determine the relative significance of the constituents of tripartite digitalis compounds in their inhibitory action on these Na/K-ATPase isoforms; to evaluate the potential significance of the receptor kinetics for pharmacological characteristics. The analytical method has been the recording of the inhibitory interaction of various digitalis derivatives with the Na/K-ATPase isoforms. The protein structure basis for the isoform differences in digitalis susceptibility has been explored by analysing in free-energy plots the kinetics of their inhibitory interaction with 53 digitalis derivatives of grossly different structure. The slope of the regression line and the parameters of the regression equation proved to be similar for the two isoforms in spite of the great difference in their digitalis susceptibilities. This surprising uniformity indicates that a uniform "macroscopic" mechanism underlies the inhibitory effect of the various derivatives on the two isoforms. On the other hand, the differences in the positions of delta G*on and delta G*off values for particular inhibitors relative to the regression line reveal differences in the "microscopic" interaction energy surfaces of the two isoforms. In conclusion, the origin of the isoform distinctions in their susceptibility towards inhibition by various digitalis derivatives is essentially confined to differences in the chemotopology of the digitalis recognition matrix and binding cleft. Specific observations allowed to disentangle the impact of various steroid derivatizations at carbon atoms 3, 17, and diverse other positions on the kinetics of their interaction with the enzyme isoforms. The steroid nucleus of the cardiac glycosides, 5 beta, 14 beta-androstane, proves to be the basal structural element for discrimination of Na/K-ATPase isoforms. This discrimination becomes much enlarged by steroid glycosidation at C3 beta-OH and/or by steroid substitution of C17 beta-H by a lactone ring. The higher inhibitory sensitivity of the human isoform is based either on an increased association rate or a decreased dissociation rate, depending on the nature of derivatization.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
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↗
PubMed1985

An "account" of digitalis and atrial fibrillation.

This review deals with the mechanisms by which digitalis exerts its "opium-like" action on the ventricular rate in patients with atrial fibrillation. To understand the effect of digitalis on ventricular rate and rhythm, it is essential to learn more about the basic electrophysiologic principles responsible for: atrial fibrillation as such, and the scaling function of the atrioventricular (AV) node-His system. It may be assumed that during atrial fibrillation, the atrial excitatory process results in randomly spaced impulses that reach the AV junction from random directions with random strength. The refractory period of and concealed conduction in the AV node enable the AV conduction system to scale down the shower of atrial impulses to a random ventricular response with a considerably lower rate. Digitalis decreases the ventricular rate through two synergistic pharmacologic actions: digitalis increases the refractory period of the AV node, and digitalis decreases the refractory period of the atrial myocardium through a direct and indirect effect (vagotonic and vagomimetic). A decrease in the refractory period of the atrial myocardium results in more atrial impulses reaching the AV junction in a given unit of time. More atrial impulses result in a greater degree of concealed conduction in the AV node and, thus, in a slower ventricular rate. The ventricular rhythm remains random during digitalis treatment. Digitalis is the only drug that effects an increase in the refractory period of and concealed conduction within the AV node. Two hundred years after its discovery, digitalis remains the drug of choice for the treatment of patients with sustained atrial fibrillation.

Atrial Fibrillation↗
PubMed1985

200 years of digitalis: the emerging central role of the sodium ion in the control of cardiac force.

Digitalis has been used therapeutically for two centuries, but the mechanism by which it enhances the ability of cardiac muscle to produce force (the positive inotropic effect) has not been fully elucidated. The major controversy concerns the question of whether the inhibition of the Na+-K+ pump by digitalis, particularly at low (therapeutic) concentrations, increases the intracellular Na+ concentration and thus is causally related to the positive inotropic effect. Na+-selective microelectrodes, introduced recently, have made it possible to measure small changes in intracellular Na+ activity (aiNa) in beating preparations of cardiac muscle and, in particular, to follow the exact time course of change in both aiNa and contractile force during the positive inotropic effect of digitalis. It has been demonstrated that digitalis at low and high concentrations produces a parallel increase in aiNa and in contractile force during the onset of its effect; washout of the drug results in a parallel and complete recovery of aiNa and contractile force. Additional strong evidence for a correlation between the pump inhibition and digitalis inotropy is the fact that the magnitude of increase in aiNa and contractile force produced by digitalis depends on the level of aiNa and therefore on the rate of Na+ extrusion by the Na+-K+ pump. The study on the quantitative relationship between aiNa and contractile force reveals that the force of contraction is a power function of aiNa, such that a small rise in aiNa produces a significant increase in contractile force. Direct measurements of aiNa and intracellular free Ca2+ during digitalis inotropy strongly support the hypothesis that an increase in aiNa raises intracellular Ca2+ via Na+-Ca2+ exchange, thus producing the positive inotropic effect. In conclusion, the recent data available from the simultaneous and continuous measurements of aiNa and contractile force strongly indicate that the inhibition of the Na+-K+ pump is causally related to the positive inotropic effect of digitalis on cardiac muscle.

Calcium↗
PubMed1977

Dissociation of Na+,K+-ATPase inhibition from digitalis inotropy.

Recent findings from our laboratory as well as those of other laboratories do not support the postulation that the mechanism of the positive inotropic action of digitalis is due to inhibition of NA,K-ATPase. Using short-acting digitalis steroids and drug washout experiments, in isolated myocardial preparations, it has been demonstrated that Na,K-ATPase isolated from such preparations is still significantly inhibited, whereas the positive inotropic effect is no longer present. Also, based on kinetic measurements the two exponential rate constants observed for drug half-life, a rapid and slow phase, were found to be associated, respectively, with the very short inotropic half-life and the very long enzyme inhibition half-life. In addition, a dissociation of the transient inotropic effects of digitalis was observed from the long lasting cardiotoxic effects of digitalis during drug washout. Moreover, a temporal correlation was noted between the persistent inhibitory effects of digitalis on Na,K-ATPase and the persistent cardiotoxic effects of digitalis. Therefore, it is concluded that inhibition of Na,K-ATPase is not responsible for the positive inotropic action of digitalis, but may be the mechanism, at least in part, for certain cardiotoxic effects of digitalis.

Adenosine Triphosphatases↗
PubMed1989

Current concepts in the use of digitalis.

After more than two centuries of administration of digitalis glycosides to patients with cardiac disease, empirical observation and tradition remain the basis for much of the clinical application of these drugs. Many questions remain, and the role of digitalis in the management of congestive heart failure and cardiac rhythm disturbances is changing with improvement in our understanding of the pathophysiology of these conditions and the availability of newer effective agents that may have less potential to cause life-threatening toxicity. Nevertheless, digitalis glycoside therapy is a familiar therapeutic intervention for the majority of physicians and remains appropriate in carefully selected patients. The development of digoxin-specific Fab fragments has led to improvement in treatment of advanced and refractory digitalis toxicity and opens up the possibility of improvement in diagnosis of less clinically obvious cases of digitalis intoxication. The role of digitalis glycosides in the management of supraventricular tachyarrhythmias and congestive heart failure in the presence of sinus rhythm should now be revised. In each of these clinical circumstances, alternative drugs or other modes of therapy have been developed that reduce the dependence of clinicians on digitalis as the sole or primary approach to management. In the immediate management of paroxysmal reentrant supraventricular tachyarrhythmias, verapamil has largely replaced digoxin as the drug of choice, although digoxin has an ancillary role, especially in patients with impaired ventricular function. In the management of patients with atrial fibrillation or atrial flutter with a rapid ventricular response, verapamil or diltiazem and beta-adrenergic-blocking drugs will effectively slow the ventricular response, thus reducing the likelihood of approaching the threshold of digitalis toxicity to achieve adequate rate control. In the treatment of patients with congestive heart failure and normal sinus rhythm, one must now recognize a subset of patients with diastolic rather than systolic dysfunction who are best treated by correcting underlying causes of left ventricular hypertrophy or ischemia rather than inotropic support with cardiac glycosides. Symptomatic patients with dilated ventricles and impaired contractile function should undergo correction of abnormalities of preload with vasodilators acting on the venous bed as well as diuretics, and reduction of elevated afterload with vasodilators that reduce arteriolar resistance and thus improve ventricular emptying.(ABSTRACT TRUNCATED AT 400 WORDS)

Digitalis Glycosides↗
PubMed1977

Studies on digitalis. XIII. A prospective study of 649 patients on maintenance treatment with digitoxin.

In a prospective study of digitalis intoxication in 649 patients on maintenance treatment with digitoxin a low incidence of digitalis toxicity was found, namely, 5.8 per cent. This is mainly due to a more careful use to digitalis glycosides. It is especially important to reduce the dose of digitoxin in the liver and partly excreted metabolized in the liver and partly excreted through the kidneys as metabolities. Serum half-time of digitoxin is shortened in patients with impaired renal function. Patients with reduced renal function may be treated with digitoxin in the same doses as individuals with normal renal function. This is in contrast to patients treated with digoxin. Digitoxin should therefore be the cardiac glycoside of choice in treatment of patients with renal failure. Digitoxin is further rapidly eliminated in patients with reduced liver function in spite of its extensive hepatic metabolism. In this study extracardia symptoms were found equally often as cardiac signs of toxicity. Patients intoxicated usually had several symptoms and signs of toxicity at the same time. The specificity of commonly used symptoms and signs a digitalis intoxication is very low. In this study atrial tachycardia with block, which has been considered to be an important cardiotoxic arrhythmia, very seldom was found in digitalis intoxication. There is an overlap in digitalis serum concentration between toxic and nontoxic patients. The diagnosis of toxicity was made on clinical grounds. Most of the intoxicated patients had high serum concentrations, but some had concentrations in the normal or low range. Apart from being a guide to the diagnosis of digitalis intoxication, serum digitalis levels may further be a guide to underdigitalization of cardiac patients, especially patients in sinus rhythm.

Age Factors↗
PubMed1983

Modification of the baroreceptor control of atrio-ventricular conduction induced by digitalis in man.

Several studies in animals and in man have suggested that the inhibitory influence of baroreceptors on heart rate and peripheral circulation is enhanced by digitalis. Because the atrio-ventricular node represents a key site for the clinical action of digitalis we studied how baroreceptor control of atrio-ventricular conduction is modified by digitalis at therapeutical doses. In eight subjects heart rate was kept constant by atrial pacing to assess neural influences on atrio-ventricular conduction rate without the modifications caused by simultaneous changes in cardiac cycle length. Arterial baroreceptors were stimulated by increasing or reducing blood pressure (intra-arterial recording), via an iv bolus of phenylephrine or nitroglycerine. The baroreflex sensitivity was assessed in ms . mmHg-1 as the slope of the linear regressions relating the rise or fall in systolic blood pressure to the lengthening or shortening in St- (atrial stimulus artifact) Q interval (ECG recording). The study was performed before and 45 min after iv administration of digitalis (0.8 mg of Lanatoside C). Baroreflex sensitivity during baroreceptor stimulation was 2.9 +/- 1.1 ms . mmHg-1 (mean +/- SE) before digitalis, whereas after digitalis a significantly and markedly greater value of 5.6 +/- 1.5 ms . mmHg-1 was found. Baroreflex sensitivity during baroreceptor deactivation was 0.9 +/- 0.1 ms . mmHg-1 before digitalis, and was not significantly affected by the drug. Thus in man the baroreceptor control of atrio-ventricular conduction is strikingly potentiated by digitalis although this potentiation is only evident in the upper portion of the stimulus-response curve of the reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The pathophysiological role of digitalis-like substance in essential hypertension.

In order to investigate the role of digitalis-like substance in patients with essential hypertension, levels of plasma digitalis-like substance were measured in nine normotensive, 12 normal-renin and seven low-renin essential hypertensive subjects. The level of plasma digitalis-like substance was determined by using two different methods, the digoxin radio-immunoassay established by our laboratory and Na+,K+-ATPase inhibitory activity (modified Hamlyn's method). There was a significant positive correlation between plasma immunoreactive digitalis-like substance and Na+,K+-ATPase inhibitory activity in plasma samples. Both values were significantly higher in hypertensives than in normotensives. Moreover, Na+,K+-ATPase inhibitory activity was significantly higher in low-renin hypertensives than in normal-renin hypertensives or normotensives. These findings suggest (1) digoxin radio-immunoassay may be able to determine the level of plasma digitalis-like substance; (2) digitalis-like substance is increased in essential hypertensives, especially in low-renin hypertensives; (3) the level of digitalis-like substance might be related to plasma renin activity, and mediated by a change in plasma volume; and (4) the activity of the digitalis-like substance may contribute to the pathophysiology of essential hypertension.

Adult↗
PubMed1991

Contrasting effects of digitalis and dobutamine on baroreflex sympathetic control in normal humans.

BACKGROUND: Digitalis glycosides augment cardiopulmonary baroreceptor mechanisms in animals. This could result from inotropic actions or from direct sensitization of cardiac mechanoreceptors. METHODS AND RESULTS: To determine if digitalis has similar actions in humans and to evaluate the mechanisms involved, we measured muscle sympathetic nerve activity (MSNA; microneurography) during unloading of cardiopulmonary baroreceptors with incremental lower body negative pressure (LBNP; 0 to -15 mm Hg) and during the cold pressor test in 22 normal subjects (age 22 +/- 1 year, mean +/- SEM). Arterial and central venous pressures, heart rate, and MSNA were measured during LBNP before and after intravenous digitalis (Cedilanid 0.02 ng/kg, n = 8), dobutamine (2.8 +/- 0.5 micrograms/kg/min, n = 8), or placebo (n = 6). Digitalis and dobutamine produced similar increases in baseline mean arterial pressure and decreases in central venous pressure and MSNA. LBNP produced similar decreases in central venous pressure in all groups before and after drug administration. The MSNA responses to LBNP were markedly potentiated by digitalis but not by dobutamine or placebo. CONCLUSIONS: Digitalis did not alter responses to the cold pressor test. Thus, digitalis selectively potentiated cardiopulmonary baroreflex regulation of sympathetic neural responses in normal humans, whereas dobutamine (another positive inotropic agent) did not produce this effect. We conclude that digitalis augments cardiopulmonary baroreflex control of sympathetic activity, probably by direct baroreceptor sensitization.

Adult↗
PubMed1987

The mortality risk associated with digitalis treatment after myocardial infarction.

We examined the effects of digitalis therapy on postinfarction mortality throughout a 24-month to 48-month follow-up in 867 patients who survived an acute myocardial infarction. During follow-up, 145 patients died (16.7% mortality). At the time of hospital discharge, 31% of the patients were taking digitalis. The digitalis-treated patients were older, had more medical-cardiac risk factors, and had a higher mortality rate throughout the follow-up than the nondigitalis-treated patients. Statistical techniques were used to adjust for clinical imbalances between the digitalis-treated patients and nondigitalis-treated patients. The survival analysis (n = 728 patients) utilized the Cox regression model, and the digitalis-associated mortality risk was identified only after all significant covariates were allowed, so that mortality could be predicted as accurately as possible. Digitalis therapy was associated with a significantly increased postinfarction mortality risk after adjustment for the predictor covariates (relative risk 2.3, 95% confidence interval 1.4-3.7, p less than 0.001). The findings from this large multicenter study suggest that it would be prudent to exercise caution in the use of digitalis in postinfarction patients.

Aged↗
PubMed1985

Effect of digitalis treatment on survival after acute myocardial infarction.

To determine whether treatment with digitalis is associated with decreased survival after acute myocardial infarction (AMI), data from 504 patients who were enrolled in a postinfarction natural history study were analyzed. At the time of discharge, 229 patients (45%) were taking digitalis. After 3 years of follow-up, the cumulative survival rate for patients discharged on a regimen of digitalis was 66%, compared with 87% for those not treated (p less than 0.001). Univariate analysis showed that statistically significant differences existed between the 2 groups with respect to age, previous AMI, left ventricular failure in the coronary care unit, atrial fibrillation in the coronary care unit, peak creatine kinase levels, enlarged heart and pulmonary vascular congestion on the discharge chest x-ray, ventricular arrhythmias and treatment with diuretic, antiarrhythmic and beta-blocking drugs. Survival analysis using Cox's regression model showed that the association between digitalis and decreased survival was of borderline significance after adjustment for atrial fibrillation and left ventricular failure. Serum digoxin concentration was measured in 83% of the patients who took digitalis. Survival was inversely and significantly related to serum digoxin, i.e., the higher the serum digoxin concentration, the lower the long-term survival rate. After adjusting for atrial fibrillation and left ventricular failure, serum digoxin was not significantly related to survival. Taken together with the results of 3 other large, nonrandomized studies of digitalis treatment after AMI, this study suggests that digitalis treatment may have adverse effects on survival during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Fibrillation↗
PubMed1985

Effects of hyperkalemia on the electrocardiogram of patients receiving digitalis.

In a prospective and a retrospective study, the effects of hyperkalemia on the electrocardiogram (ECG) of patients treated with customary maintenance doses of digoxin were examined and the results were compared with the effects of hyperkalemia in patients not receiving digitalis. The prospective study included 11 patients treated and 11 not treated with digitalis, and the retrospective study 27 patients treated and 61 not treated with digitalis. In all patients serum potassium concentrations (Ks) were determined within 1 hour of the recorded electrocardiogram. Serum digoxin concentrations, measured in 11 patients in the prospective and in 4 in the retrospective study, ranged from 0.7 to 5.0 ng/ml, and exceeded 2.0 ng/ml in 10 of 15 patients. Since the results of the prospective and of the retrospective study were similar, they were combined. In patients treated with digitalis, Ks ranged from 5.5 to 6.6 mEq/liter in 21 patients, from 6.7 to 7.5 mEq/liter in 17 and from 7.6 to 8.5 mEq/liter in 6; the Ks was 9.1 mEq/liter in 1 patient. The ventricular rate in patients treated with digitalis ranged from 48 to 140 beats/min, and was not significantly different from that in untreated patients within each range of Ks. Atrioventricular (AV) junctional rhythm occurred more frequently in the electrocardiograms of digitalis-treated patients (15 of 45 vs 2 of 76, p less than 0.001). The average PR intervals were longer in patients treated with digitalis who had Ks greater than 6.6 mEq/liter, but no patient in the study had greater than first-degree AV block, and no patient required a pacemaker.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2004

Consistency of the beneficial effect of metoprolol succinate extended release across a wide range dose of angiotensin-converting enzyme inhibitors and digitalis.

BACKGROUND: The effects of beta-blockade with different extent of angiotensin-converting enzyme inhibitors (ACEI) and digitalization are unknown. To assess the effect of metoprolol succinate controlled release/extended release (CR/XL) combined with high versus low doses of ACEI and digitalis, we analyzed data from The Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) in which patients with heart failure and left ventricular ejection fraction < or =40% were randomized to metoprolol CR/XL versus placebo. METHODS AND RESULTS: Outcome was analyzed separately for those on a low dose (< or =median) of the ACEI or digitalis versus high dose (> median). The mean dose of ACEI in the high-dose group (n = 1457) was 3 times higher than that in the low-dose group (n = 2094). Mortality was reduced to a similar extent in the high- and low-dose ACEI subgroups (RR = .69 versus .64, respectively). Corresponding figures for combined mortality/all hospitalization and for mortality/hospitalization for heart failure were .85 versus .83, and .70 versus .68, respectively. Likewise, reduction in total mortality with metoprolol CR/XL was similar in patients receiving no digitalis (n = 1447; RR = .56), low dose (n = 1122; RR = .71), or high dose (n = 1421; RR = .71). CONCLUSION: This analysis of MERIT-HF demonstrates consistent and similar improvement in outcome of patients receiving metoprolol CR/XL when combined with either a high or low dose of an ACEI or digitalis, or no digitalis at all. Thus regardless of ACEI and digitalis dose and whether patients are treated with digitalis or not, it is very important to add a beta-blocker to the existing heart failure therapy. beta-blockers should not be withheld until target doses of ACEI have been achieved.

Adrenergic beta-Antagonists↗
PubMed1983

Digitalis poisoning: historical and forensic aspects.

Since the introduction of digitalis into therapy approximately 200 years ago, there have been continuing admonitions concerning its toxicity. Over 400 years ago, herbalists listed the plant as being poisonous. In fiction, the homicidal use of digitalis has appeared in the writings of Mary Webb, Dorothy Sayers and Agatha Christie. Ten instances in real life of alleged homicide by digitalis and trials of the accused are listed. The drug has been used with suicidal intent rather infrequently, compared with other medications. Possibly, it is more commonly used for such a purpose in France than in England or the United States. The fraudulent use of digitalis in the support of claims for disability because of heart disease has occurred, and one large conspiracy of physicians and lawyers in the swindle of insurance companies during the 1930s is a shameful episode in the record of these professions. Although innocent, one professor of medicine who was involved committed suicide. Two pharmaceutical (manufacturing) blunders that occurred in Belgium and Holland with mislabeling are mentioned. These resulted in numerous deaths and the profession seemed rather slow to recognize the nature of these small epidemics of poisoning. Instances of psychiatric illness with digitalis seem well documented. The story of digitalis toxicity continues into the present and physicians should be vigilant regarding the drug's potential for poisoning that can result from prescribing digitalis with ignorance of proper dosage, pharmacodynamics or drug interactions, as well as from accidental overdose as in children and use with self-destructive or homicidal intent.

Cardiology↗