digoxin and Diabetes-Mellitus

Cardiotonic steroids (CTS), long used to treat heart failure, are endogenously produced in mammals. Among them are the hydrophilic cardenolide ouabain and the more hydrophobic cardenolide digoxin, as well as the bufadienolides marinobufagenin and telecinobufagin. The physiological effects of endogenous ouabain on blood pressure and cardiac activity are consistent with the "Na(+)-lag" hypothesis. This hypothesis assumes that, in cardiac and arterial myocytes, a CTS-induced local increase of Na(+) concentration due to inhibition of Na(+)/K(+)-ATPase leads to an increase of intracellular Ca(2+) concentration ([Ca(2+)](i)) via a backward-running Na(+)/Ca(2+) exchanger. The increase in [Ca(2+)](i) then activates muscle contraction. The Na(+)-lag hypothesis may best explain short-term and inotropic actions of CTS. Yet all data on the CTS-induced alteration of gene expression are consistent with another hypothesis, based on the Na(+)/K(+)-ATPase "signalosome," that describes the interaction of cardiac glycosides with the Na(+) pump as machinery activating various signaling pathways via intramembrane and cytosolic protein-protein interactions. These pathways, which may be activated simultaneously or selectively, elevate [Ca(2+)](i), activate Src and the ERK1/2 kinase pathways, and activate phosphoinositide 3-kinase and protein kinase B (Akt), NF-kappaB, and reactive oxygen species. A recent development indicates that new pharmaceuticals with antihypertensive and anticancer activities may be found among CTS and their derivatives: the antihypertensive rostafuroxin suppresses Na(+) resorption and the Src-epidermal growth factor receptor-ERK pathway in kidney tubule cells. It may be the parent compound of a new principle of antihypertensive therapy. Bufalin and oleandrin or the cardenolide analog UNBS-1450 block tumor cell proliferation and induce apoptosis at low concentrations in tumors with constitutive activation of NF-kappaB.

Topics: Animals; Antihypertensive Agents; Antineoplastic Agents; Blood Pressure; Bufanolides; Calcium; Cardiac Glycosides; Cardiovascular System; Cell Death; Cell Proliferation; Diabetes Mellitus; Digoxin; Humans; Hypertension; Molecular Structure; Myocardial Contraction; Myocytes, Cardiac; Neoplasms; Ouabain; Sodium Chloride; Sodium-Potassium-Exchanging ATPase; Structure-Activity Relationship

Endoxin is a factor with a digitalis-like biological activity. It is a Na+ pump inhibitor and may be an endogenous medium of digitalis receptor. There are abnormal plasma levels of endoxin in some pathophysiologic states such as hypertension, acute myocardial infarction, arrhythmia, heart failure, etc. Some studies have demonstrated that the abnormal endoxin levels may be implicated in pathogenesis of these diseases or pathophysiologic process involved. Therefore, to clarify the effects of endoxin has much significance in understanding pathogenesis, prevention and treatment of hypertension and other cardiovascular diseases.

Topics: Animals; Cardenolides; Cardiomegaly; Cardiovascular System; Diabetes Mellitus; Digoxin; Enzyme Inhibitors; Heart Diseases; Heart Failure; Humans; Hypertension; Myocardial Infarction; Pulmonary Heart Disease; Saponins; Sodium-Potassium-Exchanging ATPase

The vascular Na+ pump maintains intracellular ionic concentration and controls membrane potential. Its inhibition by cardiac glycosides enhances the intracellular Na+ concentration. This in turn activates the Na+-Ca2+ exchange mechanism, which induces intracellular Ca2+ increase, membrane depolarization, and noradrenaline release from perivascular adrenergic nerve endings; mechanisms that promote vasoconstriction. This article reviews the relevance of the Na+ pump in vascular tone regulation and the modulation of its activity by the endothelium. The endothelium negatively modulates the vasoconstriction elicited by Na+ pump inhibition by the release of nitric oxide, according to some authors, or an unknown factor, as suggested by others. The possible existence of endogenous digitalis-like factors is also reviewed, as is the involvement of the vascular Na+ pump in some cardiovascular disorders and aging.

Topics: Aging; Animals; Blood Vessels; Cardenolides; Diabetes Mellitus; Digoxin; Endothelium, Vascular; Humans; Hypertension; Nitric Oxide; Norepinephrine; Ouabain; Saponins; Sodium-Potassium-Exchanging ATPase; Vasodilation

Endogenous factors cross-reacting with antidigoxin antibodies have been found in several tissues and body fluids of animals and humans, using commercially available digoxin radioimmunoassay or enzyme immunoassay methods. The chemical characteristics of these endogenous factors are, at present, unknown, although it has been suggested that they could be substances with low molecular weight. Experimental studies and theoretical considerations indicate that endogenous digitalis-like factors (DDLFs), in addition to the ability to react with antibodies, might also bind to the specific cellular receptor of the cardiac glycosides and thus inhibit the membrane Na+/K(+)-ATPase (sodium pump). Therefore, EDLF can be an endogenous modulator of the membrane sodium-potassium pump and several authors have suggested that EDLF could play a role in the regulation of fluids and electrolytes, muscular tone of myocardial and also in the pathogenesis of arterial hypertension. In this review, the authors discuss the hypothesis that, in metabolic diseases such as diabetes mellitus, obesity and acromegaly, the sodium retention and volume expansion, possibly due to exaggerated sodium intake, and/or exogenously induced peripheral hyperinsulinemia and high levels of growth hormone, could trigger a sustained release of EDLF, which in turn increases the blood pressure.

Topics: Acromegaly; Blood Proteins; Cardenolides; Cardiac Glycosides; Diabetes Mellitus; Digoxin; Humans; Hypertension; Natriuresis; Obesity; Saponins

Digoxin is recommended in symptomatic heart failure patients with reduced ejection fraction (HF-REF) in sinus rhythm and refractory to other evidence-based therapy. Although HF-REF patients with diabetes have worse functional status than those without, the effects of digoxin have not been specifically evaluated according to diabetes status.. We examined the efficacy and safety of digoxin in HF-REF patients with and without diabetes in the Digitalis Investigation Group trial. Mortality from all-cause, cardiovascular (CV) causes and heart failure (HF), along with HF hospitalisation and suspected digoxin toxicity were analyzed according to diabetes status and randomised treatment assignment.. Of the 6800 patients, those with diabetes (n=1933) were older, more often women, had worse clinical status and more co-morbidity than those without diabetes. All-cause and CV mortality were higher in patients with diabetes than in those without and digoxin did not reduce mortality in either sub-group. The rate of HF hospitalization (per 100 person-years) in patients with diabetes was higher than in those without and was reduced by digoxin in both patient groups: diabetes - placebo 20.5 and digoxin 16.0 (HR 0.79, 95% CI: 0.68-0.91); no diabetes - placebo 12.7 and digoxin 8.7 (HR 0.69, 0.62-0.77); interaction p=0.14. Suspected digoxin toxicity in patients randomised to digoxin was more common among patients with diabetes than without (6.5% versus 5.8%), as was hospitalisation for digoxin toxicity (1.4% versus 0.8%).. Added to an ACE inhibitor, digoxin reduced HF hospitalisation in HF-REF patients with and without diabetes without a substantial risk of toxicity.

Topics: Aged; Cardiotonic Agents; Diabetes Mellitus; Digitalis; Digoxin; Female; Heart Failure; Hospitalization; Humans; Hyperkalemia; Male; Middle Aged; Retrospective Studies; Risk Factors; Stroke Volume; Treatment Outcome

Fourteen obese patients (body mass index = 34-47 kg/m2; mean = 40 kg/m2) with lumbar cerebrospinal fluid pressure (Pcsf) above 20 cm water in 10 of the 14 patients were treated with digoxin with a serum concentration of at least 1.0 nmol/L (0.8 ng/ml) for 6 months. Pcsf decreased significantly during digoxin medication (p < 0.005). Although there were no diet restrictions, all patients decreased in weight (range: 3-25 kg; mean = 10.6 kg) during the 6 months (p < 0.001). When digoxin medication was stopped in 3 patients, prompt weight increase occurred. Most patients needed progressively increased digoxin doses to attain stabilized serum concentrations at the stipulated level, in 5 patients more than 0.5 mg a day. Five of 13 patients developed diabetes mellitus during the digoxin medication. The larger the dose of digoxin, the greater the risk for diabetes mellitus to occur.

Topics: Adult; Body Mass Index; Body Weight; Cerebrospinal Fluid Pressure; Diabetes Mellitus; Digoxin; Female; Humans; Intracranial Hypertension; Middle Aged; Obesity, Morbid; Time Factors; Treatment Outcome; Weight Loss

The present study was undertaken to investigate the possible factors which may contribute to the altered digoxin levels in diabetic patients. The digoxin levels were found to be significantly higher in diabetics (1.74 +/- 0.09 ng/ml) as compared to non-diabetics (0.76 +/- 0.07 ng /ml). There was a positive correlation between digoxin levels and glycosylated haemoglobin levels. All diabetic patients had serum creatinine, urea and potassium levels within normal limits. However, serum TSH levels were found to be significantly higher in diabetics as compared to controls. Serum tri-iodo-1-thyronine (T3) levels were found to be lower in diabetics as compared to non-diabetics. Our data suggests that diabetes-mellitus causes alteration of digoxin levels. One of the causes of this increase in digoxin levels may be a tendency towards mild hypothyroidism associated with diabetes mellitus.

Topics: Aged; Blood Glucose; Cardiotonic Agents; Cholesterol; Diabetes Mellitus; Digoxin; Female; Glycated Hemoglobin; Humans; Kidney Function Tests; Male; Middle Aged; Thyroid Function Tests; Thyroid Hormones

Digoxin is widely used in patients with atrial fibrillation (AF), but its association with adverse outcomes remains controversial.. We aimed to assess the association between digoxin and adverse outcomes in Chinese patients with AF.. We used data from the Chinese Atrial Fibrillation Registry, a prospective, multicenter, hospital-based registry study involving 31 hospitals. In total, 10,472 eligible patients with AF, enrolled from August 2011 to December 2016, were included in this study. The association between digoxin use and all-cause mortality, cardiovascular death, and cardiovascular hospitalization were investigated using Cox proportional hazards models.. In total, 1152 (11%) patients were treated with digoxin at baseline. Patients receiving digoxin were older (mean age 69.7 vs. 66.5 years) and had a higher heart rate (92.4 vs. 79.7 beats/min). A higher proportion of patients receiving digoxin therapy had a history of heart failure (62.5 vs. 15.6%), diabetes mellitus (34.4 vs. 24.4%), and persistent AF (67.9 vs. 38.4%). Digoxin use was independently associated with increased all-cause mortality (adjusted hazard ratio (aHR) 1.21; 95% confidence interval (CI) 1.02-1.43; p = 0.031), cardiovascular death (aHR 1.25; 95% CI 1.01-1.55; p = 0.043), and cardiovascular hospitalization (aHR 1.21; 95% CI 1.05-1.39; p = 0.007). The associations were also homogeneous across various subgroups except in patients with and without renal dysfunction (p value for interaction = 0.029).. In this Chinese AF cohort, for patients who had not undergone ablation, digoxin use was associated with a significant increase in adverse outcomes. Although residual confounders may exist, and serum concentrations of digoxin were unavailable, digoxin should be used with caution in clinical practice, and its effects need to be critically evaluated in randomized trials.. URL: http://www.chictr.org.cn/showproj.aspx?proj=5831. Unique identifier: ChiCTR-OCH-13003729.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus; Digoxin; Female; Glomerular Filtration Rate; Heart Failure; Heart Rate; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Factors; Socioeconomic Factors

This study assessed sex-related differences in a large cohort of unselected patients with heart failure (HF) across the ejection fraction (EF) spectrum.. Females are under-represented in randomized clinical trials. Potential sex-related differences in HF may question the generalizability of trials.. In the Swedish Heart Failure Registry population multivariate Cox and logistic regression models were fitted to investigate differences in prognosis, prognostic predictors, and treatments across males and females.. Of 42,987 patients, 37% were females (55% with HF with preserved EF [HFpEF], 39% with HF with mid-range EF [HFmrEF], and 29% with HF with reduced EF [HFrEF]). Females were older and more symptomatic and more likely to have hypertension and kidney disease but less likely to have diabetes and ischemic heart disease. After adjustments, females were more likely to use beta-blockers and digoxin but less likely to receive HF device therapy. Crude mortality/HF hospitalization rates for HFpEF (hazard ratio [HR]: 1.16) and HFmrEF (HR: 1.14) were significantly higher in females but lower in females with HFrEF (HR: 0.95). After adjustments, the risk was significantly lower in females regardless of EF (HR: 0.80 in HFrEF, HR: 0.91 in HFmrEF, and HR: 0.93 in HFpEF). The main sex-related differences in prognostic predictors concerned diabetes in HFrEF and anemia in HFmrEF.. Males and females with HF showed different characteristics across the EF spectrum. Males reported a lower crude risk of mortality/morbidity in HFpEF and HFmrEF but higher risk of HFrEF, although after adjustments, prognosis was better in females regardless of EF. The observed sex-related differences highlight the need for an adequate representation of females in HF randomized controlled trials to improve generalizability.

Topics: Adrenergic beta-Antagonists; Age Distribution; Aged; Aged, 80 and over; Cardiac Resynchronization Therapy; Cardiotonic Agents; Diabetes Mellitus; Digoxin; Female; Heart Failure; Hospitalization; Humans; Hypertension; Kidney Diseases; Logistic Models; Male; Middle Aged; Mortality; Myocardial Ischemia; Phenotype; Prognosis; Proportional Hazards Models; Registries; Severity of Illness Index; Sex Factors; Stroke Volume; Sweden

The aim of this study was to assess temporal trends and factors associated with digoxin use at discharge among patients admitted with heart failure (HF).. Digoxin has class IIa recommendations for treating HF with reduced ejection fraction (HFrEF) in the United States. Digoxin use, temporal trends, and clinical characteristics of HF patients in current clinical practice in the United States have not been well studied.. An observational analysis of 255,901 patients hospitalized with HF (117,761 with HFrEF and 138,140 with preserved EF [HFpEF]) from 398 hospitals participating in the Get With The Guidelines-HF registry between January 2005 and June 2014 was conducted to assess the temporal trends and factors associated with digoxin use.. Among 117,761 HFrEF patients, only 19.7% received digoxin at discharge. Digoxin prescriptions decreased from 33.1% in 2005 to 10.7% in 2014 (ptrend < 0.0001). Factors associated with digoxin use in HFrEF included atrial fibrillation (AF) (odds ratio [OR]: 2.14; 95% confidence intervals [CI]: 2.02 to 2.28), history of implantable cardioverter defibrillator use (OR: 1.39; 95% CI: 1.32 to 1.46), chronic obstructive pulmonary disease (OR: 1.13, 95% CI: 1.08 to 1.18), diabetes mellitus (OR: 1.10, 95% CI: 1.06 to 1.14), younger age (OR: 0.96, 95% CI: 0.95 to 0.97), lower blood pressure (OR: 0.96, 95% CI: 0.96 to 0.97), and having no history of renal insufficiency (OR: 0.91, 95% CI: 0.85 to 0.97). Use of digoxin in patients with HFpEF (n = 138,140) without AF was 9.8% in 2005, which decreased to 2.2% in 2014 (ptrend < 0.0001).. One in 5 HFrEF patients received digoxin at discharge, with a significant downward temporal trend in use over the study period. Use of digoxin in HFpEF patients without AF was very low and decreased over the study period.

Topics: Age Factors; Aged; American Heart Association; Atrial Fibrillation; Blood Pressure; Cardiotonic Agents; Comorbidity; Defibrillators, Implantable; Diabetes Mellitus; Digoxin; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Practice Patterns, Physicians'; Pulmonary Disease, Chronic Obstructive; Registries; Renal Insufficiency; Stroke Volume; United States

Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data. We studied the use and outcomes of digoxin in patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).. For this retrospective analysis, we included and classified patients from ROCKET AF on the basis of digoxin use at baseline and during the study. Patients in ROCKET AF were recruited from 45 countries and had AF and risk factors putting them at moderate-to-high risk of stroke, with or without heart failure. We used Cox proportional hazards regression models adjusted for baseline characteristics and drugs to investigate the association of digoxin with all-cause mortality, vascular death, and sudden death. ROCKET AF was registered with ClinicalTrials.gov, number NCT00403767.. In 14,171 randomly assigned patients, digoxin was used at baseline in 5239 (37%). Patients given digoxin were more likely to be female (42% vs 38%) and have a history of heart failure (73% vs 56%), diabetes (43% vs 38%), and persistent AF (88% vs 77%; p<0·0001 for each comparison). After adjustment, digoxin was associated with increased all-cause mortality (5·41 vs 4·30 events per 100 patients-years; hazard ratio 1·17; 95% CI 1·04-1·32; p=0·0093), vascular death (3·55 vs 2·69 per 100 patient-years; 1·19; 1·03-1·39, p=0·0201), and sudden death (1·68 vs 1·12 events per 100 patient-years; 1·36; 1·08-1·70, p=0·0076).. Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of digoxin having these effects. A randomised trial of digoxin in treatment of AF patients with and without heart failure is needed.. Janssen Research & Development and Bayer HealthCare AG.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Death, Sudden; Diabetes Mellitus; Digoxin; Factor Xa Inhibitors; Female; Heart Failure; Heart Rate; Humans; Intracranial Embolism; Male; Morpholines; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Rivaroxaban; Sex Distribution; Stroke; Thiophenes; Vitamin K; Warfarin

Higher levels of resting heart rate (HR) have been associated with sudden cardiac death (SCD) but mechanisms are poorly understood. We hypothesized that severe left ventricular systolic dysfunction (LVSD) and HR-modulating drugs explain the HR-SCD relationship.. To evaluate the relationship between HR, severe LVSD, HR-modulating drugs, and SCD in the community by using a case-control approach.. From the ongoing Oregon Sudden Unexpected Death Study, SCD cases (n = 378) aged ≥35 years and with electrocardiogram-documented resting HR were compared to 378 age- and gender-matched control subjects with coronary artery disease (mean age 68 ± 13 years; 69% man). Associations with SCD were assessed by using multivariable logistic regression.. Mean resting HR was significantly higher among SCD cases compared to controls (7.5 beats/min difference; P < .0001). HR was a significant determinant of SCD after adjustment for significant comorbidities and medications (odds ratio for 10 beats/min increase 1.26; 95% confidence interval 1.14-1.38; P < .0001). After considering LVSD, resting HR was slightly attenuated but remained significantly associated with SCD (P = .005). In addition to diabetes and digoxin as well as pulmonary and renal disease, LVSD was also independently associated with SCD (odds ratio 1.79; 95% confidence interval 1.11-2.87; P = .02).. Contrary to expectations, the significant relationship between increased resting HR and SCD persisted even after adjustment for LVSD and HR-modulating drugs. These findings suggest a potential role for additional novel interventions/therapies that modulate autonomic tone.

Topics: Aged; Cardiotonic Agents; Case-Control Studies; Coronary Artery Disease; Death, Sudden, Cardiac; Diabetes Mellitus; Digoxin; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Risk Factors; Ventricular Dysfunction, Left

Topics: Acute Coronary Syndrome; Algorithms; Cardiology; Cardiotonic Agents; Cardiovascular Diseases; Diabetes Mellitus; Digoxin; Female; Heart Failure; Hospitalization; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Medicare

To document the presence and treatment of selected vascular risk factors in patients with vascular cognitive impairment and elements affecting undertreatment of vascular risk factors.. Secondary analysis of the Canadian Study of Health and Aging database, which is a national, representative, cross-sectional study of the epidemiologic distribution of dementia in elderly people in Canada.. Survey.. Institutionalized and community-dwelling elderly people.. Vascular risk factors, dementia diagnosed by standard methods, and medication use.. Treatable vascular risk factors occurred significantly more often in patients with vascular cognitive impairment (with and without dementia) than in patients with probable Alzheimer disease or normal cognitive function. For example, 76% of patients with vascular dementia and 57% of those with vascular cognitive impairment without dementia had a history of stroke, compared with only 5% of those with probable Alzheimer disease and 7% of those with no cognitive loss. (For hypertension, the comparable figures are 55%, 48%, 24%, and 38%, respectively.) Potential undertreatment of vascular risk factors had little effect on mean control of vascular risk factors. For example, the mean (+/- SD) systolic blood pressure in those being treated was 144 +/- 26 mm Hg, compared with 142 +/- 25 mm Hg in those not receiving pharmacological treatment. In each group (treated vs untreated), the proportion of patients with a systolic blood pressure higher than 160 mm Hg was 20% and 16%, respectively. Potential undertreatment occurred most often in those with severe dementia and those living in nursing homes.. Vascular risk factors occurred more commonly in patients with vascular cognitive impairment compared with other patients, including those with other forms of dementia. When present, such risk factors were often treated pharmacologically, except in patients with severe dementia and those in long-term care institutions. Undertreatment does not, in general, result in worsened risk factor control.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Aspirin; Cognition Disorders; Dementia; Diabetes Complications; Diabetes Mellitus; Digoxin; Female; Humans; Hypertension; Male; Risk Factors; Vascular Diseases

Our object was to evaluate the effects of regular mild exercise on blood pressure and on circulating level of ouabainlike factors (OLF) and of nitrate anion, an endproduct of nitric oxide (NO) in humans. We measured plasma ouabainlike immunoreactivity (OLI) and nitrate ions (NO3.) before and after mild exercise for 3 months' duration in 16 patients with essential hypertension, diabetes mellitus, obesity, or hyperlipidemia. Plasma OLI was measured using an amplified ELISA system with anti-ouabain antibody and biotinyl-tyramide. Serum NO3. was measured with high-performance liquid chromatography (HPLC) with an anion-exchange column. With the reverse phase HPLC system with an octa decylsilyl silicagel column, the elution volume of plasma OLI of a healthy volunteer matched that of authentic ouabain in a gradient elution system of acetonitrile/H2O. Plasma OLI levels decreased significantly by about 34% after mild exercise, and NO3. levels tended to be within the reference interval in normal volunteers. Body weight, diastolic and systolic blood pressure, serum triglyceride and acetylcholine esterase (a marker of the fatty liver) were significantly decreased (p < 0.01) after 3 months of regular mild exercise. The plasma OLI level was significantly correlated with plasma NO3., there was a trend toward a correlation with diastolic blood pressure (p = 0.06) before and after regular exercise. Regular mild exercise led to a decrease in plasma levels of OLI, and acetylcholine esterase activity and blood pressure in adult patients. Results suggest that changes in OLF production contribute to the blood pressure regulation seen in patients who exercise regularly.

Topics: Adult; Aged; Blood Pressure; Cardenolides; Chromatography, High Pressure Liquid; Diabetes Mellitus; Digoxin; Enzyme-Linked Immunosorbent Assay; Exercise; Female; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Nitrates; Nitric Oxide; Obesity; Ouabain; Saponins

A comparison of the results of a newly developed fluorescence-derivatization/HPLC method and a commercial immunoassay method (ACA, Dupont) for the measurement of serum digoxin concentrations in patients indicates that (1) the results from the ACA method agree well with those from the HPLC method in patients with cardiovascular disease but without renal, diabetic, and liver disease, (2) serum digoxin concentrations determined by the ACA method are overestimated in patients with renal, diabetic, or liver disease, and (3) the steady-state serum concentrations of hydrolyzed and reduced metabolites are relatively insignificant in patients receiving digoxin therapy, including patients with renal failure. The excellent reproducibility of the HPLC and immunoassay methods (coefficient of variation < 9.0%), together with the demonstrated specificity of the HPLC method with respect to potential interference from digoxin metabolites, endogenous digoxin-like immunoactive substances, and coadministered drugs and their metabolites, allows quantitation of the degree of interference in digoxin immunoassays under actual therapeutic drug monitoring conditions. Clinically significant interferences (0.3 to 1.1 ng/ml) with immunoassay determination were found in the majority of patients in all three diseases studied.

Topics: Adult; Aged; Cardiotonic Agents; Chromatography, High Pressure Liquid; Diabetes Mellitus; Digoxin; Female; Fluorescence; Humans; Immunoassay; Kidney Diseases; Liver Diseases; Male; Middle Aged

Topics: Adrenal Glands; Atrial Natriuretic Factor; Autonomic Nervous System; Cardenolides; Diabetes Mellitus; Digoxin; Enzyme Inhibitors; Humans; Hypothalamus; Saponins

Substances with digoxin- and ouabain-like immunoactivity (DLIA) are specific inhibitors of Na(+)-K(+)-ATPase which increase the total amount of intracellular stored calcium (Ca2+i). In diabetic patients, DLIA levels have been reported to be increased. Although this increase is probably secondary to sodium retention and volume expansion (included in diabetic subjects by hyperinsulinemia and/or diabetic nephropathy), the question arises of whether it has pathophysiological consequences: namely, whether substances with DLIA, via their effect on Na(+)-K(+)-ATPase activity and Ca2+i stores, could in diabetic subjects facilitate development of hypertension and/or modulate insulin sensitivity or insulin secretion. Clinical findings of correlations of DLIA to blood pressure, insulin levels and to degree of insulin resistance, together with experimental findings of decreased Na(+)-K(+)-ATPase activity, increased Ca2+i and decreased Mg2+i in both diabetic and hypertensive subjects, support these hypotheses. However, the issue of whether or not these relations are causative and whether or not defects in intracellular milieu are primary or secondary to non-insulin-dependent diabetes mellitus has not been resolved yet. Moreover, pathogenesis of both diabetes mellitus and hypertension is multifactorial and includes many other factors. Therefore, further efforts should be made to elucidate the exact role of substances with DLIA in diabetes mellitus.

Topics: Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Digoxin; Glucose; Humans; Hyperinsulinism; Hypertension; Immunoassay; Insulin; Insulin Secretion; Models, Biological; Ouabain

To examine the relationship between administration of selected medications and falls experienced by hospitalized elderly patients. Benzodiazepines and other medications previously associated with falls in elderly patients residing in the community and nursing homes were the primary focus.. Retrospective case control.. Private, not-for-profit, 575-bed acute care hospital.. A total of 100 patients who had fallen and 100 control patients, aged at least 70 years, admitted during the same 17-month time period.. We examined the relationship between falls and patient demographics, underlying disease states, number of concurrent disease states, and length of hospitalization. Possible associations between the administration of narcotics, benzodiazepines, antidepressants, antipsychotics, other sedating agents, antihypertensives, diuretics, nitrates, and digoxin 48 hours prior to the fall or reference day were explored. The relationships between benzodiazepine half-life, dosage, administration frequency, cumulative dose, and falls were also examined.. Demographically the groups were similar except that patients who had fallen were hospitalized significantly longer (mean 18.8 vs 12.2 d; p < 0.00001) than control patients. Benzodiazepines were received by more (40% vs 20%, odds ratio = 2.67) patients who had fallen than control patients. The use of long (> 24 h) half-life benzodiazepines was similar in patients who had fallen (48%) and control patients (45%). Long half-life benzodiazepines were commonly administered (65%) to patients who had fallen in doses greater than that recommended for the elderly. Benzodiazepine use, expressed as milligrams of diazepam equivalents received during the 48-hour study, was higher in patients who had fallen than in control patients (15.00 +/- 17.80 vs 9.73 +/- 6.58 mg), but this was not statistically significant (p = 0.1030). Congestive heart failure (37% vs 24%), digoxin therapy (35% vs 22%), or administration of 3 or more psychoactive agents (17% vs 4%) were all more common in patients who had fallen than in control patients.. Falls experienced by the elderly patients in our acute care institution were associated with the presence of congestive heart failure along with digoxin therapy, benzodiazepine use, or the use of at least 3 psychoactive agents.

Topics: Accidental Falls; Aged; Aged, 80 and over; Benzodiazepines; Cardiovascular Diseases; Case-Control Studies; Diabetes Mellitus; Digoxin; Diuretics; Female; Half-Life; Heart Failure; Hospital Bed Capacity, 500 and over; Hospitalization; Humans; Hypnotics and Sedatives; Inpatients; Length of Stay; Lung Diseases; Male; Pharmaceutical Preparations; Psychotropic Drugs; Retrospective Studies; United States

The relationship between levels of potassium in the serum and the development of malignant arrhythmias was examined in a retrospective study involving 1011 patients presenting with acute myocardial infarction. Thirteen percent of the overall patients studied had significant hypokalemia (k less than 3.5 mmol/liter). The average initial level of potassium in patients who developed malignant arrhythmias was (4.10 mmol/liter) significantly lower (P less than 0.01) than those patients who did not develop such arrhythmias (4.19 mmol/liter). To determine whether the level of potassium was, in itself, the primary cause of malignant arrhythmias following myocardial infarction, a subgroup analysis of factors influencing these levels was performed. It was determined that diabetics have a higher level of potassium than nondiabetics (4.2 mmol/liter versus 4.11 mmol/liter - P = 0.01) and a lower incidence of malignant arrhythmias (50.5% versus 63.5% - P = 0.002). No correlation was found between treatment with either digitalis or diuretics and malignant arrhythmias. Size and location of infarcted areas was found to have a direct relationship with development of arrhythmias. Size and location of infarctions, however, were not found to be related to levels of potassium in the serum. Our findings support and clarify earlier suggestions establishing the levels of potassium in the serum as an important causative factor, together with size and location of infarctions, in the development of malignant arrhythmias.

Topics: Adrenergic beta-Antagonists; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Diabetes Mellitus; Digoxin; Diuretics; Female; Heart Block; Homeostasis; Humans; Hyperkalemia; Hypokalemia; Male; Middle Aged; Myocardial Infarction; Potassium; Retrospective Studies; Tachycardia; Ventricular Fibrillation

Topics: Blood Proteins; Cardenolides; Catecholamines; Diabetes Mellitus; Diabetic Neuropathies; Diabetic Retinopathy; Digoxin; Erythrocyte Membrane; Humans; Hypertension; Insulin; Obesity; Saponins; Sodium-Potassium-Exchanging ATPase

We assessed the role of circulating digitalis-like substance(s) on the blood pressure regulation in patients with essential hypertension, cardiac diseases, diabetes mellitus and renal diseases by measuring digoxin-like immunoreactivity (DLI). Plasma DLI concentrations tended to correlate with blood pressure in all patient groups. Plasma DLI correlated to plasma aldosterone concentration in patients with essential hypertension, which suggested close interrelationship between DLI and electrolytes metabolism with adrenal steroids. Serum immunoreactive insulin (IRI) levels significantly correlated with blood pressure. Because plasma DLI levels correlated with serum IRI, increased levels of insulin could have induced sodium retention leading to increased DLI levels. Digitalis-like substance, but not insulin, would have directly increased blood pressure in patients with abnormal glucose tolerance. Plasma DLI levels significantly correlated with the severity of renal insufficiency in patients with renal diseases. Plasma DLI highly correlated with amounts of plasma proteins, particularly with albumin, which would be due to the binding of DLI with albumin in plasma. Because the level of non-binding DLI is extremely low when assayed with a digoxin-radioimmunoassay, it was impossible to assess the level of a free-form of DLI, i.e., active DLI. That could be a reason why the correlation between the DLI and the other parameters was not highly significant. Collectively, these findings suggest that the DLI is one of the major determinants of blood pressure rises, regardless of any cause.

Topics: Adult; Aged; Blood Pressure; Blood Proteins; Cardenolides; Diabetes Mellitus; Digoxin; Female; Humans; Hypertension; Kidney Diseases; Male; Middle Aged; Obesity; Saponins

In a population-based study in southern Wisconsin, 1370 diabetic persons diagnosed after 29 years of age were examined using standard protocols to determine the prevalence of proteinuria and associated risk variables. Proteinuria (greater than or equal to 0.30 g/L) was present in 18.0% of persons taking insulin and 12.2% of the persons not taking insulin. Proliferative retinopathy and proteinuria were associated with each other. Proteinuria was also associated with increasing duration of diabetes, high systolic blood pressure, use of digoxin, and being male, but not with a history of cigarette smoking or metabolic control as measured by glycosylated hemoglobin.

Topics: Adult; Age Factors; Aged; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Digoxin; Female; Humans; Hypertension; Male; Middle Aged; Proteinuria; Time Factors

Topics: Acute Kidney Injury; Adult; Aged; Arrhythmias, Cardiac; Diabetes Mellitus; Digoxin; Female; Half-Life; Hemoperfusion; Humans; Hypotension; Kidney Failure, Chronic; Male; Middle Aged; Polystyrenes; Polyvinyls; Renal Dialysis

Topics: Action Potentials; Adolescent; Adult; Aged; Ajmaline; Bunaftine; Coronary Disease; Diabetes Mellitus; Digoxin; Electrocardiography; Female; Heart; Heart Diseases; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Ventricular Function

Tolbutamide belongs to those drugs responsible for the majority of drug interactions. E.g. Tolbutamide metabolism has been shown to be inhibited by coumarole derivatives. We determined plasma-tolbutamide levels in diabetic out-patients for one year. The results obtained indicate no difference in patients additionally treated with either digoxin or digoxin and alpha-methyldopa, or buformin and phenprocumone as compared with control groups. Interactions with respect to biotransformation should not be expected as far as digoxin, alpha-Methyldopa, or buformine were concerned, since these compounds do not share a common metabolic pathway with tolbutamide. In a different group of patients the elimination half life of tolbutamide under the influence of phenprocoumone was additonally determined. Differences could not be detected. This finding can be explained by means of enzyme-kinetic considerations, since phenprocumone, in contrast to dicoumarole, becomes metabolized according to a first order reaction. Competitive enzyme inhibition with tolbutamide which is metabolized similarly to phenprocoumone, therefore appears improbable.

Topics: Buformin; Diabetes Mellitus; Digoxin; Drug Interactions; Enzyme Inhibitors; Half-Life; Humans; Methyldopa; Phenprocoumon; Tolbutamide

This survey deals with the 5 most important internal problems of old aged people undergoing surgery: chronic emphysematous bronchitis, geriatric heart, Diabetes mellitus, bleeding tendency during operation and venous thromboembolism.

Topics: Aged; Bandages; Blood Coagulation Disorders; Bronchitis; Diabetes Mellitus; Digitoxin; Digoxin; Emphysema; Exercise Therapy; Heart Failure; Humans; Hypoglycemic Agents; Preoperative Care; Respiratory Therapy; Strophanthins; Thromboembolism

Topics: Adenocarcinoma; Aged; Blood Glucose; Carbutamide; Diabetes Mellitus; Diethylstilbestrol; Digoxin; Drug Interactions; Heart Diseases; Humans; Jaundice; Lipids; Liver Cirrhosis; Liver Function Tests; Male; Nitroglycerin; Prostatic Neoplasms; Triglycerides

Topics: Adult; Angina Pectoris; Diabetes Mellitus; Digoxin; Electrocardiography; Female; Heart Conduction System; Heart Ventricles; Humans; Hypertension; Hypokalemia; Tachycardia

Topics: Adult; Aged; Diabetes Mellitus; Digoxin; Female; Glomerulonephritis; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Tritium

Topics: Addison Disease; Dexamethasone; Diabetes Mellitus; Digoxin; Humans; Hydrocortisone; Penicillins; Streptomycin; Sulfonylurea Compounds; Tuberculosis; Tuberculosis, Endocrine

Topics: Acute Kidney Injury; Anuria; Chlorothiazide; Diabetes Mellitus; Digoxin; Geriatrics; Gout; Hydrochlorothiazide; Hypertension; Hypertension, Renal; Kidney; Renal Insufficiency; Toxicology