digoxin and Hypokalemia

The prevalence of herb-drug interactions has been exaggerated. Nonetheless, some herbs, including garlic, ginkgo, ginseng, and St John's wort, can have a significant influence on concurrently administered drugs. Herbal medicines may mimic, decrease, or increase the action of prescribed drugs. This can be especially important for drugs with narrow therapeutic windows and in sensitive patient populations such as older adults, the chronically ill, and those with compromised immune systems.

Topics: Anticoagulants; Cardiovascular Agents; Digoxin; Drug Interactions; Herb-Drug Interactions; Humans; Hypericum; Hypertension; Hypokalemia; Phytotherapy; Plant Preparations

Significant digitalis toxicity, although uncommon, is a medical emergency. Recognition of the problem and good supportive care (eg, administration of activated charcoal and binding resins, correction of potassium levels, restoration of heart rhythm) are the cornerstones of treatment. If indicated, immunotherapy with digoxin immune Fab (Digibind) is a valuable and effective tool.

Topics: Arrhythmias, Cardiac; Charcoal; Digitalis Glycosides; Digoxin; Emergencies; Humans; Hypokalemia; Immunoglobulin Fab Fragments; Poisoning

The electrical stability of the heart is more sensitive to the extracellular than to the intracellular potassium concentration. During exercise, extracellular potassium varies rapidly. Catecholamines also modulate the plasma potassium concentration. Hypokalaemia of any cause can precipitate arrhythmias. Ischaemic myocardium loses potassium into the extracellular space within seconds and the cell becomes depolarized. The rise of the extracellular potassium ion concentration accounts for many of the early electrophysiological changes. Abrupt changes of plasma potassium concentration in normal myocardium and a high potassium concentration in ischaemic myocardium can set up electrical forces which initiate arrhythmias. The same phenomenon can account for changes on the electrocardiogram early after the cessation of an exercise test in a patient with ischaemic heart disease. Accumulation of potassium between cells in response to an increase of heart rate is a possible mechanism for false positive exercise tests and Syndrome X.

Topics: Acidosis; Action Potentials; Angioplasty, Balloon; Animals; Catecholamines; Coronary Disease; Digoxin; Diuretics; Exercise Test; False Positive Reactions; Heart; Heart Rate; Humans; Hyperkalemia; Hypokalemia; Myocardium; Physical Exertion; Potassium; Syndrome

Topics: Acidosis, Renal Tubular; Amiloride; Animals; Bicarbonates; Chlorides; Digoxin; Hypokalemia; Lithium; Phosphates; Pyrazines; Rats

Topics: Age Factors; Calcium; Digitalis Glycosides; Digitoxin; Digoxin; Drug Interactions; Humans; Hypercalcemia; Hypokalemia; Intestinal Absorption; Methods; Potassium; Saliva; Suicide

Topics: Age Factors; Creatinine; Diet; Digitalis; Digitalis Glycosides; Digitoxin; Digoxin; Diuretics; Heart Failure; Humans; Hypercalcemia; Hypokalemia; Kidney; Kinetics; Liver; Magnesium; Ouabain; Plants, Medicinal; Plants, Toxic; Rest; Thyroid Gland; Time Factors

The effect of multiple oral doses of montelukast, a cysLT1 receptor antagonist, on the pharmacokinetics of oral digoxin was studied in healthy male volunteers in a randomized double-blind two-period crossover study. Subjects received 10 mg of montelukast or placebo daily for 11 days. On day 7, they received a single 0.5 mg oral dose of digoxin elixir. The pharmacokinetic parameters of digoxin (AUC0-->24' AUC0-->infinity' Cmax' tmax' t1/2) and cumulative urinary excretion over 120 hours were not affected by the multiple doses of montelukast. The 90% confidence interval for each of these parameters fell within prespecified clinically acceptable bounds. Side effects were mild and transient. This suggests that concurrent administration of montelukast and digoxin was well tolerated. Concurrent treatment with montelukast has no effect on the pharmacokinetics of digoxin.

Topics: Acetates; Adult; Anti-Arrhythmia Agents; Cross-Over Studies; Cyclopropanes; Digoxin; Double-Blind Method; Drug Interactions; Electrocardiography; Female; Humans; Hypokalemia; Immunochemistry; Leukotriene Antagonists; Male; Middle Aged; Patient Dropouts; Quinolines; Sulfides; Time Factors

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Heart Conduction System; Humans; Hypokalemia; Male

An 87-year-old male, prescribed digoxin and furosemide for congestive heart failure and Alzheimer disease, had dehydration and anemia due to poor food intake and hemorrhagic cystitis. Repeated vomiting due to an upper respiratory infection caused disturbance of consciousness and hypotension. The patient was admitted to hospital and diagnosed with digoxin intoxication and hypernatremia. The serum sodium (Na(+)) level was corrected, but the patient died 4 days after admission following uncontrollable seizure. A histologic examination after an autopsy revealed characteristic findings of central pontine myelinolysis (CPM). This is the first autopsy report on CPM triggered by vomiting in association with digoxin administration.

Topics: Aged, 80 and over; Brain; Cardiotonic Agents; Digoxin; Fatal Outcome; Forensic Pathology; Humans; Hypernatremia; Hypokalemia; Male; Myelinolysis, Central Pontine; Respiratory Tract Infections; Seizures; Staining and Labeling; Vomiting

Topics: Acute Disease; Arrhythmias, Cardiac; Cardiotonic Agents; Causality; Colectomy; Confusion; Digoxin; Diuretics; Electrocardiography; Emergencies; Humans; Hypokalemia; Male; Middle Aged; Muscle Weakness; Nursing Assessment; Paresthesia; Patient Care Planning; Patient Education as Topic; Potassium

We describe a case of unintentional poisoning from a cardioactive steroid and the subsequent analytic investigation. A 36-year-old woman with no past medical history and taking no conventional medications ingested an herbal preparation marketed for "internal cleansing." Its ingredients were neither known to the patient nor listed on the accompanying literature. The next morning, nausea, vomiting, and weakness developed. In the emergency department, her blood pressure was 110/60 mm Hg, and her pulse rate was 30 beats/min. Her ECG revealed a junctional rhythm at a rate of 30 beats/min and a digitalis effect on the ST segments. After empiric therapy with 10 vials of digoxin-specific Fab (Digibind), her symptoms resolved, and she reverted to a sinus rhythm at a rate of 68 beats/min. Her serum digoxin concentration measured by means of the fluorescence polarization immunoassay (Abbott TDx) was 1.7 ng/mL. Further serum analysis with the Tina Quant digoxin assay, a more digoxin-specific immunoassay, found a concentration of 0.34 ng/mL, and an enzyme immunoassay for digitoxin revealed a concentration of 20 ng/mL (therapeutic range 10 to 30 ng/mL). Serum analysis by means of high-performance liquid chromatography revealed the presence of active digitoxin metabolites; the parent compound was not present. When the diagnosis of cardioactive steroid poisoning is suspected clinically, laboratory analysis can confirm the presence of cardioactive steroids by using immunoassays of varying specificity. An empiric dose of 10 vials of digoxin-specific Fab might be beneficial in patients poisoned with an unknown cardioactive steroid.

Topics: Adult; Bradycardia; Cardiac Glycosides; Dietary Supplements; Digoxin; Electrocardiography; Female; Humans; Hypokalemia; Immunoglobulin Fab Fragments; Muscle Weakness; Nausea; Plant Preparations; Treatment Outcome; Vomiting

Topics: Aged; Cardiotonic Agents; Confusion; Digoxin; Female; Humans; Hypokalemia; Muscle Weakness; Nursing Assessment; Risk Factors; Tachycardia; Vomiting

Topics: Adrenergic beta-Antagonists; Angioedema; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Chronic Disease; Digoxin; Diuretics; Dose-Response Relationship, Drug; Heart Failure; Humans; Hypokalemia; Hypotension; Spironolactone; Vasodilator Agents

Topics: Aged; Cardiotonic Agents; Diagnosis, Differential; Digoxin; Electrocardiography; Female; Humans; Hypokalemia; Syncope; Tachycardia, Ventricular; Ventricular Premature Complexes

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

Poorly controlled supraventricular arrhythmias in a hypokalaemic 74 year old woman were treated with oral amiodarone. This caused torsades de pointes, and was preceded by marked prolongation of the QT interval. The induction of torsades de pointes by amiodarone is thought to be an idiosyncratic reaction to amiodarone itself which is facilitated by electrolytic abnormalities. The present case, however, indicates the possibility of a pro-arrhythmic effect secondary to an interaction between amiodarone and digoxin.

Topics: Administration, Oral; Aged; Amiodarone; Digoxin; Drug Interactions; Electrocardiography; Female; Humans; Hypokalemia; Tachycardia, Supraventricular; Torsades de Pointes

Topics: Digoxin; Humans; Hypokalemia; Magnesium Deficiency

To examine the relation between preoperative hypokalemia and frequency of intraoperative arrhythmias, Holter monitoring was employed in 447 patients undergoing major cardiac or vascular operations, the group at greatest risk for life-threatening arrhythmias. Based on serum potassium levels measured immediately before surgery, 57% of patients were normokalemic (greater than or equal to 3.6 mEq/L), 34% hypokalemic (3.1-3.5 mEq/L), and 9% severely hypokalemic (less than or equal to 3.0 mEq/L). No arrhythmia occurred at any time in 63% of patients and minor arrhythmias (premature atrial and occasional premature ventricular contractions) occurred in 16%. Frequent or complex ventricular ectopy appeared before and during operation in 92 patients (21%) but was not related to preoperative potassium level or history of long-term diuretic therapy. Frequent and complex ventricular arrhythmias were more common in patients with a history of long-term digoxin therapy or congestive heart failure. Even among these patients, hypokalemia or diuretic therapy did not increase the incidence or severity of ectopy. These data fail to support the common practice of delaying operation for acute potassium replacement in patients whose preoperative serum potassium is less than normal, even in the presence of cardiovascular disease.

Topics: Adult; Anesthesia, General; Arrhythmias, Cardiac; Cardiovascular Diseases; Chronic Disease; Digoxin; Diuretics; Female; Humans; Hypokalemia; Intraoperative Complications; Male; Potassium; Prospective Studies; Time Factors

Heart failure is a major health problem, particularly among the elderly who experience the long term consequence of coronary artery disease. Over the past several years, the heart failure program at Michael Reese Hospital has seen a large number of elderly patients with heart failure. Two-thirds of these patients had a previous myocardial infarction, while 20% had an idiopathic (dilated) cardiomyopathy. Herein, we review that experience, focusing particularly on clinical presentation, our non-invasive approach to objectively determining their functional capacity and the severity of their failure, and, finally, a consideration of the various aspects of their medical management.

Topics: Aged; Digoxin; Diuretics; Dyspnea; Heart Failure; Heart Function Tests; Humans; Hypokalemia; Vasodilator Agents

The electrocardiographic diagnosis of uncomplicated hypokalemia rests on ST segment depression, a decrease in T-wave amplitude, prominent U waves and a U-wave to T-wave ratio of greater than 1. The diagnosis is more difficult in a patient receiving digitalis, but the upsloping ST segment of digitalis can be distinguished from that of hypokalemia. The changes of hypokalemia are most apparent in leads V2 and V3.

Topics: Atrial Fibrillation; Diagnosis, Differential; Digoxin; Electrocardiography; Humans; Hypokalemia

Beta 2-receptor stimulation is required for catecholamine-induced hypokalemia to occur. This hypokalemia is not mediated by insulin, renin or aldosterone. Catecholamine-induced hypokalemia can be prevented by selective beta 2 blockade, which does not abolish the inotropic effect of epinephrine.

Topics: Adrenergic beta-Antagonists; Digoxin; Dose-Response Relationship, Drug; Epinephrine; Heart Rate; Humans; Hypokalemia; Insulin; Isoproterenol; Myocardial Infarction; Physical Exertion; Potassium; Propanolamines; Time Factors

We examined the frequency of hypokalemia and hypomagnesemia in patients receiving digitalis. Serum sodium, magnesium, and potassium levels were determined in 136 serum samples sent to the laboratory for digoxin assay. Hyponatremia (less than or equal to 130 mEq/L) occurred most frequently (21%), followed by hypomagnesemia (less than or equal to 1.25 mEq/L) in 19%, hypokalemia (less than or equal to 3.5 mEq/L) in 9%, and hypermagnesemia (greater than or equal to 2.25 mEq/L) in 7%. The twofold frequency of hypomagnesemia (19%) contrasted with hypokalemia (9%) indicates that clinicians are more attuned to avoiding hypokalemia than hypomagnesemia in patients receiving digitalis. Because hypokalemia and/or hypomagnesemia may contribute to the toxic effects of digitalis, our observation suggests that hypomagnesemia may be a more frequent contributor than hypokalemia to induction of toxic reactions to digitalis. Routine serum magnesium determination in patients receiving digitalis, who often are also receiving potent diuretics, may assist in identifying additional patients at risk for the toxic effects of digitalis.

Topics: Digitalis Glycosides; Digitoxin; Digoxin; Hospitalization; Humans; Hypokalemia; Hyponatremia; Magnesium

Kidney independent glycosides offer a high measure of therapeutic safety in comparison with kidney dependent glycosides. The intoxication rate lies between 4 and 6%. The pharmacokinetic properties of pentaformylgitoxin (INN: gitoformate) are comparable with those for digitoxin. The active glycoside 16-formylgitoxin (INN: gitaloxin) is formed by rapid deformylation of the formyl residue on the sugar chain. The maintenance dose of 0.06 mg daily, based on the half-life, produces therapeutic concentrations in the range 6-30 ng/ml. The required loading dose, as for digitoxin, amounts to 10 times the maintenance dose.

Topics: Cardiac Glycosides; Digitoxin; Digoxin; Heart Failure; Humans; Hypokalemia; Kidney; Protein Binding; Risk; Serum Albumin

Specific binding sites have been demonstrated to exist in the heart for several drugs and hormones such as beta-blocking agents, cardiac glycosides, catecholamines, insulin, glucagon and acetylcholine. The specific binding sites for cardiac glycosides in the human heart have certain properties which make it likely that they are the pharmacological receptors for the therapeutic and toxic actions of digitalis glycosides: they are located in the cell membrane and bind cardioactive steroids reversibly with high affinity: half-maximal receptor binding occurs at approximately 2 nM (approximately 1.5 ng/ml) for digoxin; potassium decreases receptor affinity, calcium increases it; specific binding of ouabain, digoxin or digitoxin is related to inhibition of (Na+ + K+)-ATPase activity--which is supposed to be the receptor enzyme for cardiac glycosides. Human left ventricle contains approximately 1.5 x 10(14) binding sites/g wet weight, right ventricle approximately 0.9 x 10(14). In disease the number of receptors may decrease (hypothyroid states, myocardial infarction) or increase (hyperthyroidism, chronic hypokalaemia). Certain drugs (such as phenytoin) or different temperatures or pH changes cause a change in digitalis-receptor affinity. Thus, the number of receptors and possibly their properties are subject to regulation in clinically relevant situations. Further investigations will probably reveal those pathophysiological states, which allow the explanation of toxicity or digitalis refractoriness.

Topics: Animals; Binding Sites; Cats; Cell Membrane; Cells, Cultured; Digitoxin; Digoxin; Guinea Pigs; Humans; Hypokalemia; Myocardial Infarction; Myocardium; Ouabain; Receptors, Drug; Sodium-Potassium-Exchanging ATPase; Thyroid Diseases

Serum levels of sodium, potassium, calcium, magnesium and digoxin were studied in 67 patients on maintenance dose of digoxin, 42 with digitoxicity and 25 without. The mean serum digoxin level of toxic group was significantly higher (p less than 0.001) than non-toxic group. The mean serum potassium was significantly lower in toxic group (p less than 0.05) as compared to the non-toxic group. Of the toxic patients, 23.8% had hypokalemia. Hypokalemia resulted by significantly higher (p less than 0.005) dose of diuretic used in toxic group. The mean serum digoxin level of hypokalemic toxic group was significantly lower as compared to the normokalemic toxic group (p less than 0.001) and it was interesting to note that all hypokalemic toxic patients had their serum digoxin levels below 3 ng/ml (3.84 n mol/ml) and well within therapeutic range. There was a positive correlation between serum digoxin and potassium level amongst toxic patients (p less than 0.001). Thus, in patients on maintenance dose of digoxin therapy, use of large dosage of diuretics may result in hypokalemia, causing digitalis toxicity even at low serum digoxin levels. Serum digoxin level alone may fail as an independent guide in diagnosis of digoxin toxicity in presence of hypokalemia.

Topics: Adult; Digoxin; Diuretics; Electrolytes; Humans; Hypokalemia; Middle Aged

Topics: Acid-Base Imbalance; Acute Kidney Injury; Blood Volume; Cardiac Surgical Procedures; Cardiac Tamponade; Child; Child, Preschool; Digoxin; Humans; Hypokalemia; Infant; Patient Care Team; Postoperative Care; Postoperative Complications

A case of cardiac arrest due to digitalis toxicity is described. The patient had normal serum digoxin levels and hypokalemia, and treatment with potassium chloride, phenytoin, and pacing was successful. Comment is made on the serum digoxin levels in relation to serum potassium.

Topics: Digoxin; Female; Heart Arrest; Humans; Hypokalemia; Middle Aged

The arrhythmogenic and inotropic effects of digoxin were studied in normokalemic controls, chronically hypokalaemic, and potassium-repleted dogs instrumented to maintain heart rate, mean aortic pressure, mean left atrial pressure and autonomic tone constant. The duration of digoxin infusion needed to produce ventricular tachycardia (VT) was 56.7 +/- 3.6 min in depleted dogs, 69.0 +/- 2.7 min in controls (P less than 0.005 compared with depleted dogs), and 60.5 +/- 3.0 min in repleted dogs. Baseline left ventricular dP/dt (LV dP/dt) was similar in all groups. After digoxin, LV dP/dt increased more in controls and repleted dogs than in chronically hypokalaemic dogs; eg, after 45 min of digoxin infusion LV dP/dt increased 12.7 +/- 4.4% in hypokalaemic dogs; eg, after 45 min of digoxin infusion LV dP/dt increased 12.7 +/- 4.4% in hypokalaemic dogs, 43.8 +/- 3.3% in controls (P less than 0.025) and 39.3 +/- 8.5% in repleted dogs (P less than 0.025). The inotropic response to isoprenaline was also attenuated in the chronically hypokalaemic dogs. Plasma digoxin was similar in all groups. LV digoxin was also similar in control and depleted dogs. Although inhibition of Na+, K+-ATPase and the initial velocity of 3[H]-ouabain specific binding was less in depleted dogs at VT than in controls (P less than 0.05), the magnitude of this difference was not sufficient to explain the attenuated inotropic response. No histological abnormalities were seen on light or electron microscopy in any of the groups. Therefore chronic hypokalaemia has two deleterous effects. It increases sensitivity to the arrhythmogenic effects of digoxin and impairs the inotropic response to digoxin, and isoprenaline.

Topics: Animals; Arrhythmias, Cardiac; Binding Sites; Digoxin; Dogs; Female; Heart Conduction System; Heart Rate; Hypokalemia; Isoproterenol; Male; Myocardial Contraction; Myocardium; Ouabain; Potassium; Sodium-Potassium-Exchanging ATPase; Stimulation, Chemical

Arrhythmias induced by digitalis are believed to be secondary to changes in ion concentrations in the myocardial cells or changes in the transcellular ion gradient. Both diuretic induced hypokalemia and digitalis inhibit the membrane-Na+K+ ATPase activity which cause a decrease of the intracellular potassium concentration. This may explain the risk of cardiac arrhythmias during digitalis treatment and during severe hypokalemia, and may further explain the increase for myocardial sensitivity for digitalis when hypokalemia is present. The myocardial uptake of digitalis however is markedly increased at low extracellular potassium concentration and this may be the explanation of the interaction between digitalis and hypokalemia. Not only the myocardial digoxin kinetic is changed during hypokalemia but the renal excretion rate of digoxin is markedly reduced during hypokalemia leading to increased serum digoxin concentration and thereby the risk of digitalis intoxication.

Topics: Animals; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Diuretics; Drug Interactions; Humans; Hypokalemia; Kinetics

1. We have examined the inter-relationships between erythrocyte sodium content and sodium transport in a group of healthy subjects and in groups of patients with disorders known to change the sodium content of erythrocytes. 2. In the healthy subjects the sodium content of erythrocytes was inversely related to both the permeability of the erythrocyte membrane to sodium (as measured by the unidirectional, ouabain-sensitive, sodium efflux) and the total activity of the sodium pumps (as measured by the rate constant of ouabain-sensitive sodium efflux). There was a correlation between the total activity of the sodium pumps and the membrane permeability to sodium. 3. Changes in the erythrocyte sodium content were due to a decrease in the activity of the sodium pumps (as in hypokalaemia and digoxin treatment), or a decrease in the permeability of the erythrocyte membrane to sodium (as in chronic renal failure) or a reduction of both the membrane permeability and the number of sodium pumps (as in hyperthyroidism or elderly patients). 4. One interpretation of the results in the healthy subjects is that there are two components of sodium influx; one associated with the sodium pumps in what we have called 'membrane-units' and the other determined by the ground permeability of the membrane. 5. On the basis of this model we suggest that in the geriatric and hyperthyroid patients there is a reduction in the number of 'membrane-units', that in hypokalaemia and during digoxin treatment there is inhibition of the sodium-pump component of the 'membrane-units' and that in chronic renal failure there is a decrease in the permeability of the membrane to sodium.

Topics: Adult; Age Factors; Aged; Biological Transport, Active; Digoxin; Erythrocytes; Female; Humans; Hyperthyroidism; Hypokalemia; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Ouabain; Sodium

Topics: Acidosis; Acidosis, Renal Tubular; Amiloride; Animals; Chlorides; Digoxin; Dogs; Electrolytes; Humans; Hypokalemia; Lithium; Syndrome; Tromethamine

Topics: Aged; Atrial Fibrillation; Digoxin; Dose-Response Relationship, Drug; Humans; Hypokalemia; Male

Hypokalemia potentiated the arryhthmogenic effects of digoxin and promoted inhibition of cardiac Na+,K+-ATPase. Acute hypokalemia did not modify digoxin-induced inotropy and therefore altered the quantitative relationship between inhibition of Na+,K+-ATPase and positive inotropy. Chronic hypokalemia impaired the positive inotropic response to digoxin and to isoproterenol in the absence of an electron microscopically detectable cardiomyopathy.

Topics: Acute Disease; Adenosine Triphosphatases; Animals; Chronic Disease; Digoxin; Dogs; Hypokalemia; Isoproterenol; Myocardial Contraction; Potassium; Sodium

Topics: Digoxin; Diuretics; Heart Failure; Humans; Hypoglycemia; Hypokalemia; Hyponatremia; Hypothermia; Magnesium; Protein-Energy Malnutrition

Topics: Arrhythmias, Cardiac; Barbiturates; Digitalis Glycosides; Digitoxin; Digoxin; Diuretics; Drug Interactions; Humans; Hypokalemia; Phenylbutazone; Potassium; Quinidine

Arrhythmias often complicate the course of patients with severe respiratory disease; the frequency of arrhythmias in patients with this condition approaches that seen with acute myocardial infarction. No one rhythm disturbance predominates, but rapid atrial and ventricular rhythms are characteristic. In the setting of acute respiratory failure, several conditions may predispose to arrhythmias. Hypoxemia, a serum pH that is too high or too low, and a low serum potassium may produce arrhythmias by disturbing the myocardial cellular milieu. Drugs such as digitalis, epinephrine, and theophylline may also act as myocardial irritants. The first step in therapy is to careful examination, it is helpful to note the specific effect of the arrhythmia on the patient. Some rhythm disturbances are well tolerated, while others are associated with serious problems in ventilation and perfusion. In many cases the control of respiration, correction of pH and electrolyte imbalance, and provision of bronchial hygiene will restore a normal sinus rhythm. Such measures are essential even when antiarrhythmic drugs or cardioversion are needed.

Topics: Arrhythmias, Cardiac; Chronic Disease; Digoxin; Humans; Hypokalemia; Hypoxia; Lidocaine; Lung Diseases; Oxygen Inhalation Therapy; Procainamide; Propranolol; Pulmonary Atelectasis; Quinidine

Topics: Aged; Arrhythmias, Cardiac; Berlin; Cardiac Complexes, Premature; Digitalis Glycosides; Digoxin; Diuretics; Drug Therapy, Combination; Drug Tolerance; Female; Heart Block; Humans; Hypokalemia; Male; Myocardium; Pacemaker, Artificial; Potassium; Prospective Studies; Retrospective Studies; Ventricular Fibrillation

Inulin and digoxin clearances were simultaneously measured in 19 normokalemic and 4 hypokalemic patients. In normokalemia the renal digoxin clearance exceeded the inulin clearance, indicating both glomerular filtration and active tubular secretion of digoxin. The tubular secretion increased with increasing plasma digoxin concentration. In hypokalemia, however, the tubular secretion of digoxin was significantly reduced but increased after the plasma potassium level was raised to normal.

Topics: Adult; Digoxin; Glomerular Filtration Rate; Humans; Hypokalemia; Inulin; Kidney; Kidney Tubules; Middle Aged

Correlative studies of serum digoxin levels, cardiac rhythm and related clinical laboratory data were carried out in 114 patients. Seventy-three patients who presented with 79 episodes of arrhythmias typical of digitalis intoxication could be separated into a normokalemic group of 55 patients whose serum digoxin level was 6.68 +/- 0.17 ng/ml (mean +/- standard error of the mean), and a hypokalemic group of 24 with a mean serum digoxin level of 1.13 +/- 0.04 ng/ml (P less than 0.001). Of 45 consectutive normokalemic patients with a high serum digoxin level (more than 2 mg/ml) who underwent serial studies, 17 had arrhythmias. Serial studies in 10 hypokalemic patients revealed an inconsistent relation between presence of arrhythmia and serum digoxin level. During repletion of serum potassium in seven of these patients with an arrhythmia, the arrhythmia disappeared without a significant change in serum digoxin level in four patients. A group of seven patients had 16 episodes of serum digoxin level greater than 2.2 ng/ml, but an arrhythmia occurred during only 3 of these episodes. A sharp border between toxic and therapeutic serum digoxin values was not found in these groups of study patients. The serum digoxin level at which arrhythmias occurred appeared to be variable for both groups and individual patients. However, correlative studies utilizing serum digoxin levels can define existing thresholds for therapeutic and toxic effects and may often be more useful than isolated observations.

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Humans; Hypokalemia; Male; Middle Aged; Myocardial Contraction; Potassium; Radioimmunoassay

Topics: Adenosine Triphosphatases; Animals; Digoxin; Dogs; Glucose; Hypokalemia; Insulin; Tachycardia

Topics: Arrhythmias, Cardiac; Digoxin; Humans; Hypokalemia

Topics: Biological Availability; Cardiac Glycosides; Creatinine; Deslanoside; Digitalis Glycosides; Digitoxin; Digoxin; Drug Interactions; Humans; Hypokalemia; Kidney Diseases; Liver Diseases; Malabsorption Syndromes; Obesity; Ouabain; Thyroid Diseases

Topics: Adrenergic beta-Antagonists; Aged; Aging; Antihypertensive Agents; Biological Availability; Coronary Disease; Digoxin; Diuretics; Dose-Response Relationship, Drug; Drug Interactions; Female; Heart Diseases; Humans; Hypertension; Hypokalemia; Male; Potassium; Risk

Topics: Animals; Depression, Chemical; Digoxin; Dogs; Hypokalemia; Myocardial Contraction; Tachycardia

Topics: Aminophylline; Digitalis Glycosides; Digoxin; Diuretics; Heart Failure; Heart Rate; Humans; Hypokalemia; Hyponatremia; Intermittent Positive-Pressure Breathing; Mineralocorticoid Receptor Antagonists; Oxygen; Potassium Deficiency; Pulmonary Edema; Tachycardia; Thyroid Diseases

Thirty intact dogs were studied to determine digoxin concentration in various tissues after ventricular tachycardia had been induced by digoxin infusion. A control group was infused solely with digoxin. A second group was made acutely hypokalemic by glucose-insulin infusion before the digoxin infusion. A third group was infused with glucose and digoxin to determine the effect of increased blood glucose levels and osmalarity on the induction of ventricular tachycardia. Results were: (1) The amount of digoxin infused to produce ventricular tachycardia did not differ getween the normal and hypokalemic groups. (2) The concentration of digoxin in various parts of the heart, other muscle tissue, renal cortex, and liver did not differ between the normal and acutely hypokalemic dogs although the amount excreted in bile and urine was reduced in hypokalemia. (3) Acute hypokalemia did not sensitize the myocardium to the arrhythmogenic effects of digoxin. (4) Ventricular tachcardia occurred at a similar plasma digoxin level in normal and acutely hypokalemic dogs. (5) In dogs with a lowered plasma potassium level, junctional tachycardia occurred whereas it did not occur in normal dogs or those with only a high blood glucose level. (6) Ventricular tachycardia occurred in the hyperglycemic dogs at a plasma digoxin level of 170 ng/ml, which was significantly greater than in the other experiments (7) Acute hyperglycemia reduced the mean rate of myocaridal uptake of digoxin into atria and right and left ventricular tissue; and the concentration of digoxin in atria, left ventricle, and interventricular septum was lower at the time of ventricular tachycardia than occurred in normal dogs. (8) Lowering the plasma potassium level in the presence of acute hyperglycemia, which occurred with the glucose-insulin infusion, did increase the myocardial uptake of digoxin. Similar effects of hyperglycemia were noted on mean hepatic uptake and excretion of digoxin and also the renal uptake of the glycoside.

Topics: Animals; Body Temperature; Digoxin; Dogs; Electrocardiography; Hyperglycemia; Hypokalemia; Myocardium; Tachycardia

Twelve patients with congestive heart failure receiving maintenance therapy with digoxin and potent diuretics were followed closely during development of hypokalemia and potassium loss. Cardiac arrhythmias compatible with digoxtin toxicity developed in 6 patients in the presence of stable, normal serum digoxin concentrations. The mechanisms involved in the development of the rhythm disturbances are discussed with regard to hypokalaemia, intracellular potassium loss, intra-/extracellular potassium gradients and digoxin, and the significance of maintaining a normal potassium balance in this setting is stressed.

Topics: Arrhythmias, Cardiac; Creatinine; Digoxin; Diuretics; Electrocardiography; Heart Failure; Humans; Hypokalemia; Middle Aged; Potassium; Potassium Deficiency

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Humans; Hypokalemia; Myocardium; Potassium; Potassium Deficiency

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Drug Hypersensitivity; Humans; Hypokalemia; Myocardium; Potassium

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Humans; Hypokalemia; Male

Ouabain binding capacity of cell membranes is directly related to (Na+ + K+)-ATPase activity. The extent of ouabain inhibition of (Na+ + K+)-ATPase is a measure of ouabain receptor sites occupied. Dissociation constants of the ouabain-receptor complexes are identical in all organs in a single species but vary among different species. K+ decreases the association rate constant of the ouabain receptor interaction without altering the dissociation rate constants. Titration of digoxin-inhibited (Na+ + K+)-ATPase from guinea pig heart with digoxin antibodies shows a reversal of the inhibition at lower antibody concentrations in the presence of K+ than in the absence of K+. It is concluded that digitalis intolerance in acute hypokalemia reflects the increased affinity of the cardiac glycoside receptor under these conditions.

Topics: Adenosine Triphosphatases; Animals; Binding Sites; Brain; Cattle; Cell Membrane; Digoxin; Dogs; Dose-Response Relationship, Drug; Erythrocytes; Guinea Pigs; Hypokalemia; Kidney; Myocardium; Ouabain; Potassium; Receptors, Drug; Species Specificity

Seventy-six patients with clinical and ECG evidence of digitalis toxicity and serum-digoxin concentrations over 2.5 ng/ml were investigated for possible correlation between certain ECG changes and the level of serum digoxin, but no correlation was found. However, radioimmunological determination of digoxin level proved to be a reliable means of deciding whether abnormalities of impulse formation or conduction were due to digitalis. In only one case (during haemodialysis) was there a fall in potassium level below normal, with signs of digitalis toxicity electrocardiographically. In five other patients with serum digoxin levels above 6 ng/ml high potassium values were found. Caution in the administration of potassium is advised: it should be given only if it is demonstrated to be below normal. Fifty-one of the patients had impaired renal function.

Topics: Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Electrocardiography; Female; Humans; Hypokalemia; Kidney Failure, Chronic; Male; Middle Aged; Potassium; Radioimmunoassay; Renal Dialysis

4 patients tried to commit suicide by ingestion of 45 to 100 tablets of digoxin (Lanicor 0,25 mg) and acteyldigoxin (Novodigal 0,2 mg) respectively. In all patients cardiac arrhythmias occurred including 3 rd degree av-block, tachyarrhythmias and ventricular fibrillation which was lethal in two patients. After a short period hyperkaliaemia a rapid decrease of potassium in the serum was observed 3-12 hours after administration of digoxin. This loss of potassium was due to an increased excretion of potassium and sodium in the urine. It is thought that a reversible tubular leakage is responsible for the loss of electrolytes by the kidney rather than an inhibition of the ATPase in kidney tissue. From our observations the following therapy scheme for digitalis-intoxication is recommended: 1. Gastric lavage and administration of absorbents (charcoal, cholestyramin) in order to decrease the absorption of the glycosides and to interrupt the enterohepatic circulation. 2. Substitution of electrolytes by infusions and by oral route to balance sodium and potassium levels in the serum. 3. Administration of diphenylhydantoin for treatment of cardiac arrhythmias. 4. Implantation of a temporary pacemaker for treatment of cardiac arrhythmias especially for the management of bradycardias. 5. Plasmapheresis to lower the glycosid concentration in the heart muscle and in other tissues.

Topics: Adult; Arrhythmias, Cardiac; Charcoal; Digoxin; Female; Gastric Lavage; Humans; Hyperkalemia; Hypokalemia; Kidney; Male; Middle Aged; Pacemaker, Artificial; Phenytoin; Plasmapheresis; Poisoning; Potassium; Sodium; Suicide; Water-Electrolyte Balance

Topics: Biological Transport, Active; Digoxin; Heart Diseases; Humans; Hypokalemia; Leukocytes; Myocardium; Potassium; Sodium

Topics: Biological Transport; Digoxin; Erythrocytes; Humans; Hypokalemia; Potassium; Radioisotopes; Sodium; Sodium Isotopes; Time Factors

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Glucose; Heart; Heart Rate; Hypokalemia; Insulin; Liver; Muscles; Myocardium; Potassium; Time Factors; Tritium

Topics: Alkalosis; Biological Transport, Active; Cell Membrane Permeability; Depression, Chemical; Digitalis Glycosides; Digoxin; Erythrocytes; Fludrocortisone; Humans; Hypokalemia; Leg; Potassium; Radioimmunoassay; Sodium; Stimulation, Chemical; Time Factors

Topics: Acidosis; Atrial Fibrillation; Bundle-Branch Block; Calcium; Colon, Sigmoid; Diagnosis, Differential; Digoxin; Electrocardiography; Female; Humans; Hyperkalemia; Hypocalcemia; Hypokalemia; Infant; Potassium; Tachycardia; Urinary Diversion; Water-Electrolyte Balance

Topics: Adipose Tissue; Arrhythmias, Cardiac; Child; Child, Preschool; Creatinine; Digoxin; Extracorporeal Circulation; Heart Defects, Congenital; Humans; Hypokalemia; Muscles; Myocardium; Postoperative Complications; Radioimmunoassay

Topics: Biological Transport, Active; Cell Membrane Permeability; Cell Separation; Centrifugation; Depression, Chemical; Digoxin; Erythrocytes; Female; Humans; Hypokalemia; Male; Osmolar Concentration; Potassium; Sodium; Stimulation, Chemical; Water-Electrolyte Balance

Topics: Diet Therapy; Digitalis Glycosides; Digoxin; Diuretics; Heart Failure; Humans; Hypokalemia; Hyponatremia; Morphine; Pulmonary Edema; Rest; Water-Electrolyte Balance

Topics: Arrhythmias, Cardiac; Digoxin; Humans; Hyperkalemia; Hypokalemia; Suicide

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

Topics: Acidosis; Digitalis Glycosides; Digoxin; Electric Countershock; Electrocardiography; Female; Heart Block; Humans; Hypokalemia; Infant, Newborn; Infant, Newborn, Diseases; Male; Tachycardia, Paroxysmal

Topics: Animals; Bile; Binding Sites; Cell Membrane Permeability; Digoxin; Dogs; Extracellular Space; Hypokalemia; Insulin; Muscles; Myocardium; Potassium; Tritium

Topics: Acute Disease; Animals; Blood Pressure; Digitalis Glycosides; Digoxin; Dogs; Electrocardiography; Heart Rate; Hypokalemia; Muscles; Myocardium; Potassium; Renal Dialysis; Sodium; Tritium

Topics: Digoxin; Electrocardiography; Female; Humans; Hypokalemia; Middle Aged; Potassium; Tachycardia

Topics: Animals; Digoxin; Dogs; Hyperkalemia; Hypokalemia; Myocardium; Tritium

Topics: Acute Kidney Injury; Animals; Digitalis; Digoxin; Hypokalemia; Membrane Potentials; Mice; Myocardium; Plants, Medicinal; Plants, Toxic; Potassium Deficiency; Tritium

Topics: Adolescent; Chlorides; Cortisone; Diet Therapy; Diet, Sodium-Restricted; Digoxin; Drug Therapy; Genetics, Medical; Glucose; Humans; Hypokalemia; Insulin; Paralyses, Familial Periodic; Paralysis; Periodicity; Phosphates; Potassium; Prednisone; Sodium; Sodium, Dietary; Spironolactone; Urine; Water-Electrolyte Balance

Topics: Adolescent; Arrhythmias, Cardiac; Child; Digoxin; Heart Defects, Congenital; Humans; Hypokalemia; Infant; Infant, Newborn; Rheumatic Heart Disease; Toxicology