benzofurans and Arrhythmias--Cardiac

Topics: Acetanilides; Adenosine A1 Receptor Agonists; Amiodarone; Anisoles; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzazepines; Benzofurans; Clinical Trials as Topic; Dronedarone; Humans; Ivabradine; Piperazines; Pyrrolidines; Ranolazine

The value of programmed electrical stimulation (PES) and Holter monitoring in the assessment of amiodarone efficacy was reviewed. Many physicians have been disturbed by the persistent inducibility of arrhythmias in patients treated with amiodarone, who nevertheless do very well during the follow-up period. Noninducibility was associated with a favorable prognosis among 366 VT patients. Eighty-eight (24%) were noninducible on amiodarone, and 10% of these had recurrences, vs 39% in patients who remained inducible. Further, increased difficulty of induction with PES or induction of a slower or better tolerated VT may indicate a favorable outlook, and add to the value of PES. Few papers rigorously employed Holter monitoring in the assessment of amiodarone. In general, suppression of previously frequent arrhythmias implies excellent protection for patients with benign arrhythmias and moderate protection with malignant arrhythmias. By Holter assessment in 186 VT patients, arrhythmias were suppressed in 114 (61%), and 18% of these had recurrences vs 50% in patients whose arrhythmias were not suppressed. Studies attempting to correlate the results of PES and Holter monitoring in the same patients are lacking and may prove useful.

Topics: Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Cardiac Pacing, Artificial; Clinical Trials as Topic; Electrocardiography; Electrophysiology; Female; Follow-Up Studies; Heart Conduction System; Humans; Male; Middle Aged; Monitoring, Physiologic; Pre-Excitation Syndromes; Prognosis; Tachycardia

Topics: Administration, Oral; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiomyopathy, Hypertrophic; Heart; Heart Conduction System; Humans; Tachycardia, Paroxysmal; Thyroid Diseases; Thyroid Gland; Wolff-Parkinson-White Syndrome

Amiodarone is unique among the antiarrhythmic agents. Despite its unusual pharmacokinetics and its potential toxicity, it is successful in managing both supraventricular and ventricular arrhythmias. Therefore, it is destined to become an important drug in our antiarrhythmic armamentarium.

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Corneal Diseases; Electrophysiology; Heart; Humans; Hyperthyroidism; Hypothyroidism; Kinetics; Lung Diseases; Skin Diseases

Topics: Amiodarone; Arrhythmias, Cardiac; Autonomic Nervous System; Benzofurans; Blood Coagulation; Digitalis Glycosides; Drug Synergism; Electrocardiography; Heart; Heart Conduction System; Hemodynamics; Humans; Kinetics; Quinidine; Sick Sinus Syndrome; Thyroid Diseases; Thyroid Gland

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Dose-Response Relationship, Drug; Drug Interactions; Half-Life; Humans; Pneumonia

Amiodarone is an effective antiarrhythmic drug which has been used successfully to treat a variety of cardiac arrhythmias. Early reports emphasized both the striking efficacy of this agent and the relative paucity of side effects necessitating discontinuing treatment with this drug. As amiodarone has been used more widely and in more diverse patient populations, reports of serious thyroid, pulmonary, cardiovascular, and other adverse reactions have appeared in the literature. In this paper, we review the serious adverse effects that have been reported to date. The incidence of these reactions varies considerably in different series, and cannot be explained solely by different doses employed or by varying methods of drug administration. The final role of amiodarone in the therapy of cardiac arrhythmias cannot be determined until the long-term toxicity has been more thoroughly investigated.

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Heart; Heart Conduction System; Humans; Hyperthyroidism; Infusions, Parenteral; Lung; Thyroid Gland

Interest in amiodarone has increased because of its remarkable efficacy as an antiarrhythmic agent. The purpose of this report is to review what is known about the electrophysiologic actions, hemodynamic effects, pharmacokinetics, alterations of thyroid function, response to treatment of supraventricular and ventricular tachyarrhythmias and adverse effects of amiodarone. Understanding the actions of amiodarone and its metabolism will provide more intelligent use of the drug and minimize the development of side effects. The mechanism by which amiodarone suppresses cardiac arrhythmias is not known and may relate to prolongation of refractoriness in all cardiac tissues, suppression of automaticity in some fibers, minimal slowing of conduction in fast channel-dependent tissue, or to interactions with the autonomic nervous system, alterations in thyroid metabolism or other factors. Amiodarone exerts definite but fairly minor negative inotropic effects that may be offset by its vasodilator actions. Amiodarone has a reduced clearance rate, large volume of distribution, low bioavailability and a long half-life that may last 2 months in patients receiving short-term therapy. Therapeutic serum concentrations range between 1.0 and 3.5 micrograms/ml. The drug suppresses recurrences of cardiac tachyarrhythmias in a high percent of patients, in the range of 80% or more for most supraventricular tachycardias and in about 66% of patients with ventricular tachyarrhythmias, sometimes requiring addition of a second antiarrhythmic agent. Side effects, particularly when high doses are used, may limit amiodarone's usefulness and include skin, corneal, thyroid, pulmonary, neurologic, gastrointestinal and hepatic dysfunction. Aggravation of cardiac arrhythmias occurs but serious arrhythmias are caused in less than 5% of patients. Amiodarone affects the metabolism of many other drugs and care must be used to reduce doses of agents combined with amiodarone.

Topics: Administration, Oral; Amiodarone; Animals; Arrhythmias, Cardiac; Atrioventricular Node; Benzofurans; Biological Availability; Drug Interactions; Electrophysiology; Eye Diseases; Half-Life; Heart Conduction System; Humans; Injections, Intravenous; Kinetics; Lung Diseases; Metabolic Clearance Rate; Photosensitivity Disorders; Purkinje Fibers; Tachycardia; Thyroid Diseases; Wolff-Parkinson-White Syndrome

Topics: Amiodarone; Animals; Arrhythmias, Cardiac; Benzofurans; Drug Interactions; Heart Ventricles; Humans; Infusions, Parenteral; Kinetics; Recurrence; Tachycardia; Ventricular Fibrillation

Amiodarone, an investigational drug in the United States, has had considerable use in this country and worldwide in the treatment of cardiac arrhythmias. This article reviews the clinical pharmacology of this potentially useful antiarrhythmic agent.

Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Autonomic Nervous System; Benzofurans; Bradycardia; Drug Interactions; Eye; Heart Conduction System; Heart Ventricles; Hemodynamics; Humans; Injections, Intravenous; Kinetics; Liver; Lung; Skin; Tachycardia; Thyroid Gland

Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Drug Interactions; Flecainide; Heart; Hemodynamics; Humans; In Vitro Techniques; Myocardial Contraction; Piperidines; Verapamil

Although synthesized as a coronary dilator for use as an antianginal agent over 20 years ago, amiodarone hydrochloride has recently drawn much attention as a potent antiarrhythmic compound for the control of a variety of cardiac dysrhythmias. The rapidly expanding clinical and experimental data continue to emphasize the unusual electrophysiologic, pharmacologic, and especially pharmacokinetic properties of this benzofuran derivative. The compound is a potent coronary dilator and has minimal negative inotropic propensity of a direct nature while exhibiting a mild degree of noncompetitive sympathetic antagonism. Pharmacokinetically, it has a long elimination half-life with a correspondingly long and variable latency of onset of therapeutic effect. Electrophysiologically, the drug has the propensity to lengthen the action potential duration and hence the voltage-dependent effective refractory period in all cardiac tissues after long-term, rather than short-term, administration. It has little effect on depolarization, conduction velocity, or the slow response. The precise ionic mechanisms mediating its effects on repolarization are not known. Clinically, the electrophysiologic effects of the drug differ significantly when it is given by mouth over a longer period and when it is given intravenously, a difference that remains to be explained in terms of mechanism. These differences, however, account for the varying spectrum of the drug's action after single intravenous doses (when its antiarrhythmic effects are essentially explained by the drug's action on the atrioventricular node and possibly its antiadrenergic actions) in comparison to long-term oral administration, which predictably suppresses ectopic activity and lengthens the effective refractory period in all cardiac tissues. These features may account for the drug's remarkable efficacy in the control of supraventricular and ventricular tachyarrhythmias. The safe and rational therapeutic uses of amiodarone as an antiarrhythmic agent presuppose detailed understanding of its manifold pharmacodynamic and pharmacokinetic properties.

Topics: Action Potentials; Amiodarone; Angina Pectoris; Animals; Arrhythmias, Cardiac; Benzofurans; Electrophysiology; Heart; Heart Conduction System; Hemodynamics; Humans; Kinetics; Thyroid Hormones; Triiodothyronine; Vasodilation

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Dose-Response Relationship, Drug; Drug Interactions; Electrocardiography; Female; Humans; Hyperthyroidism; Hypothyroidism; Kinetics; Lung Diseases; Photosensitivity Disorders; Pregnancy; Skin Pigmentation; Sleep Wake Disorders; Thyroxine; Triiodothyronine

Topics: Acute Disease; Administration, Oral; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Cardiovascular System; Dose-Response Relationship, Drug; Electrophysiology; Eye Manifestations; Heart Block; Humans; Injections, Intravenous; Muscle, Smooth, Vascular; Myocardial Infarction; Skin Manifestations; Tachycardia; Thyroid Gland; Wolff-Parkinson-White Syndrome

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Amiodarone; Angina Pectoris; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Drug Evaluation; Humans; Hypothyroidism; Myocardial Contraction; Oxygen Consumption; Parasympatholytics; Structure-Activity Relationship; Tachycardia, Paroxysmal; Thyroid Gland; Vascular Resistance; Vasodilator Agents; Wolff-Parkinson-White Syndrome

Topics: Action Potentials; Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Benzyl Compounds; Bretylium Compounds; Calcium; Carbamazepine; Chemical Phenomena; Chemistry; Diethylamines; Disopyramide; Heart; Humans; Imidazoles; Iodobenzoates; Lidocaine; Membrane Potentials; Phenyl Ethers; Phenytoin; Procainamide; Propylamines; Quinidine; Verapamil

Vilazodone is a potent serotonin reuptake inhibitor and 5-HT1A receptor partial agonist approved for the treatment of major depressive disorder (MDD) in adults. The effect of clinical and supratherapeutic doses of vilazodone on cardiac repolarization was determined in healthy volunteers.. In this Phase 1, randomized, doubleblind, placebo- and active-controlled, 3-arm, parallel, single-center study, healthy subjects received placebo; moxifloxacin 400 mg; or vilazodone (sequentially escalated every 3 days) 10, 20, 40, 60, and 80 mg/day. The primary endpoint was the time-matched change from baseline in the QT interval corrected for heart rate (QTc) using an individual correction method (QTcI).. Placebo-corrected time-matched analysis of the QTcI duration for the vilazodone treatment effect indicated that no vilazodone dose had an upper bound that approached or exceeded 10 ms, demonstrating no signal for a significant vilazodone effect on cardiac repolarization. Vilazodone had no significant effect on heart rate, PR, or QRS interval duration. The pharmacokinetic/pharmacodynamic model showed that the QTcI slope for vilazodone was not different from 0.0 and that the predicted increase from baseline in the QTc at Cmax for the highest therapeutic dose (156 ng/ml after 40 mg/day) was < 1 ms. The incidence of adverse events (AEs) was higher in the vilazodone group (57.6%) than in the moxifloxacin (37.0%) and placebo (35.6%) groups, though AEs were generally mild to moderate in severity and resulted in few discontinuations.. Vilazodone had no significant effect on cardiac repolarization, heart rate, PR or QRS interval duration, or ECG morphology in healthy adult participants.

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Benzofurans; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Female; Heart Rate; Humans; Indoles; Male; Middle Aged; Models, Biological; Piperazines; Selective Serotonin Reuptake Inhibitors; Serotonin 5-HT1 Receptor Agonists; Vilazodone Hydrochloride; Young Adult

Implantable cardioverter-defibrillators (ICDs) remain the treatment of choice for the prevention of life-threatening arrhythmias. However, many patients with ICDs require additional antiarrhythmic therapy to reduce the morbidity associated with recurrent arrhythmia-triggered ICD interventions.. Our study aimed to evaluate the safety and efficacy of celivarone in reducing these interventions.. A total of 153 eligible ICD recipients were randomized to receive either placebo or celivarone 100 or 300 mg once daily for 6 months. The primary end point was the prevention of arrhythmia-triggered ICD therapies.. Fewer ventricular tachycardia and ventricular fibrillation episodes were observed in the 300-mg celivarone group than in the placebo group, with a relative risk reduction of 46%, which was not statistically significant. The analysis of all-cause shocks showed a trend toward a decreased number of events in the celivarone 300-mg group. A post hoc analysis of the primary end point in a subgroup of patients in the celivarone 300-mg group, who had received ICD therapy within 1 month of randomization, showed a significant benefit (P = .032). Celivarone was not associated with an increased risk of torsades de pointes, thyroid dysfunction, or pulmonary events. More heart failure events were reported in the celivarone groups than in the placebo group, but the difference was not statistically significant.. Celivarone tends to reduce ventricular tachycardia-/ventricular fibrillation-triggered ICD therapies. This effect was not statistically significant. There was a trend toward greater efficacy in the 300-mg group, especially in patients undergoing ICD therapy within 30 days prior to randomization. Overall, celivarone was well tolerated.

Topics: Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Defibrillators, Implantable; Double-Blind Method; Female; Follow-Up Studies; Heart Ventricles; Humans; Male; Middle Aged; Tachycardia, Ventricular; Ventricular Fibrillation

Chronic constipation is common among nursing home residents. The aim of this study was to evaluate safety, tolerability and pharmacokinetics of the selective 5HT(4) receptor agonist prucalopride in elderly, chronically constipated patients in nursing homes. A multicentre, phase II, randomized, double-blind dose-escalation study in 89 elderly constipated nursing home residents treated with placebo, 0.5, 1 or 2 mg prucalopride once daily for 28 days was analysed. Adverse events, vital signs, ECG, Holter monitor and pharmacokinetics were assessed (Clinicaltrials.gov identifier: NCT00627692). Patients' mean age was 83 years; 88% had a history of cardiovascular diseases. Most frequent adverse events, at least possibly related to prucalopride, were diarrhoea and abdominal pain. Relative to placebo, there were no differences in vital signs, ECG corrected QT interval, ECG morphology parameters, or incidence of supraventricular or ventricular arrhythmias on Holter monitoring. Plasma prucalopride concentrations increased proportionally with administered dose. Prucalopride up to 2 mg once daily for 4 weeks was safe and well-tolerated by constipated elderly patients, with no differences vs placebo in ECG or a range of Holter-monitoring parameters.

Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Benzofurans; Cohort Studies; Constipation; Double-Blind Method; Electrocardiography; Electrocardiography, Ambulatory; Female; Gastrointestinal Agents; Hemodynamics; Humans; Male; Middle Aged; Serotonin Receptor Agonists

Amiodarone is very effective against a variety of dysrhythmias but has poor pharmacodynamic properties and many undesired side-effects. Its short- and rapid-acting derivative E 047/1 may circumvent some of these drawbacks. It is easier to titrate while retaining the high efficacy of amiodarone and may have acceptable influences on haemodynamics and cardiac conduction in patients who develop serious, destabilizing ventricular tachydysrhythmias after cardiac surgery.. Testing E 047/1 was performed prospectively in two consecutive phase II open, clinical studies. Out of 504 patients scheduled for surgery using cardiopulmonary bypass for coronary artery grafting and/or valve repair, 35 developed serious, haemodynamically destabilizing ventricular dysrhythmias (Lown 2-Lown 4b) after surgery and were treated with a 1 mg kg(-1) (pilot study, n = 15) or randomized to a 2 or 3 mg kg(-1) bolus of E 047/1, followed by a 1 mg kg(-1) h(-1) continuous infusion for 2 h (n = 10 in each group). Dysrhythmias, PQ, QTc intervals and haemodynamics using the thermodilution technique were evaluated for up to 24 h after drug initiation.. At the time of final inclusion the patients had between 6 and 12 (or more) ventricular ectopics per minute. Within the first 2-3 min of application in the pilot trial E 047/1 induced a decrease of ventricular dysrhythmias to between 0 and 4 per min, a decrease that held for the duration of treatment. The area under the curve decreased from 434 (322, 855; median, quartiles) to 114 (9, 477, P < 0.01) events per hour. In the randomized trial, E 047/1 administered in either dose rapidly reduced ventricular dysrhythmias at least as effectively as in the pilot trial 565 (478, 701) to 33 (8, 238, P < 0.05) after a 2 mg bolus; 482 (339, 482) to 95 (13, 540, P < 0.01) events per hour after a 3 mg bolus. Approximately 4-6 h after drug termination, dysrhythmias reappeared in the majority of patients. In only three patients did the incidence of dysrhythmias return to inclusion criteria levels. In contrast to the pilot trial, in the randomized trial there was a slight increase of mean pulmonary artery pressure, central venous pressure and pulmonary arterial wedge pressure and a slight decrease of LCWI in both groups. E 047/1 did not cause QTc prolongation.. E 047/1 appears to be a safe alternative to amiodarone in the perioperative setting of cardiac surgery when serious, destabilizing dysrhythmias occur.

Topics: Aged; Amiodarone; Analysis of Variance; Anti-Arrhythmia Agents; Area Under Curve; Arrhythmias, Cardiac; Benzofurans; Cardiopulmonary Bypass; Cardiovascular Diseases; Female; Hemodynamics; Humans; Male; Perioperative Care; Prospective Studies; Time Factors

The efficacy, pharmacokinetics, safety, and tolerability of E 047/1, an amiodarone derivative, were evaluated in patients with acute supraventricular or ventricular arrhythmia. In an open, nonrandomized prospective multicenter trial, 20 patients were treated with three different i.v. dosage regimens of E 047/1. Arrhythmia termination indicated efficacy. Pharmacokinetics were determined by measurements of drug plasma levels. Safety was judged by changes of blood pressure, heart rate, ECG parameters, and appearance of adverse events. For local tolerability, effects at the site of infusion were assessed. In patients with atrial fibrillation and/or atrial flutter, drug plasma levels and prolongation of QT interval were correlated with efficacy. In 10 (50%) patients, therapeutic intervention with E 047/1 was successful. Drug plasma levels rapidly decreased within 1 h after administration. Blood pressure values and ECG parameters stayed constant during the observation period. Proarrhythmic effects were not observed. As adverse events, vertigo, vomiting, and nausea in three (15%) and hypotension in one (5%) patient, respectively, occurred in the high-dose bolus regimen only. At the site of infusion, no adverse effects were found. No dependency between drug plasma levels and arrhythmia termination was found. E 047/1 has proven to be efficient and safe in the treatment of arrhythmia. E 047/1 is characterized by rapid plasma elimination, absence of proarrhythmic or cardiodepressive effects, mild adverse events, and excellent local tolerability. For further investigation, we recommend a combined bolus- and weight-adapted infusion regimen.

Topics: Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Female; Hemodynamics; Humans; Male; Middle Aged; Prospective Studies

Perioperative malignant ventricular tachyarrhythmias pose an imminent clinical danger by potentially precipitating myocardial ischemia and severely compromising hemodynamics. Thus, immediate and effective therapy is required, which is not always provided by currently recommended IV drug regimens, indicating a need for more effective drugs. We examined antiarrhythmic effects of the new benzofurane compound E 047/1 on spontaneous ventricular tachyarrhythmia in a conscious dog model. One day after experimental myocardial infarction, 40 dogs exhibiting tachyarrhythmia randomly received (bolus plus 1-h infusion) E 047/1 6 mg/kg plus 6 mg x kg(-1) x h(-1), lidocaine 1 mg/kg plus 4.8 mg x kg(-1) x h(-1), flecainide 1 mg/kg plus 0.05 mg x kg(-1) x h(-1), amiodarone 10 mg/kg plus 1.8 mg x kg(-1) x h(-1), or bretylium 10 mg/kg plus 20 mg x kg(-1) x h(-1). Electrocardiogram was evaluated for number of premature ventricular contractions (PVC), normally conducted beats originating from the sinoatrial node, and episodes of ventricular tachycardia. Immediately after the bolus, E 047/1 reduced PVCs by 46% and increased sinoatrial beats from 4 to 61 bpm. The ratio of PVCs to total beats decreased from 98% to 58%. Amiodarone and flecainide exhibited antiarrhythmic effects with delayed onset. Lidocaine did not suppress PVCs significantly, and bretylium was proarrhythmic. The antiarrhythmic E 047/1 has desirable features, suppressing ischemia-induced ventricular tachyarrhythmia quickly and efficiently, and may be a useful addition to current therapeutic regimens.. Life-threatening arrhythmias of the heart after myocardial infarction or ischemia may be treated quickly and efficiently by the new drug E 047/1.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Blood Pressure; Body Weight; Coronary Vessels; Dogs; Excipients; Heart Rate; Infusions, Intravenous; Ligation; Myocardial Ischemia; Pilot Projects; Polysorbates

The value of programmed electrical stimulation (PES) and Holter monitoring in the assessment of amiodarone efficacy was reviewed. Many physicians have been disturbed by the persistent inducibility of arrhythmias in patients treated with amiodarone, who nevertheless do very well during the follow-up period. Noninducibility was associated with a favorable prognosis among 366 VT patients. Eighty-eight (24%) were noninducible on amiodarone, and 10% of these had recurrences, vs 39% in patients who remained inducible. Further, increased difficulty of induction with PES or induction of a slower or better tolerated VT may indicate a favorable outlook, and add to the value of PES. Few papers rigorously employed Holter monitoring in the assessment of amiodarone. In general, suppression of previously frequent arrhythmias implies excellent protection for patients with benign arrhythmias and moderate protection with malignant arrhythmias. By Holter assessment in 186 VT patients, arrhythmias were suppressed in 114 (61%), and 18% of these had recurrences vs 50% in patients whose arrhythmias were not suppressed. Studies attempting to correlate the results of PES and Holter monitoring in the same patients are lacking and may prove useful.

Topics: Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Cardiac Pacing, Artificial; Clinical Trials as Topic; Electrocardiography; Electrophysiology; Female; Follow-Up Studies; Heart Conduction System; Humans; Male; Middle Aged; Monitoring, Physiologic; Pre-Excitation Syndromes; Prognosis; Tachycardia

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Captopril; Cardiomyopathy, Dilated; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Humans; Lung Diseases; United States; United States Food and Drug Administration

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Drug Evaluation; Eye Diseases; Humans; Lung Diseases; Risk; Thyroid Diseases

In an attempt to assess their respective values for purposes of drug monitoring, plasma, red blood cell, atrial, and ventricular concentrations of amiodarone and N-desethylamiodarone (NDA) were measured, in 50 surgical patients, after a single oral dose (30 mg/kg); hemodynamic changes were assessed also. Amiodarone concentration was lower in red blood cells than in plasma and in myocardium. A relationship was found between the red blood cell concentration and plasma or myocardial concentrations of amiodarone (r = 0.79 and r = 0.68, p less than 0.00001). Hemodynamic studies were available in 17 treated patients and 13 control subjects before and at the time of surgery. In control subjects, hemodynamics did not change with time and general anesthesia. Oral amiodarone decreased the cardiac index (p less than 0.05) and heart rate (p less than 0.001) without significant changes in arterial pressure, systemic vascular resistance, or stroke volume index. The increase in capillary wedge pressure was related to amiodarone or NDA plasma, myocardial, and red blood cell concentrations (for amiodarone: r = 0.61, p = 0.006; r = 0.69, p less than 0.001; and r = 0.53, p = 0.02, respectively). We concluded that oral amiodarone impairs hemodynamics and that measurement of the amiodarone plasma concentration rather than the red blood cell concentration is the easiest method of monitoring the drug. However, establishment of the clinical utility of drug monitoring during chronic administration of amiodarone needs further investigation.

Topics: Administration, Oral; Adult; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Blood Pressure; Erythrocytes; Female; Heart Rate; Heart Valves; Hemodynamics; Humans; Male; Middle Aged; Myocardium; Postoperative Complications; Stroke Volume; Vascular Resistance

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Humans

The effects on ventricular arrhythmias of a new class IA drug, flecainide, were compared with those of amiodarone in 10 patients with frequent, chronic, and stable ventricular ectopic beats (VEBs). The study consisted of an initial 1-week, placebo-controlled, baseline period followed by two 12-day, randomized, crossover, double-blind treatment periods with incremental dosage and 1 month of placebo between drug periods. Frequent VEBs, which were present in all 10 patients during both placebo control periods (30 or more VEBs/hour every hour, during 24-hour Holter monitoring), were markedly suppressed (reduction greater than 80%) in nine patients with both drugs (p less than 0.01). There was almost total abolition of the VEBs in six patients with flecainide, and the satisfactory results with a minimal dose in three demonstrate its fast onset of action. Side effects from either agent were infrequent and no discontinuation was necessary. We conclude from our study that flecainide is a highly effective antiarrhythmic agent.

Topics: Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Double-Blind Method; Electrocardiography; Female; Flecainide; Heart Ventricles; Hemodynamics; Humans; Male; Middle Aged; Myocardial Contraction; Piperidines; Random Allocation

Low-dose (7 mg/kg per day) disopyramide administration to arrhythmic chagasic patients decreased the frequency of ventricular extrasystoles in 4 of 17 patients (24%) and suppressed most complex ventricular arrhythmias in 12 of 15 patients (80%). This assessment was made from 72-h continuous Holter monitoring recorded during the course of this double blind, placebo-controlled randomized crossover study. Seven patients (41%) complained of anticholinergic side effects, but no contractile or conduction system depression was seen. Amiodarone (200 mg) given on a single blind, placebo-controlled basis to 9 of these patients reduced the frequency of ventricular extrasystoles in 6 of 9 patients (67%) and suppressed complex ventricular ectopy in 6 of 7 patients (85%). One patient was unable to tolerate this drug (11%). Both drugs seemed less effective in controlling supraventricular arrhythmias, although disopyramide eliminated paroxysms of supraventricular tachycardia in 9 of 13 (69%) and amiodarone in all 6 patients with this arrhythmia. Amiodarone appears to be a better antiarrhythmic drug for chagasic patients, due to its greater effectiveness and lower incidence of side effects.

Topics: Administration, Oral; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Chagas Cardiomyopathy; Clinical Trials as Topic; Disopyramide; Double-Blind Method; Female; Heart Atria; Heart Ventricles; Humans; Male; Middle Aged; Myocardium; Random Allocation

The long term efficacy of class I antiarrhythmic drugs and of amiodarone was investigated in 34 patients with severe organic heart disease accompanied by frequent complex ventricular arrhythmias. All patients had undergone cardiac catheterisation which included coronary angiography, and each patient underwent a short and a long term study phase. During the short term study 6 class I antiarrhythmic agents were administered orally in a randomised, single-blind fashion. The drugs investigated were disopyramide, flecainide, mexiletine, prajmalium, propafenon and tocainide. The response was judged to be effective when there was a 90% reduction of couplets and a 100% reduction of salvos. For long term treatment the patient was given one of the agents found to be effective in the short term testing. Holter monitoring was performed after 1 week, and 1, 3 and 6 months. If the drug administered initially was later found to be ineffective, the patient was given another effective class I agent. If during the short term study or the follow-up phase there was no positive response to any class I agent, the patient was given amiodarone. In 78% of the patients, one or more of the class I agents administered short term was effective. The percentage of effectively treated patients after 1 week was 56%, and was 28, 14, and 9% after 1, 3, and 6 months' treatment, respectively. In amiodarone-treated patients there was an effective response rate of 40% after 10 days, 50% after 1 month and 70% after 3 and 6 months.

Topics: Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Drug Administration Schedule; Humans

Lidocaine (L) in still considered the drug of choice in the treatment of life threatening ventricular arrhythmias in the setting of acute myocardial infarction (A.M.I.): this is mainly due to its proved efficacy and high therapeutic index. Since however L has well defined electrophysiologic properties (class 1 B) and does not seem to be effective in all of these patients we compared its antiarrhythmic efficacy with the one of amiodarone (A), an antiarrhythmic agent provided of electrophysiologic properties quite different from L (class 4) and usually well tolerated. Twenty-five consecutive patients with A.M.I. without haemodynamic consequences, were randomly assigned to L (bolus of 1 mg/kg followed by an infusion of 10 mg/min for 20 minutes and thereafter of 1,5 mg/min) or A (bolus of 5 mg/kg and an eventual repeat dose of 150 mg followed by an infusion of 1,8 g/24 h) The baseline arrhythmia was classified as Lown class 2 ore more in all the patients. The ventricular arrhythmias were completely relieved in 47% of the patients assigned to L and in 60% of those treated with A (p = N.S.); a minor efficacy was found in 40% of the patients of both groups; in two cases ventricular fibrillation occurred after the acute infusion of L. The antiarrhythmic effectiveness kept fit with both drugs over a 24 hours period. A prolongation of QTc interval was found to occur both after the bolus and 24 hours of treatment with A. In addition A provoked a slight decrease of systolic blood pressure. No important side effects were observed with both drugs regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Injections, Intravenous; Lidocaine; Male; Middle Aged; Myocardial Infarction

The clinical efficacy of a low-dosage schedule of amiodarone was tested in 58 patients with severe ventricular arrhythmias refractory to other drug treatments. The initially chosen regimen of 400 mg was effective at the end of the first controlled trial period (after 4 weeks) in 73% of the patients. The responsiveness was maintained with the smaller dosage of 200 mg in 68% of this group. The response was reestablished also in the patients who became nonresponders during the low-dose regimen when they returned to the initial (400-mg) dosage. No relation was found between clinical response and blood levels of amiodarone and of its deethylated metabolite. Adverse effects more often associated with amiodarone therapy were rare. However, careful monitoring of thyroid function allowed the detection in 10% of the patients of biochemically and functionally documented, but clinically silent, cases of hypo- or hyperthyroidism.

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Clinical Trials as Topic; Electrocardiography; Female; Heart Ventricles; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Prospective Studies; Systole

Fifty-two patients with refractory symptomatic supraventricular and ventricular arrhythmias were treated with amiodarone (Cordarone-X; Reckitt & Colman) and followed up for a mean period of 36,4 months (range 3-54 months). Amiodarone was effective in controlling supraventricular arrhythmias in 18 of 22 patients (82%) and ventricular arrhythmias in 18 of 30 (60%), giving an overall success rate of 72%. The incidence of sudden death in the patients with ventricular arrhythmias was significantly higher (P less than 0,01) in patients whose symptoms were not controlled by amiodarone than in those in whom control was achieved. Although side-effects occurred in 50 of the 52 patients they seldom necessitated withdrawal of the drug. This is the first report in which a substantial number of patients have been closely followed up for a mean period exceeding 22 months. The results described here demonstrate that the potent antiarrhythmic properties of amiodarone, previously observed for shorter periods of time, are maintained for up to 4 1/2 years, and that there is neither an increased incidence nor progression of side-effects in patients exposed to the drug for these longer periods of time.

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Clinical Trials as Topic; Female; Follow-Up Studies; Heart Ventricles; Humans; Male; Middle Aged; Sinoatrial Node

Large initial doses of amiodarone hydrochloride for the treatment of ventricular arrhythmias refractory to conventional therapy were demonstrated to shorten the time to achieve control of the arrhythmia. As compared with a lower-dose regimen, the mean time to achieve partial control (suppression of ventricular tachycardia) was 10.6 +/- 5.2 days in the highest-dose group (group C), 9.5 +/- 6.4 days in the medium-dose group (group B), and 16.9 +/- 9.1 days in the lowest-dose group (group A). Complete control (suppression of virtually all ventricular ectopy) was similarly earlier in groups B and C (16.1 +/- 7.5 days and 16.0 +/- 11.3 days, respectively) as compared with group A (31.0 +/- 10.1 days). The final mean dose for long-term treatment was independent of the initial dose schedule (551 +/- 245 mg/day; range, 200 to 1,200 mg/day). The large doses were shown to be well tolerated and without serious side effects.

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Half-Life; Heart Ventricles; Humans; Kinetics; Time Factors

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged

Topics: Aged; Amiodarone; Angina Pectoris; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Female; Humans; Male; Middle Aged

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Amiodarone; Angina Pectoris; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Drug Evaluation; Humans; Hypothyroidism; Myocardial Contraction; Oxygen Consumption; Parasympatholytics; Structure-Activity Relationship; Tachycardia, Paroxysmal; Thyroid Gland; Vascular Resistance; Vasodilator Agents; Wolff-Parkinson-White Syndrome

Topics: Acute Disease; Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Electrocardiography; Humans; Infusions, Parenteral; Middle Aged; Time Factors

Amiodarone, administered orally in doses of 200 to 600 mg/day, was remarkably effective in the treatment and prevention of a wide variety of atrial and ventricular arrhythmias. Total suppression and control was provided in 98 (92.4 percent) of 106 patients with supraventricular arrhythmias and in 119 (82 percent) of 145 patients with ventricular arrhythmias. The rates of total control of the arrhythmia were: 96.6 percent in 30 patients with recurrent atrial flutter or fibrillation, 96.6 percent in 59 patients with repetitive supraventricular tachycardia, 100 percent in 27 patients with Wolff-Parkinson-White syndrome and 77.2 percent in 44 patients with recurrent ventricular tachycardia unsuccessfully treated with other drugs. Excellent results were obtained in 6 to 8 patients with repetitive ventricular tachycardia and ventricular fibrillation related to postinfarction ventricular aneurysm and in 12 of 14 patients with ventricular extrasystoles and ventricular tachycardia related to Chagasic myocarditis. Amiodarone proved safe in patients with severe congestive heart failure and severe myocardial damage. Its clinical efficacy was related to its electrophysiologic properties and to two unique properties: its wide safety margin and its cumulative effect. The latter liberates patients from a rigid hourly schedule and provides for continuous antiarrhythmic control, days and even weeks after treatment is discontinued.

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Cornea; Drug Evaluation; Heart Conduction System; Humans; Tachycardia; Thyroid Gland; Ventricular Fibrillation

Topics: Adolescent; Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Male; Middle Aged; Time Factors

The effects of amiodarone by injection have been studied in 100 patients. 50% of these patients were in cardiac failure. Amiodarone was given intravenously over 30 seconds in a dose of 300 mg; in 15 of the patients a further dose of 150 mg was given after ten minutes. Amiodarone was found to be particularly effective in the tachy-arrhythmias (90% successful) in which it brought about slowing (18 cases out of 30) or conversion (17 cases out of 30). Just as good results were obtained for the atrial tachycardias (90% success rate) and in the junctional tachycardias. This treatment is less effective for atrial flutter (50% successful) and for ventricular arrhyrthmia, in which the success rate was only 60%. It is possible to use the defibrillator after amiodarone has been administered. This drug is well tolerated, and no increase in cardiac failure has been noted in these patients. There does remain, however, the possibility of hypotension and perhaps of circulatory collapse, which is rapidly reversable; this is probably due to vasodilator activity. Intracavitary studies in 8 patients have shown that amiodarone causes slowing of sino-atrial and of atrio-ventricular conduction. Amiodarone may equally worsen a distal conduction defect. The uses for this anti-arrhythmic drug, which is particularly effective at the atrial level, are discussed in this paper.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Depression, Chemical; Drug Tolerance; Female; Heart Block; Heart Conduction System; Heart Failure; Heart Rate; Humans; Injections, Intravenous; Male; Middle Aged

The aim of this study was to analyse the effect of an intra-atrial injection of 5 mg/kg of amiodarone on the heart rate, the A-V conducting pathways, and the right atrium and ventricle of 23 patients. By recording the potentials in the bundle of His, it was possible to measure the nodal A-V conduction time (A-H interval) and the conduction time below the bundle of His (H-V interval) during atrial pacemaking. The refractory periods were calculated by the stimulus-test method. The results were subjected to statistical analysis using Student's test. They may be summarised as follows: - slowing of the sinus rhythm; - depressed conduction in the A-V node, but without any effect on the speed of conduction infranodally; - an increase in the atrial effective refractory period; - persistant lengthening of both the effective and the functional refractory periods of the A-V node; - an increase in the relative refractory period in the His-Purkinje system, and in the effective refractory period of the ventricle. These findings throw light on the mechanism of the anti-arrhythmic action of amiodarone in man.

Topics: Action Potentials; Adolescent; Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Bundle of His; Clinical Trials as Topic; Depression, Chemical; Drug Evaluation; Female; Heart; Heart Atria; Heart Conduction System; Heart Rate; Heart Ventricles; Humans; Male; Middle Aged

Topics: Adult; Aged; Amiodarone; Animals; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Dogs; Drug Evaluation; Female; Humans; Male; Middle Aged

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Humans; Injections, Intravenous

Topics: Adult; Aged; Angina Pectoris; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Male; Middle Aged; Vasodilator Agents

Topics: Adrenergic beta-Antagonists; Adult; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Humans; Hyperthyroidism; Middle Aged; Placebos; Propranolol; Tachycardia

Topics: Action Potentials; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Corneal Opacity; Diethylamines; Electrocardiography; Female; Heart Atria; Heart Rate; Humans; Iodobenzoates; Male; Methods; Middle Aged; Time Factors

DL-3-n-butylphthalide (NBP) is used in the treatment of ischemic stroke. It was demonstrated NBP also has a cardioprotective effect in acute myocardial infarction (MI) model. However, the chronic effects of NBP on ventricular function, remodeling, and arrhythmias in post-MI stage are unknown. This study was to investigate the effect of NBP on reducing ventricular remodeling and arrhythmias in post-MI stage. Post-MI rats were randomly treated with 100 mg/kg NBP daily (n = 21) or vehicle (n = 21) for 5 weeks. Sham-operated rats were treated with the same dose vehicle (n = 18). Echocardiographic assessment, ventricular arrhythmias inducibility test, morphological and collagen analysis, immunohistochemistry, and western blot were studied. NBP significantly improved cardiac function, inhibited the severity and inducibility of ventricular arrhythmias, reduced cardiac index, fibrosis and hypertrophy, improved the protein expression and distribution of Cx43 gap junction, and upregulated PI3k/Akt/Nrf2 pathway and the downstream antioxidant response elements (ARE), including heme oxygenase-1, Glutathione, Cu-Zn superoxide dismutase, and Fe/Mn superoxide dismutase. These results suggest NBP improves LV function and reduces ventricular arrhythmias by mitigating LV fibrosis, hypertrophy, and Cx43 gap junction remodeling. PI3k/Akt/Nrf2/ARE signaling pathway may contribute to its anti-ventricular remodeling effects.

Topics: Animals; Arrhythmias, Cardiac; Benzofurans; Cardiotonic Agents; Connexin 43; Fibrosis; Heart Ventricles; Myocardial Infarction; NF-E2-Related Factor 2; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Ventricular Function; Ventricular Remodeling

Cisapride and prucalopride act as 5-HT

Topics: Animals; Arrhythmias, Cardiac; Atrial Function; Benzofurans; Cardiotonic Agents; Cisapride; Heart Rate; In Vitro Techniques; Mice, Transgenic; Myocardial Contraction; Receptors, Serotonin, 5-HT4; Serotonin Receptor Agonists

An increased propensity towards cardiac arrhythmias and aggravated heart function is observed in myocardial infarction (MI), the development of which is associated with the calcium handling system in the myocardium. It was hypothesized that the abnormal changes in the MI model may be a consequence of the abnormal expression and function of the RyR2-FKBP12.6 channel complex and that these abnormalities may be related to an over-activated endothelin (ET) system. Salvianolic acid B is expected to suppress life-threatening arrhythmias and to restore the abnormality of the RyR2-FKBP12.6 complex in rats. MI was produced by ligating the coronary artery for 4 weeks. Salvianolic acid B (100 mg/kg/day, p.o. for 4 weeks) was administered to rats 0.5 h before surgery. Measurements of cardiac arrhythmias, cardiac function, calcium transient, cardiac calcium release channel handling proteins and the endothelin system were conducted. The aggravated arrhythmia and compromised cardiac function in MI rats was accompanied by elevated diastolic Ca(2+) levels in the cytosol and a significant down-regulation of expression of RyR2-FKBP12.6. These were closely linked with an over-activated ET pathway in the myocardium. After a 4-week treatment with salvianolic acid B, all abnormalities were reversed significantly. Salvianolic acid B was capable of normalizing FKBP12.6 expression levels and decreasing the propensity towards arrhythmias by attenuating the up-regulated ET pathway.

Topics: Animals; Arrhythmias, Cardiac; Benzofurans; Calcium; Disease Models, Animal; Drugs, Chinese Herbal; Gene Expression; Hemodynamics; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; Rats; Rats, Sprague-Dawley; Receptors, Endothelin; Ryanodine Receptor Calcium Release Channel; Signal Transduction; Tacrolimus Binding Proteins

The main objective of this study was to establish background levels of serum PCDD/Fs and biochemistry of residents living near municipal waste incinerators (MWIs) which had been operating between 1 and 8 years, and also to examine the association between the serum PCDD/Fs levels and health outcomes of interest. Information on medical history, life-style, and dietary habits was obtained by questionnaire interview. Significantly elevated levels of glucose and blood urea nitrogen (BUN) were found in those with low to high serum PCDD/Fs levels (p<0.05), and PCDD/Fs levels were found to be positively associated with glucose levels, and marginally with GGT levels even after adjusting for age, sex, BMI and smoking status. Although no conclusive findings on health disorder were associated with the accumulation of serum PCDD/Fs in our study participants, we suggest that the current biochemistry examinations only reflect partially the physiological change in glucose modulation and liver function. However, the low serum PCDD/Fs level does not seem to be sufficient in eliciting pathological process for diabetes or liver-related diseases. The findings suggest that the human body's biochemistry functions such as liver and glucose modulation were affected by PCDD/Fs exposure at even these low serum PCDD/Fs levels found in the general population. Other biochemical functions therefore should be further analyzed, especially for hormone-related and immune functions.

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Benzofurans; Blood Glucose; Diabetes Mellitus; Dibenzofurans, Polychlorinated; Environmental Monitoring; Environmental Pollutants; Epidemiological Monitoring; Female; gamma-Glutamyltransferase; Headache; Humans; Hypothyroidism; Incineration; Male; Middle Aged; Polychlorinated Dibenzodioxins; Taiwan

We previously reported that imidazoline receptors in the central nervous system are involved in modulation of halothane-epinephrine arrhythmias. These receptors have been subclassified as I1 and I2 subtypes, but it is not known which receptor subtype is involved in halothane-epinephrine-induced arrhythmias. We designed the present study to clarify the involvement of central imidazoline receptor subtype in the modulation of halothane-epinephrine-induced arrhythmias. Rats were anesthetized with halothane and monitored continuously for systemic arterial blood pressure and premature ventricular contractions. The arrhythmogenic dose of epinephrine was defined as the smallest dose that produces three or more premature ventricular contractions within a 15-s period. Intracisternal moxonidine dose-dependently inhibited the epinephrine-induced arrhythmias during halothane anesthesia. Intracisternal efaroxan, a selective I1 antagonist with little affinity for I2 subtype, but not rauwolscine, an alpha2 antagonist without affinity for imidazoline receptors, blocked the antiarrhythmic effect of moxonidine. Intracisternal BU 224 and 2-BFI, selective I2 ligands, also inhibited the epinephrine-induced arrhythmias dose-dependently; however, these effects were abolished by efaroxan. We conclude that central I1, but not I2, receptors play an important role in inhibition of halothane-epinephrine arrhythmia.

Topics: Animals; Arrhythmias, Cardiac; Benzofurans; Blood Pressure; Dose-Response Relationship, Drug; Epinephrine; Halothane; Heart Rate; Imidazoles; Imidazoline Receptors; Male; Rats; Rats, Sprague-Dawley; Receptors, Drug

Agonists of the serotonin 5-hydroxytryptamine 4 (5-HT4) receptor are widely used to activate motility in the gastrointestinal tract. Among these, cisapride was recently withdrawn from the U.S. market because of its proarrhythmic effects. Cisapride is a potent blocker of human ether-à-gogo (HERG) K(+) channels and prolongs the cardiac action potential in a reverse use dependence manner. We compared the effects of four different 5-HT4 receptor agonists (cisapride, prucalopride, renzapride and mosapride) on cloned HERG channels with the objective to evaluate and compare their proarrhythmic potential. K(+) currents from HERG-transfected COS-7 cells were recorded under physiological conditions using the whole cell configuration of the patch-clamp technique. Short (500 ms) depolarizing prepulses were used and following deactivating HERG currents were measured. Cisapride inhibited the HERG channels in a concentration-dependent manner with an IC(50) of 2.4 10(-7) M. The IC(50) value for prucalopride to block HERG (5.7 10(-6) M) was 20-fold higher than that of cisapride. Renzapride was slightly more potent than prucalopride (IC(50) = 1.8 10(-6) M). Mosapride produced no significant effects on the recombinant HERG current. The voltage dependence of HERG block was also investigated. The block mediated by cisapride or renzapride was voltage-dependent whereas that produced by prucalopride was not. We conclude that the rank order of potency of 5-HT4 agonists to block HERG is cisapride > renzapride > prucalopride > mosapride. We also conclude that 5-HT4 agonists devoid of side effects on the HERG current such as mosapride can be found as a safe alternative to cisapride.

Topics: Animals; Arrhythmias, Cardiac; Benzamides; Benzofurans; Bridged Bicyclo Compounds, Heterocyclic; Cation Transport Proteins; Cisapride; DNA-Binding Proteins; Electrophysiology; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels; Gastrointestinal Agents; Glycosaminoglycans; Humans; Morpholines; Potassium Channels; Potassium Channels, Voltage-Gated; Recombinant Proteins; Serotonin Antagonists; Trans-Activators; Transcriptional Regulator ERG

We compared the ability of a new amiodarone-like agent, SR 33589, with that of amiodarone, D,L-sotalol, and lignocaine to reduce the incidence of ventricular fibrillation (VF) and associated arrhythmias caused by acute coronary artery occlusion in anesthetized pigs. Ischemia was induced by occlusion of the left coronary descending artery (LAD) for 30 min. Premature ventricular complexes (PVCs), ventricular tachycardia (VT), and ventricular fibrillation (VF) were recorded during coronary occlusion. SR 33589 (1.25, 2.50, and 5 mg/kg intravenously, i.v.) markedly reduced the occurrence of ventricular arrhythmias during ischemia. The incidence of VF was reduced from 90% in the control group to 30% (p < 0.05) with 1.25 mg/kg, to 10% (p < 0.001) with 2.50 mg/kg, and to 20% (p < 0.01) with 5 mg/kg. In addition, SR 33589, especially at the two higher doses, caused a sustained reduction in both the incidence of VT and the number of PVCs per minute. In comparison, amiodarone 10 and 20 mg/kg i.v. reduced the incidence of VF (40 and 50%, respectively), but these reductions never reached a level of statistical significance. The incidence of VT and the number of PVCs per minute were also decreased significantly by amiodarone. D,L-sotalol 3 mg/kg i.v. exerted significant anti-arrhythmic activity; the incidence of VF was reduced 20% (p < 0.01), and both the incidence of VT and number of PVC per minute were also reduced. In contrast, lignocaine given as a 2-mg/kg bolus followed by an infusion at 70 micrograms/kg/min had no antiarrhythmic or antifibrillatory activity in this preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amiodarone; Analysis of Variance; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Death, Sudden, Cardiac; Disease Models, Animal; Dronedarone; Female; Lidocaine; Male; Myocardial Ischemia; Sotalol; Stereoisomerism; Swine; Tachycardia, Ventricular; Ventricular Fibrillation

We have assessed the ability of the new amiodarone-like antiarrhythmic agent, SR 33589, to reduce the incidence of ischemia- and reperfusion-induced arrhythmias, in comparison to amiodarone, D-sotalol, and lignocaine. Rats were anesthetized, artificially ventilated, and the thorax opened by a left thoracotomy. Ischemia was induced by left coronary artery ligation, and reperfusion was achieved (after a 5-min period of ischemia) in a separate group of rats by removing the ligature. Agents were given intravenously 5 min before occlusion or orally 4 h before study. During a 20-min period of ischemia, SR 33589 reduced significantly the incidence of ventricular fibrillation (VF) from 80 to 30% (p < 0.05) at 3 mg/kg i.v. and eliminated VF and mortality at 10 mg/kg i.v. In contrast, amiodarone at 10 mg/kg i.v. reduced significantly only the incidence of mortality during ischemia (from 60 to 0%, p < 0.01), while having no significant effect on 3 mg/kg i.v. On reperfusion (after a 5-min period of ischemia), SR 33589 reduced significantly the incidence of mortality (from 90 to 20%, p < 0.01) at 1 mg/kg and eliminated VF and mortality when administered at 3 and 10 mg/kg. Against both ischemia- and reperfusion-induced arrhythmias, approximately 20% of animals showed AV block at the highest dose of SR 33589 tested. This was not observed with lower doses. Amiodarone (10 mg/kg i.v.) eliminated completely reperfusion-induced VF and mortality while having no significant effect at 1 and 3 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Amiodarone; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Chi-Square Distribution; Disease Models, Animal; Dose-Response Relationship, Drug; Dronedarone; Electrocardiography; Heart Block; Heart Rate; Injections, Intravenous; Lidocaine; Myocardial Reperfusion Injury; Random Allocation; Rats; Sotalol; Ventricular Fibrillation

We have developed a new method to measure [Na+]i and Ca2+ transients of a beating cardiac myocyte using a Na(+)-sensitive fluorescent probe, sodium-binding benzofuran isophthalate (SBFI) and a Ca(2+)-sensitive fluorescent probe, fluo-3. There was no interaction between two probes, and the artifact due to contraction could be eliminated in the measurement of [Na+]i. [Na+]i in guinea pig ventricular myocytes stimulated at 1 Hz was 8.0 +/- 0.7mM. Strophanthidin (10 microM), initially, increased the amplitude and the basal level of Ca2+ transients in association with an increase in [Na+]i. When arrhythmias were induced, the amplitude of Ca2+ transients decreased while [Na+]i and the basal level of Ca2 transients continued to increase. These results suggested that the diastolic [Ca2+]i was closely related to [Na+]i. However, the systolic [Ca2+]i, which could be influenced by other factors, was dissociated from [Na+]i in the condition of Ca2+ overload.

Topics: Aniline Compounds; Animals; Arrhythmias, Cardiac; Benzofurans; Calcium; Electric Stimulation; Ethers, Cyclic; Female; Fluorescent Dyes; Guinea Pigs; Myocardium; Sodium; Spectrometry, Fluorescence; Strophanthidin; Xanthenes

Two routes of synthesis of 2-acetyl-7-hydroxy-6-methoxy-3-methylbenzofuran and some of its aminoalkanol ethers are described. Six compounds proved to exert the expected antiarrhythmic and hypotensive effects.

Topics: Adrenergic beta-Agonists; Animals; Anti-Arrhythmia Agents; Antihypertensive Agents; Arrhythmias, Cardiac; Benzofurans; Blood Pressure; Drug Evaluation, Preclinical; Heart Conduction System; Hypertension; Male; Mice; Propanolamines; Rats

The case of a patient who developed interstitial pneumopathy after 4 1/2 years of treatment with a normal dose of amiodarone is reported. Drug interruption and additional steroid therapy normalized the pulmonary picture and lung function within 4 months. During this period serum iodine, amiodarone, its metabolite desethyl-amiodarone and urinary iodides were measured and the results compared with the improvement of the clinical and radiological situation. Possible interrelationships between the drug and the pneumopathy, and hypotheses regarding pathogenesis are discussed. During long-term amiodarone therapy radiological checks at regular intervals are important.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiac Complexes, Premature; Humans; Male; Pulmonary Fibrosis; Radiography

Pulmonary function, chest radiographic appearances, and the cellular composition of bronchoalveolar lavage fluid were assessed in 13 patients who were receiving amiodarone treatment. Eight of the patients had developed clinical and radiological evidence of lung disease and five were symptom free. The proportions of lymphocytes (mean 8.6 (SD 6.9)) and neutrophils (mean 3.4 (3.3)) obtained by bronchoalveolar lavage were similar in patients with and without lung complications. Electron microscopic examination of alveolar macrophages showed intralysosomal inclusion bodies in all subjects, regardless of clinical state. There was no significant difference in the mean number of inclusion bodies per macrophage transection between those with and those without lung disease. The differential cell count in bronchoalveolar lavage fluid and the presence of macrophage inclusion bodies were therefore not useful as markers of disease activity. Among those who developed clinical and radiological evidence of lung disease, the cumulative drug dose per kilogram of body weight and the duration of treatment (mean 16.5 (SD 9.0) months) were significantly correlated with the degree of lung restriction as measured by total lung capacity and forced vital capacity. It is concluded that, while the severity of the restrictive pulmonary defect that is induced by amiodarone is largely dose related, the development of lung toxicity is to some extent idiosyncratic.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Inclusion Bodies; Leukocyte Count; Lung Diseases; Lymphocytes; Macrophages; Male; Microscopy, Electron; Middle Aged; Neutrophils; Pulmonary Alveoli; Respiratory Function Tests; Therapeutic Irrigation

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Chagas Cardiomyopathy; Drug Evaluation; Humans; Prognosis

Topics: Adolescent; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Child, Preschool; Corneal Diseases; Humans; Infant; Infant, Newborn; Male; Photosensitivity Disorders

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Child, Preschool; Drug Evaluation; Female; Humans; Infant; Infusions, Parenteral; Male; Middle Aged; United Kingdom

Topics: Adult; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiomyopathies; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Child; Female; Humans; Male; Middle Aged

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Electrophysiology; Heart; Humans

Although amiodarone is effective for the suppression of complex ventricular arrhythmias, a major problem with its use is the long delay between the initiation of therapy and the onset of effective suppression of arrhythmia. To test the hypothesis that rapid loading with oral amiodarone to a target serum concentration can overcome much of this delay, eight patients with refractory, sustained, hemodynamically compromising ventricular arrhythmias and 10 patients with potentially life-threatening ventricular arrhythmias were treated with a flexible, very high dose, oral loading protocol (800 to 2000 mg two to three times a day). Dosage was adjusted on the basis of amiodarone serum concentrations to maintain the trough serum concentrations between 2.0 and 3.0 micrograms/ml. Comparison of 24 hr Holter electrocardiograms obtained before and during therapy revealed statistically significant reductions in premature ventricular complexes (PVCs) and paired PVCs beginning the first day of therapy and a reduction in ventricular tachycardia (VT) beginning the second day. By day 2, four of eight patients with sustained VT and six of 10 patients with nonsustained VT showed no VT. Pulmonary arterial catheterization during the first 24 hr (mean amiodarone dose 3933 mg) revealed no significant hemodynamic alterations. Minor side effects were common (10 patients) but major side effects were rare (one patient). High-dose oral loading with amiodarone utilizing serum concentration guidelines is a safe and effective method of rapidly controlling life-threatening arrhythmias in selected patients.

Topics: Administration, Oral; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Administration Schedule; Electrocardiography; Follow-Up Studies; Heart Rate; Heart Ventricles; Hemodynamics; Humans; Kinetics

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Interactions; Heart Diseases; Heart Ventricles; Humans; Kinetics; Pulmonary Fibrosis

Thyroid function was systematically evaluated in 15 consecutive children (mean age 13.7 years, range 0.5 to 19.5 years) before and serially during treatment with amiodarone (Cordarone), a potent antiarrhythmic agent. Amiodarone is known to affect thyroid homeostasis by competitive inhibition of 5'-monodeiodinase, which converts L-thyroxine (T4) to triiodothyronine (T3) and reverse T3 (rT3) to 3,3'-diodothyronine (T2), and also by the direct effects of its high iodine content (37% by weight). Clinical and/or biochemical evidence of hypothyroidism occurred in three patients, two of whom required treatment with L-thyroxine. An additional patient had persistent hyperthyroxinemia but no clinical evidence of hyperthyroidism. Results from the patients who remained euthyroid showed characteristic alterations in serum thyroid function tests. These included significant increases in serum T4, rT3, basal thyroid-stimulating hormone and thyroid-stimulating hormone response to thyrotropin-releasing hormone testing. These changes were considered to be compensatory adjustments by the pituitary-thyroid axis to competitive inhibition of 5'-monodeiodinase by the amiodarone. Routine screening of thyroid function is needed to allow early detection of hypothyroidism when these compensations fail to occur.

Topics: Adolescent; Adult; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Child; Child, Preschool; Female; Humans; Hypothyroidism; Infant; Iodide Peroxidase; Male; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones

A patient with acute changes suggesting acute hepatitis after parenteral amiodarone administration is described. A 77-year-old man with previous myocardial infarction was admitted with chronic left heart failure and atrial tachycardia. Initial hepatic function tests were strictly normal. After therapy with parenteral amiodarone (2300 mg in 3 days) and other measures, signs of congestive heart failure disappeared; subsequently the patient developed jaundice, marked increase in serum transaminase levels and fall in prothrombin time, and histologic changes of severe centrilobular necrosis were observed in hepatic biopsy. Clinical, laboratory (absence of others markers of hepatic disease), and histological findings seem to rule out common causes of hepatic disease. Therefore, parenteral amiodarone was implicated as the cause of acute hepatitis in this patient. In addition, there were findings suggesting a possibly immunologically mediated mechanism.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Biopsy; Chemical and Drug Induced Liver Injury; Coronary Disease; Dose-Response Relationship, Drug; Humans; Infusions, Parenteral; Liver; Liver Function Tests; Male

Five cases of amiodarone-induced syncope due to torsades de pointes or ventricular fibrillation are described. Amiodarone was used for recurrent supraventricular tachycardia in four cases and frequent ventricular extra systoles complicating congenital QT prolongation in the remaining case. Each was associated with a marked prolongation in the QTc interval following amiodarone. Three cases had had a previous history of life-threatening ventricular arrhythmias secondary to anti-arrhythmic drugs. Hypokalemia may have been a contributory factor in two. The clinical features, predisposing factors, and treatment are discussed.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Benzofurans; Drug Therapy, Combination; Electrocardiography; Female; Heart Arrest; Heart Failure; Humans; Long QT Syndrome; Tachycardia

The time to onset of action of amiodarone is often long in patients treated for arrhythmias; one reason might be a slow entry of the drug into the target organ, the heart. Amiodarone and desethylamiodarone, its active metabolite, were measured in the plasma, atrial tissue and pericardial fat of patients undergoing cardiac surgery. Two groups were studied: patients treated with amiodarone for less than 28 days (short-term group) and those treated for 28 days or more (long-term group). Plasma levels of amiodarone in the two groups were not different, whereas levels of desethylamiodarone were significantly higher in the long-term group. Average concentrations of amiodarone in the atrium were higher with longer treatment periods (30.2 +/- 5.6 versus 13.2 +/- 2.5 micrograms/g wet weight of tissue); the same was true for desethylamiodarone (40.3 +/- 7.7 versus 15.7 +/- 3.7 micrograms/g). Amiodarone concentrations in fat were also significantly higher in the long-term than in the short-term group. Atrium/plasma concentration ratios of desethylamiodarone were higher than those of amiodarone, whereas fat plasma concentration ratios of desethylamiodarone were lower. In conclusion, the equilibration of amiodarone and desethylamiodarone concentrations between myocardium and plasma appears to occur slowly in patients undergoing long-term treatment with amiodarone.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adipose Tissue; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiac Surgical Procedures; Heart Atria; Humans; Kinetics; Middle Aged; Myocardium; Time Factors

For the 5-year period 1979 to 1983, 242 patients were followed up who had received amiodarone treatment, 156 for supraventricular tachycardia (SVT) and 86 for ventricular arrhythmias. Five patients were lost to follow-up overseas; the rest were followed to cessation of therapy, death or recent review for a mean of 24 +/- 15 months. Male/female incidence was 1.8:1 and mean age was 58 years (range 4 to 88). Half the group had impaired left ventricular function. Adverse effects were recorded in 59% of the patients and led to drug withdrawal in 26% of the total group. In contrast, unsuccessful treatment was the cause of drug withdrawal in only 5% of the patients, although an additional 25% stopped taking the drug for various reasons. Actuarial survival for the whole group, and subgroups with SVT and ventricular tachycardia/fibrillation were 66%, 74% and 52%, respectively, at 50 months. For the whole group, the actuarial probability of being alive and continuing with amiodarone therapy was only 19% at 50 months. Thus, although amiodarone was effective, few patients tolerated the drug on a long-term basis. Although amiodarone remains a valuable treatment for patients with ventricular tachycardia, its long-term effectiveness for patients with SVT is less certain.

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Child, Preschool; Drug Tolerance; Female; Humans; Male; Middle Aged

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans

The efficacy and safety of combined amiodarone and mexiletine treatment was investigated in 16 patients with chronic complex ventricular arrhythmias previously refractory to conventional antiarrhythmic agents and, in a lesser degree, to mexiletine or amiodarone. Many patients had a poor left ventricular function. Oral amiodarone was started using a loading dose of 600 mg daily for one week, 400 mg daily for one week, and a subsequent dosage of 200 mg daily five times a week. After twenty-one days of this treatment mexiletine was administered in combination (600 mg/day orally), if a 24-hour ambulatory ECG had revealed a partial suppression of the ventricular arrhythmias (14 out of 16 patients). On the fourth day of combined amiodarone and mexiletine treatment, analysis of a 24-hour ambulatory ECG showed a marked diminution of the ventricular ectopic activity compared with the pretreatment period. The average percentages of reduction for PVCs and couplets were 88% and 97%. Total suppression of TV runs/24 hr was achieved in all patients. Ventricular arrhythmias relapse was found in all patients during early mexiletine washout (phase 4) and in 12 patients during late mexiletine washout (phase 5). Amiodarone and mexiletine combination did not appear to reduce left ventricular function. Minor side effects occurred in some patients. Follow-up from 3 months to two years (mean 16 months) showed that maintenance treatment had achieved remarkable antiarrhythmic effects (Holter control). However, sudden cardiac death occurred in two patients with very depressed left ventricular function. We conclude that a combined amiodarone and mexiletine treatment effectively reduces the frequency and grade of PVCs and does not impair left ventricular performance. However, it does not prevent sudden cardiac death in patients with poor left ventricular function.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Therapy, Combination; Electrocardiography; Female; Follow-Up Studies; Heart Ventricles; Humans; Male; Mexiletine; Middle Aged; Propylamines

The effects of chronic amiodarone treatment on several thyroid and cardiac function parameters were studied in 50 euthyroid patients with refractory ventricular arrhythmias, divided in responders and nonresponders according to their sensitivity to the antiarrhythmic action of the drug. No differences in the severity of cardiac disease and blood amiodarone concentrations were found in the two groups. Amiodarone induced a significant inhibition of peripheral T4 monodeiodination, more pronounced in responders compared to nonresponders. On the contrary, only in responsive patients, elevated basal and TRH-stimulated TSH levels were observed (despite serum T3 levels were not different from those in nonresponders) and the indirect indices of cardiac performance, particularly the systolic time intervals, fell in a range usually observed in the hypothyroid states. These findings suggest that amiodarone, besides the well-known inhibition of T4 to T3 conversion, also induces a partial resistance to the thyroid hormones, which is probably involved in the therapeutical effectiveness of the drug.

Topics: Adolescent; Adult; Aged; Amiodarone; Antithyroid Agents; Arrhythmias, Cardiac; Benzofurans; Female; Heart Function Tests; Humans; Hypothalamo-Hypophyseal System; Male; Middle Aged; Thyroid Function Tests; Time Factors

Amiodarone is an antiarrhythmic agent known to cause prolongation of action potential duration which is reflected in the electrocardiogram as a prolongation of the QT interval. Prolongation of the QT interval in patients dying suddenly was compared with that in patients who remained alive to determine whether a difference existed between these two groups. The electrocardiogram and amiodarone levels were evaluated in 33 patients who presented with cardiac arrest and symptomatic ventricular tachycardia in whom no other antiarrhythmic agent was found effective in preventing induction of ventricular tachycardia during electrophysiologic studies. There were 30 men and 3 women (mean age 52 +/- 10 years). Twenty-three are alive after a mean follow-up period of 12 +/- 7 months. Ten died: six suddenly, three of non-cardiac causes and one of congestive heart failure. Using a two-way analysis of variance, the percent change in QT, QTc, JT and JTc intervals before and after amiodarone therapy was analyzed. Marked prolongation in the QT interval was present in patients who remained alive with amiodarone therapy. A significant difference in percent QT prolongation was seen between the latter patients and those who died suddenly (p less than 0.005). No difference was observed in the percent change in QRS interval between the two groups. The levels of amiodarone (2.5 versus 3.2 micrograms/ml) and its metabolite (desethylamiodarone) were not significantly different between the living patients and those who died suddenly. These findings suggest that a prolongation of the QT interval may be a marker for the therapeutic antiarrhythmic effect of amiodarone.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiac Pacing, Artificial; Electrocardiography; Female; Follow-Up Studies; Heart Ventricles; Humans; Male; Middle Aged; Monitoring, Physiologic; Tachycardia; Time Factors

Over a 10-year period 130 patients with drug-resistant cardiac arrhythmias associated mainly with coronary artery disease and its complications were treated with amiodarone. The drug controlled all the tachyarrhythmias associated with the Wolff-Parkinson-White syndrome, 95% of the ventricular arrhythmias, including recurrent ventricular tachycardia and fibrillation, and 92% of the supraventricular arrhythmias. The maximum duration of therapy was 111 months and the mean 34 months. Side effects occurred in 34% of the patients, and there was one withdrawal from therapy per 15.3 patient-years of treatment. The commonest cause of withdrawal was nausea, which was significantly related (p less than 0.01) to a drug interaction with digoxin and diuretics. Reversible neurologic complications occurred in eight patients (6%), and acute myositis was recognized for the first time. Pulmonary infiltration developed in four patients (3%), who were receiving 600 mg of amiodarone per day. The rates of side effects and of withdrawal from therapy differed significantly between the patients whose maintenance doses were 600 and 200 mg/d, at 59% v. 6% (p less than 0.01) and 32% v. 0% (p less than 0.05) respectively. Thus, amiodarone is a very effective antiarrhythmic that can be administered over long periods with acceptable rates of side effects and withdrawal provided the minimal effective dose is used; 400 mg/d or less is desirable.

Topics: Adolescent; Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Coronary Disease; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Male; Middle Aged; Recurrence; Tachycardia; Ventricular Fibrillation

Cardiac patients taking amiodarone, a potent anti-arrhythmic drug, often have supranormal serum thyroxine (T4) levels and normal or mildly reduced serum triiodothyronine (T3) levels. We studied T4 and T3 kinetics and conversion of T4 to T3 in 5 men with recurrent paroxysmal tachycardia before and after 5-6 weeks of therapy with amiodarone (dose 200-800 mg/day). The patients were also receiving various medicines for cardiac disease. Each was injected with tracer doses of labelled T4 and T3; serum samples were processed by TCA precipitation and ethanol extraction. The data were analyzed with the aid of six-compartment model for T4 and T3 kinetics. Mean total body T3 production rate, total body T3 pool size, and conversion of T4 to T3 were all reduced in patients taking amiodarone.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Humans; Kinetics; Middle Aged; Thyroxine; Triiodothyronine

Eleven critically ill patients with life-threatening cardiac arrhythmias refractory to currently approved antiarrhythmic drugs were treated with intravenous amiodarone. Two patients had acute myocarditis, five had acute myocardial infarction, two had left ventricular failure secondary to ischemic heart disease, one had Wolff-Parkinson-White syndrome, and one manifested postoperative atrial fibrillation. Eight of the patients had severe cardiac failure and five had hypotension requiring intravenous dopamine. Five patients were treated for recurrent ventricular fibrillation, two for recurrent ventricular tachycardia, and four for recurrent atrial arrhythmias. Six patients had repeated cardioversions. The arrhythmias had lasted a mean of 88.3 hours resistant to a mean of 2.7 different intravenous antiarrhythmic drugs. The ventricular arrhythmias did not recur after commencing intravenous amiodarone, but some minor atrial arrhythmias occurred for 24 hours. One patient died of intractable left ventricular failure, chronic obstructive lung disease, and respiratory arrest during treatment. The dose of amiodarone was 150 mg over 5 minutes, followed by 600 mg/24 hr for 3 to 4 days; one patient on total parenteral nutrition required intravenous amiodarone for 20 days. Hypotension, cardiac failure, and bradyarrhythmias were not induced by this treatment. Intravenous amiodarone can be used safely in critically ill patients with impaired left ventricular function to control life-threatening refractory cardiac arrhythmias.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Blood Pressure; Dopamine; Electrocardiography; Female; Follow-Up Studies; Heart Rate; Humans; Hypotension; Infusions, Parenteral; Male; Middle Aged; Myocardial Infarction; Myocarditis; Time Factors

The interrelationships between serum levels of amiodarone, desethylamiodarone, and reverse T3, and changes in the corrected QT interval (delta QTc) were examined in 22 patients during long-term treatment with amiodarone. At 1, 3, and 6 months of follow-up, the correlation coefficient between serum levels of amiodarone or desethylamiodarone and reverse T3 ranged from 0.01 to -0.2 (p greater than 0.4). At the same time intervals, the correlation coefficient between both amiodarone and desethylamiodarone levels and delta QTc ranged from 0.1 to -0.1 (p greater than 0.6), and the correlation coefficient between reverse T3 and delta QTc also ranged between 0.1 to -0.1 (p greater than 0.5). Substituting percent delta QTc for delta QTc also did not reveal a significant correlation. These data demonstrate that serum levels of reverse T3 cannot be used as a substitute for serum levels of amiodarone in monitoring patients being treated with amiodarone. The absence of a correlation between serum reverse T3 levels and delta QTc suggests that the delay in repolarization which occurs during amiodarone therapy is not secondary to an amiodarone-induced abnormality in thyroid hormone metabolism.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Time Factors; Triiodothyronine, Reverse

The anaesthetic management of a patient with a phaeochromocytoma and cardiomyopathy is described. The control of dysrhythmias was the major problem. Ventricular dysrhythmias were treated with lignocaine, and intravenous amiodarone was used to control the supraventricular rhythm disturbances.

Topics: Adrenal Gland Neoplasms; Aged; Amiodarone; Anesthesia, General; Arrhythmias, Cardiac; Benzofurans; Cardiomyopathy, Dilated; Humans; Intraoperative Complications; Male; Pheochromocytoma

The antiarrhythmic effects of verapamil, 17-monochloracetylajmaline, mexiletine and amiodarone were compared in 14 patients with chagasic myocarditis. Drugs and placebo were administered orally in the following order: placebo and verapamil, placebo and 17-monochloracetylajmaline, placebo and mexiletine (1 week each) and placebo and amiodarone (4 weeks each). A 24 hour ambulatory electrocardiographic recording was obtained after administration of each placebo and drug. Verapamil had no effect on the number of ventricular premature complexes, ventricular couplets and runs of ventricular tachycardia. 17-Monochloracetylajmaline did not reduce the number of ventricular premature complexes and ventricular couplets but caused a moderate reduction in runs of ventricular tachycardia. Mexiletine failed to significantly reduce ventricular premature complexes but caused a moderate decrease in both ventricular couplets and runs of ventricular tachycardia. Amiodarone was the only one of the four drugs that caused a substantial reduction of ventricular premature complexes (logarithmic mean 97.8%; p less than 0.001), total suppression of runs of ventricular tachycardia in 11 of 11 patients and suppression of ventricular couplets in 8 of 14 patients and a significant reduction in the remaining 6 patients. The much greater efficacy of amiodarone as compared with the two sodium channel modifiers (17-monochloracetylajmaline and mexiletine) and one calcium channel blocker (verapamil) suggests that its potent antiarrhythmic activity is probably related to other peculiar and still undefined electrophysiologic and pharmacologic properties.

Topics: Adult; Ajmaline; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Chagas Cardiomyopathy; Female; Humans; Male; Mexiletine; Middle Aged; Placebos; Propylamines; Verapamil

Oral amiodarone therapy was given to seven patients already taking oral flecainide regularly. In one additional patient, administration of flecainide was temporarily discontinued when amiodarone therapy was begun, and then resumed. Amiodarone produced a rise in mean dose-adjusted flecainide plasma level (trough plasma level at steady state/daily dose) from 2.3 +/- 0.8 to 3.4 +/- 0.9 (ng/ml)(mg/day) (p less than 0.01). Accordingly, the mean dose of flecainide required to maintain similar plasma levels of the drug was one-third lower during combined treatment than during therapy with flecainide alone. This drug interaction must be accounted for when amiodarone and flecainide are used concomitantly.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Interactions; Female; Flecainide; Humans; Male; Middle Aged; Piperidines

Topics: Acetanilides; Amiodarone; Animals; Arrhythmias, Cardiac; Benzofurans; Cardiac Complexes, Premature; Dogs; Drug Therapy, Combination; Female; Humans; Male; Myocardial Infarction; Procainamide; Quinidine; Trimecaine

In the adult, Amiodarone is a very effective drug in the treatment of ventricular and supraventricular arrhythmias. The presence of severe side effects such as some alterations in the thyroid function and/or pulmonary fibrosis have restricted the use in children. Nevertheless, research has shown that there is a low incidence of collateral side effects and this therapy in infancy can be very effective. For this reason we evaluated a group of 27 children with supraventricular (19 patients) and ventricular (8 patients) arrhythmias. The mean age of patients treated was 6 +/- 5 years (2 days-13 years). The follow-up period was of 13 +/- 10 months. Amiodarone has been used in 9 patients intravenously, with the loading dose of 5 mg/Kg followed by an infusion of 10 mg/Kg/day. In 18 patients we administered the drug orally with a loading dose of 10 mg/Kg/day for a period of 10 days, thereafter the maintenance was of 5-7 mg/Kg/day for 5 days every week. The patients were all checked for thyroid function and Holter monitoring quarterly; they were given an ophthalmologic examination (every 6 months) and a chest-x-ray and echocardiography annually. The efficacy of intravenous treatment was judged successful in 56% of patients, partially successful in 22% and ineffective in the remaining 22%. The oral treatment was completely effective in 77% of children, partially in 5% and ineffective in 18%. In one case we had to suspend the therapy because we found high values of T3 and T4. During the treatment, in 86% of cases, we had blood level fluctuations of T3 and T4, however these did not exceed the normal ranges. The most important side effect observed has been the photosensitivity found in 22% of children. Moreover we observed a reduction of sinusal automatism, which was more marked in patients less than year old. In 4 cases an A/V block of first degree appeared. In all patients we found changes of ventricular repolarization, while corneal deposits appeared in only one child after a year of therapy and did not cause an impairment of visual acuity. In conclusion we can assert that Amiodarone is a very effective drug in children, specially in small babies, where it can safety be used as a first choice drug.

Topics: Administration, Oral; Adolescent; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiomegaly; Child; Child, Preschool; Female; Follow-Up Studies; Heart Conduction System; Heart Rate; Humans; Infant; Infant, Newborn; Infusions, Parenteral; Male; Photosensitivity Disorders; Thyroid Gland

Amiodarone is a widely used antiarrhythmic drug, which contains 75 mg of iodide per 200 mg of active substance. Eight of our patients receiving long-term amiodarone therapy became hypothyroid. Seven of these patients had no previous history of thyroid dysfunction or goiter. Antithyroid antibodies were absent, and standard perchlorate discharge tests were positive in seven patients when hypothyroidism was diagnosed. In one patient, amiodarone therapy was withdrawn; over the next nine months, the hypothyroidism resolved, and results of the perchlorate discharge test reverted to normal. We conclude that amiodarone-induced hypothyroidism is similar to previously described iodide-induced hypothyroidism. It may develop in the absence of a previous history of thyroid disease, and all patients receiving long-term amiodarone therapy should therefore be regularly monitored for hypothyroidism.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Hypothyroidism; Iodides; Iodine Radioisotopes; Male; Middle Aged; Perchlorates; Sodium Compounds; Thyroid Function Tests; Thyroid Gland; Thyroxine

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Drug Interactions; Eye Diseases; Female; Humans; Lung Diseases; Male; Peripheral Nervous System Diseases; Skin Diseases; Thyroid Diseases; Time Factors

To assess the incidence of adverse effects associated with long-term amiodarone therapy, we reviewed the records of 217 consecutive patients who were treated for refractory arrhythmia. After an average of 11.8 months of therapy, one or more side effects occurred in 113 patients (52%). These were considered clinically significant in 42 patients (19.3%), mandating discontinuation of amiodarone in 18 (8.3%). The untoward reactions requiring discontinuation of amiodarone included thyroid dysfunction, visual disturbances, pulmonary infiltrates, ataxia, cardiac conduction abnormalities, and drug interactions. The mild side effects included corneal microdeposits, skin rashes, and gastrointestinal symptoms. There was a weak correlation between blood levels of amiodarone, the daily dose, and the cumulative dose (r = 0.23, p = 0.015). Drug levels were higher in symptomatic patients (p less than 0.03), although they received lower doses of amiodarone. While amiodarone is associated with frequent side effects, they are generally mild and do not necessitate drug discontinuation. Careful monitoring of therapy is essential to detect the potentially serious adverse reactions which are encountered in nearly 20% of patients.

Topics: Amiodarone; Arrhythmias, Cardiac; Ataxia; Benzofurans; Drug Eruptions; Drug Interactions; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Respiratory Tract Diseases; Thyroid Diseases; Time Factors; Vision Disorders; Warfarin

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Eruptions; Facial Dermatoses; Humans; Male; Middle Aged; Pigmentation Disorders

A single bolus of 5 or 40 mg/Kg of amiodarone was injected 24 hours after inducing coronary artery occlusion in the closed-chest dog preparation. Plasma pharmacokinetic profile was determined and the calculated t1/2 beta of 3.5 +/- 2.8 and 3.2 +/- 0.6 hour after 5 or 40 mg/Kg dose, respectively, were obtained. The major metabolite, desethylamiodarone, was detected within 15 minutes of the single bolus of amiodarone. At 6 hours after amiodarone administration, the animals were killed and tissue concentrations of amiodarone and desethylamiodarone were measured. Two additional peaks in the HPLC chromatograms were observed in plasma and tissue samples of most dogs given 40 mg/Kg I.V. amiodarone and these most likely are due to unidentified metabolites of the drug. The highest drug concentration was found in the lungs. Tissue to plasma drug rations suggested that accumulation of amiodarone and perhaps desethylamiodarone was different for different tissues. Ventricular arrhythmias were not abolished by either of the two doses of amiodarone; however, there was a gradual and statistically significant decrease in the number of ventricular premature beats and ventricular tachycardia beats over the six-hour period after a single 40 mg/Kg I.V. bolus. At the time of reduction in the arrhythmia frequency, tissue levels of both amiodarone and desethylamiodarone in the border and infarct zone of the myocardium were approximately 50% as high as in the normal zone. Plasma drug levels did not correlate well with tissue concentrations. However, there was an excellent correlation between drug levels in WBCs and various tissues except the lung. It is concluded that amiodarone is rapidly metabolized into desethylamiodarone and at least two other unidentified compounds; a large dose of amiodarone is necessary to produce some decrease in ventricular arrhythmias associated with acute coronary artery occlusion; tissue concentrations may be better correlated with drug levels in WBCs than in plasma, and coronary artery occlusion does not affect acute pharmacokinetic profile of the drug.

Topics: Amiodarone; Animals; Arrhythmias, Cardiac; Benzofurans; Biotransformation; Chromatography, High Pressure Liquid; Dogs; Dose-Response Relationship, Drug; Electrocardiography; Female; Heart Conduction System; Hemodynamics; Male; Myocardial Infarction; Myocardium

During treatment with amiodarone, digoxin and nadolol, asystole occurred repeatedly in a patient with chronic persistent automatic atrial tachycardia. Asystole did not occur after discontinuation of drug therapy, and rechallenge with amiodarone alone produced marked overdrive suppression of all pacemakers resulting in asystole. Amiodarone serum level was within therapeutic range. The possible electrophysiologic mechanisms by which amiodarone might suppress both normal and abnormal pacemakers are discussed. The occurrence of asystole at therapeutic serum concentration of amiodarone suggests that this drug should be used with caution.

Topics: Adult; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Digoxin; Drug Therapy, Combination; Electrocardiography; Female; Heart Arrest; Heart Atria; Heart Rate; Humans; Nadolol; Propanolamines; Tachycardia

Therapeutic use of the potent antiarrhythmic drug amiodarone requires early detection of impending hyperthyroidism, a potentially life-threatening adverse reaction in cardiac patients. Since amiodarone inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3), serum T4 and T3 levels become unreliable parameters of thyroid function. In 44 patients treated with amiodarone for a median period of 7.3 months, up to seven TRH-TSH tests were performed. The TSH response to TRH was normal in 23 patients, partially suppressed in eight, totally suppressed in eight and overshooting in five patients. Two of the eight patients with suppressed TRH-TSH tests were clinically hyperthyroid, in four others thyrotoxicosis developed within 1 to 2 1/2 months after the first observation of a suppressed TSH response, while two patients remained euthyroid. In all patients with negative TRH-TSH tests. TSH response to TRH returned to normal between 2 and 29 months after withdrawal of amiodarone. We conclude that the TRH-TSH test, repeated at intervals, is a reliable tool for assessing thyroid function in patients on long-term treatment with amiodarone. Patients with a suppressed response under amiodarone therapy are at risk of developing thyrotoxicosis. Normalization of the TSH response indicates that this risk is over.

Topics: Adolescent; Adult; Aged; Amiodarone; Angina Pectoris; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Hyperthyroidism; Iodine; Male; Middle Aged; Risk; Thyroid Function Tests; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

The use of amiodarone, a drug which is prescribed increasingly as an anti-anginal and anti-arrhythmic agent, necessitates a high index of suspicion for the development of thyroid disorders, especially thyrotoxicosis. Two cases, which illustrate the diagnostic dilemma of hyperthyroxinaemia and the poor response to antithyroid medication, are described. During amiodarone therapy, the clinical features of thyrotoxicosis may be masked or atypical, and the choice of therapy is complicated by a delayed response to thioamide drugs and possible contraindication for beta-blocking agents which necessitates the use of glucocorticoid drugs in some patients.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Carbimazole; Coronary Disease; Humans; Hyperthyroidism; Male; Prednisone; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

This study demonstrated the rapid antiarrhythmic effects of oral amiodarone (Am). A single 30 mg/kg dose was given to 67 patients, 18 with supraventricular arrhythmias (atrial extrasystoles: 11 cases, reciprocating tachycardia: 4 cases, intraatrial reentrant tachycardia: 2 cases, paroxysmal atrial fibrillation, AF: 1 case). Eighteen patients had permanent AF. Thirty-one patients had ventricular arrhythmias (ventricular extrasystoles, VES, isolated or in salvos: 22 cases, and ventricular tachycardia, VT: 19 cases). The effect on atrial extrasystoles was significant 4 to 13 hours after AM and maximal (-98% +/- 3.6%) at 7.7 +/- 1 hours. They recurred in 3 cases at the 18th hour. No significant effects were observed on the other supraventricular tachycardias. The effect on the atrioventricular node (AVN) assessed by the ventricular response to permanent AF, was significant after the 3rd hour and maximal ( = 38 +/- 6 bpm) at the 7th hour. The reduction in the frequency of VES was significant from the 5th to the 19th hour of treatment. Control of VT was obtained in 5 cases between the 3rd and 8th hours. The treatment was well tolerated as no side effects were reported. The plasma concentration (PC) of amiodarone (54 patients) and of N-desethylamiodarone (NDA) (36 patients) were measured; the maximal values were 2.53 +/- 1.5 mg/l for Am and 0.22 +/- 0.1 mg/l for NDA. A 60% decrease in the number of VES was observed with PC of Am of 1.90 +/- 0.3 mg/l and a 20% reduction in the ventricular response to AF at PC of Am of 1.50 +/- 0.33 mg/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Dose-Response Relationship, Drug; Female; Humans; Kinetics; Male

The pharmacokinetic characteristics of amiodarone suggest extensive tissue deposition. We confirmed this by measuring tissue concentrations of the drug and of its major metabolite, desethylamiodarone, in human tissues. These were obtained at autopsy (n = 9), surgery (n = 7), or biopsy (n = 2) from 18 patients who had been treated with amiodarone for varying periods of time. High concentrations of amiodarone were found in fat (316 mg/kg wet weight in autopsy specimens, 344 mg/kg wet weight in biopsy specimens). Amiodarone and desethylamiodarone concentrations (mg/kg wet weight, autopsy samples) were also high in liver (391 and 2354), lung (198 and 952), adrenal gland (137 and 437), testis (89 and 470), and lymph node (83 and 316). We also found high concentrations of amiodarone (306 mg/kg wet weight) and desethylamiodarone (943 mg/kg wet weight) in abnormally pigmented ("blue") skin from patients with amiodarone-induced skin pigmentation. These values were 10-fold higher than those in unpigmented skin from the same patients. These high concentrations were associated with lysosomal inclusion bodies in dermal macrophages in the pigmented skin. The inclusion bodies were intrinsically electron dense and were shown to contain iodine by energy dispersive x-ray microanalysis. Lysosomal inclusion bodies shown by electron microscopy to be multilamellar were seen in other tissues. These tissues included terminal nerve fibers in pigmented skin, pulmonary macrophages, blood neutrophils, and hepatocytes and Kupffer cells. These characteristic ultrastructural findings occur in both genetic lipidoses and lipidoses induced by other drugs, e.g., perhexiline. We conclude that during therapy with amiodarone, widespread deposition of amiodarone and desethylamiodarone occurs. This leads to ultrastructural changes typical of a lipidosis. These changes are seen clearly in tissues associated with the unwanted effects of amiodarone, e.g., skin, liver and lung.

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Coronary Disease; Female; Humans; Liver; Long-Term Care; Lung; Male; Middle Aged; Skin

To determine whether combined intravenous (i.v.) and oral loading with amiodarone can shorten its onset of action, a comparative study was conducted. Twenty patients with refractory ventricular arrhythmias were treated with amiodarone. All patients had frequent (greater than or equal to 30/hour) and complex (repetitive) ventricular premature beats on a 48-hour baseline Holter recording. Ten patients (group A) received oral loading alone: 800 mg/day for 7 days, 600 mg/day for 3 days, then a maintenance dose 200 to 400 mg/day. Ten patients (group B) received i.v. and oral loading: 5 mg/kg i.v., and then the same regimen as for group A. Follow-up 24-hour Holter recordings were obtained daily for 7 days, weekly for 1 month, and then monthly. Arrhythmia control was defined as at least a 70% reduction in ventricular premature beats, a 90% or greater reduction in couplets and abolition of ventricular tachycardia. The time to optimal ventricular arrhythmia control was shorter for group B (20 +/- 18 vs 105 +/- 83 days, p less than 0.05) and the cumulative amiodarone dose at the time of control was smaller for group B (10 +/- 8 vs 48 +/- 39 g, p less than 0.05). No complications were encountered with i.v. amiodarone. Thus, initial loading with i.v. amiodarone can shorten the time to optimal ventricular arrhythmia control and lower the cumulative dose required.

Topics: Administration, Oral; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Chronic Disease; Heart Ventricles; Humans; Injections, Intravenous; Middle Aged; Time Factors

Seventy-four patients with sustained ventricular tachyarrhythmias had 22 +/- 3 hours of Holter monitoring before and after 11 +/- 6 days of amiodarone treatment. On control Holter recordings, 55 patients (group I) had frequent (more than 10 extrasystoles per hour) and/or complex (at least couplets) ventricular ectopic activity (VEA), and 19 patients (group II) had infrequent and simple VEA. A positive Holter monitor response to amiodarone was defined as a decrease in VEA by more than 85% and abolition of all complex VEA. In group I, 34 patients (62%) had a positive Holter monitor response. In group II, 16 patients (84%) had persistent, infrequent and simple VEA and 3 had frequent and/or complex VEA. During a mean follow-up of 13 +/- 12 months, 22 patients (30%) had ventricular tachycardia (VT) or sudden death. In group I, VT or sudden death occurred in 6 of 34 (18%) patients with a positive Holter monitor response and 11 of 21 (52%) with a negative Holter monitor response (p less than 0.01), and in group II, VT or sudden death occurred in 5 of 16 patients (31%) with persistent, infrequent and simple VEA. All episodes of VT or sudden death occurred after at least 2 weeks of amiodarone therapy (mean 5 +/- 6 months). The predictive accuracy of a positive Holter monitor response as an indicator for subsequent prevention of sustained ventricular tachyarrhythmias and sudden cardiac death was 82% and for a negative Holter monitor response as an indicator of tachyarrhythmia or sudden death recurrence on therapy it was 52%.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Ambulatory Care; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Electrophysiology; Female; Follow-Up Studies; Heart Ventricles; Humans; Male; Middle Aged; Monitoring, Physiologic; Prospective Studies; Recurrence; Risk; Ventricular Fibrillation

In 65 patients a single oral dose of amiodarone (30 mg/kg) produced an antiarrhythmic effect on supraventricular or ventricular arrhythmias within 3 to 8 hours and lasted for 17 to 19 hours. On the second day a 15-mg/kg dose reproduced this effect within 3 to 9 hours. Plasma concentration of amiodarone increased to a maximum (2.2 +/- 1.7 mg/liter) mean +/- standard deviation) at 6 +/- 3.5 hours and plasma levels of N-desethylamiodarone (NDA) rose to 0.2 +/- 0.08 mg/liter at 12 +/- 6.4 hours. Sixty-one other patients were given a single 30-mg/kg dose 7 hours to 4 days before open heart surgery. Biopsies of the right atrial and left ventricular walls were taken during surgery. Myocardial concentration of amiodarone was maximal in the atrium after 7 hours (13 +/- 8 mg/kg) and in the ventricle after 24 hours (17 +/- 11 mg/kg). NDA myocardial concentration increased progressively until 24 hours and then remained stable over 4 days (1.5 mg/kg). The amiodarone myocardial to plasma concentration ratio was similar in the atrium and in the ventricle and averaged 22 and 10 for amiodarone and NDA, respectively. A significant relation existed between amiodarone concentration and the effect on ventricular premature complexes (r = 0.74, p less than 0.001) and between amiodarone plasma concentration and the effect on the atrioventricular conduction (r = 0.58, p less than 0.001). The plasma concentration of amiodarone corresponding to a 60% decrease in arrhythmias averaged 1.5 to 2 mg/liter.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Atrioventricular Node; Benzofurans; Dose-Response Relationship, Drug; Electrocardiography; Female; Heart Atria; Humans; Male; Middle Aged; Myocardium; Tachycardia; Time Factors

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Iopanoic Acid; Male; Middle Aged; Thyroxine; Triiodothyronine

Both hyperthyroidism and hypothyroidism have been noted to occur in some patients treated with amiodarone for cardiac arrhythmias. To determine the frequency of the development of thyroidal abnormalities in patients receiving amiodarone, 45 euthyroid patients were prospectively evaluated. Serum samples were obtained for measurement of thyroxine, thyrotropin, triiodothyronine, and triiodothyronine resin uptake prior to initiation of amiodarone treatment and serially over a 12- to 27-month period during which amiodarone was administered. The patients were divided into four subgroups as follows: Group I (n = 22) had elevated thyroxine levels, Group IIA (n = 13) had normal thyroxine levels and normal thyrotropin levels, Group IIB (n = 7) had normal thyroxine levels and elevated thyrotropin levels, and Group III (n = 3) had subnormal thyroxine levels. Demographic factors (such as route of administration, cardiac diagnosis, sex of the patient, or indication for amiodarone therapy) and amiodarone levels had no significant effect on the thyroid hormone parameters. However, Group I patients were statistically older than the patients in the other groups. Linear regression analysis revealed a negative correlation for thyroxine levels and a positive correlation with thyrotropin levels with age for the whole group. The various groups were not statistically affected by duration of therapy, but a positive trend existed for increasing thyroxine levels. Although virtually all patients showed changes in their thyroid hormone levels, chemical hyperthyroidism (elevated thyroxine and triiodothyronine levels without symptoms) developed in only two patients (4 percent), and clinical hyperthyroidism (elevated thyroxine and triiodothyronine levels with symptoms) developed in no patients. Four patients (9 percent) became biochemically and clinically hypothyroid. Thus, amiodarone frequently influences thyroid hormonal parameters, but less commonly causes a change in actual thyroid function. However, hyperthyroidism and hypothyroidism do occur in a significant number of patients.

Topics: Age Factors; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Prospective Studies; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine

In clinically euthyroid subjects on long-term amiodarone therapy free thyroxine (T4) concentrations were increased and free triiodothyronine (T3) levels reduced. There was also a marked increase in reverse T3 in the treated group. These changes are consistent with inhibition of peripheral deiodination of T4 and reverse T3. Despite the rise in T4 serum thyrotrophin (TSH) levels were increased, suggesting an effect of amiodarone on the anterior pituitary. To investigate the interaction of amiodarone with the cellular actions of thyroid hormones we examined the influence of the drug in vitro on the binding of T3 to isolated nuclei prepared from rat anterior pituitary tissue. Amiodarone inhibited the nuclear binding of T3 in a dose dependent fashion. Addition of amiodarone in vitro also stimulated TSH release from cultured rat anterior pituitary cells, consistent with a T3 antagonistic effect. These studies provide evidence for a direct influence of amiodarone on the thyrotroph, mediated via nuclear T3 receptor binding.

Topics: Adult; Aged; Amiodarone; Animals; Arrhythmias, Cardiac; Benzofurans; Cell Nucleus; Coronary Disease; Female; Humans; Male; Middle Aged; Pituitary Gland, Anterior; Protein Binding; Rats; Rats, Inbred Strains; Tachycardia, Paroxysmal; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Two cases are reported in which amiodarone was administered during pregnancy for longer periods than has been reported previously. Limited placental transfer of amiodarone and its desethyl metabolite was observed in both cases. A normal child resulted from each pregnancy despite, in one case, amiodarone therapy throughout the entire pregnancy. However, caution is urged in the use of amiodarone during pregnancy in view of the limited data available.

Topics: Adult; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Cardiovascular

The haemodynamic changes during intravenous amiodarone administration in laboratory animals and human studies are reviewed and compared with the results from our investigations. While the results of previous human studies have been rather variable, our investigations suggest that the cardiovascular changes following intravenous amiodarone include an early and usually short reduction of systemic and coronary vascular resistance, which may be partially due to the vasodilating properties of the solvent, polysorbate 80. As a result, a decrease in afterload and cardiac work and increases in cardiac output and coronary blood flow occur. Contrary to the observations in the animal experiments, heart rate increases in man, presumably as a result of the relatively greater fall in afterload which occurs. However, in spite of this increase in heart rate, contractility is reduced at the end of amiodarone administration and remains depressed after the infusion, resulting in a significant increase in left ventricular filling pressure. Neither myocardial oxygen demand nor consumption change during amiodarone administration. Although the intrinsic negative inotropic effects of amiodarone warrant a cautious approach in patients with left ventricular dysfunction, worsening of heart failure or the occurrence of myocardial ischaemia has been reported in only very few cases so far. In contrast, the drug was demonstrated to protect against pacing-induced myocardial ischaemia, in patients with both normal and depressed left ventricular function. These anti-ischaemic properties of amiodarone were investigated in a second study using a double pacing stress test protocol. Overall myocardial oxygen consumption did not change during pacing after amiodarone, but it clearly reduced (regional) myocardial ischaemia, as demonstrated by a reduction of ST-segment changes and anginal pain, and in particular by the absence of myocardial lactate production during pacing after amiodarone. These anti-ischaemic properties are mainly based on a reduction of myocardial oxygen demand, rather than on an improvement in coronary flow. It is concluded then, that amiodarone has significant haemodynamic effects as manifested by an early reduction in vascular resistance and a late negative inotropic effect. Although vasodilatation of short duration caused by its solvent, polysorbate 80, also occurs, the overall cardiovascular changes are caused by the direct, intrinsic haemodynamic effects of amiodarone al

Topics: Amiodarone; Animals; Arrhythmias, Cardiac; Benzofurans; Coronary Disease; Hemodynamics; Humans; Myocardial Contraction; Oxygen Consumption; Polysorbates

Amiodarone has been used in the therapy of supraventricular and ventricular tachycardia, and has often been categorised as a class III rather than a class I agent. However, in patients with ventricular arrhythmias, amiodarone 800mg daily for 14 days prolonged the right ventricular effective refractory period by a mean of 18.8 msec (p less than 0.05), and HV interval by a mean of 5.2 msec (p less than 0.05), these changes being similar to those noted with drugs such as quinidine, procainamide, disopyramide and encainide. The antiarrhythmic efficacy of amiodarone was evaluated in 196 patients with recurrent sustained ventricular tachycardia, recurrent ventricular fibrillation or recurrent nonsustained ventricular tachycardia. Coronary artery disease, dilated (congestive) cardiomyopathy, or other forms of heart disease were present in most patients. After 1 month of therapy, 177 patients continued to receive amiodarone and, during the remainder of the follow-up period, 139 patients had no recurrence of spontaneous ventricular tachycardia or ventricular fibrillation. Sudden cardiac death occurred in 15 patients after a mean treatment period of 10.4 months. Overall, amiodarone was an effective form of therapy in patients with ventricular tachycardia and ventricular fibrillation.

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Administration Schedule; Female; Half-Life; Humans; Male; Middle Aged

A retrospective study was conducted in a group of 460 patients in order to evaluate the effectiveness and frequency of side effects of amiodarone over a mean observation period of 2 years. The effectiveness was considered to be excellent or good in 71.5 p. cent of cases of ischaemic heart disease, in 84.8 p. cent of cases of supraventricular arrhythmia and in 92.3 p. cent of cases of ventricular arrhythmia. Side effects were observed in 32.8 p. cent of patients and treatment had to be suspended in 19.8 p. cent of cases. The most frequent side effects were photosensitisation (11.9%), thyroid disorders (5.6%) and bradycardia or sinus dysfunction (11.9%). Some of these side effects appear to be related to the cumulative dose received.

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Coronary Disease; Female; Humans; Male; Middle Aged; Retrospective Studies; Time Factors

Two asymptomatic patients from a group of 30 being treated with the antiarrhythmic drug amiodarone developed roentgenographic pulmonary and pleural reactions. Computed tomography in one patient with an uncommon radiographic pattern of fuzzy nodules showed the spatial distribution of the parenchymal changes, as well as unrecognized pleural thickening. The disease in these asymptomatic patients was presumably detected on the periodic chest roentgenogram at an early stage because the changes disappeared after withdrawal of the drug. Periodic chest radiographs are recommended during amiodarone therapy and CT may be useful in evaluation of patients with unusual chest radiographic findings.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Lung Diseases; Radiography, Thoracic; Tomography, X-Ray Computed

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Male; Middle Aged; Triiodothyronine, Reverse

Topics: Adams-Stokes Syndrome; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Male; Middle Aged

Topics: Adolescent; Adult; Aged; Amiodarone; Animals; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Male; Middle Aged; Rabbits; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

We report two patients who developed symptomatic life-threatening ventricular tachyarrhythmias with changing QRS axes (resembling torsades de pointes), during treatment of their supraventricular tachycardias with oral amiodarone. Like other effects of amiodarone on the body, the arrhythmias became evident several days after initiating therapy, at which time electrocardiographic QT prolongation was present. The arrhythmias subsided after amiodarone treatment was withdrawn. No other drugs or electrolyte disturbances could be incriminated as a cause.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Digoxin; Electrocardiography; Female; Humans; Tachycardia

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Evaluation; Humans

Amiodarone therapy is difficult to monitor because of the poor correlation between plasma amiodarone levels and clinical efficacy or toxicity. Monitoring tissue levels may give a better measure of effectiveness, but tissue levels cannot be easily measured. The iodine-containing amiodarone and its major metabolite, desethylamiodarone (DA), are highly tissue-bound, and it has been shown that computerized tomographic (CT) scanning of the abdomen will detect drug deposition in the liver. Ten patients receiving chronic amiodarone therapy were studied by abdominal CT scanning. Liver CT density was increased in 6; 68 to 94 CT units (normal 50 to 65) and liver/spleen relative CT density increased in 5; 1.4 to 2.0 (normal 1.0 to 1.3). Estimates of liver drug levels (based on a calibration curve with inorganic iodide) gave values of up to 3 g of amiodarone and DA per kilogram weight of liver. Absolute and relative liver CT density correlated significantly with plasma levels of DA (r = 0.65, p less than 0.05), but not with amiodarone (r = 0.55, p less than 0.1). No significant correlation was found with QTc intervals. This indirect estimate of liver deposition of amiodarone and DA may prove useful in guiding antiarrhythmic therapy.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Female; Humans; Liver; Male; Middle Aged; Tomography, X-Ray Computed

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Injections, Intravenous

Antiarrhythmic agents may depress cardiac contractility and worsen heart failure. Few data are available describing the chronic effects of amiodarone on myocardial function. To assess the effects of amiodarone on cardiac function, we studied 41 consecutive patients with first-pass or equilibrium radionuclide angiography prior to and 3 months after drug therapy was initiated. The mean heart rate, systolic blood pressure (BP), and diastolic BP were not significantly altered by treatment. The mean ejection fraction was 36% +/- 19 (mean +/- 1 SD) at the time of drug initiation and 36% +/- 17 3 months later (p less than 0.05). Nineteen patients had an ejection fraction greater than 30% and 16 had an ejection fraction less than 30%. The mean change in ejection fraction for these two subgroups showed no statistically significant difference, although a decrease in EF greater than 10% was seen in three patients (symptomatic in two), necessitating an increase in diuretic dose. No correlation between amiodarone dose and change in ejection fraction (r = -0.12, p greater than 0.05) was noted. There was no correlation between baseline ejection fraction and change in ejection fraction over this 3-month period (r = -0.36, p greater than 0.05). In summary, amiodarone does not depress left ventricular function and as a result can be used safely in patients with mild to moderate impairment of left ventricular function. In patients with stable left ventricular function, serial tests of left ventricular function may not be necessary.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Blood Pressure; Female; Heart; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction; Radionuclide Imaging; Stroke Volume; Time Factors

Oral amiodarone's slow absorption handicaps rapid treatment of life-threatening arrhythmias. We used iv amiodarone to treat ten patients with hemodynamically significant atrial arrhythmias and life-threatening ventricular arrhythmias refractory to all conventional medical treatment. Arrhythmias were controlled in nine patients, five of whom became long-term survivors on oral amiodarone. Two patients died of cardiovascular collapse within 24 h of initiation of iv amiodarone. One other patient died postoperatively of cardiovascular collapse while on oral amiodarone, 2 wk after iv amiodarone. Another patient died of an unrelated cause 13 months after initiation of amiodarone. These results suggest that iv amiodarone is effective in controlling refractory atrial and ventricular arrhythmias and may shorten the latency period.

Topics: Administration, Oral; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Critical Care; Heart Atria; Heart Ventricles; Humans; Injections, Intravenous; Male; Middle Aged

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Evaluation; Electrophysiology; Humans; Recurrence; Risk

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Evaluation; Drug Tolerance; Electrocardiography; Female; Heart Ventricles; Humans; Male; Mexiletine; Middle Aged; Monitoring, Physiologic; Propylamines

The clinical efficacy of amiodarone in the management of patients with complex cardiac arrhythmias refractory to therapy with two or more conventional or other investigational anti-arrhythmic agents was studied by long-term follow-up of patients who had received the drug for a period of at least three months. A total of 181 patients, classified into four groups (Group 1--supraventricular arrhythmias, n = 42; Group 2--frequent VPBs, n = 46; Group 3--nonsustained V-tach, n = 16; and Group 4--sustained V-tach, n = 77) received a daily maintenance dose of 200-800 mg of Amiodarone for a period of up to 30 months. There were a total of 26 deaths (14%). Ten of these were classified as probable arrhythmic deaths; however, all had either good or excellent response to therapy over a mean follow-up period of 14.9 months prior to death. The drug had to be permanently discontinued due to side effects only in three patients and in the majority of patients with side effects symptoms could be alleviated with adjustment of dosage, thyroid replacement therapy or transient cessation of therapy. We conclude that amiodarone is highly effective in the management of high-risk patients with complex refractory cardiac arrhythmias and that close monitoring and prompt recognition of side effects and appropriate adjustment of dosage or institution of supplemental or replacement therapy (in less than 5% of patients) will allow continuation of amiodarone. The benefit of suppression of symptomatic arrhythmias and the potential of prevention of sudden death, far outweighs the incidence of severe side effects.

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Resistance; Electrocardiography; Female; Follow-Up Studies; Heart Conduction System; Heart Ventricles; Humans; Long QT Syndrome; Male; Metabolic Clearance Rate; Middle Aged

In 23 patients treated with the iodine-containing antiarrhythmic drug amiodarone, the plasma concentrations of amiodarone, desethylamiodarone and iodine have been studied. Besides amiodarone and desethylamiodarone, a pool of iodine-containing substances, NANDAI (non-amiodarone-, non-desethylamiodarone-iodine), was present. At steady state the iodine content of NANDAI amounted to 64% and the iodine content of amiodarone plus desethylamiodarone to 36% of total serum iodine. At steady state 26% of the NANDAI fraction was made up of inorganic iodide, the average plasma concentration of which was at least 40 times above the upper limit of the normal range. The serum elimination half-life of NANDAI of 57-160 days exceeded that of amiodarone (35-68 days) and of desethylamiodarone (31-110 days). At steady state the serum concentration of desethylamiodarone appears to be related to the concentration of amiodarone by a Michaelis-Menten type function, yielding a Km of amiodarone of 2.45 mumol/l and a maximal desethylamiodarone concentration of 3.61 mumol/l.

Topics: Adolescent; Adult; Aged; Amiodarone; Angina Pectoris; Arrhythmias, Cardiac; Benzofurans; Female; Half-Life; Humans; Iodides; Iodine; Kinetics; Male; Middle Aged; Time Factors

Numerous cytoplasmic lamellar bodies were seen in many cell types in an open lung biopsy from a patient on amiodarone therapy. These membrane-bound lamellar bodies were characterized by distinct, concentric parallel membranes and peripheral granular densities. Their morphology and distribution suggest a metabolic disorder of phospholipid degradation induced by this drug. The differential diagnosis of lamellar body accumulation in the lung is discussed. This case emphasizes the desirability for ultrastructural study of lung biopsies in such potentially reversible lung disease.

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Therapy, Combination; Heart Ventricles; Humans; Inclusion Bodies; Lung Diseases; Macrophages; Male; Microscopy, Electron; Middle Aged; Pulmonary Alveoli

Amiodarone hydrochloride is a relatively new antiarrhythmic agent, the properties of which differ in a significant manner electrophysiologically, pharmacokinetically and structurally from those of conventional as well as other investigational antidysrhythmic compounds. It is also pharmacologically unique in so far as its fundamental action on cardiac muscle following chronic therapy differs markedly from that found during the intravenous administration; its I.V. action is dominated by the lengthening of intranodal (AV) conduction time and the effective refractory period of the AV node, the electrophysiologic basis for which is unclear but accounts for the slowing of the ventricular response in atrial flutter and fibrillation and the variable conversion rate of narrow QRS reentrant paroxysmal supraventricular tachycardia. Intravenous amiodarone is ineffective in most other arrhythmias; it does not lengthen repolarization, nor does it prolong the effective refractory period of atria, ventricle, His-Purkinje system or the accessory pathways of the heart in the WPW syndrome. In contrast, chronically administered amiodarone lengthens repolarization and the effective refractory period of all cardiac tissues as a function of dose and duration of therapy consistent with its wide spectrum of antiarrhythmic activity in the prophylactic control of supraventricular and ventricular tachyarrhythmias. The nature of the slow onset of action of the oral drug is not well-understood; it may be due to the slow formation of active metabolites or the gradual and selective inhibition of T3 action on the myocardium since the effects of amiodarone on cardiac repolarization are identical to those of hypothyroidism and are negated by the concomitant administration of thyroxine. Serum reverse T3 levels increase as a function of dose and duration of amiodarone therapy and tentative data indicate that serial measurements of rT3 levels may provide a reliable index for gauging efficacy and toxicity of amiodarone during chronic therapy. The role of serum drug and metabolite levels appears less reliable in this regard. The exceedingly long and variable elimination half-life of amiodarone necessitates individualized loading and maintenance dosage regimens, and the latency of onset of antiarrhythmic action during oral therapy is not shortened by intravenous bolus injections or sustained infusions. However, the judicious choice of oral dosage as discussed herein permits the development of an

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Dose-Response Relationship, Drug; Heart Conduction System; Humans; Kinetics; Thyroxine; Triiodothyronine

Muscle weakness, neuropathy, and transient rises in hepatic enzyme activity have been reported with the use of the antiarrhythmic agent amiodarone. A 68 year old teetotaller with normal liver function was given amiodarone for resistant supraventricular arrhythmias. He presented 19 months later with vomiting, muscle weakness and wasting, sensory neuropathy, and hepatomegaly. Liver biopsy showed fibrosis and the presence of hyaline. The amiodarone was withdrawn. Three months later he developed ascites. Oesophageal varices were found and he later died. The liver showed micronodular cirrhosis. The large volume of distribution and long half life of amiodarone may explain the persistence of toxicity, which may have been aggravated by simultaneously administered doxepin in this case. Amiodarone should be withdrawn if abnormal liver function or neuropathy develops.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Chemical and Drug Induced Liver Injury; Humans; Liver Cirrhosis; Male; Peripheral Nervous System Diseases

An antiarrhythmic treatment was done in 56 patients with recurrent ventricular tachycardias using amiodarone. The dosage was 400 to 600 mg/d following a loading dosage of 1000 mg for 8 to 12 days. Amiodarone and desethylamiodarone concentration in serum (control group n = 33) and in erythrocyte haemolysate (control group n = 13) were determined in relapses of ventricular tachycardias (n = 7) and in pulmonary fibrosis as serious side effect (n = 3). It was shown that amiodarone levels rise continuously during loading treatment until the 8th to 12th day and that desethylamiodarone can be demonstrated after the 3rd day of treatment. The mean concentrations (+/- standard deviation) of amiodarone and desethylamiodarone were 2.21 +/- 0.89 microgram/ml and 1.3 +/- 0.74 microgram/ml in serum and 0.97 +/- 0.65 microgram/ml and 1.95 +/- 1.9 micrograms/ml in erythrocyte haemolysate. Amiodarone levels did not correlate with efficacy and with incidence of side effects. However, in pulmonary fibrosis high desethylamiodarone concentrations in serum (greater than 2.5 micrograms/ml) and in erythrocyte haemolysate (greater than 4 micrograms/ml) were found. Four out of 7 patients with recurrent ventricular tachycardia showed relatively low desethylamiodarone concentrations in serum (desethylamiodarone/amiodarone ratio less than 0.4). Thus control of amiodarone treatment can be enlarged by determination of desethylamiodarone levels as its concentrations correlate with relapses of ventricular tachycardias and serious side effects.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Erythrocytes; Humans; Long-Term Care; Middle Aged; Pulmonary Fibrosis

Serum thyroxine (T4), triiodothyronine (T3), resin uptake of T3 (RT3U), thyroid stimulating hormone (TSH) and TSH response to thyrotropin releasing hormone (TRH) were measured in 92 patients treated with amiodarone for up to 4 years. Two patients developed thyrotoxicosis, while euthyroid hyperthyroxinemia occurred in 29 (32%). Hypothyroidism was diagnosed in 11 patients (12%), and a further 11 had tests consistent with a "failing thyroid." Of 39 patients with normal values of T4, 15 had abnormal responses to TRH. Of the 92 patients, 24 were tested before administration of amiodarone and then sequentially; alterations in thyroid function were frequent within the first 3 months. A scheme is proposed for early recognition of disturbed thyroid function due to amiodarone.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Hyperthyroidism; Hypothyroidism; Longitudinal Studies; Male; Middle Aged; Thyroid Diseases; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

Topics: Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Drug Therapy, Combination; Flecainide; Humans; Piperidines

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Male; Middle Aged

Amiodarone is a potent antiarrhythmic agent that is effective in controlling both atrial and ventricular arrhythmias. Recently, intravenous administration was demonstrated to be effective in the acute management of rhythm disorders and, in addition, appeared to shorten the loading period normally required for oral drug administration. This investigation examined the hemodynamic effects of amiodarone after both acute intravenous bolus and continuous intravenous administration. Patients with a left ventricular ejection fraction greater than 0.35 experienced improved cardiac performance due to both acute and chronic peripheral vasodilation. However, patients with a lower ejection fraction developed a 20% decrease in cardiac index and clinically significant elevation of right heart pressures after acute bolus administration; these changes were variably compensated for by peripheral vasodilation when the drug was administered intravenously over 3 to 5 days continuously. Therefore, intravenous amiodarone can result in significant impairment of left ventricular performance in patients with preexisting left ventricular dysfunction.

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Blood Pressure; Cardiac Output; Female; Hemodynamics; Humans; Injections, Intravenous; Male; Pulmonary Artery; Vascular Resistance

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Male; Middle Aged; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Thyroid function was investigated in 41 patients on chronic treatment with amiodarone. 27% of the patients had elevated total thyroxine levels together with elevated free thyroxine levels. Thyrotropin (TSH) secretion was completely suppressed in 15% of the patients. Elevated free or total thyroxine levels were frequently observed together with normal TSH secretion, although 5 of the 6 patients with suppressed TSH had markedly elevated levels. Triiodothyronine (T3) levels were low normal or below the normal range in all patients but one. This was the only patient who apparently developed amiodarone-induced hyperthyroidism. The clinical symptoms of this patient were equivocal. Thyroid function parameters including T3 levels returned to normal only 3 months after withdrawal of the drug. The patient did not need any thyrostatic treatment. The duration of treatment with amiodarone did not influence thyroid hormone concentrations, although there was an insignificant trend of increasing total thyroxine levels after a year of treatment. There was, moreover, no significant influence of the dose (200-500 mg orally/day) of amiodarone on thyroid hormone levels. Our results show that the usual screening parameters of thyroid function, namely total and free thyroxine serum concentrations, are not reliable in patients on chronic amiodarone treatment. The incidence of amiodarone-induced hypothyroidism was 2.4%. We did not observe an amiodarone-induced hypothyroidism, although there was one patient with increased TSH levels but normal T3 and thyroxine levels.

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Hyperthyroidism; Male; Middle Aged; Thyroid Gland; Thyroid Hormones; Time Factors

The relationship of apparent steady-state serum concentrations of amiodarone and its metabolite, desethylamiodarone, to therapeutic and toxic effects was assessed in 127 patients who had treatment-resistant ventricular or supraventricular arrhythmias or were intolerant to other agents. After at least 2 months (mean, 9.8) of treatment with daily maintenance doses of 200 to 600 mg, arrhythmias were effectively suppressed in 78% of patients. Arrhythmias recurred in 47% of patients with serum amiodarone concentrations of less than 1.0 mg/L, whereas only 14% of patients with higher concentrations had recurrences (p less than 0.005). Side effects, most of them mild, occurred in 57%; only 9 patients required discontinuation of drug therapy. The risk of developing adverse reactions was related to serum amiodarone concentrations (p less than 0.0001). Adverse reactions were common in patients with serum values exceeding 2.5 mg/L, although pulmonary complications did occur at lower concentrations. Monitoring serum amiodarone concentrations may differentiate failure of drug therapy from suboptimal dosing and reduce the incidence of concentration-related side effects.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Middle Aged; Recurrence; Tachycardia; Ventricular Fibrillation

Topics: Adult; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Female; Heart Atria; Humans

Oral amiodarone is a potent antiarrhythmic agent with a slow onset of action. Its electrophysiologic properties following chronic administration are well known, but its acute electrophysiologic actions are poorly defined. The objectives of the present study were to correlate the electrophysiologic actions of intravenous amiodarone in humans with the acute and chronic effects of the drug relative to plasma and tissue concentrations of the drug. In humans (n = 10), 5 mg/kg intravenous amiodarone (serum concentration 6.50 +/- 3.34 micrograms/ml at 10 minutes; 2.13 +/- 0.71 micrograms/ml at 20 minutes, n = 7) increased the AH interval by 16.4% (p less than 0.005), the antegrade effective refractory period (ERP) of the atrioventricular (AV) node by 14.4% (p less than 0.025), and the functional refractory period (FRP) of the AV node by 15.5% (p less than 0.005). The ERP or FRP of the atrium of the right ventricle was not significantly changed; there was no effect on the HV interval or the QT and R-R intervals of the ECG. In rabbits (n = 11) given 10 mg/kg intravenous amiodarone (mean +/- SD serum concentration 0.49 +/- 0.17 micrograms/ml; mean myocardial concentration 7.0 +/- 1.9 micrograms/gm, n = 3), there were no significant effects on the ECG intervals. In isolated rabbit sinoatrial (SA) node, atria, and AV node (three preparations) superfused with 5 X 10(-6)M amiodarone (3.41 micrograms/ml), there was no effect on the action potential duration (APD) or other parameters of the transmembrane potential.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Action Potentials; Aged; Amiodarone; Animals; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Heart; Humans; Infusions, Parenteral; Male; Middle Aged; Myocardium; Rabbits

Myocardial size and contractility were measured by gated radionuclide ventriculography in 70 patients before and a mean of 66 days after beginning amiodarone therapy. The mean dose of amiodarone at the time of the second study was 481 mg. The mean left ventricular (LV) ejection fraction (EF) increased slightly, from 40% to 43% (p = 0.001). The mean right ventricular EF remained unchanged (38% to 39%, difference not significant [NS]). The LV end-diastolic volume (count-based method) increased by 9% (p = 0.01), but no change could be demonstrated for end-systolic volume (4%, NS). The LV stroke volume increased 19% (p = 0.001), but cardiac output remained unchanged (5%, NS) because the heart rate decreased by 9 beats/min (p = 0.001). The right ventricular end-diastolic volume increased by 12% (p = 0.01) and end-systolic volume increased by 11% (p = 0.03). Stroke volume increased by 18% (p = 0.005). There was no significant correlation between the change in LVEF and the pre-amiodarone LVEF, the time interval between studies, or with indexes of amiodarone effect (change in heart rate, QRS, QTc, TSH, amiodarone dosage). In 5 patients (7%), LVEF decreased significantly, requiring discontinuation of amiodarone therapy in 1 patient. At the time of the second study congestive heart failure was manifest in 19%, and there was a trend suggesting that congestive heart failure was more likely if the initial LVEF was less than or equal to 35% (p = 0.10). Thus, amiodarone may rarely adversely affect contractility, although myocardial contractility is typically unchanged. There is an associated small increase in the size of both ventricles.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiac Output; Female; Heart; Heart Diseases; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction; Radionuclide Imaging; Stroke Volume

Amiodarone hydrochloride is currently being investigated in the United States as a cardiac antiarrhythmic agent. Previous reports from Europe indicate that amiodarone occasionally causes a cutaneous photosensitivity reaction that may be associated with a peculiar blue-gray discoloration of the skin. In addition, corneal microdeposits of yellow-brown granules may occur. We report observations on a case of amiodarone photosensitivity and corneal deposits developing in a patient shortly after amiodarone therapy was begun. Symptoms included burning and stinging of the skin, with redness and swelling that developed immediately after sun exposure. Phototesting showed that the photoactivating wavelengths were primarily in the long-wave UV-A spectrum between 350 and 380 nm. Prior application of a 10% dioxybenzone sunscreen greatly reduced the phototest reaction. Four weeks after the patient stopped taking amiodarone, the UV-A sensitivity was still present but diminished, and by ten weeks it had disappeared. During this time, the corneal deposits were reduced in number. All ten patients we have treated so far with amiodarone for cardiac arrhythmias have shown a similar photosensitivity, indicating that this is probably a phototoxic reaction.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Erythema; Humans; Male; Photosensitivity Disorders; Skin; Time Factors; Ultraviolet Rays

Amiodarone is a very active antiarrhythmic agent, but true incidence of Amiodarone-related side effects is still questionable. In a prospective trial of 400 or 200 mg of Amiodarone day for 56 days in 58 patients, we monitored thyroid and liver function, blood count, chest x-ray, ecg. In addiction we took regularly notice of subjective disturbances and physical signs. Side effects were: conduction disturbances 6%, bradycardia less than 50/min. 2%, gastrointestinal 12%, sleep disorders 12%, hyperthyroidism 4,15% and hypothyroidism 6.25%. Blood levels of Amiodarone and desethylamiodarone were not predictive of side effects. Noteworthy was the absence of cutaneous and pulmonary side effects. On the other hand, thyroid function should be monitored carefully because disfunction is not rare (10.4%) and in the case of hyperthyroidism could be related to worsening of arrhythmias.

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Female; Humans; Male; Middle Aged; Prospective Studies; Thyroid Diseases

Topics: Adult; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Dose-Response Relationship, Drug; Humans; Male; Pneumonia

Amiodarone (AM) is one of the most potent antiarrhythmic drugs, the value of which is limited by reversible and irreversible side-effects (SE). 59 patients, 50 male, 9 female (age 33 to 81 years) entered the study with ventricular tachycardia (VT, 68%), WPW-tachycardia (12%), non-sustained VT (12%) or untreatable paroxysmal atrial fibrillation or supraventricular tachycardia (8%). Prior to AM the patients had received 1 to 8 different antiarrhythmic drugs (m 3.5) and maximal 9 different combinations of antiarrhythmics. The drug regimen started with a loading dose of 1200 mg/d for 1 to 2 weeks and was continued with a maintenance dose of 200 to 600 mg/d. The patients were followed up 1 to 41 months (m 14 m). The drug effect was evaluated using clinical criteria (recurrence of arrhythmias, death), computer-assisted analysis of several 24 hr long-term ECGs and programmed electrophysiological stimulation. Three- to six-monthly the patients were seen in our outpatient department for check up and blood-sample analysis (liver, thyroid gland etc.). Also in the majority of the patients frequent ophthalmological and dermatological investigations, as well as lung functions tests were carried out.. under AM therapy the initial arrhythmias were no longer detectable in 41% of the patients. In 37% a significant amelioration of the formerly life-threatening arrhythmias was found. 7 patients (12%), predominantly with reduced left ventricular function, died during follow up. No pulmonary, hepatotoxic or neurological SE were found. All patients developed reversible AM keratopathy. In 27% ETR and T4 were elevated, but only one patient developed hyperthyroidism with an increase in TT3. Another patient showed signs of hypothyroidism with an elevated TSH prior to TRH stimulation. Increased phototoxicity was found in 31%, whereas in two patients typical AM hyperpigmentation occurred, especially on the face. In conclusion, AM is a highly effective antiarrhythmic agent, despite a negatively selected collective, but it should only be used in patients with refractory arrhythmia in view of the SE.

Topics: Adult; Aged; Airway Resistance; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cornea; Corneal Opacity; Electric Stimulation; Electrocardiography; Female; Humans; Male; Middle Aged; Skin Pigmentation; Thyroid Function Tests; Ventricular Fibrillation

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Injections, Intravenous; Male; Middle Aged

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Follow-Up Studies; Heart Rate; Humans; Middle Aged; Time Factors

Thirty-eight patients received an average of 325 mg of amiodarone per day (range, 100 to 600 mg/day) for an average period of 16 months (range, nine to 30 months). Visible corneal microdeposits developed in all patients. Ninety-five percent of our patients had grade I or grade II keratopathy with no effect on vision. Five percent (5%) had grade III keratopathy with loss of one line of visual acuity and experienced subjective blurring and colored halos. Although there was a relationship of the total cumulative dose of the drug to the density of the corneal microdeposits, there was great variability from patient to patient, which limited the usefulness of this relationship.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Corneal Diseases; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged

The increasing use of amiodarone as antiarrhythmic drug has raised the possibilities of dangerous effects from amiodarone-digitalis interaction. We have studied twelve patients who were taking digitalis and to whom amiodarone was administered because of arrhythmias. We found a 75,42% increase of digitalis plasma levels (p less than 0,001) in the early days of amiodarone therapy, and a 52,1% increase (p less than 0,001) in the medium term. An inverse correlation was found (r = -0,65; p less than 0,05) between the plasma levels of digitalis during the steady-state control period and during the following 2-to-6 months evaluation. Acute episodes of cardiac failure caused in our patients an abrupt increase of digitalis plasma levels: in three patients digitalis toxicity occurred. Based on our experience, we recommend that the dose of digitalis be halved when the two drugs are given together in patients with various degree of cardiac failure; moreover digitalis plasma levels should be frequently monitored in these patients. On the other hand digitalis administered according to age, sex, weight, kidney function, together with amiodarone, can be given at full dosage in patients without cardiac failure.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digitalis Glycosides; Digoxin; Drug Interactions; Female; Heart Diseases; Humans; Male; Medigoxin; Middle Aged

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Tachycardia

Fifty-three patients with hypertrophic cardiomyopathy who had serious arrhythmias (45 patients), refractory chest pain (5 patients) or a high risk of sudden death (3 patients) received amiodarone for 6 to 96 months (median 18) after completion of a loading and an initial maintenance period. The dose of amiodarone was altered by 50 to 200 mg/day at 3- to 6-month intervals, guided by electrocardiographic monitoring, plasma drug level measurements and side-effect questionnaires. Ventricular tachycardia was suppressed in 24 patients (92%) with doses of 100 to 400 mg/day (median 300); none died suddenly during a mean follow-up of 27 months. Although symptomatic episodes of frequent or prolonged supraventricular tachycardia or paroxysmal atrial fibrillation/flutter were abolished in 8 of 9 patients on 100 to 600 mg/day (median 300), in 1 patient incessant atrial flutter developed that was relatively refractory to direct-current cardioversion. In 11 patients with atrial fibrillation, sinus rhythm was restored in 7 (after direct-current cardioversion in 3) with doses of 100 to 600 mg/day (median 300) and has been maintained in 5 with associated improvement in symptoms. Despite discontinuation of beta-blocker therapy, chest pain was unchanged in 17 patients, was impaired in 11 and was worse in only 2. Amiodarone was discontinued in 3 patients; in 1 because of hair loss, in 1 because of neurologic symptoms and in 1 because of facial discoloration; in the latter 2 patients, amiodarone was restarted after 1 and 14 months, and was tolerated and effective at the lower dosage.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Cardiomyopathy, Hypertrophic; Echocardiography; Electrocardiography; Heart Rate; Humans; Middle Aged; Pain; Thorax

Topics: Adult; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Humans

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Corneal Opacity; Humans

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Male; Middle Aged; Myocardial Infarction; Sotalol

Amiodarone hydrochloride, a new antiarrhythmic agent, has been associated with pulmonary toxicity characterized by cough, dyspnea and diffuse pulmonary infiltrates. We describe a case of fibrosing alveolitis, diagnosed by lung biopsy, in a patient receiving amiodarone which responded to corticosteroid therapy. The pulmonary symptoms recurred after discontinuing corticosteroids, five months after amiodarone was stopped, and were associated with a persistent amiodarone level. To our knowledge, this recurrence of amiodarone pulmonary toxicity has not been reported previously.

Topics: Adrenal Cortex Hormones; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Biopsy; Humans; Lung; Male; Microscopy, Electron; Middle Aged; Recurrence

Thirty-three consecutively referred patients with cardiac arrest from ventricular arrhythmias unassociated with a new acute myocardial infarction (AMI) were commenced on amiodarone therapy and followed for a minimum of 12 months. The dose of amiodarone was adjusted to maximum tolerance and not according to the incidence of asymptomatic ventricular premature complex activity. Eight patients died including five sudden deaths. Five out of the eight deaths occurred either within 3 months of therapy or when the dose of amiodarone was less than 400 mg/day. The majority of patients were found to have corneal microdeposits or either thyroid or liver function abnormalities, although none had any clinical manifestation. Ten patients had neurologic side effects. In summary, although the overall cardiac mortality seemed to be reduced by amiodarone therapy and the drug appears to be well tolerated by patients, its role in the prophylaxis against recurrent ventricular fibrillation may be enhanced by a regimen of higher loading and maintenance doses.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Death, Sudden; Dose-Response Relationship, Drug; Drug Evaluation; Female; Follow-Up Studies; Heart Arrest; Humans; Male; Middle Aged; Myocardial Infarction; Prognosis; Time Factors

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Heart Ventricles; Humans; Middle Aged

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Dose-Response Relationship, Drug; Humans

Amiodarone was administered orally to 30 patients with chronic stable coronary artery disease and severe ventricular arrhythmias. Control studies revealed frequent (more than 30/hr) ventricular premature beats (VPBs) (27 patients), bigeminy (21 patients), couples (29 patients), R-on-T phenomenon (14 patients), ventricular tachycardia (16 patients), and ventricular fibrillation (1 patient). Two 24-hour Holter recordings and stress tests were performed before treatment, and an average of 3.6 per patient were done during treatment. Amiodarone caused suppression of all ventricular arrhythmias in 13 (43%) of the 30 patients and suppression of all complex forms and greater than 90% reduction of VPB number in 14 patients (47%) during a follow-up of 12.4 months. The mean dose was 590 mg/day in the 27 responders and 300 mg/day in the three nonresponders. A similar antiarrhythmic response was observed during stress testing. One of the 30 patients died due to massive pulmonary embolism and no arrhythmias were detected. In addition, amiodarone suppressed the occurrence of anginal pain and effort-induced ST changes in 9 of 10 patients and in 11 of 13 patients, respectively. The rate-pressure product and peak heart rate were significantly reduced in all patients. Our results suggest that amiodarone may be ideally suited for treatment of ventricular arrhythmias and for possible prevention of sudden death in patients with ischemic heart disease.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Coronary Disease; Electrocardiography; Exercise Test; Female; Heart Ventricles; Humans; Male; Middle Aged

Oral amiodarone was administered to 24 patients with chronic chagasic myocarditis (CCM) and malignant ventricular arrhythmias. Control 24-hour Holter recordings revealed frequent ventricular premature beats (VPBs) (157 to 2572/hr; mean 714 +/- 125), multiform VPBs, and countless numbers of ventricular couplets in all patients, R-on-T phenomenon in 17 patients, and ventricular tachycardia in 21 patients. Amiodarone caused total and persistent suppression of ventricular couplets and tachycardia and greater than 93% reduction of VPB number in 22 patients, during a follow-up of 26.6 months (range 2 to 55 months). In 1 patient, ventricular couplets and tachycardia persisted despite the fact that a 98.2% reduction of VPB number was achieved. This latter patient was the only one in the whole group who experienced sudden death. The maximal antiarrhythmic effect was attained gradually after 3 to 26 weeks (mean 7.4). In four patients in whom treatment was discontinued after 3 to 12 months, the antiarrhythmic protection lasted 4 to 9 weeks. In nine patients the dose of amiodarone was 600 to 800 mg/day. In 15 patients the dose had to be increased to 800 to 1000 mg/day. Despite the presence of congestive heart failure in seven patients and intraventricular block in 17 patients, no limiting side effects were observed. Amiodarone proved to be extremely effective and safe against the most malignant ventricular arrhythmias of CCM.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Chagas Cardiomyopathy; Chronic Disease; Dose-Response Relationship, Drug; Electrocardiography; Humans; Middle Aged

Clinical and chemical variables of thyroid function were studied in 26 patients with symptomatic ventricular tachyarrhythmias before and during long-term oral treatment with amiodarone. The mean (+/-SEM) pretreatment thyroxine (T4) level in the 26 patients was 7.32 +/- 0.33 micrograms/dL, and increased notably to 10.15 +/- 0.47 micrograms/dL by 30 to 120 days after treatment. The free thyroxine index (FT4I) was also notably elevated. Clinical hyperthyroidism or goiter did not develop, but clinical hypothyroidism occurred in four patients during and in one patient after discontinuation of amiodarone treatment. Notable titers of antithyroid antibodies were found in the serum of two of the five and a family history of thyroid disease was present in three of the five hypothyroid patients. An elevation of both the T4 level and the FT4I above the normal range is an expected finding in patients receiving amiodarone and does not by itself indicate hyperthyroidism. Patients with positive antithyroid antibodies or a family history of thyroid disease prior to treatment with amiodarone may be at an increased risk of hypothyroidism developing when treated with this drug.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Hypothyroidism; Male; Middle Aged; Prospective Studies; Thyroid Function Tests; Thyroid Hormones

During treatment with the antiarrhythmic agent amiodarone pulmonary infiltrates may be observed occasionally. Such a side-effect was seen in a 67-year-old patient after several months of amiodarone therapy (200 mg/d during 5 days of the week). After withdrawal of the drug the infiltrates regressed over a period of two months. No other causes for the pulmonary opacities could be established. So far, 13 patients with pulmonary changes during amiodarone treatment have been reported in the literature.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Lung Diseases; Male; Radiography, Thoracic; Tomography, X-Ray Computed

Serum levels of quinidine or procainamide were measured in patients who had amiodarone added to their antiarrhythmic regimen. Dosages of quinidine or procainamide were held constant. Eleven of 11 patients had an increase in the serum quinidine level, and 11 of 12 other patients had an increase in the serum procainamide level. The dose requirement to maintain a stable plasma level of quinidine or procainamide decreased by 37% and 20%, respectively. Clinical toxicity occasionally occurred with the increase in serum levels of quinidine and procainamide, and the dose of these drugs should be decreased when amiodarone is administered concurrently.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Interactions; Female; Humans; Male; Middle Aged; Procainamide; Prospective Studies; Quinidine

Topics: Action Potentials; Adult; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Heart Conduction System; Humans; Injections, Intravenous; Male; Middle Aged

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Corneal Diseases; Female; Humans; Male; Middle Aged; Pulmonary Edema; Time Factors

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Male; Methods; Middle Aged

Amiodarone, a potent antiarrhythmic agent, has been shown to depress sinus node function. Therefore, this study was undertaken to assess the effect of chronic amiodarone therapy on heart rate during graded exercise testing. 13 patients treated with amiodarone for ventricular arrhythmias were administered symptom-limited graded exercise testing before and 12 weeks after drug therapy. None of the patients had prior evidence of sinus node dysfunction. The mean resting heart rate (beats per minute; bpm) before and after amiodarone therapy was 75 +/- (SD) 13 versus 60 +/- 7 bpm, respectively (p less than 0.005), and the maximal heart rate was 135 +/- 30 versus 109 +/- 24 bpm (p less than 0.005). However, the change in heart rate from rest to maximum exercise (heart rate reserve) was not affected by the drug. Heart rate measured at comparable exercise levels before and during amiodarone therapy was 124 +/- 25 versus 104 +/- 31 (p less than 0.025). There was no change in the systolic blood pressure readings at these respective measured heart rates. Estimated maximal functional capacity before and after drug therapy was 4.9 +/- 1.8 versus 4.7 +/- 2.2 METs (p = NS). In conclusion, chronic amiodarone therapy significantly decreases heart rate at rest and during exercise without altering systolic blood pressure and functional capacity.

Topics: Adult; Aged; Amiodarone; Animals; Arrhythmias, Cardiac; Benzofurans; Blood Pressure; Depression, Chemical; Digoxin; Exercise Test; Female; Heart Rate; Heart Ventricles; Humans; Male; Middle Aged; Physical Exertion; Rabbits; Sinoatrial Node; Thyroxine

Twenty-two patients were given amiodarone for refractory cardiac arrhythmias, and pre- and post-amiodarone serum digoxin levels were studied. The interval between pre- and post-amiodarone serum digoxin levels ranged from five days to nine months (mean interval, seven weeks). The mean (+/- SD) pre-amiodarone serum digoxin level was 1.0 +/- 0.4 ng/ml, and the post-amiodarone serum digoxin level was 1.9 +/- 0.8 ng/ml (p less than .001). To develop an animal model for study of the digoxin-amiodarone interaction, 18 pigs were given digoxin for a four-week period. Half of the animals were given amiodarone as well as digoxin for the last two weeks of the study. At the end of the initial two-week period, there was no difference in serum digoxin levels between the two groups. At the end of the second two-week period, the serum digoxin level in the group receiving digoxin alone was 0.6 +/- 0.2 ng/ml, and the serum digoxin level in the group receiving the digoxin and amiodarone was 1.2 +/- 0.6 ng/ml (p less than .01). These data confirm the presence of an amiodarone-digoxin interaction in man and show that the pig is an appropriate model for study of this clinical phenomenon in the animal laboratory.

Topics: Adolescent; Adult; Aged; Amiodarone; Animals; Arrhythmias, Cardiac; Benzofurans; Digoxin; Drug Interactions; Female; Humans; Male; Middle Aged; Models, Biological; Retrospective Studies; Swine

Although the antiarrhythmic aspect of amiodarone has been extensively studied, its effects on His-Purkinje system conduction and refractoriness have not been systematically investigated in human beings. In 24 patients, anterograde His-Purkinje system conduction (HV intervals) and variables of His-Purkinje system refractoriness using the ventricular extrastimulus (V2) technique were analyzed before and after long-term therapy with amiodarone. The mean duration of amiodarone therapy at the time of repeat study was 16.2 +/- 7.7 weeks (range 11 to 42). The anterograde His-Purkinje system conduction time (HV interval) measured 49.6 +/- 9.5 ms (range 40 to 80) before and 60.6 +/- 10.7 ms (range 45 to 90) after amiodarone (p less than 0.005). During retrograde refractory period studies, the longest V1V2 interval at which a retrograde His bundle potential (H2) emerged from the V2 electrogram (relative refractory period of the His-Purkinje system) was consistently longer after amiodarone as compared with the control period (376.4 +/- 46.6 versus 318.8 +/- 33.1 ms, p less than 0.005). Similarly, the shortest and longest His-Purkinje system conduction times ( V2H2 interval) at comparable V1V2 intervals were uniformly and significantly prolonged after administration of the drug. Amiodarone also abolished macroreentry in the His-Purkinje system in six of the nine patients who showed such reentry during the control period. The effective refractory period of the ventricular myocardium was also increased from a mean of 227.1 +/- 13.9 to 259.2 +/- 20.2 ms (p less than 0.005) in this series of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Bundle of His; Cardiac Pacing, Artificial; Electrocardiography; Female; Heart Conduction System; Heart Rate; Heart Ventricles; Humans; Male; Middle Aged; Purkinje Fibers; Tachycardia

Two patients, one with and one without preexisting conduction system abnormalities, were treated with amiodarone for refractory ventricular arrhythmias. Electrophysiologic testing before and during amiodarone therapy revealed amiodarone-induced HV interval prolongation and second degree intra-His Wenckebach block with no change in QRS configuration during atrial pacing at relatively long cycle lengths. The mechanism responsible for this phenomenon is unclear. These cases illustrate that amiodarone can induce distal conduction system block even in the absence of clinical conduction system disease in a pattern that mimics atrioventricular nodal block.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Atrioventricular Node; Benzofurans; Bundle of His; Electrocardiography; Heart Block; Heart Conduction System; Humans; Male

Topics: Adult; Amiodarone; Arrhythmias, Cardiac; Atrioventricular Node; Benzofurans; Electrocardiography; Female; Heart Conduction System; Humans; Male; Middle Aged; Sinoatrial Node

Topics: Adult; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Chemical and Drug Induced Liver Injury; Diagnosis, Differential; Humans; Liver; Liver Diseases; Liver Diseases, Alcoholic; Male; Transaminases

Forty patients with atrial fibrillation (AF), 23 patients with ventricular extrasystoles (VES), and 11 patients with various arrhythmias (VA) were treated with amiodarone (0.2-0.6 g/day). Suppression of arrhythmia was 67.5% in AF, 78.2% in VES, and 81.8% in others with VA. Median age of converted patients was higher than that of nonconverted. The duration of AF before treatment was inversely related to drug efficacy. Average time needed for conversion was 6-8 days of treatment. Plasma amiodarone concentration at the day of conversion did not differ from that of nonconverted patients. Amiodarone concentration levels off after the 8th day of treatment, whereas that of the metabolite increases with time of treatment. Biologic half-life of plasma amiodarone after discontinuation of treatment varied, but was higher than 4 days. The percent of decline of the metabolite concentration was lower than that of the parent drug.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Electrocardiography; Female; Half-Life; Humans; Kinetics; Male; Middle Aged; Time Factors

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Therapy, Combination; Female; Heart Ventricles; Humans; Male; Mexiletine; Middle Aged; Quinidine

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Pneumonia

The electrophysiologic basis for the use of amiodarone in the treatment of cardiac arrhythmias is outlined, with reference to studies in isolated cardiac tissues, whole animal, and human studies. Amiodarone appears to have the distinctive property of directly prolonging action potential duration (and hence refractory periods) in nearly all cardiac tissues. Independent of its effects on refractory periods, conduction may also be impaired in the His-Purkinje system, possibly due to depression of phase 0 of the action potential. Sinus node and atrial automaticity, as well as that arising from diseased Purkinje fibers, may be depressed. Normal ventricular escape pacemakers appear relatively unaffected, however. A nonspecific anti-adrenergic action may contribute to its observed effects. These electrophysiological effects are more obvious and predictable after several weeks of oral treatment than after intravenous administration, suggesting a time-dependent mechanism of action. The drug appears well suited to the prevention of enhanced automaticity in the ventricle and re-entry throughout the heart, and its frequent clinical success in a broad spectrum of cardiac arrhythmias attests to this. Unwanted side effects include sinus node depression, His-Purkinje conduction delay or block, and ventricular arrhythmias enhanced by QT prolongation. However, the frequency of clinically significant examples of unwanted arrhythmic effects appears to be acceptably low.

Topics: Action Potentials; Amiodarone; Animals; Arrhythmias, Cardiac; Benzofurans; Dogs; Electrocardiography; Humans; In Vitro Techniques; Sinoatrial Node

Our use of amiodarone in 200 patients during an 8-year period confirms our previous experience which indicated that the drug was close to being the ideal antiarrhythmic agent in children's arrhythmias. Its absence of cardiac toxicity, its powerful antiarrhythmic properties, its depressive effect on the AV nodal conduction, combined with its beta-inhibitory effect makes it effective and harmless in practically all forms of atrial, junctional and ventricular arrhythmias, whatever the reentrant or automatic mechanism of the arrhythmia. The metabolism is much faster in children than in adults, making the drug active in a few hours, with a lesser prolonged duration of action. Though there is practically no limitation for its use on a short- or mean-term basis, the long-term use must be limited to truly refractory arrhythmias, a situation which is rarely encountered. In such cases, combining amiodarone with conventional therapy allows a decrease in the maintenance dosage and a lower incidence of extracardiac side effects.

Topics: Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Benzofurans; Bundle-Branch Block; Child; Electrocardiography; Heart Conduction System; Heart Defects, Congenital; Heart Valve Diseases; Heart Ventricles; Humans; Infant; Tachycardia

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Corneal Diseases; Dose-Response Relationship, Drug; Female; Heart Conduction System; Humans; Liver; Male; Middle Aged; Peripheral Nervous System Diseases; Photosensitivity Disorders; Pigmentation Disorders; Pulmonary Fibrosis; Thyroid Diseases; Time Factors

Amiodarone, a drug used to treat refractory cardiac arrhythmias, produced a peripheral neuropathy in 5 of 50 cases (10%). Although the neuropathy may be severe, it tends to improve with lowering of the dosage or discontinuation of the medication.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Male; Middle Aged; Nervous System Diseases; Paresthesia; Peripheral Nervous System Diseases; Tremor

Amiodarone was administered to 80 patients with recurrent cardiac tachyarrhythmias previously resistant to drug treatment. Forty nine patients were treated for ventricular tachycardia or fibrillation and 31 for supra-ventricular arrhythmias. The mean (range six days to 51 months), permitting a total of 100 patient years of observation. Adverse reactions were observed in 69 patients. Severe side effects were encountered in 13: four patients developed interstitial pneumonitis, four patients developed incessant ventricular tachycardia, three patients taking amiodarone and digoxin sustained sinus node arrest with depression of escape foci, one patient developed hepatitis, and one patient developed hypercalcaemia with renal failure. Furthermore, a rise in the serum concentration of digoxin and potentiation of warfarin anticoagulation occurred in cases in which these agents were combined with amiodarone. Amiodarone was stopped in 14 patients because of side effects. Although amiodarone is effective in suppressing arrhythmias in most patients in whom extensive use of antiarrhythmic drugs has been unsuccessful, it is associated with diverse and serious toxicity. These observations suggest that at present the use of amiodarone should be reserved for patients with life threatening or seriously disabling arrhythmias in whom longer established drugs have been ineffective or are contraindicated.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digoxin; Drug Interactions; Female; Humans; Male; Middle Aged; Pulmonary Fibrosis; Recurrence; Respiratory Function Tests; Tachycardia

Topics: Alopecia; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Middle Aged

Amiodarone, an iodinated benzofuran derivative, has electrophysiologic effects on cardiac muscle akin to those of hypothyroidism. It is possible that the drug exerts its salutary effect, at least in part, by selectively inhibiting the action of triiodothyronine (T3) on the myocardium. The drug produces complex changes in thyroid hormones, with significant elevations in thyroxine (T4) and reverse T3 (rT3), with minor decreases in T3, and with minor and transient increases in thyroid-stimulating hormone, but without effect on thyroid-binding globulin. These changes may interfere with the biochemical evaluation of thyroid function. Rarely, hypothyroidism or hyperthyroidism may develop during the course of amiodarone therapy, a complication caused by the iodine contained in the drug rather than by the direct pharmacologic actions of the compound. The incidence of altered thyroid function induced is likely to vary with populations susceptible to iodine-induced goiter. Under the action of amiodarone, serum rT3 levels increase as a function of dose and duration of therapy and therefore provide a basis for judging the magnitude of in vivo drug cumulation. It was found that therapeutic efficacy was usually predictable on the basis of the attainment of a defined range of serum values, established by a correlation of rT3 levels with therapeutic responses both during loading and maintenance phases as well as after withdrawal of treatment of steady-state drug effects. Serious adverse effects occurred nearly always in association with four- to fivefold increases of rT3 above baseline values, and disappeared when such levels fell as a result of dosage reduction or after temporary drug discontinuation. The data suggest that the determination of serum rT3 levels during amiodarone therapy provides a simple and reliable technique for monitoring the drug's antiarrhythmic efficacy and toxicity, thereby enhancing its clinical utility. The use of rT3 levels may permit the development of a safe but optimal therapeutic regimen for the control of a wide spectrum of refractory atrial and ventricular tachyarrhythmias. The use of this technique, however, presupposes the allowance that must be made for variations in the methods for the serum assay of rT3 and of the systemic conditions in which the rT3 levels fluctuate relative to severity of the illness.

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Hyperthyroidism; Hypothyroidism; Iodides; Male; Middle Aged; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans

Amiodarone was used in 40 patients with life-threatening or refractory tachyarrhythmias. Eighteen patients had recurrent ventricular tachycardia of whom 13 had suffered a cardiac arrest. Control has been excellent or good in 17 of these 18 patients during an average follow-up period of 10 months. A further 22 patients had supraventricular arrhythmias, including three with Wolff-Parkinson-White syndrome and paroxysmal atrial fibrillation. In 20 of these control has been excellent or good. The mean daily maintenance dose of amiodarone was 300 mg for patients with ventricular tachyarrhythmias and 200 mg for those with supraventricular tachyarrhythmias. Side-effects were common and included corneal microdeposits, skin rash and discolouration, alteration in thyroid function, and symptomatic bradycardia. Serious adverse effects were uncommon however and necessitated discontinuation of the drug in only two patients. Amiodarone did not appear to precipitate or exacerbate cardiac failure in any patient although many had severe left ventricular dysfunction. We conclude that amiodarone is effective in the therapy of life-threatening or refractory cardiac arrhythmias.

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Kinetics; Male; Middle Aged; Tachycardia; Ventricular Fibrillation; Wolff-Parkinson-White Syndrome

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans

The systemic hemodynamic effects of intravenously administered amiodarone were evaluated in patients with depressed left ventricular function and recurrent sustained ventricular tachycardia. Heart rate decreased linearly up to 1 hour after amiodarone infusion (5 mg/kg). Cardiac index varied in a cubic fashion, diminishing at 10 minutes and returning to baseline by 60 minutes (p less than 0.05). Stroke work index also showed a similar decrease at 10 minutes, which was transient (p less than 0.005). These changes occurred without any significant change in systemic vascular resistance and with slight or no increase in pulmonary capillary wedge pressure, indicating a negative inotropic effect of amiodarone. The depression of left ventricular function in these patients, however, was mild and transient, and intravenously administered amiodarone was tolerated by the vast majority of patients. In two patients with overt heart failure and severely depressed left ventricular ejection fraction and marked hemodynamic abnormalities, profound hypotension occurred during amiodarone therapy; in such patients, therefore, hemodynamic monitoring is preferable. Limited data are available on the hemodynamic effects of orally administered amiodarone, but the determination of left ventricular ejection fraction by radionuclide ventriculography before and during long-term amiodarone administration has shown no reduction of function even in patients with severely reduced myocardial performance.

Topics: Administration, Oral; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Blood Pressure; Cardiac Output; Depression, Chemical; Heart Rate; Heart Ventricles; Hemodynamics; Humans; Infusions, Parenteral; Myocardial Contraction; Vascular Resistance

Amiodarone was administered to 121 patients (82 males, 39 females; average age 59 years) with refractory atrial tachyarrhythmias. All patients had experienced recurrent atrial fibrillation, atrial flutter, or reentrant supraventricular tachycardia previously refractory to digitalis drugs, beta-adrenergic blocking agents, and an array of membrance-active preparations. Seventy-four of 121 patients (61.2%) had no evidence of organic heart disease, whereas 17 patients experienced arrhythmia as a result of coronary heart disease, nine had preexcitation syndromes, 16 had primary valvular heart disease, and five patients, had congenital heart disease. Atrial fibrillation alone or in combination with atrial flutter was the primary dysrhythmia in 95 of 121 patients (78.5%), whereas in 26 patients (21.5%) supraventricular tachycardia was the primary refractory dysrhythmia. Fifty-one patients (42%) had experienced tachyarrhythmias for more than 10 years prior to the use of amiodarone. During an average follow-up of 27.3 months, complete suppression of atrial arrhythmias occurred in 98 of 121 patients (81%), and partial suppression occurred in seven (5.8%). In 16 patients (13.2%) the drug was deemed ineffective, and in eight patients (6.6%) amiodarone was discontinued because of intolerable side effects. The average blood serum concentration among successfully treated patients was 1.9 micrograms/ml, whereas the average concentration for those with side effects was 2.3 micrograms/ml. Thus, amiodarone is an extremely effective (greater than 85%) agent for refractory atrial tachyarrhythmias. Once daily administration, generally tolerable side effects, and excellent patient tolerance render this agent an attractive option for the management of these dysrhythmias.

Topics: Adolescent; Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Benzofurans; Drug Evaluation; Drug Resistance; Female; Humans; Male; Middle Aged

The clinical utility of electrophysiologic testing in assessing the long-term efficacy of amiodarone for treatment of life-threatening ventricular arrhythmias is controversial, most investigators reporting little or no correlation between the early effects of the drug on arrhythmia inducibility and subsequent prognosis. We have evaluated 69 consecutive patients given amiodarone for ventricular tachycardia (VT) or fibrillation (VF). All patients underwent provocative electrophysiologic testing with programmed electrical stimulation before and after amiodarone loading. After a standardized amiodarone loading regimen, the patients' arrhythmias were not inducible in 22 patients (group 1) and remained inducible in 47 patients (group 2). No patient in group 1 has had a recurrence of VT/VF, whereas 15 (32%) of 47 patients in group 2 have had recurrences. The characteristics of the arrhythmia induced by programmed stimulation in group 2 accurately predicted the severity of the recurrence. We conclude that electrophysiologic testing may be useful in evaluating the efficacy of amiodarone for the long-term treatment of VT/VF and that its precise role in this context should be further investigated by stringently controlled studies.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Electrophysiology; Female; Follow-Up Studies; Heart Ventricles; Humans; Male; Middle Aged; Ventricular Fibrillation

Patients resuscitated after out-of-hospital cardiac arrest have electrical instability of the myocardium, with 30% to 40% propensity for recurrent arrest in the first year. About 85% to 90% of such patients have complex ventricular ectopy and runs of ventricular tachycardia; in 70% to 80%, ventricular tachycardia or fibrillation are inducible by programmed electrical stimulation. The attempt to control recurrent cardiac arrest using these parameters and conventional antiarrhythmic drugs has yielded conflicting or variable results. Amiodarone was therefore studied in 40 consecutive patients (with previous cardiac arrests) in whom conventional antiarrhythmic therapy had proved ineffective or was not tolerated. The mean ejection fraction of the group was 0.29 +/- 0.12. At a mean follow-up of 16 months (range 5 to 40 months) six patients had died, three from heart failure, one from liver failure (not drug induced), and two from sudden (presumably arrhythmic) death. Late occurrences of arrhythmia were found in two patients (complicated by digitalis intoxication in one). Ambulatory ECG recordings showed that amiodarone had a potent suppressant effect on ventricular ectopy and runs of VT, but electrophysiologic studies demonstrated that it did not inhibit inducible VT/VF in greater than 65% despite an excellent clinical outcome. Limiting adverse reaction was seen in only one patient; other relatively minor side effects occurred in 10% to 15% of patients receiving maintenance therapy. Our data provide further evidence for the effectiveness of amiodarone in life-threatening ventricular arrhythmias, with a potential for the prolongation of survival in patients resuscitated after out-of-hospital cardiac arrests.

Topics: Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Electric Stimulation; Electrophysiology; Heart Ventricles; Humans; Ventricular Fibrillation

The clinical antiarrhythmic efficacy of amiodarone treatment was examined in 196 patients with recurrent ventricular tachycardia (VT) or ventricular fibrillation (VF) resistant to other antiarrhythmic drugs. Patients had received a mean of 4.4 +/- 1.9 unsuccessful drug trials over a mean of 15.2 months prior to amiodarone treatment of recurrent VF in 57 patients; recurrent, sustained VT in 95 patients; and recurrent, nonsustained VT in 44 patients. Amiodarone dosage during the first 2 to 4 weeks of treatment was 800 to 1600 mg/day. During long-term follow-up, amiodarone dosage was reduced to 200 to 600 mg/day, based on the control of arrhythmia and patient tolerance. Electrophysiologic studies were performed prior to and after 2 or more weeks of amiodarone treatment. After a mean follow-up of 16.2 +/- 13.0 months, 126 (64%) of 196 patients continued successful treatment with amiodarone. At electrophysiologic study, amiodarone prevented VT induction in 13 patients, and although VT was induced in 101 patients, 80 patients continued treatment for 14.2 months without recurrence of spontaneous VT. Amiodarone treatment was discontinued because of recurrent VT in 22 patients, sudden cardiac death in 15 patients, adverse effects in 12 patients, and noncardiac death in 21 patients. In nine patients, recurrent VT/VF appeared related to amiodarone-induced exacerbation of arrhythmia. Pulmonary toxicity occurred in seven patients, and 19 patients developed blue skin discoloration. Other adverse effects were usually dosage related. In summary, amiodarone was a highly effective antiarrhythmic drug, but at the dosages employed, the risk of significant adverse effects warrants careful surveillance during treatment.

Topics: Adolescent; Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Drug Evaluation; Drug Therapy, Combination; Electric Stimulation; Electrophysiology; Female; Follow-Up Studies; Heart Ventricles; Humans; Male; Middle Aged; Ventricular Fibrillation

Topics: Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Blood Coagulation Disorders; Dose-Response Relationship, Drug; Drug Interactions; Heart Atria; Heart Ventricles; Humans; Tachycardia; Warfarin

The clinical efficacy of amiodarone in the management of complex cardiac arrhythmias refractory to therapy with two or more conventional or other investigational antiarrhythmic agents was determined by long-term follow-up in patients who had received the drug for at least 3 months. A total of 181 patients, classified into four groups (group 1, supraventricular arrhythmias, n = 42; group 2, frequent ventricular premature complexes, n = 46; group 3, nonsustained ventricular tachycardia, n = 16; and group 4, sustained ventricular tachycardia, n = 77) received a daily maintenance dose of 200 to 800 mg amiodarone for up to 30 months. There was a total of 26 deaths (14%). Ten of these were probably attributable to arrhythmia, although all patients had either good or excellent response to therapy over a mean follow-up of 14.9 months prior to death. The drug had to be permanently discontinued because of side effects in only three patients, and in the majority of patients with side effects, symptoms could be alleviated with adjustment of dosage, thyroid replacement therapy, or temporary cessation of therapy. We conclude that amiodarone is highly effective in high-risk patients with complex refractory cardiac arrhythmias, and that close monitoring and prompt recognition of side effects and appropriate adjustment of dosage or institution of supplemental or replacement therapy (in less than 5% of patients) will allow continuation of amiodarone. The benefit of suppression of symptomatic arrhythmias and the potential of prevention of sudden death clearly outweigh the modest incidence of severe side effects.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digoxin; Dose-Response Relationship, Drug; Drug Interactions; Drug Resistance; Female; Follow-Up Studies; Humans; Male; Middle Aged; Warfarin

The available data concerning amiodarone dosing may be summarized as follows: (1) there is an empirically demonstrated improvement in lag before onset of antiarrhythmic effect if amiodarone is given initially in large "loading" doses. (2) A regimen such as that described in this article may allow more predictable and safe therapy and should be evaluated in patients, in order to develop uniform dosing guidelines. (3) Amiodarone clearance appears to decrease with time, and for this reason guidance of long-term therapy by plasma concentration determinations could potentially improve safety and efficacy. However, a close correlation between drug levels and drug toxicity and efficacy is lacking. (4) Finally, plasma concentrations, although potentially useful for monitoring long-term therapy, are likely to be unhelpful or misleading during the 4- to 6-week loading period at the beginning of treatment.

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Half-Life; Humans; Kinetics; Models, Biological

Arrhythmias may be controlled in most patients with recurrent supraventricular tachycardia or atrial fibrillation with small to moderate maintenance doses of amiodarone (100 to 400 mg/day). Moderate doses (400 mg/day) are also highly effective in suppressing "warning" ventricular arrhythmias in patients with chronic ischemic heart disease, particularly if the goal of treatment is to eliminate ventricular couplets, runs of ventricular tachycardia (VT), and the "R on T" phenomenon. Treatment and prevention of sustained recurrent VT and the malignant arrhythmias of chagasic myocarditis require, however, doses of about 800 mg/day, which may be higher than those needed for ischemic heart disease complicated by VT and ventricular fibrillation. Clinical studies suggest an elimination half-life for amiodarone of about 30 days (range 15 to 100 days). Thus there is a pretherapeutic latency period that varies according to the type of arrhythmia and the doses employed. The maximal effects (as well as the most significant adverse effects) are not attained before 90 to 150 days of treatment, and the antiarrhythmic protection may persist for varying intervals, up to 150 days or more, after the drug has been discontinued. Side effects are not negligible but are generally dose dependent. Despite these side effects, many patients have been treated by us with amiodarone for as long as 5 to 8 years--and for up to 10 years in some cases. Amiodarone appears to be one of the most promising drugs for the possible prevention of ventricular fibrillation and sudden death.

Topics: Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Chagas Cardiomyopathy; Dose-Response Relationship, Drug; Drug Interactions; Half-Life; Heart Ventricles; Humans; Kinetics; Wolff-Parkinson-White Syndrome

Two patients in chronic renal failure receiving amiodarone for the treatment of refractory arrhythmias were commenced on dialysis, in one case, intermittent peritoneal dialysis, in the other, haemodialysis. Plasma concentrations of amiodarone and its desethyl metabolite were consistent with the dose received, whilst neither compound was recovered in the dialysate. In these patients and in 10 additional patients with normal renal function taking amiodarone, only negligible amounts of either compound were detected in urine. These findings suggest that amiodarone may be a suitable antiarrhythmic agent for use in patients with chronic renal failure.

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Renal Dialysis

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Hyperthyroidism

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Electric Countershock; Heart; Humans; Middle Aged

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Electrocardiography; Humans; Injections, Intravenous; Middle Aged

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Middle Aged; Myocardial Infarction

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Electrocardiography; Female; Humans; Male; Middle Aged

Amiodarone was used to treat cardiac arrhythmias that had been refractory to conventional medical therapy. The first 70 consecutive patients treated with amiodarone in this study had at least 6 months of follow-up (range 6 to 24, mean 11) and form the basis for this report. Sixty-six patients were treated for ventricular arrhythmias and four for supraventricular tachycardias. Amiodarone therapy consisted of a loading dose of 600 mg orally twice a day for 7 days, and 600 mg daily thereafter. Doses were reduced only if side effects occurred. Because of frequent side effects, the dose was reduced from 572 +/- 283 mg per day (mean +/- standard deviation) at 45 days to 372 +/- 174 mg per day at 6 months. With a mean follow-up of 11 months in the 54 patients who continued to take amiodarone, only 4 patients had ventricular fibrillation. Three additional patients experienced recurrent sustained ventricular tachycardia in long-term follow-up. All 70 patients had extensive clinical and laboratory evaluation in follow-up. Side effects were common, occurring in 93% of patients. Thirteen patients (19%) had to discontinue the medication because of severe side effects. Fifty-six patients had gastrointestinal side effects, most commonly constipation. All patients but 1 eventually developed corneal microdeposits, and 43 patients were symptomatic. Cardiovascular side effects were uncommon. Symptomatic pulmonary side effects occurred in seven patients, with unequivocal pulmonary toxicity occurring in five. Neurologic side effects, most commonly tremor and ataxia, occurred in 52 patients. Thyroid dysfunction occurred in 3 patients, and 32 patients had cutaneous abnormalities. Miscellaneous other side effects occurred in 32 patients. Amiodarone appears to be useful in the management of refractory arrhythmias. Because virtually all patients develop side effects when given a maintenance daily dose of 600 mg, lower maintenance doses should be used. It is unknown if the more severe side effects are dose-related. Amiodarone is difficult to administer because of its narrow toxic-therapeutic range and prolonged loading phase. More importantly, the first sign of antiarrhythmic failure may be manifest as sudden cardiac death.

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Corneal Diseases; Digitalis Glycosides; Drug Interactions; Dyspnea; Epididymitis; Follow-Up Studies; Heart Failure; Humans; Hypotension, Orthostatic; Liver Function Tests; Male; Pulmonary Fibrosis; Stroke Volume; Thyrotropin

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Evaluation; Female; Heart Diseases; Humans; Male; Middle Aged; Postoperative Complications

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Female; Heart Ventricles; Humans; Middle Aged

Topics: Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Humans

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Male; Middle Aged; Pneumonia; Prednisone; Pulmonary Fibrosis

Topics: Adolescent; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Child, Preschool; Female; Humans; Male

Topics: Adult; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Infant, Newborn; Maternal-Fetal Exchange; Milk, Human; Pregnancy; Pregnancy Complications, Cardiovascular

Ninety-six patients with life-threatening ventricular arrhythmias refractory to two or more conventional agents were treated with amiodarone and followed for 6 to 40 months (mean, 15 months). Currently, 75 are alive and well. Seven patients died from nonarrhythmic and five from arrhythmic causes. Nonfatal arrhythmias recurred in four patients, one with early and three with late onset. Intolerable side effects occurred in five patients but heart failure was not aggravated by the drug. On 24-hour Holter recordings done before and serially during therapy in 72 patients, amiodarone eliminated episodes of ventricular tachycardia and complex ectopy and reduced total ectopic beat counts by 90% or more in all but 4 patients. In contrast, ventricular tachycardia inducible by programmed electrical stimulation was suppressed in only 50% of patients, but failure of such suppression did not compromise an excellent clinical outcome. Thus, amiodarone is highly effective in the prophylaxis of recurrent refractory life-threatening ventricular arrhythmias.

Topics: Acute Disease; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Female; Follow-Up Studies; Gastrointestinal Diseases; Heart Ventricles; Humans; Male; Middle Aged; Prognosis; Recurrence; Sleep Initiation and Maintenance Disorders; Tachycardia

Five cases of amiodarone-induced polymorphous ventricular tachycardia (torsade de pointes) are presented. All patients had recurrent syncope or dizziness due to polymorphous ventricular tachycardia and in all cases the QT interval was prolonged. In two cases hypokalemia was present at the time the arrhythmia was first recorded, but in both cases polymorphous ventricular tachycardia persisted despite correction of the electrolyte imbalance. Standard treatment for polymorphous ventricular tachycardia (isoproterenol, ventricular pacing, or both) was successful in all patients, however, therapy had to be continued for 5 to 10 days, most probably because of the long elimination half-life of amiodarone.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiac Pacing, Artificial; Electrocardiography; Female; Half-Life; Humans; Isoproterenol; Male; Middle Aged; Syncope; Tachycardia

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Evaluation; Drug Resistance; Electrocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged; Time Factors

Using a high-pressure liquid chromatographic assay, we measured serum amiodarone concentrations serially in 122 patients treated with amiodarone for 1.5-53 months (mean 9.3 months) for control of refractory symptomatic atrial or symptomatic and life-threatening ventricular tachyarrhythmias. The atrial tachyarrhythmias were successfully controlled in 45 of 54 patients (83%) during a mean follow-up of 10.0 months. In the ventricular tachyarrhythmia group, which included 22 survivors of sudden cardiac death, 38 of 50 patients (76%) responded to amiodarone during a mean follow-up of 10.9 months. Although the mean serum amiodarone concentration did not differ between responders and nonresponders, eight responders relapsed when their serum concentration fell below 1.0 mg/l. Side effects resulted in withdrawal of amiodarone in only 10 of 122 patients (9%) despite a 30% overall incidence of side effects. Central nervous system and gastrointestinal side effects became more frequent with serum concentrations greater than 2.5 mg/l, although only central nervous system side effects achieved statistical significance. Absorption and disposition kinetics of a single oral 800-mg dose of amiodarone were studied in eight patients. Serum values were measured for 24 hours in five patients during maintenance therapy, and elimination kinetics after long-term therapy were evaluated in three patients. The tissue concentration of amiodarone was determined in two patients who died during long-term amiodarone therapy and an attempt was made in 14 patients to correlate serum concentrations with daily dosages during maintenance therapy. The pharmacokinetics of oral amiodarone support the practice of using high loading dosages until arrhythmia suppression or apparent steady state is achieved (usually 2-4 weeks), followed by low-dose maintenance therapy (200-600 mg once a day) for treatment of symptomatic atrial and ventricular tachyarrhythmias.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiac Pacing, Artificial; Chromatography, High Pressure Liquid; Female; Heart Atria; Heart Ventricles; Humans; Kinetics; Male; Middle Aged; Tachycardia; Time Factors; Tissue Distribution

Ninety-six patients with recurrent, drug-refractory tachyarrhythmias were treated with amiodarone for 8.0 +/- 7.5 months (range 1 day to 27 months): 77 for recurrent ventricular tachycardia or ventricular fibrillation (VT/VF), two for complex ventricular ectopy, and 17 for supraventricular tachyarrhythmias. The actuarial incidence of successful amiodarone therapy was 52 +/- 7% at 12 months and 28 +/- 9% at 24 months for patients with VT/VF. Neither patient with complex ventricular ectopy was successfully treated. Among the patients with supraventricular tachyarrhythmias, 64.7% were successfully treated for 7.7 +/- 7.6 months (range 1 to 22 months). Amiodarone toxicity occurred in 66 of 91 patients (72.5%) treated for more than 1 week. Fourteen patients had therapy-limiting toxicity. Of these 14, six had pulmonary toxicity, four had arrhythmia exacerbation, one had hepatitis, one had renal toxicity, one had rash, and one had erythema nodosum. The actuarial incidence of therapy-limiting side effects was 27 +/- 7% at 15 months. We conclude that amiodarone is useful in the treatment of refractory tachyarrhythmias but that the rate of efficacy in VT/VF is lower and the incidence of significant toxicity is higher than has been generally appreciated.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Male; Middle Aged; Tachycardia; Ventricular Fibrillation

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Electrophysiology; Heart Ventricles; Humans; Tachycardia; Ventricular Fibrillation

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Death, Sudden; Electrocardiography; Humans; Male; Middle Aged; Tissue Distribution

4 children, ages 11-14 years, were diagnosed as having primary ventricular arrhythmias (3 ventricular tachycardia, 1 multifocal premature ventricular contractions) without underlying heart disease. All 4 patients were treated initially with standard antiarrhythmic drugs (quinidine, propranolol, procainamide) and either did not respond (3 patients) or experienced drug toxicity (quinidine - 1 patient) necessitating withdrawal of antiarrhythmic therapy. Amiodarone, a new antiarrhythmic agent, was initiated in a single oral daily dose of 10 mg/kg/day. All patients have shown a significant clinical response to oral amiodarone with either complete suppression of ventricular tachycardia in 2 patients, near complete suppression in 1 and abolition of multifocal premature ventricular contractions in the fourth patients. 2 patients have had corneal microdeposits detected by slitlamp examination and are receiving methylcellulose eye drops; no other adverse reactions have been encountered during the follow-up of 6 months to 3 years.

Topics: Adolescent; Age Factors; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Corneal Diseases; Drug Therapy, Combination; Female; Heart Ventricles; Humans; Male; Prognosis; Propranolol; Quinidine; Retrospective Studies; Tachycardia

In 17 patients on long term therapy with amiodarone, serum drug levels measured by HPLC were related to pharmacological effects. At steady state, serum levels were directly proportional to the dose, 5 mg/kg per day leading to an average serum level of approximately 2.5 mumol/l. The non-amiodarone level of iodine averaged 4-times higher than the level of amiodarone iodine. The elimination half-life of amiodarone ranged from 21 to 78 days, and of non-amiodarone iodine from 24 to 160 days. Control of arrhythmias was satisfactory in all 12 evaluable patients, when the serum amiodarone level exceeded 1.5 mumol/l. Deterioration of vision and polyserositis occurred only at amiodarone levels above 4 mumol/l. Tentatively, a therapeutic range of 1.5 to 4 mumol/l is proposed. In contrast, thyroid dysfunction was observed at any amiodarone level. In view of the narrow therapeutic window, therapy with amiodarone may be optimized by monitoring its serum level and in addition, thyroid function should be regularly checked.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Corneal Diseases; Eye Diseases; Female; Half-Life; Humans; Iodine; Kinetics; Male; Middle Aged

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Male; Middle Aged; Pneumonia; Tachycardia

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Interactions; Drug Therapy, Combination; Electrocardiography; Humans; Male; Middle Aged; Quinidine; Tachycardia

Topics: Adult; Amiodarone; Animals; Arrhythmias, Cardiac; Benzofurans; Corneal Diseases; Dose-Response Relationship, Drug; Drug Eruptions; Heart Ventricles; Humans; Rabbits; Tachycardia

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Eye Diseases; Female; Humans; Iodides; Male; Middle Aged; Retina

Six patients are presented who developed pulmonary infiltrates of undetermined origin while being treated for severe ventricular arrhythmias with amiodarone hydrochloride. Biopsy material was available in four patients and revealed interstitial or alveolar fibrosis and pneumonitis. Four patients recovered and two died of severe cardiopulmonary decompensation; all of the patients who recovered received corticosteroid therapy. Pulmonary fibrosis is a previously unreported complication of amiodarone therapy.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Coronary Disease; Female; Heart Failure; Humans; Lung; Male; Middle Aged; Myocardial Infarction; Pneumonia; Pulmonary Fibrosis

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digoxin; Drug Interactions; Heart Ventricles; Humans

Amiodarone hydrochloride, a benzofurane derivative used for the treatment of cardiac arrhythmias, is known to cause a verticillate epithelial keratopathy, which has been classified into three stages. Patients receiving low dosages of 100 to 200 mg of amiodarone daily retain clear corneas or show stage 1 changes only, regardless of duration of treatment or total amount of substance ingested. Patients receiving higher dosages of 400 to 1,400 mg/day show stage 2 and 3 changes, depending on duration of treatment. This keratopathy progresses, even with reduced dosage; however, complete regression occurs once administration of medication is discontinued.

Topics: Administration, Oral; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Corneal Diseases; Drug Administration Schedule; Humans

The potentiation of the anticoagulant effect of sodium warfarin by amiodarone is reported in 10 patients. Amiodarone appears to augment the depression of vitamin K-dependent coagulation factors caused by warfarin by an uncertain mechanism, and may lead to serious bleeding. The maintenance dose of warfarin should be halved when amiodarone and warfarin are prescribed together.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Blood Coagulation; Blood Coagulation Factors; Drug Synergism; Female; Humans; Male; Middle Aged; Prothrombin Time; Vitamin K; Warfarin

Topics: Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Electrophysiology; Heart Rate; Humans; Male; Middle Aged; Tachycardia

Topics: Action Potentials; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Heart; Humans; Time Factors

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Dose-Response Relationship, Drug; Humans; Ischemic Attack, Transient; Thyroid Gland

Amiodarone, a powerful antiarrhythmic agent recently made available in Britain, is known to cause corneal changes, but the clinical implications of this unwanted effect are still controversial. We have made serial observations on 105 patients treated with the drug for periods ranging from 3 months to over 7 years. Corneal abnormalities were detected by slit-lamp examination in 103 patients (98%). These always progressed over several months but subsequently showed a stable pattern which changed only with alteration of dose. The abnormalities regressed and disappeared within 7 months in the 16 patients whose treatment was discontinued for reasons unconnected with ocular changes. No macular changes or permanent sequelae occurred. Ocular symptoms were unusual: 6 patients had reactions in the skin of the eyelids, and 6 others had minor symptoms related to the corneal changes. We do not believe that ophthalmological surveillance is mandatory in asymptomatic patients on long-term amiodarone therapy.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Corneal Diseases; Dose-Response Relationship, Drug; Eyelid Diseases; Humans; Middle Aged; Time Factors; Visual Acuity

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Risk

Detailed electrophysiologic studies were performed in nine patients with chronic refractory ventricular arrhythmias before and after 7 to 20 weeks (mean 11 weeks) of amiodarone therapy. The amiodarone dose at the time of the repeat study ranged from 400 to 800 mg/day. The drug reduced the sinus rate (p less than 0.001) and prolonged the sinoatrial conduction time (p less than 0.05) with some prolongation of the corrected sinus node recovery time. Intra-atrial conduction was slightly prolonged both in sinus rhythm and during atrial pacing. Anterograde conduction through the AV node was significantly prolonged both in sinus rhythm (p = 0.001) and during atrial pacing (p less than 0.005), and Wenckebach AV block was seen at significantly lower atrial pacing rates after the drug (p less than 0.005). The HV interval was prolonged both in sinus rhythm (p less than 0.05) and during atrial pacing (p = 0.001), and so was the QRS width during atrial pacing (p less than 0.005) and the QT interval in sinus rhythm (p less than 0.005) and during atrial pacing (p less than 0.005). Significant prolongation of the refractory periods in the atrium, AV node, and ventricular muscle were also seen following the drug. We concluded that the significant electrophysiologic effects of this drug throughout the heart during chronic oral use attest to its clinical effectiveness in patients with atrial and ventricular arrhythmias. With due care and despite its effects on the HV interval and QRS width, it can be used in patients with intraventricular conduction defects complicating severe organic heart disease.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Atrioventricular Node; Benzofurans; Bundle of His; Cardiac Pacing, Artificial; Electrocardiography; Female; Heart Atria; Heart Conduction System; Heart Ventricles; Humans; Male; Middle Aged; Sinoatrial Node

Topics: Amiodarone; Angina Pectoris; Arrhythmias, Cardiac; Benzofurans; Corneal Diseases; Coronary Vessels; Drug Interactions; Humans; Thyroid Diseases; Tremor

Six patients treated with a combination of amiodarone and class I antiarrhythmic agents for a minor arrhythmia developed atypical ventricular tachycardia "en torsades de pointe". All patients had QT-interval prolongation in the ECG. Combined administration of quinidine and amiodarone in a normal volunteer resulted in an increase in plasma quinidine concentration and in QT prolongation, thus confirming the clinical observation of a clinically relevant interaction between the two drugs.

Topics: Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Drug Interactions; Drug Therapy, Combination; Electrocardiography; Female; Humans; Male; Middle Aged; Quinidine; Tachycardia

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Injections, Intravenous; Male; Middle Aged

Oral amiodarone was evaluated in 24 patients with complex forms of ventricular premature depolarizations (VPD) by means of ECG monitoring and measurement of systolic time intervals. The patients received 800 mg daily for 3 days, 600 mg daily for 7 days and 400 mg daily thereafter. Follow-up lasted from 6 to 17 months. Advanced forms of VPD were abolished and the VPD rate was reduced in 98% of patients. After 10 days repetitive VPD were absent in more than 80% and after 4 months more than 70% were completely free from arrhythmia. ECG changes revealed heart rate reduction and prolongation of PR, QRS and QTc intervals. Left ventricular performance was not influenced. After 6 months of treatment, 10 randomly selected patients received placebo instead of amiodarone in a single blind fashion until arrhythmia reappeared; the latter was again abolished by reinstituting amiodarone, The most frequent side effect were corneal microdeposits which were reversible and did not impair vision. It is concluded that amiodarone is effective and well tolerated in patients with high-risk VPD.

Topics: Administration, Oral; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Coronary Disease; Drug Evaluation; Electrocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged; Systole

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Male; Middle Aged

Pharmacokinetics and pharmacodynamics were studied in three dogs with interventricular coronary artery ligatures (ligature of Harris) and in three control animals. Weighted nonlinear analysis was used to fit equations describing two and three compartment open models to the experimental data, obtained after intravenous injection (5 mg/kg) of the drug. The three compartment model gave a reduction in the weighted sum of squared residuals and an improvement in the randomness of scatter of the experimental points about the theoretical curve. The postdistribution elimination half-life was longer, the area under the plasma elimination curve larger, and the total body plasma clearance and apparent volume of distribution was reduced in the animals with arrhythmias. The pharmacological response was assessed by recording the ECG and calculating the percentage of normal sinus rhythm/min. A combined pharmacokinetic-pharmacodynamic model was used to analyze data from individual animals. keO, a measure of the lag time of pharmacological response behind changes in plasma concentration, and Ce (50), a measure of the sensitivity of the cardiac site of action of the drug, were determined.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Dogs; Electrocardiography; Kinetics; Male

Topics: Amiodarone; Angina Pectoris; Arrhythmias, Cardiac; Benzofurans; Heart; Humans; Membrane Potentials

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiac Complexes, Premature; Exercise Test; Female; Heart Ventricles; Humans; Male; Middle Aged; Placebos

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiac Complexes, Premature; Electrocardiography; Female; Humans; Male; Middle Aged

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digoxin; Drug Interactions; Humans

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Corneal Diseases; Humans; Male; Middle Aged; Pigmentation Disorders

Amiodarone was used in 30 patients with tachyarrhythmias refractory to treatment with several antiarrhythmic agents. In 18 patients with supraventricular arrhythmias (recurrent atrial tachycardia in seven; atrial fibrillation, recurrent in four and persistent in five; Wolff-Parkinson-White syndrome in two), complete control was obtained in eight and marked improvement in eight patients. Conversion of persistent atrial fibrillation to sinus rhythm was documented in three patients. Congestive heart failure improved markedly in three patients who had persistent atrial fibrillation during amiodarone therapy. In 12 patients with tachycardia of ventricular origin effective control was obtained in nine. The incidence of side effects was low. Amiodarone is effective in maintaining sinus rhythm in many patients with both supraventricular and ventricular tachyarrhythmias when standard antiarrhythmic agents have failed.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Female; Heart Atria; Heart Ventricles; Humans; Male; Middle Aged; Recurrence; Tachycardia; Wolff-Parkinson-White Syndrome

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiomyopathy, Hypertrophic; Female; Humans; Male; Middle Aged; Verapamil

Amiodarone was utilized in 70 patients with symptomatic, sustained refractory tachyarrhythmias. Of these, 29 had atrial arrhythmia (20 recurrent atrial fibrillation and nine sustained supraventricular tachycardia). Control was achieved in eight with supraventricular tachycardia and in 16 with atrial fibrillation. Recurrence has been prevented in these 24 patients (83%) during an average follow-up of 13.4 months. An additional 41 patients had recurrent ventricular tachycardia. In 19 with symptoms consisting of dizziness of lightheadedness without syncope or clinically apparent hemodynamic compromise, treatment was limited to amiodarone. Of these, 14 responded (74%) and have been free of arrhythmia during an average follow-up of 13 months. In 22 who had experienced either syncope or life-threatening hemodynamic impairment, amiodarone was added to those agents which had only partially suppressed advanced grades of ventricular premature beats. Fourteen of these patients (64%) have remained free pf recurrent ventricular arrhythmia during an average follow-up of 12 months. After drug loading, maintenance therapy consisted of a daily dose ranging from 200 to 600 mg. Only mild side effects have been encountered in the 17 patients (23%) with any untoward responses. This experience confirms that oral amiodarone is an effective and safely applied agent against recurrent refractory atrial tachyarrhythmia and sustained intractable ventricular tachycardia with moderate symptoms. While also efficacious in refractory sustained life-threatening ventricular tachyarrhythmia, usage of the agent is often difficult in this condition owing in part to insufficient information concerning amiodarone pharmacokinetics.

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Male; Middle Aged; Tachycardia; Time Factors; Wolff-Parkinson-White Syndrome

A patient with the familial syndrome of Q-T prolongation, ventricular arrhythmias, and syncope was effectively treated with amiodarone.

Topics: Adolescent; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Heart Ventricles; Humans; Male; Syncope; Syndrome

The efficacy of amiodarone in the treatment of cardiac arrhythmias is discussed in the light of published results and our own experience. Oral and intravenous administration are compared with respect to electrophysiologic changes in the heart. The possibility that these changes are mediated by amiodarone-induced inhibition of metabolic pathways in cardiac tissue which depends on thyroid hormone is discussed. Among the undesirable effects, chief consideration is given to thyroid function disturbances.

Topics: Administration, Oral; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Humans; Injections, Intravenous

Topics: Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged

Amiodarone is one of the most effective antiarrhythmic and anti-anginose drugs. A rare but typical side-effect with an incidence of 1:100 is sunburn, and of 1:1,000 a black-violet to slaty pigmentation of the sun-exposed skin areas. According to histochemical and ultrastructural findings the skin pigment deposits are considered to be lipofuscin.

Topics: Adult; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Dose-Response Relationship, Drug; Humans; Male; Photosensitivity Disorders; Pigmentation Disorders; Skin; Skin Pigmentation; Sunburn

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Evaluation; Humans; Middle Aged

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans

Pituitary-thyroid function was tested in 15 euthyroid patients before, during, and after long term oral treatment with amiodarone (2-n-butyl-3,4'-diethylaminoethoxy-3',5'-diiodobenzoylbenzofurane; 600-1200 mg daily), an iodine-containing potent antiarrhythmic drug. The drug caused increases in serum total T4, free T4, and rT3, with a concomitant decrease in T3. Baseline serum TSH was significantly higher after 1 week of drug treatment and returned to normal levels after 12 weeks of treatment. All patients receiving amiodarone had a slowing of their heart rate (P less than 0.01), and heart rate gradually increased 6 weeks after drug withdrawal, concurrent with the slow fall in T4 and rT3 levels. Amiodarone did not cross-react in the iodothyronine RIAs. The results suggest that amiodarone inhibits the peripheral conversion of T4 to T3 and may block the metabolic action of thyroid hormone in man.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Heart Rate; Humans; Male; Middle Aged; Thyroid Function Tests; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

In an estimated 5% of patients, antiarrhythmic therapy with amiodarone (Cordarone) may have side effects involving thyroid function. These unwanted effects on the thyroid gland can be classified into three entirely different categories. In addition, amiodarone invariably interferes in a characteristic way with the peripheral metabolism of thyroid hormones at the cellular level. These effects are reviewed. 1. Amiodarone contains 39% of iodine. Since its metabolism involves deiodination to inorganic iodide, classical iodine-induced thyrotoxicosis may occur in patients with nodular goiters containing autonomous follicles. 2. An entirely different form of thyrotoxicosis, resembling Graves' disease, may be induced by amiodarone in individuals with previously normal thyroid. The pathogenesis of this phenomenon is unknown. 3. In rare patients of the thyroid gland is unable to cope with pharmacological quantities of iodide, possibly due to genetic anomaly of thyroid metabolism. In these individuals amiodarone may induce hypothyroidism. 4. In contrast to the possible side effects of amiodarone involving the thyroid gland, the drug has an obligate impact on the metabolism of thyroid hormones at the level of the peripheral cells. It inhibits the peripheral conversion of thyroxin to triiodothyronine (T3) and favours the generation of reverse T3, which has no T3 activity. This and other arguments favour the assumption that the effects on the heart observed after prolonged amiodarone treatment are in fact due to selective local hypothyroidism.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Thyroxine; Triiodothyronine

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Corneal Diseases; Heart; Heart Ventricles; Humans; Middle Aged; Tachycardia; Thyroid Gland

Nine patients with life-threatening ventricular arrhythmias were administered oral amiodarone over a period of months. Sustained ventricular tachycardia (VT) was induced during programmed stimulation in seven of the nine patients prior to their receiving amiodarone therapy. Despite an excellent clinical response to the drug over a period of 10 to 24 months (median 15 months), sustained VT was still able to be initiated in seven patients after 7 to 20 weeks of therapy, with multiform VT induced in several patients both before and after amiodarone. Some effects of the drug were noted, however, in that the induced VT was often slower with an increased QRS width, and right ventricular refractory periods were prolonged. Repeated ambulatory ECG monitoring in six patients showed a reduction in the frequency and complexity of spontaneous ventricular arrhythmias, but there was no consistent effect on the prematurity of the ventricular complexes. The reason for the disparity in some patients between the effects of amiodarone on the electrical initiation of VT and its clinical recurrence is unclear, but the findings suggest that the clinical efficacy of amiodarone in patients with ventricular arrhythmias may not be reliably predicted by electrophysiologic studies (EPS).

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Cardiac Pacing, Artificial; Electrocardiography; Electrophysiology; Female; Follow-Up Studies; Humans; Male; Middle Aged; Recurrence

The Authors tested the effectiveness of amiodarone hydrochloride i.v. in 50 cases of supraventricular hyperkinetic arrhythmias recently aroused. 50 patients, aged 41 to 85 years, with paroxysmal supraventricular tachycardia (PSVT, 21 cases), atrial flutter (7 cases) or fibrillation (22 cases) were treated with 4 mg/Kg of body weight of amiodarone i.v. over 2 min., followed by other 1500 mg/24 hours over 48 hours while amiodarone per os was started for antiarrhythmic prophylaxis; a 12 leads surface ECG and blood pressure were periodically recorded. The sinus rhythm was restored within 3 hours in every case of PSVT (100% of success), within 30 hours in 19 cases of atrial fibrillation (86% of success) and in 5 cases of atrial flutter (71% of success). A slowing down of ventricular frequency ranging from 15 to 40% occurred within 10 min. in case of failure of restoration of sinus rhythm; a slight and transient lengthening of P-R occurred in 1 case; no particular side effects nor noteworthy changes of blood pressure were observed. Amiodarone i.v. proved to be a very effective remedy, handy and well tolerated for the arrhythmias considered above.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Benzofurans; Female; Humans; Injections, Intravenous; Male; Middle Aged; Tachycardia, Paroxysmal

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Female; Humans; Longitudinal Studies; Male; Middle Aged; Tachycardia

In clinical Arrhythmology it is often necessary to associate digitalis and antiarrhythmic agents. This calls for study of possible interaction between the employed drugs. We found a statistically significant correlation between digitalis and amiodarone plasma level in patients on long term treatment with both drugs. A statistically significant linear correlation between plasma amiodarone level and digoxin (0.25 mg/day) or beta-methyldigoxin (0.20 mg/day) was documented in 33 patients. 23 patients had been treated with these drugs for paraxysmal reciprocating supraventricular tachycardia since an average of 52 months (computerized follow-up). (Amiodarone average weekly dose was 1078 +/- 168 mg after a loading dose of 12 gm given over one month). 10 patients were on chronic treatment with higher weekly doses of amiodarone (average dose 2380 +/- 731 mg per week). Thyroid function tests (T4; T3; T3UP; TSH; rT3) were checked in every patients. Further studies are warranted to understand the mechanism of the interaction between amiodarone and digitalis. As a clinical implication we point out that amiodarone-digoxin (or betamethyldigoxin) interaction in our patients has neither resulted in over-therapeutic plasma level nor in signs of digitalis toxicity.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digoxin; Drug Interactions; Female; Humans; Male; Medigoxin; Middle Aged; Tachycardia, Paroxysmal

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Male; Middle Aged

In a group of 95 patients having cardiac operations with extracorporeal circulation, intravenous (IV) amiodarone, administered in doses of 2.5 to 5 mg/kg, was used in the treatment of various perioperative arrhythmias. Conversion to sinus rhythm was achieved in 55 (61%) of 90 patients with supraventricular arrhythmias, the other patients showing a satisfactory slowing of their heart rate. Total suppression and control was obtained in 18 patients with persistent ventricular extrasystoles associated with various supraventricular arrhythmias. Amiodarone was administered in five patients with life-threatening ventricular arrhythmias resistant to other antiarrhythmic agents: Suppression was obtained in one of two patients with recurrent ventricular tachycardias and control was achieved in three patients with repetitive ventricular tachycardia and ventricular fibrillation, allowing the effective use of intra-aortic balloon counterpulsation (IABP) needed for hemodynamic support. Seven patients experienced minor side effects such as nausea or flushing. No complete atrioventricular (AV) block was noted. Significant hypotension occurred at the end of the IV injection in 17 (18%) patients. In all but five patients, hypotenion was transient, without clinical complications. In the five others, adrenergic drugs in four cases and IABP in one case were necessary. Those five patients had marked cardiomegaly with poor myocardial contractility. IV bolus injection of amiodarone seems prohibited in such patients; constant infusion would be preferable.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiac Surgical Procedures; Female; Humans; Infusions, Parenteral; Injections, Intravenous; Male; Middle Aged; Postoperative Complications

Topics: Administration, Oral; Adolescent; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Thyroid Diseases; Time Factors

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Chagas Cardiomyopathy; Female; Humans; Male; Middle Aged

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Exercise Test; Female; Humans; Male; Middle Aged

Topics: Adult; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged

Topics: Adult; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Cardiomyopathies; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Mitral Valve; Quinidine

Cordarone was used in the treatment of 15 patients with various forms of parasystole. There were 9 cases with ventricular and 5 with atrial parasystole. Cordarone was prescribed according to the following schedule: 200 mg three times daily for the first 10 days and 200 mg twice daily in the next 20 days. A clear positive effect was produced in 14 patients. In 13 cases parasystoles disappeared on the first to tenth day of treatment. The number of parasystoles reduced considerably in one case. The drug had no positive effect on one patient.

Topics: Adolescent; Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Drug Evaluation; Electrocardiography; Female; Humans; Male; Middle Aged; Sinoatrial Node; Systole

Oral amiodarone has been used to treat 21 patients with various supraventricular arrhythmias; 13 had Wolff-Parkinson-White syndrome, which was complicated by atrial fibrillation and re-entry atrioventricular tachycardia in four, and re-entry tachycardia alone in the other nine. The remaining eight patients had paroxysmal atrial fibrillation or flutter without pre-excitation. All were refractory to conventional treatment and had undergone intracardiac electrophysiological study. Fifteen have been controlled with amiodarone, this treatment proving most effective in atrial fibrillation or flutter with or without pre-excitation. Amiodarone was successful in only four of the nine patients with re-entry atrioventricular tachycardia. In two patients who responded well the drug had to be discontinued because of side effects.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Benzofurans; Electrocardiography; Humans; Middle Aged; Wolff-Parkinson-White Syndrome

Oral amiodarone was given to 135 children (mean age, 10.2 years) for a mean duration of 4.1 months (range, 1 day to 6 years) for mainly idiopathic (25%) and postoperative (61%) arrhythmias. Complete ECG control or partial ECG control with clinical improvement was obtained in 60% and 33% of cases, respectively, regardless of the arrhythmia location (atrial 69%, junctional 16%, and ventricular 15%), mechanism, resistance (55%) or sensitivity (45%) to other drugs, and presence of cardiomegaly (40%) or clinical signs of heart failure (27%). The only factor favoring improvement was a short history (< 2 months in 54%). The rapid onset of drug effect (4.1 days), the early relapses after treatment discontinuation (3.3 weeks), and the absence of side effects due to drug accumulation reflect a faster metabolism than that in adults, with no cardiac toxicity and a low incidence of thyroid dysfunction (2 hyperthyroid, 1 hypothyroid).

Topics: Adolescent; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Child, Preschool; Drug Tolerance; Electrocardiography; Female; Heart Conduction System; Heart Rate; Humans; Infant; Infant, Newborn; Male; Tachycardia; Time Factors

Amiodarone is used in the treatment of previously drug-resistant supraventricular and ventricular arrhythmias. We report our experience with amiodarone in 8 patients. Five patients had paroxysmal atrial flutter, one had paroxysmal atrial fibrillation, one had supraventricular tachycardia, and one ventricular tachycardia. Considerable improvement, both objectively and subjectively, was observed in all patients. Side effects were as follows: all patients had corneal microdeposits, one developed left bundle branch block which resolved on stopping amiodarone, and one reported constipation and abdominal pains. Six patients have been treated for 10-28 months; 3 developed tolerance at 4-14 months after the introduction of amiodarone therapy, but symptoms improved with increased dosage. It is important to watch for the development of tolerance to this drug.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Corneal Diseases; Drug Resistance; Drug Tolerance; Female; Humans; Male; Middle Aged

Topics: Amiodarone; Animals; Arrhythmias, Cardiac; Barium; Benzofurans; Chlorides; Dogs; Electrocardiography; Female; Male

Topics: Amiodarone; Angina Pectoris; Arrhythmias, Cardiac; Benzofurans; Drug Evaluation; Humans

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Humans; Male; Stimulation, Chemical; Thyroid Gland; Thyroxine

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digoxin; Female; Humans; Male; Middle Aged

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Corneal Diseases; Drug Administration Schedule; Humans; Middle Aged; Myocardial Infarction

Amiodarone hydrochloride was used to treat 19 patients with symptomatic arrhythmias refractory to quinidine sulfate, procainamide hydrochloride, disopyramide phosphate, antazoline hydrochloride, lidocaine hydrochloride, bretylium tosylate, propranolol hydrochloride, phenytoin sodium, and practotol acetanilide given to the limit of tolerance. In 17 patients, attacks were completely controlled. Arrhythmias treated successfully included recurrent supraventricular tachycardias, recurrent supraventricular tachycardias with Wolff-Parkinson-White syndrome, and refractory ventricular arrhythmias including recurrent ventricular tachycardia and ventricular fibrillation complicating acute coronary heart disease. Control was confirmed by continuous ECG monitoring both in the hospital and when ambulatory and was maintained for up to four years. Attacks of supraventricular tachycardia were reduced from 7.9/mo to one attack every 53.5 months on amiodarone. Hospital admissions for arrhythmias were reduced from 34 the year before treatment to none the year after. Therefore, amiodarone is an excellent drug for control of many refractory arrhythmias, but two patients with recurrent atrial fibrillation were refractory to this treatment.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Male; Middle Aged; Recurrence; Tachycardia

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Humans

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Evaluation; Humans

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cornea; Electrocardiography; Female; Humans; Male; Middle Aged

Topics: Amiodarone; Angina Pectoris; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Benzofurans; Humans; Tachycardia

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Corneal Diseases; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Respiration

Topics: Adult; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Heart Block; Humans; Hypothyroidism; Middle Aged; Tachycardia, Paroxysmal; Thyroid Function Tests

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cornea; Female; Humans; Male; Middle Aged; Myocardial Infarction; Pigmentation Disorders; Skin; Skin Pigmentation

The employment of Cordaron (Amidaron) in 50 patients with different arrhythmias proved effective in 86% of the cases. Cordaron was most effective in the treatment and prevention of paroxysmal tachycardia, ventricular extrasystole, paroxysmal cardiac fibrillation. It decreases the pulse rate and moderately decreases the arterial pressure without imparing the patients' state. The drug has practically no toxic effect, is well tolerated, convenient for administration and dosage. Cardiovascular insufficiency is no contraindication for its prescription. Carefulness is needed in prescribing Cordaron to patients with atrioventricular conductivity disorders.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Cardiac Complexes, Premature; Drug Evaluation; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Contraction; Tachycardia, Paroxysmal

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Evaluation; Electrocardiography; Female; Humans; Male; Middle Aged; Tachycardia, Paroxysmal

The amiodarone is studied in the context of cardiac surgery to evaluate its anti-arrythmic properties in its injectable form and possible interference with the anaesthetic drugs. Two groups of patients were established: - the first group of 10 patients received the amiodarone per-os in the immediate pre-operative period, - the second group of 19 patients received injectable amiodarone either by direct intraveinous injection at a dose of 5 mg/kg or in I.V. drip for rhytmic irregulatities during surgery. The anti-arrythmic property of the product is confirmed. No incompatibility with the anaesthetics employed (neuroleptanalgesia) was observed. Howerer, a potentialization of the sympatholytic alpha-effects by the anaesthesia is observed. The fall in arterial pressure, when it is measureable, is of the order of a third of the initial value, with a return to the previous level within about ten minutes.

Topics: Adolescent; Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Blood Pressure; Cardiac Surgical Procedures; Child; Female; Humans; Injections, Intravenous; Male; Middle Aged; Neuroleptanalgesia; Vascular Resistance

The authors report four new cases of hyperthyroidism associated with prolonged treatment with amiodarone. Massive doses of beta-blockers were required to deal with the severely disordered rhythm in one of the patients. Amiodarone, which is an effective treatment for angina, is not free from risk, even at the doses which are currently accepted. Hyperthyroidism, which may occur even in patients who have had no past history of any thyroid troupble at all, remains a most unusual complication.

Topics: Adult; Amiodarone; Angina Pectoris; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Female; Humans; Hyperthyroidism; Male; Middle Aged; Pindolol; Propranolol

Topics: Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Cardiac Surgical Procedures; Heart; Humans; Injections, Intravenous; Postoperative Complications; Resuscitation; Vascular Surgical Procedures

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Drug Evaluation; Female; Humans; Male

Topics: Administration, Oral; Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Depression, Chemical; Drug Evaluation; Electrocardiography; Female; Heart Conduction System; Humans; Injections, Intravenous; Male; Middle Aged

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Evaluation; Female; Humans; Injections, Intravenous; Male; Middle Aged

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiac Complexes, Premature; Drug Evaluation; Humans; Tachycardia, Paroxysmal; Ventricular Fibrillation

Topics: Aged; Amiodarone; Angina Pectoris; Arrhythmias, Cardiac; Benzofurans; Coronary Disease; Dipyridamole; Electrocardiography; Female; Heart Failure; Heart Function Tests; Humans; Hypertension; Male; Middle Aged

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Bretylium Compounds; Humans

15 patients with ventricular and supraventricular arrhythmias treated with Amiodarone hydrochloride via oral were studied. The results obtained show that in 86'6% of the cases the arrhythmia disappeared immediately, in 6'6% the arrhythmia disappeared late and in only one case the arrhythmia persisted. Statistical significance was found in the reduction of cardiac frequency as well as in the corrected QT interval for the frequency. The latter is an indirect consequence of the mode of action of the drug. The only side effect observed was the appearance of corneal opacification. It was demonstrated that this side effect is negligible when low doses which are equally effective are administered. The conclusion that Amiodarone is an excellent oral antiarrhythmic drug is reached. A daily dose of 400 mg during the first 20 days of each month with a rest of 10 days is recommended. In this way, the corneal opacification is minimal or nil. The possibility that the association of the drug with Quinidine could be effective in maintaining sinus rhythm post D.C. is suggested.

Topics: Administration, Oral; Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Drug Evaluation; Female; Heart Rate; Humans; Male; Middle Aged

Topics: Action Potentials; Arrhythmias, Cardiac; Benzofurans; Bretylium Compounds; Cell Membrane Permeability; Ethanolamines; Heart; Humans; Hypothyroidism; Lidocaine; Phenytoin; Propranolol; Quinidine; Ventricular Fibrillation

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Diethylamines; Electrocardiography; Heart Block; Heart Conduction System; Iodobenzoates; Rats

Topics: Adult; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Evaluation; Female; Humans; Male; Middle Aged

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Benzofurans; Digitalis Glycosides; Electric Countershock; Lidocaine; Phenytoin; Potassium; Procainamide; Quinidine; Tachycardia; Verapamil

Topics: Anti-Arrhythmia Agents; Antihypertensive Agents; Arrhythmias, Cardiac; Benzofurans; Female; Heart Aneurysm; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Ethylamines; Female; Humans; Iodobenzoates; Male

Topics: Angina Pectoris; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Coronary Disease; Humans

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Female; Humans; Male; Middle Aged; Tachycardia

Topics: Angina Pectoris; Antihypertensive Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Benzofurans; Cardiac Complexes, Premature; Humans; Tachycardia; Tachycardia, Paroxysmal

Topics: Acetylcholine; Animals; Arrhythmias, Cardiac; Atrial Fibrillation; Barium; Benzofurans; Cardiac Complexes, Premature; Chlorides; Dogs; Rabbits; Strophanthins; Tachycardia

Topics: Adult; Aged; Angina Pectoris; Antihypertensive Agents; Arrhythmias, Cardiac; Benzofurans; Coronary Disease; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Tachycardia