benzofurans and Corneal-Diseases

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

Amiodarone, 2-N-butyl-3-(4'diethylaminoethoxy-3',5-diiodobenzoyl)benzofuran, also known as Cordarone, is presently under clinical investigation in the United States. It is an alpha and beta antagonist and is extremely effective in treating otherwise uncontrollable ventricular arrhythmias. To date, 27 patients participating in our ongoing study since 1977 have had corneal deposits. The deposits are in the corneal epithelium basal cell layer, and occur in stages (mild, moderate, and severe), which seem to correlate with dosage and duration of treatment. Vision is rarely diminished by these deposits, and if it is, discontinuation of the drug therapy will cause regression of the deposits with eventual return to normal beginning within two to four weeks but possibly taking as long as 1 1/2 years. The deposits look similar to those seen in chloroquine toxicity and Fabry's glycolipidosis. Other adverse effects reported in the European literature include thyroidopathy, cutaneous pigmentation, and neuromyopathy.

Topics: Amiodarone; Benzofurans; Corneal Diseases; Humans

Eighteen patients receiving the cardiac drug amiodarone were followed prospectively for the development of amiodarone keratopathy. Seventeen of 18 patients (94%) developed characteristic epithelial keratopathy in at least one eye within three months of the initiation of therapy. The pattern of the epithelial deposits was noted to undergo progressive changes in configuration as a function of the duration of amiodarone therapy. These evolving changes are well defined and allow development of a grading system for amiodarone keratopathy. A grading system as well as a proposed mechanism for evolving pattern of the keratopathy are presented.

Topics: Aged; Amiodarone; Benzofurans; Cornea; Corneal Diseases; Corneal Opacity; Dose-Response Relationship, Drug; Epithelium; Female; Humans; Male; Middle Aged

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

Topics: Aged; Amiodarone; Benzofurans; Contact Lenses, Extended-Wear; Contact Lenses, Hydrophilic; Cornea; Corneal Diseases; Female; Humans; Male

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

Topics: Amiodarone; Benzofurans; Corneal Diseases; Humans; Male; Middle Aged; Pigmentation Disorders; Vision Disorders

Topics: Amiodarone; Benzofurans; Contact Lenses, Hydrophilic; Corneal Diseases; Humans

Ocular observations in a series of 100 patients treated with amiodarone, along with the pathological changes observed in the eye tissues of two patients treated with this drug, are described in this paper. In the latter two patients intracytoplasmic membrane-bound lamellar bodies similar to myelin were observed by electron microscopy not only in the corneal epithelium and fibroblasts, the conjunctiva and the lens, but also in the corneal endothelium, the iris, the ciliary body, the choroid and the retina. It is suggested that patients taking amiodarone in high dosage for long periods have their eyes and retinal function monitored.

Topics: Amiodarone; Benzofurans; Corneal Diseases; Eye; Eye Diseases; Female; Humans; Male; Retinal Diseases

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

The ocular complications of long-term amiodarone therapy have been recognized for many years, but systematic data on the prognostic significance and the precise incidence of such effects have not been evaluated until recently. One hundred seventy-five patients receiving long-term amiodarone treatment have thus been followed for periods ranging from 3 months to nearly 10 years. Of 103 of these patients studied in greater depth, 98% have shown the characteristic patterns of corneal microdeposits, which progressed over several months and ultimately formed a stable appearance that changed only with an alteration of dose. The abnormalities, the nature of which is not clearly understood, disappeared within 7 months in the 16 patients whose drug was withdrawn for unrelated reasons, and no permanent ocular damage has been detected. Visual symptoms associated with the corneal deposits developed in 6% of patients: 3% had photophobia, 2% halos, and 1% blurring of vision but without impairment of visual acuity. It is concluded that ocular complications of amiodarone therapy are insignificant; they do not pose a threat to vision, and routine ophthalmologic surveillance does not appear mandatory in the majority of patients during long-term drug therapy.

Topics: Amiodarone; Benzofurans; Corneal Diseases; Eye Diseases; Humans; Vision Disorders

With the increasing use of amiodarone, several unwanted effects have been recognized. We reviewed 140 patients treated with amiodarone over a 5-year period in an attempt to identify patients at risk, to assess the incidence of these effects and their possible relation to dose, and to determine their outcome. The most common effect was photosensitivity (57% of patients responding to a questionnaire), whereas asymptomatic corneal microdeposits were found in all patients undergoing ophthalmologic examination. In contrast, symptomatic eye changes (colored halos) and slate-gray skin pigmentation were rare. Of the metabolic alterations, the rise in hepatic enzymes correlated with dose and plasma drug and metabolite concentrations (r = 0.59, p less than 0.001; r = 0.62, p less than 0.001, respectively) but was not associated with clinical disease. This relation to dose was not evident in patients developing clinical thyroid abnormalities (two hypothyroidism, two hyperthyroidism), all of whom had normal thyroid function prior to therapy. Four of the five hypothyroid patients were over 70 years of age. No patients developed peripheral neuropathy, but tremor and sleeplessness were common complaints (30% and 28% of patients, respectively) that responded to a decrease in dose. One patient with an abnormal chest x-ray film prior to therapy developed pulmonary fibrosis. We suggest the restricted use of high doses of amiodarone for protracted periods. Patients at particular risk are the older age group (hypothyroidism) and those with abnormal lung function prior to therapy who may be predisposed to pulmonary alveolitis. Most of the observed unwanted effects resolve when amiodarone is decreased in dose or discontinued.

Topics: Aged; Alanine Transaminase; Amiodarone; Aspartate Aminotransferases; Benzofurans; Corneal Diseases; Dose-Response Relationship, Drug; Female; Humans; Hyperthyroidism; Hypothyroidism; Lung Diseases; Male; Middle Aged; Photosensitivity Disorders; Pigmentation Disorders; Risk; Vision Disorders

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; Benzofurans; Corneal Diseases; Female; Humans; Male; Middle Aged

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

We evaluated the electrophysiologic effects of amiodarone and its ability to control ventricular arrhythmia in a selected group of 51 patients with refractory sustained ventricular arrhythmia. Amiodarone in doses of 400 to 800 mg/day prolonged refractoriness in the atria, atrioventricular (AV) node, and ventricle as well as conduction through the AV node and His-Purkinje system. Although it had no effect on measurements of sinus nodal function (sinus nodal recovery time and sinoatrial conduction time), it prolonged the sinus cycle length and 2 patients required a permanent pacemaker for symptomatic sinus bradycardia. Amiodarone did not alter the ease of inducibility in any consistent manner, and only 5 of 43 patients (12%) who had inducible ventricular tachycardia before amiodarone therapy had none induced during amiodarone treatment. The clinical effectiveness of amiodarone could be evaluated in 46 patients followed up for 8.6 +/- 6 months (range 0.5 to 22). It provided effective therapy in 23 patients (50%), partly effective therapy in 13 (28%), and was ineffective in 10 (22%). Adverse effects were noted in 28 of 51 patients (55%), and in 11 of these (22%) the drug had to be discontinued because of adverse effects. We conclude that amiodarone is a useful agent for the treatment of refractory sustained ventricular arrhythmia. Its use should be reserved for patients with life-threatening sustained arrhythmia because of the significant incidence of adverse effects. Furthermore, good clinical response can be observed in patients receiving amiodarone in spite of continued inducibility.

Topics: Adolescent; Adult; Aged; Amiodarone; Benzofurans; Cardiac Pacing, Artificial; Chemical and Drug Induced Liver Injury; Corneal Diseases; Electrophysiology; Female; Heart Conduction System; Heart Failure; Humans; Male; Middle Aged; Myocardial Contraction; Peripheral Nervous System Diseases; Photosensitivity Disorders; Pulmonary Fibrosis; Stroke Volume; Tachycardia; Ventricular Fibrillation

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

Topics: Adolescent; Adult; Aged; Amiodarone; Benzofurans; Cataract; Color Vision Defects; Corneal Diseases; Eye Diseases; Female; Humans; Lipidoses; Male; Middle Aged; Retinal Diseases

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

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

Among 37 patients treated with amiodarone, an antiarrhythmic drug, a typical keratopathy developed in 35, none of whom had ocular complaints. The keratopathy resembled that seen with Fabry's disease and chloroquine use, as did the membrane-bound lamellar bodies detected by electron microscopy in all layers of the corneal epithelium in the one patient with marked keratopathy in whom a corneal biopsy was performed; membrane-bound bodies, mostly granular, were also noted within this patient's stromal keratocytes. The possible pathogenesis of the keratopathy as a type of drug-induced lipidosis is discussed.

Topics: Adult; Aged; Amiodarone; Benzofurans; Cornea; Corneal Diseases; Humans; Lipidoses; Microscopy, Electron; Middle Aged

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

Therapeutic administration of amiodarone, an antiarrhythmic drug, to eight patients resulted in the formation of vortex-like figures within the anterior cornea. Clinical examination disclosed no visual loss or other ocular abnormality attributable to the drug. In one patient, light and transmission electron microscopy of corneal epithelium, bulbar conjunctiva, and cataractous lens revealed complex lipid deposits within lysosome-like intracytoplasmic inclusions in corneal, conjunctival, and lens epithelium, conjunctival fibrocytes, and conjunctival vascular endothelium. Amiodarone keratopathy is compared clinically and morphologically with the corneal alterations seen in Fabry's disease and in chloroquine use as an example of a drug-induced lipid storage disorder.

Topics: Aged; Amiodarone; Benzofurans; Conjunctiva; Cornea; Corneal Diseases; Female; Humans; Inclusion Bodies; Lipid Metabolism; Male; Microscopy, Electron; Middle Aged

Twenty-three patients with sustained, recurrent, symptomatic ventricular tachycardia were treated with oral amiodarone. Initial doses were 600-2000 mg/day and maintenance doses were 200-1200 mg/day. Amiodarone was highly effective in 20 patients (87%), seven of whom had a follow-up of 30 months or longer, including two who were followed for 5 years. Three patients died within the first 45 days, three died suddenly after a follow-up of 33.5 months, and four had a nonarrhythmic death after a follow-up of 25 months. Fifteen patients (65%) had no recurrence during a follow-up of 21.5 months, while five (22%) had isolated recurrences during a follow-up of 32.2 months. The average maintenance dose was 713 mg/day in the 15 patients who did not have recurrences and 375 mg/day in the five patients who had recurrences (p less than 0.001). Both short- and long-term tolerance were excellent and there was not a single case in which treatment had to be discontinued. The main disadvantage of amiodarone was that it took an average of 9.5 days to reach anti-arrhythmic efficacy. The main advantages were prolonged duration of action (recurrences occurred only 15-60 days after the drug was discontinued or the dose lowered, virtual absence of contraindications, doses as high as 2000 mg/day were safe and patient compliance was excellent.

Topics: Adult; Aged; Amiodarone; Anti-Arrhythmia Agents; Benzofurans; Corneal Diseases; Humans; Long-Term Care; Male; Middle Aged; Photosensitivity Disorders; Recurrence; Skin Diseases; Tachycardia; Time Factors

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

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

Topics: Adolescent; Adult; Aged; Amiodarone; Benzofurans; Blinking; Corneal Diseases; Female; Heart Diseases; Humans; Male; Middle Aged; Tears

6 cardiac patients were found to present various degrees of corneal involvement following systemic treatment with amiodarone. The clinical pattern of the keratopathy, its benign course and the pathophysiology are discussed. Lacrimal insufficiency or incomplete blinking seem to contribute to the severity of the keratopathy.

Topics: Adolescent; Adult; Aged; Amiodarone; Benzofurans; Corneal Diseases; Female; Heart Diseases; Humans; Male; Middle Aged

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

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

Five patients with the bradycardia-tachycardia syndrome have been treated successfully with the antiarrhythmic agent amiodarone. Three patients were treated for over nine months and one of these patients had corneal micro deposits. One patient had to be taken off the drug because of side effects. Amiodarone should be tried in patients suffering from the bradycardia-tachycardia syndrome before resorting to cardiac pacing.

Topics: Aged; Amiodarone; Benzofurans; Bradycardia; Corneal Diseases; Female; Humans; Male; Middle Aged; Syndrome; Tachycardia