benzofurans and Lung-Diseases

Topics: Amiodarone; Benzofurans; Dose-Response Relationship, Drug; Drug Hypersensitivity; Humans; Lung Diseases; Pulmonary Fibrosis; Time Factors

Topics: Amiodarone; Benzofurans; Chemical and Drug Induced Liver Injury; Eye Diseases; Humans; Hyperthyroidism; Lung Diseases; Peripheral Nervous System Diseases; Pigmentation Disorders; Thyroid Hormones

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

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

During the past 3 years, 51 cases of pulmonary lesions associated with the use of amiodarone, an effective anti-arrhythmic and anti-angina drug, have been reported in 17 publications. Durations of treatment, daily doses and total dosage were extremely varied. Clinical symptoms as well as radiological findings, respiratory function studies and laboratory data suggested hypersensitivity pneumonia. However, the histopathological substrate remains ill-defined, and while some data suggest a toxic effect, others are in favour of an immune reaction ending in diffuse pulmonary fibrosis. Five of the 11 deaths reported seem to be directly related to the drug. It would appear that long-term treatment with amiodarone requires regular periodical examination of the respiratory system.

Topics: Amiodarone; Benzofurans; Humans; Lung; Lung Diseases; Time Factors

Of the side effects that complicate amiodarone therapy, pulmonary fibrosis is potentially the most serious. Therefore, the development of techniques to predict the onset of this troublesome reaction would be of great practical value. Reports of 39 patients who developed pulmonary toxicity with amiodarone were evaluated for clues to precipitating factors and information on the response to corticosteroid treatment. The majority of patients were being given maintenance doses greater than 400 mg/day. Patients appeared to improve after withdrawal of amiodarone, both with and without corticosteroid treatment. In addition, a case report is presented of a patient who developed pulmonary changes that disappeared when amiodarone was withdrawn and did not recur when amiodarone was reinstituted. Data from sequential pulmonary function tests and cumulative amiodarone dosage in 35 patients were also examined to determine their value in predicting pulmonary complications. Pulmonary function tests did not appear to be useful in predicting the likelihood of an individual patient's developing pulmonary complications. Although none of the available information identifies the mechanism mediating amiodarone pulmonary toxicity, the frequency of the complication probably can be reduced by timely reductions in maintenance dosage.

Topics: Adrenal Cortex Hormones; Adult; Aged; Amiodarone; Benzofurans; Dose-Response Relationship, Drug; Female; Humans; Inclusion Bodies; Lung Diseases; Male; Middle Aged; Pneumonia; Pulmonary Fibrosis; Respiratory Function Tests; Risk; Structure-Activity Relationship

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: 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

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; Antibodies, Antinuclear; Benzofurans; Humans; Lung Diseases; Male; Middle Aged

Fourteen gallium scans were obtained in 11 patients suspected of having amiodarone lung toxicity on the basis of clinical findings, pulmonary function tests, and chest radiographs. All 11 patients had abnormal scans. Gallium accumulates in various inflammatory and neoplastic lesions, but despite this nonspecificity, the findings suggest gallium scintigraphy is a useful procedure to detect amiodarone lung toxicity when used in the appropriate clinical setting.

Topics: Aged; Amiodarone; Benzofurans; Gallium Radioisotopes; Humans; Lung; Lung Diseases; Middle Aged; Radionuclide Imaging

Topics: Adult; Aged; Amiodarone; Benzofurans; Female; Humans; Lipidoses; Lung Diseases; Male; Middle Aged; Pulmonary Fibrosis

Topics: Amiodarone; Benzofurans; Humans; Lung Diseases; Radiography

Topics: Aged; Amiodarone; Benzofurans; Humans; Lung Diseases; Male; Radiography, Thoracic

The mechanism of amiodarone-induced pulmonary toxicity is unknown. Two cases of amiodarone pulmonary toxicity are presented in which abnormal inclusion bodies containing whorls of membrane were seen on electron microscopy of extrapulmonary tissues. These cytoplasmic lysosomal inclusion bodies were observed in lymphocytes, plasma cells, granulocytes, tissue macrophages, and hepatocytes. These widespread histopathologic changes in extrapulmonary tissues and in a variety of cell types are similar to more extensively investigated findings in animal models that are thought to represent a drug-induced lysosomal storage disease, phospholipidosis.

Topics: Amiodarone; Benzofurans; Biopsy, Needle; Follow-Up Studies; Humans; Inclusion Bodies; Leukocytes; Liver; Lung; Lung Diseases; Lymph Nodes; Lysosomes; Male; Microscopy, Electron; Middle Aged; Radiography; Tachycardia

Administration of high doses of amiodarone to young adult rats leads to phospholipidosis of the lung, with extensive phospholipid storage by type II pneumonocytes and alveolar macrophages. Biochemical analysis reveals an increase in the total phospholipid content of the lung and in the proportion of phosphatidylcholine. The cause of the phospholipidosis is suggested to be the inhibition of lysosomal phospholipases, responsible for catabolizing phospholipids. It is shown that amiodarone is a potent inhibitor of phospholipases prepared from the soluble fraction of adult rabbit lung lysosomes.

Topics: Amiodarone; Animals; Benzofurans; Inclusion Bodies; Lung; Lung Diseases; Lysosomes; Macrophages; Phosphatidylcholines; Phospholipases; Phospholipases A; Phospholipids; Pulmonary Alveoli; Rabbits; Rats; Rats, Inbred Strains

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

The authors report the cases of two men with coronary artery disease by amiodarone for 8 and 24 months respectively. They developed clinical and radiological changes of diffuse interstitial pneumonia, characterised by an inflammatory syndrome, restrictive changes on spirometry, reduced CO transfer and abnormal blood gases. Broncho-alveolar lavage showed a lymphocytosis with a large quantity of iodine in the macrophages and the presence of amiodarone and its metabolite in the supernatant fluid. The responsibility of this drug is imputed and the patients were cured within 3 months of its withdrawal with regression of clinical, radiological, spirometric and control alveolar lavage abnormalities. A favourable outcome without steroid therapy is practically unknown in the literature. These cases illustrate the possible risk of alveolitis or diffuse interstitial pneumonia during long term amiodarone therapy, the pathogenesis of which is discussed: iodine overload, direct drug toxicity or an immunological mechanism.

Topics: Aged; Amiodarone; Benzofurans; Humans; Lung Diseases; Male; Middle Aged

Topics: Amiodarone; Benzofurans; Humans; Lung Diseases

Topics: Amiodarone; Benzofurans; Gallium Radioisotopes; Humans; Lung Diseases; Male; Middle Aged; Radionuclide Imaging

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: Amiodarone; Benzofurans; Humans; Lung Diseases; Pneumonia; Pulmonary Fibrosis

Amiodarone is an investigational antiarrhythmic agent known to cause pulmonary toxicity. This report describes two patients with previous amiodarone pulmonary toxicity and complete resolution who at rechallenge 5 to 6 months later developed within 2 weeks of therapy a significant reduction in lung diffusion capacity before overt clinical toxicity occurred. This suggests that toxicity may present early with reduction in diffusion capacity and that such changes may warrant the need to alter treatment.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Benzofurans; Female; Humans; Lung Diseases; Middle Aged

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

Reports of pulmonary infiltrates in patients taking amiodarone, initiated the study of 69 patients for pulmonary toxicity using serial chest roentgenograms (CXRs), pulmonary function tests (PFTs), and symptoms before and during therapy. Mean PFTs did not significantly change from their baseline normal values, but 10 percent of patients had a greater than or equal to 15 percent fall in total lung capacity, and 28 percent a greater than or equal to 15 percent fall in diffusion capacity (DCO) following treatment. Initial abnormalities in pulmonary function or CXR were predictive of risk of developing pulmonary toxicity. Degree of exposure to amiodarone (dose plus duration) correlated only weakly with development of pulmonary toxicity, which could occur in patients taking relatively small doses of the drug. Pulmonary complications of amiodarone are common, in most cases reversible, and often confused with congestive heart failure or pneumonia. Patients should be evaluated before treatment by assessing symptoms, CXRs, and DCO. Patients with initial abnormalities in these parameters, particularly both CXR and DCO abnormalities, should be considered for alternative therapy.

Topics: Adult; Aged; Amiodarone; Benzofurans; Diagnosis, Differential; Female; Follow-Up Studies; Heart Failure; Humans; Infections; Lung; Lung Diseases; Male; Middle Aged; Prospective Studies; Pulmonary Diffusing Capacity; Pulmonary Ventilation; Radiography; Respiratory Function Tests; Risk; Total Lung Capacity

A case of diffuse interstitial pneumopathy which was observed by photonic microscopy and confirmed by electron microscopy is presented in a patient treated with amiodarone only. The iatrogenic origin of this pneumopathy appears certain as clinical and radiological signs improved after amiodarone treatment was withdrawn.

Topics: Amiodarone; Benzofurans; Coronary Disease; Humans; Lung; Lung Diseases; Male; Middle Aged

Mild pleuroparenchymal fibrosis associated with amiodarone pulmonary toxicity is reported in a 63-year-old white man; partial radiographic resolution and complete symptomatic resolution with decreasing the daily dosage to 200 mg permitted continued anti arrhythmic therapy.

Topics: Amiodarone; Benzofurans; Humans; Lung Diseases; Male; Middle Aged; Tachycardia

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

Amiodarone, a cardiac antiarrhythmic agent, has been associated with the development of interstitial pulmonary fibrosis in patients receiving prolonged therapy with the drug. To further assess the toxic effects of amiodarone on lung tissue, Syrian hamsters were given a single intratracheal insufflation of the agent and evaluated for histologic evidence of lung injury. Control animals received intratracheal insufflations of the vehicle in which amiodarone was dissolved. After an initial, transient alveolitis in both experimental and control animals, the amiodarone-treated lungs developed increased interstitial thickening due to fibrinous exudates, alveolar epithelial hyperplasia, inflammatory cell infiltrates, and marked deposition of collagen manifested on trichrome staining. Controls, in contrast, showed nearly complete resolution of the initial alveolitis. An unusual feature of the amiodarone-induced lung injury was reemergence of the alveolitis between 5 and 14 days, which included a marked influx of eosinophils into the lung. Although the precise mechanism of the lung injury is not known, the persistence of the acute inflammatory cells as well as the presence of eosinophils suggests a hypersensitivity-type reaction. Furthermore, the progression of lung injury to fibrosis after a single insult with the drug suggests that mere discontinuation of amiodarone therapy in humans may not reverse the disease process, but that corticosteroid therapy may also be required. Amiodarone appears to be a useful agent to induce diffuse fibrotic reactions in the lung that morphologically resemble idiopathic pulmonary fibrosis in humans.

Topics: Amiodarone; Animals; Benzofurans; Cricetinae; Hemorrhage; Inflammation; Lung; Lung Diseases; Mesocricetus; Pulmonary Fibrosis

Topics: Amiodarone; Benzofurans; Humans; Lung Diseases; Male; Middle Aged

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

The relationships between size of loading dose and drug concentration, size of maintenance dose and drug concentration, and pulmonary and cutaneous adverse side effects and drug dosage were examined in patients given amiodarone. Amiodarone and metabolite concentrations in plasma and red cell samples were measured by specific high-pressure liquid chromatography. During drug loading, a daily dose schedule of 1600 mg/day produced significantly higher drug concentrations than did a loading dose schedule of 800 mg/day. During maintenance therapy, amiodarone dosage correlated with drug concentrations but with a wide interpatient variability for any given dosage level. The ratio of desethylamiodarone to amiodarone remained relatively constant over different dosage or drug concentration ranges, but increased with duration of treatment, suggesting a time-dependent metabolic function that may be analogous to the time-dependent attainment of maximal antiarrhythmic effect. The occurrence of pulmonary toxicity from amiodarone was not related to duration of treatment or cumulative dose of drug, buy may relate to the magnitude of the maintenance dose of amiodarone. Blue skin discoloration occurred in 19 (36%) of 53 patients receiving amiodarone for longer than 17 months, and may relate to the cumulative dose.

Topics: Amiodarone; Benzofurans; Dose-Response Relationship, Drug; Humans; Lung Diseases; Pigmentation Disorders; Time Factors

Amiodarone was administered to 154 patients who had sustained, symptomatic ventricular tachycardia (VT) (n = 118) or a cardiac arrest (n = 36) and who were refractory to conventional antiarrhythmic drugs. The loading dose was 800 mg/day for 6 weeks and the maintenance dose was 600 mg/day. Sixty-nine percent of patients continued treatment with amiodarone and had no recurrence of symptomatic VT or ventricular fibrillation (VF) over a follow-up of 6 to 52 months (mean +/- standard deviation 14.2 +/- 8.2). Six percent of the patients had a nonfatal recurrence of VT and were successfully managed by continuing amiodarone at a higher dose or by the addition of a conventional antiarrhythmic drug. One or more adverse drug reactions occurred in 51% of patients. Adverse effects forced a reduction in the dose of amiodarone in 41% and discontinuation of amiodarone in 10% of patients. The most common symptomatic adverse reactions were tremor or ataxia (35%), nausea and anorexia (8%), visual halos or blurring (6%), thyroid function abnormalities (6%) and pulmonary interstitial infiltrates (5%). Although large-dose amiodarone is highly effective in the long-term treatment of VT or VF refractory to conventional antiarrhythmic drugs, it causes significant toxicity in approximately 50% of patients. However, when the dose is adjusted based on clinical response or the development of adverse effects, 75% of patients with VT or VF can be successfully managed with amiodarone.

Topics: Aged; Amiodarone; Anorexia; Ataxia; Benzofurans; Female; Heart Arrest; Humans; Lung Diseases; Male; Middle Aged; Nausea; Recurrence; Tachycardia; Thyroid Diseases; Time Factors; Tremor; Ventricular Fibrillation; Vision Disorders

Amiodarone hydrochloride, used for prophylaxis of recurrent ventricular tachyarrhythmias that are resistant to other agents, may cause toxic pulmonary reactions associated with abnormal chest radiographs. The authors review four new cases of amiodarone-induced toxicity and eight cases reported in the literature. Peripheral areas of consolidation, predominantly in the upper lobes and resembling chronic eosinophilic pneumonia or tuberculosis, and diffuse interstitial disease were seen. Clinical symptoms included dyspnea on exertion, weakness, and occasionally pleuritic pain. Radiographic abnormalities developed after a median latency period of six months on the drug (600 to 800 mg daily). Pathologic findings suggested a possible toxic effect of the drug on phospholipid metabolism in the lung. Amiodarone toxicity may lead to significant pulmonary insufficiency. The clinical symptoms and radiographic abnormalities were completely reversible upon cessation of drug use and institution of corticosteroid treatment. Resolution generally occurs within three months.

Topics: Adult; Aged; Amiodarone; Benzofurans; Biopsy; Humans; Lung; Lung Diseases; Male; Middle Aged; Radiography; Tachycardia; Time Factors

Amiodarone is an effective antiarrhythmic that has been used in Europe for over a decade and has been available for investigational use in North America for a shorter time. It has several well recognized side effects. Recent reports have related pulmonary disorders to the use of this drug; fibrosing alveolitis has been found by lung biopsy. Amiodarone's toxicity to the lung does not appear to be dose-related. Besides cessation of amiodarone administration, management of this complication includes steroid therapy. A case is described of nonspecific diffuse alveolar damage syndrome in a patient who had received amiodarone.

Topics: Adrenal Cortex Hormones; Aged; Amiodarone; Benzofurans; Humans; Lung; Lung Diseases; Male; Pulmonary Alveoli; Radiography; Respiratory Function Tests; Syndrome

Topics: Amiodarone; Benzofurans; Humans; Lung Diseases; Male; Middle Aged; Prednisone

Topics: Aged; Amiodarone; Benzofurans; Bone Marrow Diseases; Humans; Lung Diseases; Male; Radiography

Pulmonary toxicity may occur in association with amiodarone hydrochloride therapy. The clinical features of the pulmonary involvement are mild dyspnea, leukocytosis, hypoxemia, elevation in the erythrocyte sedimentation rate, and restrictive changes on pulmonary function testing. Diffuse interstitial and patchy peripheral alveolar infiltrates, which may frequently involve the upper lobes, characterize the radiologic findings. Accumulation of foamy macrophages in alveolar spaces, hyperplasia of type II pneumocytes, and widening of alveolar septae are noted histologically. Ultrastructural examination shows granular and lamellar membranous structures within distended lysosomes. With cessation of amiodarone therapy and treatment with corticosteroids, clinical symptoms and radiographic abnormalities resolve. The time interval for resolution of radiographic changes appears to be greater than 2 months. The precise role of corticosteroid therapy remains unknown in light of pathologic findings suggesting a metabolic rather than immunologic basis for the toxicity.

Topics: Adult; Aged; Amiodarone; Benzofurans; Dose-Response Relationship, Drug; Glucocorticoids; Humans; Lung; Lung Diseases; Male; Middle Aged; Radiography

Topics: Adolescent; Adult; Aged; Benzoates; Benzofurans; Coronary Disease; Coumarins; Dipyridamole; Female; Gallic Acid; Glycolates; Heart Diseases; Humans; Hypotension; Lung Diseases; Male; Middle Aged; Myocardial Infarction; Myocardium; Oxygen Consumption; Propylamines; Vasodilator Agents; Verapamil; Xanthines

Topics: Adolescent; Adult; Aged; Benzoates; Benzofurans; Blood Flow Velocity; Blood Pressure; Coronary Disease; Coronary Vessels; Coumarins; Dipyridamole; Female; Glycolates; Heart Rate; Humans; Hypertension; Hypotension; Isosorbide Dinitrate; Lung Diseases; Male; Middle Aged; Myocardial Infarction; Myocarditis; Regional Blood Flow; Vascular Resistance; Vasodilator Agents; Verapamil; Xanthines

Topics: Adult; Aged; Benzofurans; Bronchitis; Bronchodilator Agents; Ephedrine; Female; Heart Diseases; Humans; Lung Diseases; Male; Middle Aged; Phenothiazines; Pyrans; Theophylline; Tranquilizing Agents