benzofurans and Pulmonary-Fibrosis

Topics: Amiodarone; Benzofurans; Dose-Response Relationship, Drug; Drug Hypersensitivity; Humans; Lung Diseases; Pulmonary Fibrosis; 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addition, a case report is presented of a patient who developed pulmonary changes that disappeared when amiodarone was withdrawn and did not recur when amiodarone was reinstituted.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

We report the case of a 65 years old woman treated for 20 months with Amiodarone for angina who presented a picture of diffuse interstitial pneumonitis of rapid onset and of marked severity, which totally resolved once the drug was suspended and following the administration of steroid therapy. This raises the problem of the responsibility of Amiodarone in the aetiology of diffuse interstitial pneumonitis. We present 12 cases from the literature which also raise the question of the responsibility of this drug.

Topics: Adrenal Cortex Hormones; Aged; Amiodarone; Benzofurans; Female; Humans; Pulmonary Fibrosis; Radiography; Respiratory Function Tests

The purpose of this study was to investigate the antifibrotic effect and anticoagulant ability of salvianolic acid B (SAB) inhalation solution on bleomycin (BLM)-induced idiopathic pulmonary fibrosis (IPF) in rats. We investigated how the osmotic pressure and concentration of SAB in an aerosol exerted effects. We also determined the aerodynamic particle size distribution and the uniformity of the delivery dose; these parameters were found to be suitable for inhalation. Compared with BLM group, the levels of hydroxyproline (HYP), collagen-1 (Col-1), tissue factor (TF) / coagulation factor VII (TF-VIIa), activated coagulation factor X (FXa), thrombin-antithrombin complex (TAT), fibrinogen degradation product (FDP) and plasminogen activator inhibitor-1 (PAI-1) decreased in SAB group. The increased expression of coagulation factor Ⅱ (FⅡ), coagulation factor X (FX), tissue type plasminogen activator (t-PA) and urokinase type plasminogen activator (u-PA) proved that SAB has obvious antifibrotic and anticoagulant effects. Western blotting and immunofluorescence further showed that compared with the BLM group, the SAB group of rats exhibited significant reductions in the expression levels of protease-activated receptors-1 (PAR-1) and phospho-protein kinase C (p-PKC) and increased expression levels of protein kinase C (PKC) in lung tissue. Furthermore, SAB reduced the infiltration of lymphocytes and neutrophils, protected the basic structure of the lung from destruction, inhibited the proliferation of fibrous tissue. Collectively, our data revealed that SAB may exert its antifibrotic and anticoagulant effects by preventing the expression of PAR-1 and phosphorylation of PKC.

Topics: Administration, Inhalation; Animals; Anticoagulants; Antifibrinolytic Agents; Benzofurans; Bleomycin; Dose-Response Relationship, Drug; Drug Synergism; Drugs, Chinese Herbal; Male; Pulmonary Fibrosis; Rats; Rats, Sprague-Dawley

Pulmonary fibrosis (PF) is an interstitial lung disease characterized by interstitial inflammation and fibrosis. Salvianolic acid B (SAB) and sodium tanshinone IIA sulfonate (STS) are representative components in Salvia miltiorrhiza, which have been reported using in the treatment of PF. The aim of the study was to explain the role of inflammation in the process of PF and to investigate the effect of SAB and STS on inflammation and fibrosis in vitro. The results clearly indicated that lipopolysaccharide (LPS)-stimulated inflammatory response could induce fibroblast proliferation and fibroblast to myofibroblast transformation (FMT). Both SAB and STS significantly inhibited LPS-induced inflammation in vitro, including down-regulated the protein expression levels of IL-1β and TNF-α and the mRNA expression levels of IL1B and TNFA. Furthermore, both SAB and STS inhibited TGF-β1-induced the proliferation in MRC-5 cells and the overexpression of α-SMA and COL1α1, both the protein and mRNA levels. In conclusion, these results indicate that the inflammatory response is necessary for the development of PF, and the therapeutic effect of SAB and STS on PF may be related to anti-inflammatory and anti-fibrotic effects.

Topics: Actins; Anti-Inflammatory Agents; Benzofurans; Cell Proliferation; Coculture Techniques; Collagen Type I; Collagen Type I, alpha 1 Chain; Cytokines; Fibroblasts; Humans; Inflammation Mediators; Lung; Macrophages; Phenanthrenes; Pneumonia; Pulmonary Fibrosis; THP-1 Cells

Salvianolic acid B (SalB) is one of the most bioactive components extracted from Salvia miltiorrhiza, and its antioxidant capacity corresponds with its protective effects against cell injury from oxidative stress. The aim of the present study was to evaluate the effect of SalB on experimental pulmonary fibrosis and its ability to ameliorate the oxidative/antioxidative imbalance during fibrosis pathogenesis. The anti-fibrotic activity of SalB was first confirmed in Transforming growth factor β1(TGF-β1)-stimulated MRC-5 cells. The protection of SalB against oxidative stress during fibrogenesis in vitro was verified by detecting ROS production, the levels of glutathione (GSH) and malondialdehyde (MDA). The Western blot and PCR results indicated that SalB could up-regulate nuclear factor erythroid-derived 2-like 2 (Nrf2) at both the protein and mRNA levels and induce Nrf2 nuclear translocation in vitro, which may be the mechanism underlying the anti-fibrotic capacity of SalB. Furthermore, the anti-fibrotic and antioxidant capacities of SalB in vivo were confirmed in rats with BLM-induced pulmonary fibrosis. The immunohistochemistry results showed that Nrf2 was absent in fibroblastic foci (FF) areas, while the SalB treatment could increase the expression of Nrf2 in lung tissues, especially in FF areas.

Topics: Animals; Benzofurans; Cell Line; Cell Transdifferentiation; Dose-Response Relationship, Drug; Humans; Male; Myofibroblasts; NF-E2-Related Factor 2; Pulmonary Fibrosis; Rats; Rats, Wistar; Reactive Oxygen Species; Up-Regulation

Usnic acid (UA) can be found in certain lichen species. Growing evidence suggests that UA possesses antitumoral, antioxidative and anti-inflammatory activities. Bleomycin (BLM) is widely used in the treatment of malignant ascites, however, it unexpectedly causes pulmonary fibrosis (PF). Researches show that excessive inflammatory response and oxidative stress in lung tissue is conspicuous causes of BLM-induced PF. Here we investigated mechanism underlying the effect-enhancing and toxicity-reducing activity of UA on H22-bearing mice treated with BLM. UA combined with BLM was significantly more effective than BLM alone in inhibiting the tumor growth, arresting the cell cycle at G0/G1 phase, and promoting the cleaved caspase-3 and cleaved caspase-8 activities to induce cancer cellular apoptosis. The mechanism may be associated with the transcriptional regulation of p53/p21/Cyclin pathway. Furthermore, UA effectively moderated the histopathological changes, reduced the content of MDA, HYP, TNF-α, IL-1β, IL-6 and TGF-β1, and increased the level of SOD when combined with BLM in lung tissues of H22-bearing mice, which was believed to be related to the inhibition on the protein level of p-Smad2/3 and enhancement of Smad7 expression. These findings suggested that UA might be a potential effect-enhancing and toxicity-reducing candidate for BLM in the treatment of malignant ascites.

Topics: Adjuvants, Pharmaceutic; Animals; Antineoplastic Agents; Apoptosis; Ascites; Benzofurans; Bleomycin; Carcinoma, Hepatocellular; Cell Cycle Checkpoints; Cell Line, Tumor; Drug-Related Side Effects and Adverse Reactions; Humans; Lichens; Liver Neoplasms; Male; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Pulmonary Fibrosis; Smad Proteins

Pulmonary fibrosis is a progressive and fatal disorder. In our previous study, we found that the Yiqihuoxue formula (YQHX), a prescription of Traditional Chinese Medicine, had a curative effect on scleroderma, a typical fibrotic disease. The aim of this study was to determine the key ingredient mediating the therapeutic effects of YQHX and to examine its effect on pulmonary fibrosis, including its mechanism. Luciferase reporter assays showed that the most important anti-fibrotic component of the YQHX was Salviae miltiorrhiza (SM). Experiments performed using a bleomycin-instilled mouse model of pulmonary fibrosis showed that Salvianolic acid B (SAB), the major ingredient of SM, had strong anti-inflammatory and anti-fibrotic effects through its inhibition of inflammatory cell infiltration, alveolar structure disruption, and collagen deposition. Furthermore, SAB suppressed TGF-β-induced myofibroblastic differentiation of MRC-5 fibroblasts and TGF-β-mediated epithelial-to-mesenchymal transition of A549 cells by inhibiting both Smad-dependent signaling and the Smad-independent MAPK pathway. Taken together, our results suggest that SM is the key anti-fibrotic component of the YQHX and that SAB, the major ingredient of SM, alleviates experimental pulmonary fibrosis both in vivo and in vitro by inhibiting the TGF-β signaling pathway. Together, these results suggest that SAB potently inhibits pulmonary fibrosis.

Topics: A549 Cells; Animals; Benzofurans; Bleomycin; Bronchoalveolar Lavage Fluid; Cell Differentiation; Cell Proliferation; Disease Models, Animal; Drugs, Chinese Herbal; Fibroblasts; Humans; Medicine, Chinese Traditional; Mice; NIH 3T3 Cells; Pulmonary Fibrosis; Salvia; Signal Transduction; Transforming Growth Factor beta

Salvianolic acid B (Sal B), one of the major water-soluble compounds of Danshen (a popular Chinese herb), possesses many of the biological activities, such as antifibrogenic effect in liver and renal diseases. Transforming growth factor-β1 (TGF-β1) plays a central role in the development of pulmonary fibrosis by stimulating extracellular matrix (ECM) accumulation and activating fibroblasts. Here, we investigated the effects of Sal B on cell proliferation, collagen synthesis, endogenous TGF-β1 production, and α-smooth muscle actin (α-SMA, a marker of myofibroblasts) expression in human lung fibroblasts stimulated by TGF-β1 in vitro. The cell proliferation rates were analyzed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay. The expression of TGF-β1 and type I collagen at both the mRNA and protein levels was detected by reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and radioimmunoassay, respectively. The α-SMA expression was detected by Western blot. TGF-β1 treatment of lung fibroblasts increased cell proliferation rates, and enhanced the expression level of type I collagen, endogenous TGF-β1 production, and α-SMA expression (P < .05). The treatment with only Sal B did not affect the proliferation and differentiation of lung fibroblasts. Interestingly, Sal B was found to inhibit TGF-β1-induced cell proliferation, expression of type I collagen, endogenous TGF-β1 production, and α-SMA expression in lung fibroblasts. Moreover, the inhibitory effect of Sal B on TGF-β1-induced proliferation and differentiation in lung fibroblasts was more significant when treated with high-dose Sal B (1 μmol/L versus 10 μmol/L, P < .05). These data demonstrate that Sal B inhibits TGF-β1-induced cell proliferation and differentiation in vitro experiment.

Topics: Actins; Benzofurans; Cell Differentiation; Cell Line; Cell Proliferation; Collagen Type I; Down-Regulation; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Fibroblasts; Humans; Phytotherapy; Pulmonary Fibrosis; Salvia miltiorrhiza; Transforming Growth Factor beta1

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

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

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

More recently a few cases of pulmonary toxicity due to amiodarone administration and reversed following drug discontinuation and corticosteroid therapy have been reported. An unusual case of recurrence of amiodarone pulmonary toxicity is described. After receiving amiodarone 1.200 mg/week for 6 month a 54-year-old woman showed clear signs of pulmonary alveolitis with ray signs of diffuse pulmonary infiltrates. The pulmonary symptoms recurred after discontinuing corticosteroidis 17 months after amiodarone was stopped and were associated with a persistent amiodarone level in broncho alveolar lavage. Only after 20 months the complete resolution of pulmonary symptoms was achieved.

Topics: Amiodarone; Benzofurans; Eye Diseases; Female; Humans; Hyperthyroidism; Hypothyroidism; Middle Aged; Photosensitivity Disorders; Pulmonary Fibrosis; Radiography; Recurrence; Risk

A patient with atrial premature depolarizations developed pulmonary toxicity during long-term treatment with amiodarone. The clinical features were cough and dyspnea. Pulmonary function tests showed a restrictive defect and severe impairment of gas transfer. Diffuse interstitial and intra-alveolar shadows were noted on chest X-ray. Lung specimens obtained by transbronchial biopsy showed hyperplasia of pneumocytes and widening of the alveolar septa. After discontinuation of amiodarone and institution of steroid therapy the patient improved symptomatically, and after 3 weeks the chest X-ray showed clearing of the bilateral infiltrates. The patient was never given any other antiarrhythmic drugs, had no important heart disease, and received the lowest daily dose of amiodarone reported in the literature of cases of pulmonary injury.

Topics: Amiodarone; Benzofurans; Cough; Dyspnea; Female; Humans; Middle Aged; Pulmonary Fibrosis; Respiratory Function Tests

Topics: Amiodarone; Benzofurans; Humans; Male; Middle Aged; Pulmonary Fibrosis

Topics: Aged; Amiodarone; Benzofurans; Humans; Lung; Male; Pulmonary Fibrosis; Spectrometry, X-Ray Emission

A covariate analysis was performed on the major lung function indices that are affected by pulmonary fibrosis in 29 patients who had recently started amiodarone therapy and compared with those of a group of 41 patients who had been treated for a mean of 19.6 months. Patients with other factors which affect gas transfer were excluded. A trend towards reduction in transfer factor, transfer coefficient and membrane diffusion was detected but did not reach statistical significance. A lower than expected incidence of acute pulmonary fibrosis was observed. In the treated group, there was no deterioration of transfer factor, transfer coefficient or membrane diffusion with either increasing duration of therapy or total dose taken.

Topics: Amiodarone; Benzofurans; Blood Gas Analysis; Female; Forced Expiratory Volume; Humans; Lung Volume Measurements; Male; Pulmonary Fibrosis

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

Four cases of amiodarone-induced restrictive, hypoxaemic lung disease are described. The cumulative dosages of amiodarone were relatively low (30 to 100 g). Alveolar lavage studies showed a lymphocytosis and study of the lymphocytic sub-populations showed an increase in the OKT8 group, and an inversion of the OKT4/OKT8 ratio. The outcome was favourable on withdrawal of amiodarone and steroid therapy. The immunological origin of this form of lung disease was confirmed. Two patients had renal failure; in the first case, hypercalcaemia, hyperphosphoremia and renal calcification were observed. The second patient had endo- and extracapillary glomerulonephritis with C3 deposits and circulating immune complexes. Renal failure regressed in both cases on withdrawal of amiodarone and with steroid therapy.

Topics: Acute Kidney Injury; Aged; Amiodarone; Benzofurans; Drug Hypersensitivity; Female; Humans; Kidney Diseases; Lymphocytes; Male; Middle Aged; Pulmonary Alveoli; Pulmonary Fibrosis; Therapeutic Irrigation

A case of pneumonitis and pulmonary fibrosis occurring during long term treatment with amiodarone hydrochloride is described. The patient, a 68 year old woman, presented with severe dyspnoea and weakness 13 months after the institution of amiodarone therapy, 200 mg. bid 6 days/week. Chest x-ray showed patchy infiltrates involving the parahilar and medullary areas of both upper lobes. The clinical symptoms and the pulmonary signs improved only after amiodarone discontinuation and steroid treatment. Radiographic abnormalities gradually cleared over 45 days except for residual lines of fibrosis in the zones of previous alveolar consolidation still present 4 months later.

Topics: Aged; Amiodarone; Benzofurans; Coronary Disease; Female; Humans; Pneumonia; Pulmonary Fibrosis; Radiography

Amiodarone is a cardiac antiarrhythmic agent now undergoing clinical trials in the United States. Its most important side effect is pulmonary toxicity, which may present radiographically in two forms. One is similar to eosinophilic pneumonia with peripheral alveolar opacities but without any of the laboratory or pathologic findings. A second presentation is as a bilateral interstitial pattern resembling interstitial pulmonary edema. This is often mistaken for heart failure in the clinical and radiographic setting. Amiodarone also causes a phospholipidosis of the liver, which is usually asymptomatic but on occasion may present as hepatitis. On abdominal CT the liver will have an abnormally high attenuation (80-140 HU), which appears to be due to accumulation of an amiodarone metabolite in hepatocytes. This appearance is usually distinguishable from the other causes of increased hepatic attenuation by virtue of other CT criteria and clinical history. However, from a radiographic standpoint alone, the combination of acute congestive heart failure and an abnormally dense liver may result in at least an initial misdiagnosis of advanced primary hemochromatosis.

Topics: Aged; Amiodarone; Benzofurans; Chemical and Drug Induced Liver Injury; Female; Heart Failure; Humans; Liver; Liver Diseases; Lung; Pulmonary Fibrosis; Radiography

Topics: Aged; Amiodarone; Benzofurans; Humans; Male; Pulmonary Fibrosis

Topics: Amiodarone; Benzofurans; Female; Humans; Lung; Middle Aged; Pulmonary Fibrosis; Radiography; Respiratory Function Tests

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

Diffuse Interstitial Pneumonia (PID) is probably, although rarely, a complication of Amiodarone therapy. We describe two new cases and review 19 from the recent literature. The first patient was a man treated solely with Amiodarone for three years (total dose 185 g). He presented clinically with a picture of PID with slight dyspnoea, weight loss of 4 kilos and a dry cough. There were pulmonary crackles on auscultation, diffuse reticulo-nodular shadows radiographically and compatible pulmonary function tests. Broncho-alveolar lavage (LBA) was lymphocytic (30%). Stopping Amiodarone without resorting to steroids led to the disappearance of the clinical signs within 15 days and the return to normal of the LBA and pulmonary radiograph within six months though the pulmonary function was unchanged. The second case was a 78 year old man treatment with Amiodarone for six months (total dose 20 g). He presents acutely with grade IV dyspnoea and low grade fever. There were pulmonary crackles on auscultation and a bilateral pulmonary infiltrate on the chest radiograph. The pulmonary function tests were compatible with PID showing a restrictive ventilatory defect, a reduced Carbon Monoxide transfer (single breath) and hypoxia. The diagnosis was confirmed by a transbronchial biopsy showing a parieto-alveolar infiltration with increased cellularity and collagen formation. The LBA was predominantly polymorphonuclear. Stopping the Amiodarone associated with steroid treatment produced a normal chest radiograph within six weeks, whilst moderate dyspnoea and less severe restrictive ventilatory defects persisted. The clinical, radiological, functional and histological features of our patients were comparable to those 19 cases reported in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)

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

A 69 year-old woman with no previous history of lung disease was treated with 500 mg of Amiodarone per week. After 21 months of treatment, she developed a clinical picture of alveolitis with fibrosis, which was confirmed by histological examination. No other drug known for its fibrotic properties had been administered. Treatment with Nifedipine and Isosorbide dinitrate had been prescribed prior to the Amiodarone. Simply stopping the Amiodarone led to a regression or disappearance of the clinical, radiological and functional signs. Immunological investigations revealed the presence of antinuclear antibodies and a positive lymphoblastic transformation test for the drug, which are the abnormalities that one finds in other types of drug-induced fibrosis (nitrofuradantin). A new finding was the presence of cutaneous immunofluorescence of granular deposits of IgG, IgM and complement at the dermo-epidermal junction. So far, there have been 13 cases of lung disease related to the administration of Amiodarone reported in the literature.

Topics: Aged; Amiodarone; Benzofurans; Drug Hypersensitivity; Female; Follow-Up Studies; Humans; Pneumonia; Pulmonary Fibrosis

Topics: Aged; Amiodarone; Benzofurans; Humans; Male; Pulmonary Fibrosis; Tachycardia

Topics: Amiodarone; Benzofurans; Dexamethasone; Female; Humans; Lung; Middle Aged; Oxygen Inhalation Therapy; Pulmonary Fibrosis; Radiography

Amiodarone hydrochloride, an investigational drug used to suppress ventricular arrhythmias, may cause pulmonary toxicity with associated radiographic abnormalities. Two patients are presented who illustrate the variability of these abnormalities. One of these patients died of respiratory failure while the other recovered after amiodarone was stopped and corticosteroid therapy was started.

Topics: Aged; Amiodarone; Autopsy; Benzofurans; Biopsy; Follow-Up Studies; Glucocorticoids; Humans; Lung; Male; Middle Aged; Pulmonary Fibrosis; Radiography

Topics: Aged; Amiodarone; Benzofurans; Coronary Disease; Humans; Male; Middle Aged; Prednisone; Pulmonary Fibrosis

Topics: Aged; Amiodarone; Benzofurans; Humans; Male; Pulmonary Fibrosis

We report a patient with fibrosing alveolitis associated with amiodarone therapy. Review of the literature suggests that amiodarone induced pulmonary disease generally occurs on a maintenance dose of at least 400 mg of amiodarone daily; there is however a wide range in the duration of therapy or total dose administered prior to presentation.

Topics: Aged; Amiodarone; Benzofurans; Humans; Male; Pulmonary Fibrosis; Tachycardia; Time Factors

In a 61-year-old man receiving chronic low-dosage amiodarone an interstitial pneumopathy was observed. In the absence of other causes, we suspected an adverse reaction to amiodarone, not least because of the similarity with histologic findings of cases previously reported. Drug withdrawal and cortisone administration led to resolution of the disease.

Topics: Amiodarone; Atrial Fibrillation; Benzofurans; Biopsy; Humans; Lung; Male; Middle Aged; Pulmonary Fibrosis; Time Factors

Three patients are presented suffering from interstitial pneumonitis caused by amiodarone. Pulmonary Ga-67 uptake occurred in all three. There appeared to be a discrepancy between the scintigraphic and radiographic findings in two patients. Gallium-67 lung scintigraphy may offer an early, sensitive indicator for amiodarone pneumonitis.

Topics: Aged; Amiodarone; Benzofurans; Gallium Radioisotopes; Humans; Lung; Male; Middle Aged; Pulmonary Fibrosis; Radiography; Radionuclide Imaging

Interstitial pneumonitis developed in a patient who had received a cumulative dose of 985 g of amiodarone in nine years. No other cause for pneumonitis was found. The following findings favor an immunologic mechanism of hypersensitivity due to amiodarone: positive skin and basophil degranulation tests with amiodarone; lymphocytosis and inverted ratio of helper/suppressor T lymphocytes in bronchoalveolar lavage fluid; secretion of leukocyte inhibitory factor, as shown by the inhibition of migration of peripheral blood leukocytes; and positive lymphoblastic transformation in the presence of amiodarone.

Topics: Aged; Alveolitis, Extrinsic Allergic; Amiodarone; Benzofurans; Cell Migration Inhibition; Drug Hypersensitivity; Humans; Leukocyte Count; Leukocytes; Male; Pulmonary Fibrosis; Skin Tests; T-Lymphocytes; Time Factors

Topics: Amiodarone; Benzofurans; Gallium Radioisotopes; Humans; Pulmonary Fibrosis; Radionuclide Imaging

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; Anemia, Hemolytic; Benzofurans; Cardiac Complexes, Premature; Heart Failure; Humans; Male; Middle Aged; Pulmonary Alveoli; Pulmonary Fibrosis

Topics: Amiodarone; Benzofurans; Female; Humans; Middle Aged; Pulmonary Fibrosis

Five cases of interstitial fibrinogenic pneumopathy in addition to the 17 cases already published have considerably increased the suspicion that amiodarone might be responsible for this type of lung lesion. Moreover, it has been firmly established that 10 (56%) of 18 patients with fibrinogenic interstitial pneumopathy had taken the drug. Amiodarone therefore seems to play an important role in the genesis of iatrogenic pulmonary fibroses. These, however, are rare, even though they probably remain undiagnosed in a substantial number of cases.

Topics: Adult; Aged; Amiodarone; Benzofurans; Humans; Hyperplasia; Lung; Male; Pulmonary Fibrosis

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 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

Two cases of histologically proven pulmonary fibrosis resulting from amiodarone therapy but responding to corticosteroids are reported.

Topics: Adult; Amiodarone; Benzofurans; Biopsy; Humans; Lung; Male; Middle Aged; Prednisolone; Pulmonary Fibrosis

In a case of severe alveolitis and polyarthropathy occurring within two to five months of starting amiodarone treatment high plasma concentrations of immune complexes were found, suggesting a drug mediated hypersensitivity reaction. Initial symptomatic response followed high dosage corticosteroid and immunosuppressant treatment, but reduction in the dosage of corticosteroids was achieved only by successive plasma exchange with concomitant reduction in plasma concentrations of both amiodarone and immune complexes.

Topics: Amiodarone; Benzofurans; Female; Humans; Joint Diseases; Middle Aged; Plasma Exchange; Pneumonia; Prednisolone; Pulmonary Fibrosis

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Benzofurans; Female; Humans; Myocardial Infarction; Pulmonary Fibrosis; Tachycardia

Topics: Aged; Amiodarone; Benzofurans; Humans; Male; Pulmonary Fibrosis; Radiography

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

Of 25 cases of idiopathic pulmonary fibrosis, confirmed by open chest lung biopsy between January 1979 and July 1981, 5 patients had been taking amiodarone in doses less than 600 mg daily for 1 to 6 years. No lung disease had been observed in any patient before the administration of amiodarone, and other drugs, factors and diseases thought to play a role in the causation of pulmonary fibrosis were ruled out. Two patients died of respiratory insufficiency, and only 1 does not now suffer from serious sequelae. Review of a further 5 cases reported in the literature and the present data suggest a causal link between administration of amiodarone and pulmonary fibrosis, and tend to indicate a hypersensitivity mechanism.

Topics: Aged; Amiodarone; Benzofurans; Female; Humans; Male; Middle Aged; Pulmonary Fibrosis

Topics: Amiodarone; Benzofurans; Humans; Pulmonary Fibrosis

Topics: Amiodarone; Benzofurans; Central Nervous System Diseases; Drug Administration Schedule; Eye Diseases; Gastrointestinal Diseases; Heart Conduction System; Humans; Liver; Peripheral Nervous System Diseases; Pulmonary Fibrosis; Skin Diseases; Thyroid Diseases

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: Aged; Amiodarone; Benzofurans; Humans; Middle Aged; Pulmonary Fibrosis

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

We evaluated the effects of amiodarone in 45 patients with recurrent ventricular tachycardia or ventricular fibrillation. At a mean follow-up time of 12.7 +/- 8.8 months (range, three to 36), amiodarone was successful in nine of 16 patients with recurrent ventricular fibrillation and 21 of 29 with recurrent ventricular tachycardia. During amiodarone therapy, ventricular tachycardia could be induced in 18 of 19 patients in whom it had been induced before therapy, but only six of these 19 had spontaneous recurrence during follow-up. Side effects included corneal microdeposits, hyperthyroidism, blue skin, nausea, and symptomatic bradycardia. Pulmonary fibrosis occurred in three patients. Doses of up to 2000 mg a day did not produce cardiac toxicity, but neurologic side effects precluded long-term therapy at this dose. We conclude that amiodarone is effective for long-term therapy of recurrent ventricular tachyarrhythmias, that induction of arrhythmia during therapy does not always predict efficacy, and that side effects are frequent but do not usually limit therapy.

Topics: Adult; Aged; Amiodarone; Benzofurans; Drug Evaluation; Electric Stimulation; Electrophysiology; Female; Follow-Up Studies; Heart Conduction System; Humans; Long-Term Care; Male; Middle Aged; Pulmonary Fibrosis; Recurrence; Tachycardia; Ventricular Fibrillation