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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amiodarone is a Class III antiarrhythmic agent that has been implicated as a cause of human pulmonary fibrosis. Pulmonary fibrosis is associated with increased levels of connective tissue proteins such as collagen and elastin. The purpose of this investigation was to determine whether elastin synthesis would be altered by in vitro amiodarone administration. Primary hamster lung cell cultures were utilized. Cultures were treated with 2, 10, and 20 micrograms/ml amiodarone. Following treatment, elastin synthesis was monitored by a biochemical tracer assay based on the presence of the cross-linking amino acids: desmosine/isodesmosine. These cross-links are found only in elastin. Addition of [14C] lysine to cultures results in uptake of the radiolabel into the cross-links. Cross-links were isolated and identified using chromatography and electrophoresis. At all doses of amiodarone, elastin synthesis was seen to increase above control levels. Light and electron microscopy confirmed the presence of an extracellular matrix. The morphologic studies also revealed the presence of cytoplasmic inclusion bodies and vacuoles that are often associated with cationic, amphiphilic drugs such as amiodarone.
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PMID:Effects of amiodarone on elastin biosynthesis in primary hamster lung cell cultures. 200 41

Amiodarone is a potent and efficacious antiarrhythmic agent, yet associated with its use are life-threatening pulmonary fibrosis and hepatotoxicity. We have investigated the susceptibility of the male Sprague-Dawley rat to pulmonary and hepatic toxicity after repeated exposure to amiodarone and the effects of such exposure on hepatic and extrahepatic drug metabolizing enzymes. Animals received amiodarone (200 mg.kg-1.day-1 i.p., 5 days/week) for 1 week followed by 150 mg.kg-1.day-1 (5 days/week) for 3 additional weeks. No signs of pulmonary fibrosis or hepatotoxicity were observed, based on histological examination, lung hydroxyproline content, and plasma alanine aminotransferase activity. Analysis of tissues revealed extensive accumulation of amiodarone and desethylamiodarone in lung and liver, but concentrations were significantly lower in animals treated for 4 weeks than for 1 week. In a separate experiment, rats received amiodarone 150 mg.kg-1.day-1 i.p. (5 days/week) for 1 or 4 weeks. No differences in tissue concentrations of amiodarone and desethylamiodarone were detected between animals treated for 1 or 4 weeks. This regimen did not affect hepatic or extrahepatic monooxygenase activities. These results indicate that, in the male Sprague-Dawley rat, there is no observable pulmonary or hepatic toxicity following short-term amiodarone exposure, and there is enhanced elimination of amiodarone and desethylamiodarone when the daily dose of amiodarone is decreased after 1 week from 200 to 150 mg/kg.
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PMID:Repeated amiodarone exposure in the rat: toxicity and effects on hepatic and extrahepatic monooxygenase activities. 227 89

Amiodarone was used in the treatment of 21 patients with supraventricular or ventricular arrhythmias which were refractory to conventional antiarrhythmic drugs, individually or in combination. Six of seven patients with supraventricular arrhythmias and 12 of 14 with ventricular tachycardia were controlled with amiodarone. Although side effects were common, only one patient was removed from treatment due to pulmonary fibrosis. We conclude that amiodarone is an effective antiarrhythmic drug for refractory ventricular and supraventricular arrhythmias.
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PMID:Amiodarone: an effective alternative for recalcitrant supraventricular and ventricular tachycardias. 242 56

Amiodarone is an extremely effective antiarrhythmic agent for the treatment of both life-threatening ventricular arrhythmias and refractory supraventricular tachyarrhythmias. Subjective minor side effects are common with amiodarone but rarely require discontinuation of therapy and are often handled by dose reduction. Serious end-organ toxicity, including pulmonary fibrosis and drug-induced hepatitis, have been the most common indications for discontinuing amiodarone therapy in these patients.
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PMID:Adverse effects of amiodarone. Pathogenesis, incidence and management. 267 95

Amiodarone has remarkable efficacy, but it also has a high incidence of severe side effects. Nevertheless, it is extensively used. The findings of an amiodarone treatment follow-up period of one to 72 months (mean 19 +/- 17) in 95 patients with recurrent life threatening arrhythmias resistant to other antiarrhythmic drugs are described. The mean loading dose of 800 mg/day for one week was followed by an average dose of 600 mg/day for two weeks. The long term daily dose was 400 mg in 80 patients and 200 mg in the remaining 15 patients. Amiodarone was particularly effective in suppressing complex ventricular arrhythmias. It also decreased premature ventricular beats by 83% and atrial premature beats by 41%. Supraventricular tachycardias were completely controlled and the ventricular response to atrial fibrillation was slowed. Twelve of the 95 patients (12.6%) died while taking amiodarone, two of sudden death and 10 of heart failure. Side effects were recorded in 77 (81%) patients. They were generally dose related and subsided with a decrease in dose or discontinuation of the medication. There was a correlation between the concentration of rT3 and the significance of the side effects. Thirty-nine patients stopped taking amiodarone, however, only 14 of these stopped because of toxicity: five developed pulmonary fibrosis; three had neurological toxicity; two had bradyarrhythmias; two developed hepatic dysfunction; one had hypothyroidism; and one patient suffered an aggravation of a pre-existent heart failure. It was concluded that amiodarone is a very effective treatment for supraventricular and ventricular arrhythmias. However, it does have numerous and severe side effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long term efficacy and toxicity of amiodarone in the treatment of refractory cardiac arrhythmias. 270 79

Associated with amiodarone use is pneumonitis which may progress to life-threatening pulmonary fibrosis. Desethylamiodarone, a metabolite, whose role in the etiology of amiodarone-induced pulmonary toxicity has been unclear, also possesses antiarrhythmic activity and could potentially be used as an antiarrhythmic drug itself. We have used a single intratracheal administration of equimolar amounts of amiodarone or desethylamiodarone (1.83 mumol) to male golden Syrian hamsters to investigate the fibrogenicity of desethylamiodarone. Animals were terminated at 1, 7, 14, 21, and 28 days post-treatment, and toxicity was assessed by measurement of lung hydroxyproline content and by histological techniques. Amiodarone and desethylamiodarone significantly increased lung hydroxyproline content over vehicle control animals by 21 days (33 and 58% respectively). While amiodarone-treated lungs had hydroxyproline contents similar to control levels at 28 days, desethylamiodarone-treated lungs remained elevated (44% over control values). Quantitative histologic examination revealed that lungs from desethylamiodarone-treated animals displayed a greater toxic effect, while trichrome staining confirmed the increased deposition of interstitial collagen in these same animals. These results may be due to the higher affinity of the lung for desethylamiodarone and thus a prolonged exposure. The findings indicate that, in the hamster, both compounds are toxic by this route and that desethylamiodarone is not a nontoxic metabolite. Further, use of desethylamiodarone as an antiarrhythmic agent may not be devoid of the adverse effects associated with amiodarone.
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PMID:Pulmonary fibrosis induced in the hamster by amiodarone and desethylamiodarone. 278 62

In the adult, Amiodarone is a very effective drug in the treatment of ventricular and supraventricular arrhythmias. The presence of severe side effects such as some alterations in the thyroid function and/or pulmonary fibrosis have restricted the use in children. Nevertheless, research has shown that there is a low incidence of collateral side effects and this therapy in infancy can be very effective. For this reason we evaluated a group of 27 children with supraventricular (19 patients) and ventricular (8 patients) arrhythmias. The mean age of patients treated was 6 +/- 5 years (2 days-13 years). The follow-up period was of 13 +/- 10 months. Amiodarone has been used in 9 patients intravenously, with the loading dose of 5 mg/Kg followed by an infusion of 10 mg/Kg/day. In 18 patients we administered the drug orally with a loading dose of 10 mg/Kg/day for a period of 10 days, thereafter the maintenance was of 5-7 mg/Kg/day for 5 days every week. The patients were all checked for thyroid function and Holter monitoring quarterly; they were given an ophthalmologic examination (every 6 months) and a chest-x-ray and echocardiography annually. The efficacy of intravenous treatment was judged successful in 56% of patients, partially successful in 22% and ineffective in the remaining 22%. The oral treatment was completely effective in 77% of children, partially in 5% and ineffective in 18%. In one case we had to suspend the therapy because we found high values of T3 and T4. During the treatment, in 86% of cases, we had blood level fluctuations of T3 and T4, however these did not exceed the normal ranges. The most important side effect observed has been the photosensitivity found in 22% of children. Moreover we observed a reduction of sinusal automatism, which was more marked in patients less than year old. In 4 cases an A/V block of first degree appeared. In all patients we found changes of ventricular repolarization, while corneal deposits appeared in only one child after a year of therapy and did not cause an impairment of visual acuity. In conclusion we can assert that Amiodarone is a very effective drug in children, specially in small babies, where it can safety be used as a first choice drug.
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PMID:[Amiodarone therapy in childhood: efficacy and side effects]. 293 40

Amiodarone-induced bilateral diffuse pulmonary fibrosis developed in a 47-year-old woman with idiopathic hypertrophic subvalvular aortic stenosis who had been treated with amiodarone (Cordarex), 300 mg daily for about 18 months. Although the drug was discontinued and cortisone treatment begun, the pulmonary fibrosis did not regress. When gentamicin (Refobacin) and cefotaxime (Claforan) were administered for suspected fibrosis-induced right-sided bronchopneumonia, gentamicin-induced acute tubular renal damage occurred, requiring dialysis. The patient died soon after of myocardial electro-mechanical dissociation. At necropsy there was, in addition to the idiopathic hypertrophic subvalvular cardiomyopathy, extensive bilateral pulmonary fibrosis, lamellar bodies in foam-cell intraalveolar macrophages, in hepatocytes and in the epithelium of the proximal and distal tubules. Although amiodarone had been discontinued three months previously, high concentrations of the drug were still present, especially in both lungs, fat tissue and the liver.
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PMID:[Steroid-refractory amiodarone-induced pulmonary fibrosis. Clinical features and morphology after an amiodarone-free interval of 3 months]. 318 Oct 14

Amiodarone, an antiarrhythmic drug, causes pulmonary fibrosis in some patients during chronic treatment but the mechanism is unknown. We studied the effects of amiodarone on pulmonary biochemistry, morphology and function at doses of 25 and 50 mg/kg/12 hr given to rats by gavage for four weeks. Plasma and pulmonary phospholipids were significantly augmented, 13% and 88% respectively, in the group given amiodarone 50 mg/kg/12 hr compared to pair-fed controls. Typical phospholipidosis-like light and electron microscopic alterations were seen in the lung, their severity related to the extent of biochemical changes induced by amiodarone. Pulmonary function tests revealed mild but not significant changes in O2 and CO2 alveolar exchange efficiency and lung compliance (P-V curve) of treated animals in comparison to pair fed controls. Plasma average concentrations of amiodarone and its main metabolite, desethylamiodarone, after four weeks were 2.46 +/- 0.18 and 0.73 +/- 0.13 micrograms/ml, respectively, in the 50 mg/kg/12 hr group. In the same group amiodarone and desethylamiodarone concentrations in lung were 163 +/- 26 and 569 +/- 153 times higher than those in plasma. A highly significant correlation was found between amiodarone concentrations in plasma and lung and phospholipid content in the lung. A subgroup of animals received amiodarone 50 mg/kg/12 hr for 8 weeks. The pulmonary phospholipidosis-like lesions were similar to those observed after one month of treatment, no fibrosis was evident on light microscopic examination.
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PMID:Amiodarone induced phospholipidosis. Biochemical, morphological and functional changes in the lungs of rats chronically treated with amiodarone. 366 36

Amiodarone, although widely studied in Europe, is a recent addition to the investigational antiarrhythmics being used in the U.S. Pharmacologically, its primary cardiac effects are to increase coronary artery blood flow, increase the effective refractory period, and produce an atropine-resistant bradycardia. Amiodarone is incompletely (approximately 50 percent) and slowly (peak serum concentration approximately 6 h) absorbed. With chronic administration, it deposits both in adipose tissue and in organs with high blood perfusion. It has an apparent elimination half-life of 15-45 days, which presents unique dosing problems. The apparent therapeutic range is 0.6-3 microgram/ml. Amiodarone is 85-95 percent effective in the treatment of atrial tachyarrhythmias and 70-80 percent effective in ventricular tachyarrhythmias. It appears to be of particular value in chronic atrial fibrillation/flutter because it may be able to maintain sinus rhythm after cardioversion. Side effects, although uncommon, may prevent the drug from becoming a standard of therapy. Drug interactions, particularly with warfarin and digoxin, as well as pulmonary fibrosis are of concern.
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PMID:Amiodarone for tachyarrhythmias: pharmacology, kinetics, and efficacy. 633 2


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