benzofurans and Dyspnea

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

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