Clinical organ toxicity of antiarrhythmic compounds: ocular and pulmonary manifestations

The history of antiarrhythmic therapy reveals these agents to be associated with a high incidence of toxicity. Although several agents have ocular effects, amiodarone is the most widely recognized for producing adverse effects in the eyes. Corneal microdeposits are almost ubiquitous in patients being treated with amiodarone. However, they are, for the most part, benign and produce no changes in visual acuity. Lack of microdeposits should prompt the physician to investigate whether there is a problem with drug absorption or adherence to therapy. Other effects on the eye have been reported including optic neuropathy, but no causal link has been proved with amiodarone. The population of patients treated with amiodarone often have ischemic disease and/or diabetes, which affect retinal and optic nerve health. Many antiarrhythmic agents also affect lung function. The frequent association of procainamide with a lupus-like syndrome, where half the cases develop pleural-pericardial involvement, may require discontinuation of that drug. Although beta blockers and to a lesser degree, calcium antagonists, may cause bronchospasm in some patients, this is not usually a major clinical problem. Again, it is amiodarone that has the most widespread reputation for causing pulmonary toxicity. Although infrequent (< 1% incidence), it generates the most fear as it is sometimes fatal. Because of the lack of a diagnostic "gold standard," it is often overdiagnosed, placing patients at risk from overlooked congestive heart failure and infections and from recurrent arrhythmias after drug withdrawal. Patients with pre-existing pulmonary disease appear to be more at risk. Common features include indolent onset of cough, malaise and fever associated with patchy peripheral infiltrates, and severely decreased diffusion capacity. Several cases of pulmonary toxicity have had inordinately high serum desethylamiodarone to amiodarone ratios. Most cases recover with cessation of amiodarone therapy. Steroids are commonly used, but are of unproved efficacy. In terms of its toxicity, amiodarone remains the most feared of the antiarrhythmic agents. In the future, a better understanding of its pharmacokinetics, mechanisms of toxicity, and optimal dosing regimens should provide a possibility of better strategies for avoidance, early diagnosis, and more directed therapy of toxicities associated with amiodarone.