An Evaluation of Possible Mechanisms Underlying Amiodarone-Induced Pulmonary Toxicity 1

Abstract The effectiveness of amiodarone in the treatment of cardiac arrhythmias is limited due to the development of pulmonary toxicity. Although the biochemical and morphologic characteristics associated with amiodarone-induced pulmonary toxicity (AIPT) are well-defined, the mechanisms underlying this disorder remain unknown. This review focuses on proposed mechanisms of AIPT, in particular (i) direct cellular damage; (ii) the role of phospholipidosis; (iii) the correlation between drug burden and toxicity; (iv) the role of the immune system; (v) the generation of oxidants; (vi) changes in membrane properties; and (vii) miscellaneous biochemical considerations. Additional discussion of the role of amiodarone's primary metabolite, desethylamiodarone, in AIPT and the involvement of preexisting lung dysfunction in the susceptibility to AIPT is included. With a clearer understanding of the possible contributions of these mechanisms to AIPT, it may be possible to develop strategies to alleviate toxicity and prolong the usefulness of amiodarone in the treatment of cardiac arrhythmias.

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