Reasor M J, Kacew S
Department of Pharmacology and Toxicology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown 26506-9223, USA.
Proc Soc Exp Biol Med. 1996 Sep;212(4):297-304. doi: 10.3181/00379727-212-44019.
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.
由于肺毒性的发生，胺碘酮治疗心律失常的有效性受到限制。尽管与胺碘酮诱导的肺毒性（AIPT）相关的生化和形态学特征已明确，但该病症的潜在机制仍不清楚。本综述重点关注AIPT的潜在机制，特别是：（i）直接细胞损伤；（ii）磷脂质病的作用；（iii）药物负荷与毒性之间的相关性；（iv）免疫系统的作用；（v）氧化剂的产生；（vi）膜特性的变化；以及（vii）其他生化方面的考虑。此外，还讨论了胺碘酮的主要代谢产物去乙基胺碘酮在AIPT中的作用，以及既往存在的肺功能障碍在AIPT易感性中的作用。更清楚地了解这些机制对AIPT的可能影响后，或许能够制定减轻毒性的策略，并延长胺碘酮在心律失常治疗中的应用期限。
