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Amiodarone Pulmonary Toxicity

1988; Elsevier BV; Volume: 93; Issue: 6 Linguagem: Inglês

10.1378/chest.93.6.1242

1931-3543

William Martin, Edward C. Rosenow,

Sphingolipid Metabolism and Signaling

Amiodarone is classified pharmacologically as a cationic amphiphilic drug (CAD), because its molecular structure has both polar and nonpolar constituents (Fig 1). Similarly, the primary metabolite of amiodarone, desethylamiodarone, reveals the same molecular features (Fig 1). CADs, as a group of pharmacologic agents, share the tendency to induce an accumulation of phospholipids within certain target cells or tissues. 1 Lüllman-Rauch R Drug-induced lysosomal storage disorders.. in: Dingle JT Jacques PJ Shaw IH Lysosomes for applied biology and therapeutics. North Holland Publishing Co, New York1979: 49-130 Google Scholar Amiodarone also exhibits this property with many studies reporting histologic changes suggestive of “phospholipidosis” in various tissues including lung, liver, cornea, and skin. 2 Raeder EA Podrid PJ Lown B Side effects and complications of amiodarone therapy.. Am Heart J. 1983; 109: 975 Abstract Full Text PDF Scopus (178) Google Scholar However, the relationship of histologic evidence of phospholipid accumulation to clinical toxicity is less clear. Several studies suggest that phospholipid changes may occur in tissue specimens from patients without evidence of toxicity. 3 Adams PC Gibson GJ Morley AR Wright AJ Corris PA Reid DS et al. Amiodarone pulmonary toxicity: clinical and subclinical features.. Q J Med. 1986; 59: 449-471 PubMed Google Scholar , 4 Liu FL Cohen RD Downer E Butany JW Edelson JD Rebuck AS Amiodarone pulmonary toxicity: functional and ultrastructural evaluation.. Thorax. 1986; 41: 100-105 Crossref PubMed Scopus (60) Google Scholar , 5 Kennedy JI Myers JL Plumb VJ Fulmer JD Amiodarone pulmonary toxicity: clinical, radiologic, and pathologic correlations.. Arch Intern Med. 1987; 147: 50-55 Crossref PubMed Scopus (124) Google Scholar , 6 Myers JL Kennedy JI Plumb VJ Amiodarone lung in clinically toxic patients: pathologic findings.. Human Pathol. 1987; 18: 349-354 Abstract Full Text PDF PubMed Scopus (119) Google Scholar For example, pulmonary phospholipidosis is probably present in most patients with amiodarone pulmonary toxicity, but this finding may also be present in patients with no evidence of any pulmonary dysfunction. 3 Adams PC Gibson GJ Morley AR Wright AJ Corris PA Reid DS et al. Amiodarone pulmonary toxicity: clinical and subclinical features.. Q J Med. 1986; 59: 449-471 PubMed Google Scholar , 4 Liu FL Cohen RD Downer E Butany JW Edelson JD Rebuck AS Amiodarone pulmonary toxicity: functional and ultrastructural evaluation.. Thorax. 1986; 41: 100-105 Crossref PubMed Scopus (60) Google Scholar , 5 Kennedy JI Myers JL Plumb VJ Fulmer JD Amiodarone pulmonary toxicity: clinical, radiologic, and pathologic correlations.. Arch Intern Med. 1987; 147: 50-55 Crossref PubMed Scopus (124) Google Scholar , 6 Myers JL Kennedy JI Plumb VJ Amiodarone lung in clinically toxic patients: pathologic findings.. Human Pathol. 1987; 18: 349-354 Abstract Full Text PDF PubMed Scopus (119) Google Scholar The determination of whether amiodarone-induced phospholipidosis in the lung is linked to the lung parenchymal injury described in amiodarone pulmonary toxicity (APT) is critical to our understanding of the disease process.