Mitochondrial dysfunction and rod-like lesions associated with administration of beta2 adrenoceptor agonist formoterol.
Formoterol, a selective beta 2-adrenoceptor agonist, has been introduced recently in the treatment of poorly controlled asthma. A patient is presented who developed myalgia and muscle weakness, associated with an elevation of creatine kinase (CK) during treatment with formoterol. Subsequent muscle biopsy demonstrated atrophic fibres lacking cytochrome C-oxidase and succinate dehydrogenase, suggestive of mitochondrial dysfunction. There were no inflammatory changes. Immunocytochemical analysis using antibodies to alpha-actinin-2 and alpha-actinin-3 demonstrated positive staining of 'rod-like' bodies in atrophic fibres. Clinical and biochemical improvement occurred following withdrawal of formoterol. Possible mechanisms involved in the development of myopathy are explored.
Kiernan
Matthew C
MC
Prince of Wales Medical Research Institute, University of New South Wales, Sydney, NSW 2031, Australia. m.kiernan@unsw.edu.au
Bullpitt
Peter
P
Chan
Jane H L
JH
D000185:Actinin / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000009:adverse effects*; D003402:Creatine Kinase / Q000097:blood; D004983:Ethanolamines / Q000009:adverse effects*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000473:pathology; D009133:Muscular Atrophy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013997:Time Factors
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D000185:Actinin; D013385:Succinate Dehydrogenase; D003402:Creatine Kinase; D000251:Adenosine Triphosphatases; D000068759:Formoterol Fumarate