title: Acute respiratory failure mediated by reactive drug metabolites.
abstract: Reactive drug metabolites have been implicated in the pathogenesis of adverse reactions to the aromatic anticonvulsants. A patient presented with a hypersensitivity reaction to the aromatic anticonvulsants which evolved into Stevens-Johnson syndrome and was complicated by the presence of adult respiratory distress syndrome. When the patient's cells were tested for sensitivity in vitro to reactive metabolites of the aromatic anticonvulsants, they were markedly more sensitive to metabolites of the aromatic anticonvulsants than were the cells of controls (p < 0.05). The adult respiratory distress syndrome has not previously been described as a complication of hypersensitivity reactions to the aromatic anticonvulsants. In vitro testing also demonstrated cross-sensitivity to the anticonvulsants, allowing selection of a therapeutic regimen which would not be associated with a risk of exacerbating the hypersensitivity reaction.
authors.affiliation: Department of Paediatrics and Pharmacology, University of Western Ontario, London, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Murphy
authors.forename: J B
authors.initials: JB
authors.lastname: Kronick
authors.forename: M J
authors.initials: MJ
authors.lastname: Rieder
mesh_terms: D002220:Carbamazepine / Q000009:adverse effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002648:Child; D004890:Erythema / Q000139:chemically induced; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D010672:Phenytoin / Q000009:adverse effects* / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000139:chemically induced*
chemical_list: D002220:Carbamazepine; D010672:Phenytoin