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Drug-induced pulmonary disease is not a single disorder, but rather a common clinical problem in which a patient without previous pulmonary disease develops respiratory symptoms, chest x-ray changes, deterioration of pulmonary function, histologic changes, or several of these findings in association with drug therapy. Over 150 drugs or categories of drugs have been reported to cause pulmonary disease; the mechanism is rarely known, but many drugs are thought to provoke a hypersensitivity response. Some drugs (eg, nitrofurantoin) can cause different injury patterns in different patients.
Depending on the drug, drug-induced syndromes can cause interstitial fibrosis, organizing pneumonia, asthma, noncardiogenic pulmonary edema, pleural effusions, pulmonary eosinophilia, pulmonary hemorrhage, or veno-occlusive disease (see Table 4: Interstitial Lung Diseases: Substances With Toxic Pulmonary Effects ).
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Table 4
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| Substances With Toxic Pulmonary Effects |
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Condition
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Drug or Agent
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Asthma
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Aspirin, β-blockers (eg, timolol), cocaine, dipyridamole, IV hydrocortisone (rarely in aspirin-sensitive patients with asthma), IL-2, methylphenidate, nitrofurantoin, protamine, sulfasalazine, vinca alkaloids (with mitomycin-C)
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Organizing pneumonia
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Amiodarone, bleomycin, cocaine, cyclophosphamide, methotrexate, minocycline, mitomycin-C, penicillamine, sulfasalazine, tetracycline
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Hypersensitivity pneumonitis
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Azathioprine plus 6-mercaptopurine, busulfan, fluoxetine, radiation
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Interstitial pneumonia or fibrosis
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Amphotericin B, bleomycin, busulfan, carbamazepine, chlorambucil, cocaine, cyclophosphamide, diphenylhydantoin, flecainide, heroin, melphalan, methadone, methotrexate, methylphenidate, methysergide, mineral oil (via chronic microaspiration), nitrofurantoin, nitrosoureas, procarbazine, silicone (sc injection), tocainide, vinca alkaloids (with mitomycin-C)
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Noncardiac pulmonary edema
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β-Adrenergic agonists (eg, ritodrine, terbutaline), chlordiazepoxide, cocaine, cytarabine, ethiodized oil (IV, and via chronic microaspiration), gemcitabine, heroin, hydrochlorothiazide, methadone, mitomycin-C, phenothiazines, protamine, sulfasalazine, tocolytic agents, tricyclic antidepressants, tumor necrosis factor, vinca alkaloids (with mitomycin-C)
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Parenchymal hemorrhage
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Anticoagulants, azathioprine plus 6-mercaptopurine, cocaine, mineral oil (via chronic microaspiration), nitrofurantoin, radiation
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Pleural effusion
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Amiodarone, anticoagulants, bleomycin, bromocriptine, busulfan, granulocyte-macrophage colony-stimulating factor, IL-2, methotrexate, methysergide, mitomycin-C, nitrofurantoin, para-aminosalicylic acid, procarbazine, radiation, tocolytic agents
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Pulmonary infiltrate with eosinophilia
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Amiodarone, amphotericin B, bleomycin, carbamazepine, diphenylhydantoin, ethambutol, etoposide, granulocyte-macrophage colony-stimulating factor, isoniazid, methotrexate, minocycline, mitomycin-C, nitrofurantoin, para-aminosalicylic acid, procarbazine, radiation, sulfasalazine, sulfonamides, tetracycline, trazodone
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Pulmonary vascular disease
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Appetite suppressants (eg, dexfenfluramine, fenfluramine, phentermine), busulfan, cocaine, heroin, methadone, methylphenidate, nitrosoureas, radiation
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Diagnosis is based on observation of responses to withdrawal from and, if practical, reintroduction to the suspected drug.
Treatment is stopping the drug. A screening pulmonary function test is commonly done in patients about to begin or already taking drugs with pulmonary toxicities, but the benefits of screening for prediction or early detection of toxicity are unproved.
Last full review/revision April 2013 by Harold R. Collard
Content last modified April 2013
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