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Drug-Induced Pulmonary Disease

by Harold R. Collard, MD

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 Substances With Toxic Pulmonary Effects).

Substances With Toxic Pulmonary Effects

Condition

Drug or Agent

Asthma

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)

Organizing pneumonia

Amiodarone, bleomycin, cocaine, cyclophosphamide, methotrexate, minocycline, mitomycin-C, penicillamine, sulfasalazine, tetracycline

Hypersensitivity pneumonitis

Azathioprine plus 6-mercaptopurine, busulfan, fluoxetine, radiation

Interstitial pneumonia or fibrosis

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)

Noncardiac pulmonary edema

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)

Parenchymal hemorrhage

Anticoagulants, azathioprine plus 6-mercaptopurine, cocaine, mineral oil (via chronic microaspiration), nitrofurantoin, radiation

Pleural effusion

Amiodarone, anticoagulants, bleomycin, bromocriptine, busulfan, granulocyte-macrophage colony-stimulating factor, IL-2, methotrexate, methysergide, mitomycin-C, nitrofurantoin, para-aminosalicylic acid, procarbazine, radiation, tocolytic agents

Pulmonary infiltrate with eosinophilia

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

Pulmonary vascular disease

Appetite suppressants (eg, dexfenfluramine, fenfluramine, phentermine), busulfan, cocaine, heroin, methadone, methylphenidate, nitrosoureas, radiation

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.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • FURADANTIN, MACROBID, MACRODANTIN
  • DOLOPHINE
  • GEMZAR
  • CYTOXAN (LYOPHILIZED)
  • ADIPEX-P
  • MINOCIN
  • ACHROMYCIN V
  • PROZAC, SARAFEM
  • No US brand name
  • MICROZIDE
  • OLEPTRO
  • MITOSOL
  • ALKERAN
  • PURINETHOL
  • PERSANTINE
  • LIBRIUM
  • MYLERAN
  • LANIAZID
  • LEUKERAN
  • AZULFIDINE
  • IMURAN
  • CORDARONE
  • ETOPOPHOS
  • TIMOPTIC
  • MATULANE
  • PARLODEL
  • OTREXUP
  • CUPRIMINE
  • MYAMBUTOL
  • CONCERTA, RITALIN
  • TEGRETOL

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