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 Substances With Toxic Pulmonary Effects).
(See also Overview of Interstitial Lung Disease.)
Substances With Toxic Pulmonary Effects
Condition |
Drug or Agent |
|
Aspirin, beta-blockers (eg, timolol), cocaine, dipyridamole, IV hydrocortisone (rarely in aspirin-sensitive patients with asthma), interleukin-2, methylphenidate, nitrofurantoin, protamine, sulfasalazine, vinca alkaloids (with mitomycin-C) |
|
|
Organizing pneumonia |
Amiodarone, bleomycin, checkpoint inhibitors, cocaine, cyclophosphamide, methotrexate, minocycline, mitomycin-C, penicillamine, sulfasalazine, tetracycline |
|
Azathioprine plus 6-mercaptopurine, busulfan, fluoxetine, methotrexate, radiation |
|
|
Interstitial pneumonia or fibrosis |
Amphotericin B, bleomycin, busulfan, carbamazepine, checkpoint inhibitors, 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 |
Beta-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 |
|
Amiodarone, anticoagulants, bleomycin, bromocriptine, busulfan, check-point inhibitors, granulocyte-macrophage colony-stimulating factor, IL-2, methotrexate, methysergide, mitomycin-C, nitrofurantoin, para-aminosalicylic acid, procarbazine, radiation, tocolytic drugs (eg, terbutaline) |
|
|
Amiodarone, amphotericin B, bleomycin, carbamazepine, checkpoint inhibitors, cocaine, 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 of Drug-Induced Pulmonary Disease
Prevention of Drug-Induced Pulmonary Disease
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.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
hydrochlorothiazide |
MICROZIDE |
chlordiazepoxide |
LIBRIUM |
cyclophosphamide |
CYTOXAN (LYOPHILIZED) |
methylphenidate |
CONCERTA, RITALIN |
hydrocortisone |
CORTEF, SOLU-CORTEF |
mercaptopurine |
PURINETHOL |
nitrofurantoin |
FURADANTIN, MACROBID, MACRODANTIN |
bromocriptine |
PARLODEL |
penicillamine |
CUPRIMINE |
carbamazepine |
TEGRETOL |
sulfasalazine |
AZULFIDINE |
methotrexate |
OTREXUP |
Azathioprine |
IMURAN |
chlorambucil |
LEUKERAN |
tetracycline |
ACHROMYCIN V |
dipyridamole |
PERSANTINE |
procarbazine |
MATULANE |
phentermine |
ADIPEX-P |
gemcitabine |
GEMZAR |
minocycline |
MINOCIN |
terbutaline |
No US brand name |
Amiodarone |
CORDARONE |
fluoxetine |
PROZAC, SARAFEM |
ethambutol |
MYAMBUTOL |
mitomycin |
MITOSOL |
trazodone |
OLEPTRO |
etoposide |
ETOPOPHOS |
isoniazid |
LANIAZID |
methadone |
DOLOPHINE |
melphalan |
ALKERAN |
busulfan |
MYLERAN |
timolol |
TIMOPTIC |
