Drugs and Lung Injury Flashcards
Cytotoxic drugs that can cause Interstitial pneumonitis/pulmonary fibrosis
Bleomycin Cyclophosphamide Chlorambucil Busulfan Melphalan Carmustine MTX 6-MPC Cytosine arabinoside Gemcitabine Fludarabin All-trans retinoic acid
Drugs that can cause Hypersenstivity lung reaction
Nitrofurantoin Sulfasalazine Diphenylhydantoin Carbamazepine Penicillamine Amiodarone Hydroxyurea Bleomycin MTX
Drugs that can cause Pleural effusion
Bleomycin Busulfan MTX Imitanib IL-2 ATRA Nitrofurantoin Amiodarone
Drugs that can cause Eosinophilic pneumonitis/pneumonia
Bleomycin
Minocycline
Key points re: pulmonary toxicity from drugs
Some pulmonary damage is reversible, some not.
-Toxicity may result from direct injury to lung cells or be immune mediated.
- Noncytotoxic toxicity is often idiosyncratic.
- Features = fever, malaise, dyspnea, nonproductive cough.
- Diffuse alveolar or interstitial involvement on imaging.
o If segmental/lobar/unilateral disease —- look for another cause
-Path does not distinguish cytotoxic agents.
-Interstitial pneumonitis can be part of DIHS/DRESS (drug-induced hypersensitivity syndrome/drug rash
with eosinophilia and systemic symptoms)
Risk factors for drug-induced pulmonary toxicity
Dose Age Radiation Oxygen Other drugs
Criteria for diagnosis of drug-induced pulmonary toxicity
- No other likely cause
- Symptoms consistent with suspected drug
- Time course compatible with drug-induced lung disease
- Compatible tissue or BAL findings
- Improvement after drug is discontinued
2 patterns of lung toxicity for Bleomycin
- Progressive fibrosis (common)
2. Acute hypersensitivity (rare)
Mechanism of lung toxicity secondary to Bleomycin
- Direct toxicity, mediated by reactive oxygen metabolites or inactivation of antioxidants.
- Induces senescence or apoptosis of type 2 epithelial cells.
- Generates inflammatory mediators.
- Increases collagen synthesis by fibroblasts.
Presentation of lung toxicity secondary to Bleomycin
Asymptomatic with decrease in DLCO, SpO2, VC, TLC. Dry cough and dyspnea.
Fever suggests hypersensitivity reaction.
Tachypnea, fine crackles.
CXR – diffuse linear densities, widespread reticulonodular or alveolar pattern.
Pathology of lung toxicity secondary to Bleomycin
Interstitial pneumonitis, fibrosis
Extensive alveolar damage with hyperplasia of type II cells
Worse in subpleural/basilar regions.
Lung toxicity related to Cyclophosphamide
Lung toxicity is not common – but can be severe
- Interstitial pneumonitis
- Acute alveolitis
- DAH
- ARDS
- BO
Management of lung toxicity secondary to Bleomycin
Monitor DLCO, O2 therapy.
High-dose steroids has been described to reverse toxicity (especially if hypersensitivity or eosinophilic pneumonitis).
Mechanism of lung toxicity secondary to Cyclophosphamide
Oxidant and inflammatory/immune mechanisms
Acute IgE-mediated systemic reactions with angioedema and bronchospasm.
Atopy is associated with lung complications.
2 patterns of lung toxicity associated with Nitrofurantoin
- Acute fever, cough, dyspnea within hours
Within 2 weeks of initial therapy.
Rash, flulike symptoms.
Diffuse fine crackles.
Bilateral interstitial or alveolar infiltrates +/- pleural effusion. Hypoxemia, RLD, reduced DLCO.
Eosinophilia, leukocytosis, raised ESR. Symptoms resolve on discontinuing drug. - Less common – insidious onset cough, dyspnea, chest pain after months to years of therapy. +/- fever
Crackles
Diffuse interstitial infiltrates.
Path: interstitial pneumonitis with variable fibrosis. DIP, BOOP, giant cell interstitial pneumonia also reported.
Discontinue and steroids.