Drugs and Lung Injury Flashcards

1
Q

Cytotoxic drugs that can cause Interstitial pneumonitis/pulmonary fibrosis

A
Bleomycin 
Cyclophosphamide 
Chlorambucil 
Busulfan 
Melphalan 
Carmustine
MTX
6-MPC
Cytosine arabinoside
Gemcitabine Fludarabin
All-trans retinoic acid
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2
Q

Drugs that can cause Hypersenstivity lung reaction

A
Nitrofurantoin 
Sulfasalazine 
Diphenylhydantoin 
Carbamazepine 
Penicillamine 
Amiodarone
Hydroxyurea
Bleomycin 
MTX
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3
Q

Drugs that can cause Pleural effusion

A
Bleomycin 
Busulfan 
MTX 
Imitanib 
IL-2 
ATRA
Nitrofurantoin 
Amiodarone
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4
Q

Drugs that can cause Eosinophilic pneumonitis/pneumonia

A

Bleomycin

Minocycline

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5
Q

Key points re: pulmonary toxicity from drugs

A

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)

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6
Q

Risk factors for drug-induced pulmonary toxicity

A
Dose
Age
Radiation
Oxygen
Other drugs
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7
Q

Criteria for diagnosis of drug-induced pulmonary toxicity

A
  1. No other likely cause
  2. Symptoms consistent with suspected drug
  3. Time course compatible with drug-induced lung disease
  4. Compatible tissue or BAL findings
  5. Improvement after drug is discontinued
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8
Q

2 patterns of lung toxicity for Bleomycin

A
  1. Progressive fibrosis (common)

2. Acute hypersensitivity (rare)

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9
Q

Mechanism of lung toxicity secondary to Bleomycin

A
  1. Direct toxicity, mediated by reactive oxygen metabolites or inactivation of antioxidants.
  2. Induces senescence or apoptosis of type 2 epithelial cells.
  3. Generates inflammatory mediators.
  4. Increases collagen synthesis by fibroblasts.
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10
Q

Presentation of lung toxicity secondary to Bleomycin

A

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.

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11
Q

Pathology of lung toxicity secondary to Bleomycin

A

Interstitial pneumonitis, fibrosis
Extensive alveolar damage with hyperplasia of type II cells
Worse in subpleural/basilar regions.

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12
Q

Lung toxicity related to Cyclophosphamide

A

Lung toxicity is not common – but can be severe

  • Interstitial pneumonitis
  • Acute alveolitis
  • DAH
  • ARDS
  • BO
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13
Q

Management of lung toxicity secondary to Bleomycin

A

Monitor DLCO, O2 therapy.

High-dose steroids has been described to reverse toxicity (especially if hypersensitivity or eosinophilic pneumonitis).

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14
Q

Mechanism of lung toxicity secondary to Cyclophosphamide

A

Oxidant and inflammatory/immune mechanisms
Acute IgE-mediated systemic reactions with angioedema and bronchospasm.
Atopy is associated with lung complications.

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15
Q

2 patterns of lung toxicity associated with Nitrofurantoin

A
  1. 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.
  2. 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.
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