Lung Toxicity Flashcards
Mechanisms of pulmonary injury
- Oxidant injury
- Immune complex mediated
- Interference with matrix formation
- Interference with lipid metabolism
Lung toxicity treatment
- Stop offending agent
- Steroids
Drug-related risk factors
- Dose
- Administration
- Duration
- Oxygen therapy
- Radiation therapy
- Cumulative dose
Patient-related risk factors
- Age (very high or very low)
- Respiratory acidosis
- Pre-existing lung disease
- Impaired renal or hepatic function
Drug-induced interstitial pneumonitis/fibrosis (DIILD)
Can become pulmonary HTN
- Unproductive cough, dyspnea, fever, rash, eosinophilia
- Chronic: progressing SOB, decreased physical activity
- Crackles, clubbing, bilateral diffuse ground-glass opacities
DI interstitial pneumonitis/fibrosis mechanism of toxicity (DIILD)
Permanent inflammation
Damage causes (fibroblasts, apop.)
Excess extracellular matrix
What does nitrofurantoin cause and how?
DIILD
- Oxidant imbalance
- Onset 8 months -16 years
What is the presentation of nitrofurantoin toxicity?
- Acute eosinophilic pneumonia
- Pulmonary fibrosis
What do antirheumatics cause and how?
DIILD
- Hypersensitivity
- Onset days to years
Which antirheumatics are we worried about?
Leflunomide, Methotrexate (more common)
What does amiodarone cause and how?
DIILD
- Direct toxic effect
- Onset 4 weeks - 6 years
- Dose dependent, common in elderly, high mortality
Which antineoplastics are we worried about?
Bleomycin, busulfan, cyclophosphamide, gemcitabine, ICPis, mTORis
What does bleomycin* cause and how?
DIILD
- Causes fibrosis (cytokines)
- Onset weeks to months
What does busulfan cause and how?
DIILD
- Direct alveolar injury
- Onset 4 years after monotherapy but months after high dose
What does cyclophosphamide cause and how?
DIILD
- Direct alveolar injury
- Onset months to years
What does gemcitabine cause and how?
DIILD
- Endothelial dysfunction (cytokines)
Immune checkpoint inhibitors (ICPis)
DIILD
- Hypersensitivity
- Onset 3 months
- Faster when used in combo (of course)
Mechanistic Target of Rapamycin Inhibitors (mTORis)
DIILD
- Diffuse alveolar damage + hypersensitivity
- Onset 51-104 days, quicker with daily regimens
Grade 1 DIILD treatment (ICPis)
Hold the medication, see what happens
Grade 2 DIILD treatment (ICPis)
Hold medication
Prednisone/methylprednisolone
1-2 mg/kg/day
Grade 2 ICPi improves
Treat as grade 1, taper steroids 4-6 weeks
Grade 2 ICPi worsens
No improvement 48-72 hours?
-> Treat as grade 3
Grade 3,4 DIILD treatment (ICPis)
(If symptomatic, interferes with AOL)
Permanent discontinuation
Methylprednisolone 1-2 mg/kg/day
Grade 3,4 ICPi improves
Taper steroid 4-6 weeks
Grade 3,4 ICPi worsens
No improvement in 48 hours?
-> Infliximab, IVIG, MMF
mTORi DIILD grade 2 or 3
Hold or reduce dose
Prednisone 0.75-1 mg/kg/day until grade 1
mTORi DIILD grade 4
Permanently discontinue med
Prednisone 0.75-1 mg/kg/day until grade 1
Bleomycin DIILD treatment
Prednisone 0.75 mg/kg/day for 4-6 weeks (taper)
Carmustine DIILD treatment
Prednisone 60 mg PO BID
-> 30 mg QD
-> 10 mg QW
-> 5 mg QW
Amiodarone
Prednisone 0.5-1 mg/kg/day
Several months - 1 year
(Relapse seen with treatment <6 months)
Bronchiolitis Obliterans Organizing Pneumonia (BOOP) presentation
Cough, BL crackles, fever/rash, SOB
Chest X-ray bilateral patchy infiltrates***
BOOP causes
- Bleomycin
- Amiodarone
- Carbamazepine
- Cocaine
BOOP treatment
- Discontinuation
- Steroids
Eosinophilic pneumonia presentation
Interstitial pulmonary infiltrates (with eos)
Dry cough, chest pain, fever
Chest X-ray bilateral ground glass opacities***
Eosinophilic pneumonia causes
- Daptomycin
- Mesalamine
- Sulfasalazine
Eosinophilic pneumonia treatment
Steroids
Hypersensitivity pneumonia presentation
Urticaria, angioedema, rhinitis, dyspnea
Chest X-ray: localized or bilateral alveolar infiltrates
Can be chronic but commonly immediate
Hypersensitivity pneumonia causes
- NSAIDs
- Methotrexate
Hypersensitivity pneumonia treatment
Drug discontinuation
Antihistamines
Steroids
DI pulmonary edema presentation
Cough, crepitation/auscultation, cyanosis**
Chest X-ray acinar infiltrates with normal heart size (as opposed to HF)
DI pulmonary edema causes
Narcotics (moderate to high dose)
DI pulmonary edema timelines
24-48 hours: symptoms
2-5 days: X-ray changes
10-12 weeks: PFTs
DI pulmonary edema treatment
Naloxone
Drug-induced lupus presentation
Fever, myalgias, rash, arthralgias, serositis, pleuritic pain
Chest X-ray pleural effusion, diffuse interstitial pneumonitis, alveolar infiltrates
Drug-induced lupus causes
Procainamide***, hydralazine, isoniazid, anti-TNF alpha
NOT dose-dependent
Onset possible up to 3 years
Drug-induced lupus treatment
Medication withdrawal
Recovery 6 weeks
