Drug-Induced Lung Disease Flashcards
(39 cards)
What are the 4 main mechanisms of lung injury? (How do drugs cause injury?)
- Oxidant injury
- Immune complex-mediated
- Interference with Matrix Formation
- Interference with lipid metabolism
What are the two usual treatment options for drug/pulmonary toxicity?
- Stop the offending drug agent
- Corticosteroids
What two presentations are indicative of pulmonary toxicity?
- Respiratory symptoms
- Chest X-ray changes
What DRUG-RELATED risk factors are are there for pulmonary toxicity?
Dose
Oxygen Therapy
Cumulative dose
Treatment duration
Administration rate
Radiation Therapy
(DOCTAR)
What PATIENT-RELATED risk factors are are there for pulmonary toxicity?
Pre-existing lung disease
Age (extremely young/extremely old)
Impaired renal or hepatic function
Respiratory acidosis
(PAIR)
What is the mechanism of drug-induced interstitial pneumonitis/fibrosis?
Idiopathic mechanism, but drug is the source of damage
Acute pneumonitis may progress to fibrosis
What are symptoms of drug-induced interstitial pneumonitis/fibrosis? (6)
Non-productive cough
Sudden onset dyspnea (hours)
Fever/rash/eosinophilia
Crackles on exhaling, clubbing
CHRONIC SX: progressive SOB, decreased physical activity
CT results: decreased lung volume, bilateral diffuse ground-glass opacities
What are the mechanisms of drug toxicity in the lungs? (3 major)
- Permanent inflammation
- Damages
- recruit fibroblasts
- abnormal cellular repair
- apoptosis - Excess deposition of extracellular matrix
(Remodeling, honeycombing, fibrosis)
What ANTIMICROBIAL may cause toxicity/Lung disease? Describe mechanism, presentation and onset.
NITROFURANTOIN
Mechanism = oxidant injury
Presentation = eosinophilia pneumonia, fibrosis (chronic)
Onset = 8 month - 16 YEARS (long! Often chronic progression)
What ANTI-RHEUMATICS may cause toxicity/lung disease? (2) Describe mechanism and onset.
LEFLUNOMIDE
METHOTREXATE (more common)
Mechanism = hypersensitivity
Onset = Days to years (broad window)
What CARDIOLOGY agent may cause toxicity/lung disease? Decribe mechanism, onset, and who is at RISK!
AMIODARONE
Mechanism = direct effect, DOSE DEPENDENT
Onset = 4 weeks to 6 years
At-risk patients = >60 years (x3 increased risk)
Which 4 ANTINEOPLASTIC agents may cause toxicity/lung disease?
Gemcitabine
Bleomycin
Busulfan
Cyclophosphamide
(Gem BBC)
What is the mechanism of Bleomycin toxicity? (3)
Cytokines
Inflammatory cell activation
Free oxygen radical induction
What is the mechanism/onset of Busulfan toxicity? (1)
Direct alveolar injury
Onset = 4 years of monotherapy OR months after high dose
What is the mechanism of Cyclophosphamide toxicity? (1)
Direct alveolar injury
What is the mechanism of Gemcitabine toxicity? (1)
Endothelial dysfunction after cytokine release
What are two MAJOR mechanisms of drugs that can cause toxicity that are treated based on GRADE?
Immunotherapy Check-Point Inhibitors (ICPis)
Mechanistic Target of Rapamycin Inhibitors (mTORis)
- Diffuse alveolar damage, hypersensitivity
How would you treat a GRADE 2 immunotherapy check-point inhibitor DIILD?
Hold medication
OR
Give prednisone/Methylprednisolone 1-2 mg/kg/day until Grade 1
How would you treat a GRADE 3 or 4 immunotherapy check-point inhibitor DIILD? What if no improvement?
Permanent D/C of drug
OR
Methylprednisolone 1-2 mg/kg/day
No improvement in 48 hrs? -> infliximab, IVIG, MMF
How would you treat a GRADE 2/3 mTORI DIILD?
Dose reduce/hold med
OR
Prednisone 0.75-1 mg/kg/day
How would you treat a GRADE 4 mTORI DIILD?
Permanently D/C medication
OR
Prednisone 0.75 - 1 mg/kg/day
What are the differences between grade 2, 3 or 4 mTORI DIILDs?
Grade 2 = Little interference with QoL
Grade 3 = Moderate interference with QoL
Grade 4 = Unable to function normally
What is the treatment for BLEOMYCIN DIILDs?
Prednisone 0.75 mg/kg/day x 4-6 WEEKS (then taper)
What is the treatment for CARMUSTINE DIILDs?
Prednisone 60 mg po BID
-> 30 mg mg po QD
-> 10 mg po WEEKLY
-> 5 mg po WEEKLY
