Exam 2 Flashcards
Lung-induced mechanisms of injury
-oxidant injury
-immune complex mediated
-interference with matrix formation
-interference with lipid metabolism
epidemiology of pulmonary toxicities
acute or chronic lung disease
drug metabolism
if there is no reversal of toxicity–> cell death
treatment: stop the offending agent, corticosteroids
presentation: respiratory symptoms and chest x-ray changes
drug related risk factors for development
dose
administration rate
treatment duration
oxygen therapy
radiation therapy
cumulative dose
patient related risk factors for development
age (extremes)
respiratory acidosis
pre-existing lung disease
impaired renal or hepatic function
mechanism of toxicity
permanent inflammation
damage causes:
-recruitment of fibroblasts
-abnormal cellular repair
-apoptosis
excess deposition of extracellular matrix:
-remodeling
-honeycombing
-fibrosis
antimicrobial agents
Drug: Nitrofurantoin
Mechanism: oxidant injury
Presentation
-acute eosinophilic pneumonia
-pulmonary fibrosis (chronic)
Onset: 8 months-16 years
Incidence: < 10%
Mortality: chronic-8%
anti-rheumatics
Mechanism: hypersensitivity
Onset: days-years
Drug: Leflunomide
Incidence: 0.63-1.46%
Drug: Methotrexate
Incidence: 5-10%
Low dose: 0.43%
Bleomycin
Mechanism:
-cytokine
-inflammatory cells
-free oxygen radical induction
Onset:
-weeks to months
-can progress to fibrosis
Incidence: 6.8-21%
Mortality: 48%
Busulfan
Mechanism: direct alveolar injury
Onset:
-4 years after monotherapy
-Months after high dose
Incidence: 6 %
Mortality: 25%
Cyclophosphamide
Mechanism: direct alveolar injury
Onset
-early onset: months
-Late: months-years
Incidence: 1 %
Mortality: 25%
Gemcitabine
Mechanism: endothelial dysfunction after cytokine release
Incidence: 1.1-1.9%, up to 20%
Mortality: 22%
Immune checkpoint inhibitors
Hypersensitivity
Onset:
~3 months
-faster when used in combination
Incidence:
PD: 1-10%
PD-L1: 0-10%
CTLA4: 0.01%
Mechanistic target of rapamycin inhibitors
Mechanism: direct alveolar damage, Hypersensitivity
Onset: 51-104 days, daily regimens appear quicker than weekly
Incidence: <0.5-42%
Bleomycin treatment
prednisone 0.75 mg/kg/day for 4-6 weeks
taper
Carmustine treatment
prednisone 60 mg PO BID
then 30 mg PO daily
then 10 mg PO weekly
then 5 mg PO weekly
Amiodarone treatment
Prednisone 0.5-1 mg/kg/day
continue for several months to one year
relapse have been reported with treatment durations < 6 months
Bronchiolitis Obliterans Organizing Pneumonia (BOOP)
Inflammatory response in the lungs
Symptoms: cough, dyspnea, BL crackles
Chest X-ray: Bilateral patchy infiltrates
Medications:
-bleomycin
-amiodarone
-carbamazepine
-cocaine
Treatment:
-discontinuation
-steroids
Eosinophilic pneumonia
Infiltration of the pulmonary interstitial with eosinophils
Symptoms: dry cough, chest pain, fever
Chest X-ray: bilateral ground glass opacities
Medications:
-daptomycin
-mesalamine
-sulfasalazine
Treatment: steroids
hypersensitivity pneumonia
Onset: immediate is more common, must determine if it is chronic
Symptoms: urticaria, angioedema, rhinitis, dyspnea
Chest X-ray: localized or bilateral alveolar infiltrates
Medications:
-NSAIDS
-Methotrexate
Treatment:
-drug discontinuation
-antihistamines
-possible steroids
drug-induced pulmonary edema
symptoms: cough, crepitation on auscultation, cyanosis
Chest X-ray: acinar infiltrates with normal heart size
Onset: about 2 hours
TImeline:
24-48hr: symptoms
2-5 days: x-ray changes
10-12 weeks: PFTs
Treatment: Naloxone
Dose dependent effects
Medications: Narcotics most common
drug induced lupus
Mechanism: hypersensitivity
Symptoms: fever, myalgias, rash, arthralgias, arthritis, serositis, pleuritic pain
Chest X-ray: pleural effusion, diffuse interstitial pneumonitis, alveolar infiltrates
Onset: up to 3 years after initiation
Treatment: medication withdrawal
Recovery: 6 weeks post withdrawal
Not dose dependent
Medications: Procainamide most common
