Drug-Induced Pulmonary Disease Flashcards
How many medications can cause lung injury?
350 and they all manifest in a variety of ways
What is the most common drug induced respiratory problem?
Drug-induced bronchospams
Usually seen in patients with pre-existing bronchial hyper-reactivity
What are the mechanisms of bronchospams?
Anaphylaxis (IgE-mediated) Penicillins Sulfonamides Serum Cephalosporins Can occur with any drug
Cyclooxygenase inhibition
Aspirin/NSAIDs
Pharmacologic effects
β -adrenergic blockers
Direct airway irritation
Smoke
N-acetylcysteine
What is the aspirin triad (Samter’s syndrome)?
Asthma
Nasal Polyps
And aspirin intolerance
Aspirin/NSAID bronchospasm- presentation
Bronchospasm, rhinorrhea, conjunctivitis, flushing
Urticaria, periorbital edema, abdominal pain
Can present separately or blended
Aspirin/NSAID bronchospasm- sx resolution
Diminish within 24-48 hours
urticaria may continue 1-2 wks.
Aspirin/NSAID bronchospasm- diagnosis
No in vitro diagnostic test to confirm or establish aspirin sensitivity Provocation challenge Respiratory reactions 30 -150mg (average 60 mg) Completed in hospital
Aspirin/NSAID bronchospasm- management
Avoid aspirin and nonselective NSAIDs
Cross sensitivity
Ibuprofen (98%)
Naproxen (100%)
Aspirin/NSAID bronchospasm- desensitization and leukotriene modifiers
Elimination of reactions by slowly increasing doses of oral aspirin
Leukotriene modifiers
Dose response curve shifted
Aspirin/NSAID bronchospasm- therapy options
Therapy options COX-2 selective NSAIDs (Celecoxib) Generally can be used safely in patients with ASA induced asthma Acetaminophen 5% of ASA sensitive patients react < 1000 mg
Aspirin/NSAID bronchospasm- cross-sensitivity
Up to 80% of ASA-sensitive patient had AE to yellow azo dye tartrazine (FD&C Yellow No.5)
Colors food, drinks, drugs, cosmetics
FDA requires labeling
The use of ________ might increase the risk of asthma and allergic disease when used early in life?
Acetaminophen
Beta blocker bronchospasm
Effects seen with oral, IV or ophthalmic administration
Rarely seen in patients without pulmonary disease
Reaction can be fatal
Primarily with non-selective β-blockers
Patients taking β -blockers without incident for long periods of time may experience fatal asthma attacks
Beta blocker bronchospasm- symptoms
Symptoms Increased pulmonary symptoms Decreased pulmonary function tests Decrease in FEV1 or peak expiratory flow Death
Beta blocker bronchospasm- Mechanism
Direct inhibition of β2-receptors may result in bronchoconstriction
Beta blocker bronchospasm- management
Inhaled bronchodilator for bronchospasm
Avoidance
If necessary, use selective β-blockers
Use lowest dose possible
Will treatmeant with beta blockers in patients with COPD reduce the risk of exacerbations and improve survival?`
It might
Sulfite induced bronchospasm
Potassium metabisulfite Preservative in food and wine Injectable epinephrine, isoproterenol Rare in general population 1-5% in patients with asthma
Sulfite induced bronchospasm- patient presentation
Severe wheezing, chest tightness and dyspnea after ingestion
Sulfite induced bronchospasm- Diagnosis
History
Re-challenge- in a controlled setting
Sulfite induced bronchospasm- mechanism
Sulfite converted to sulfur dioxide in acidic or warm environment
Sulfur dioxide causes direct stimulation of parasympathetic receptors
IgE-mediated (anaphylactic reactions)
Reduced concentration of sulfite oxidase enzyme reported in sulfite-sensitive asthma patients
Catalyzes oxidation of sulfites to sulfates
Sulfite induced bronchospasm- management
Avoidance
Read labels
Pharmacologic agents
» Manufacturers of drugs for the treatment of asthma have discontinued use of sulfites
Food products
» Labeling required on packaged foods that contain sulfites at 10 ppm or more
Sulfite induced bronchospasm- pretreatment
Cromolyn, anticholinergics, cyanocobalamin
Inhaled agents bronchospasm
Nonspecific bronchial irritant effect
Usually NOT caused by medication
Propellant, delivery, pH, osmolality, temperature, preservative
Albuterol, cromolyn, inhaled corticosteroids, pentamidine, N-acetyl cysteine
Is the bronchospasm from inhaled medications caused by the medication itself?
No its caused by the other chemicals that are in the drug
Inhaled agents- bronchospasm- Ethylenediamine tetraacetic acid (EDTA)
Stabilizing agent Mechanism Calcium chelation property Benzalkonium chloride Bacteriostatic agent Found in some albuterol nebulization multi-dose vials
Mechanism
Mast cell degranulation
Management
Change therapy
Ace Inhibitors-cough- risk factors
Female
Asian descent
Elderly
Heart failure
Do patients with asthma or COPD appear to be at an increased risk for development of a cough with ace inhibitor use?
No
Ace Inhibitors-cough- symptoms
Cough
Tickle to debilitating cough with insomnia and vomiting
Dry, nonproductive, hacking cough
Patients have normal spirometry and chest xray
Ace Inhibitors-cough- mechanism
Not fully known Usually attributed to accumulation of bradykinin and substance P Bradykinin Stimulate cough reflex Substance P Cause bronchoconstriction
Ace Inhibitors-cough- management
Cough may resolve within a few weeks
Usually stop medication
Cough resolves within a few days to a month after discontinuation
Usually unresponsive to cough suppressants or bronchodilators
Fentanyl cough
IV formulation
Unclear mechanism
Associated with young age and absence of smoking
History of asthma/COPD not predictive
What is narcotic induced non-cardiogenic pulmonary edema most commonly assoiciated with?
IV heroin use
Also can be seen with morphine, methadone, meperidine, and propoxyphene
Narcotic induced non-cardiogenic pulmonary edema- mechanism
Idiosyncratic reaction
Often seen when Moderate and high doses are used
Mechanism is unknown
Narcotic induced non-cardiogenic pulmonary edema- sx
May be comatose with depressed respirations, dyspnea and tachypnea
Varies from cough to severe cyanosis and hypoxia
Decreased pulmonary function tests
Appear within minutes of IV administration up to 2 hours
Narcotic induced non-cardiogenic pulmonary edema- treatment
Clinical improvement within 24-48 hours Pulmonary function abnormality may last up to 12 weeks Treatment Naloxone, oxygen, ventilatory support Mortality less than 1%
What is the presentation of pulmonary edema?
Persistent cough Tachypnea Dyspnea Tachycardia Rales on auscultation Hypoxemia Decreased lung compliance
What is pulmonary edema reported with?
Hydrochlorothiazide Contrast media IV bleomycin, cyclophosphamide and vinblastine (oncology agents) Terbutaline (used as tocolytic) Salicylate overdose
What is the management for pulmonary edema?
DC medication, supportive care
What is pulmonary infiltrates with eosinophilia most frequently associated with?
Nitrofurantoin
Para-aminosalicylic acid (not a drug that you will rx to pts, anti-infective topical)
Pulmonary esoinophilia- presentation
Fever, nonproductive cough, dyspnea, cyanosis, bilateral pulmonary infiltrates and eosinophilia in blood
Pulmonary eosinophilia- nitrofurantoin
Occurs within 1 month of therapy
Complete recovery within 15 days of DC of medication
What is excessive amount of connect tissue in the the intersitial spaces of the lung?
Hint- normal airspaces and blood vessels are replaced by fibrotic tissue; lungs become small and stiff and is secondary to chronic inflammatory dz?
Chronic pulmonary fibrosis
What can chronic pulmonary fibrosis lead to?
Restrictive airway disease
Can be fatal if process is not stopped
Pulmonary fibrosis- causes
Idiopathic pulmonary fibrosis is rare
Drug induced pulmonary fibrosis
~ 50 causative agents
Prevalence increases with increasing cumulative dose
What are the chemotherapeutic agents that cause pulmonary fibrosis?
Bleomycin Busulfan Carmustine Methotrexate Amiodarone- not chemo but causes pulmonary fibrosis
Pulmonary fibrosis-acute phase
Non-productive cough Acute dyspnea Tachypnea Lung crackles PFTs- Initially normally, reduced carbon dioxide diffusing capacity Arterial blood gases- Hypoxemia
Pulmonary fibrosis- chronic phase
Slow progression Dyspnea on exertion Fatigue Non-productive cough Lung crackles Clubbing
PFTs
Restrictive disease, decreased vital capacity
Reduced carbon monoxide diffusing capacity
Pulmonary fibrosis- time of onset
Acute sx have been seen after 1st dose of bleomycin
Patients have died up to 15 years after receiving therapy.
Pulmonary fibrosis- diagnosis
Known exposure to causative drug
No known symptoms, physical findings, laboratory tests or histopathologic findings specific to pulmonary fibrosis
Pulmonary fibrosis- management
Discontinuation of medication
+/- prednisone
Amiodarone pulmonary toxicity- risk factors
Men
Increases with age
Pre-existing lung disease
Dose/duration- Usually >400 mg/day; seen with 200 mg/day for 6-12 months
Occurs 4 weeks to 6 years after initiating therapy
Amiodarone pulmonary toxicity- clinical course
Variable- some patients don’t do that bad and some do really bad
Progressive dyspnea, malaise, nonproductive cough
Rapidly progressive acute respiratory distress syndrome
Amiodarone pulmonary toxicity- proposed mechanism
Accumulation of amiodarone and metabolite in lung tissue
Interfere with normal processing of phospholipids
Breakdown of phospholipid-laden macrophages results in pulmonary inflammation and fibrosis
Amiodarone pulmonary toxicity- monitoring
Monitor PFTs and CXR at baseline
CXR every year
PFTs if symptomatic
Amiodarone pulmonary toxicity- management
Majority of patients improve with DC of medication
Clinical improvement 1-2 months
PFTs and CXR may take up to 18 months
+/- corticosteroids
What are the medications that cause pulmonary HTN?
Anorexic agents- used for weightloss Fenfluramine and dexfenfluarmine (not on the market) Part of “fen-phen” Phentermine 20% of diagnosed cases Onset between 23 days and 27 years
Pulmonary HTN- symptoms
Generally non-specific
Exertional dyspnea: most common
Chest pain
Syncope
Pulmonary HTN- mechanism
unknown
Pulmonary HTN- Management
DC medication
Improvement within 1-3 months
1997: FDA requested withdrawal of fenfluramine and dexfenfluamine (valvular damage)
Phentermine
Case reports of pulmonary hypertension
Association not supported
Oxygen toxicity- presentation
Cough, chest pain, dyspnea
Masked in ventilator dependent patients
Lungs become progressively stiffer
Ability to oxygenate is compromised
Oxygen toxicity- normal cellular respiration
Oxidants are counterbalanced by antioxidant defense system (prevents tissue destruction)
Oxygen toxicity- excess oxygen (hyperoxia)
Produces highly reactive, partially reduced oxygen metabolites
Superoxide anion, hydrogen peroxide, hydroxyl radical, singlet oxygen, hypochlorous acid
Overwhelm antioxidant system
Oxygen toxicity- lung damage determinants
Fraction of inspired oxygen–50-100%
Duration of exposure- Inversely proportional to fraction of inspired oxygen
Oxygen toxicity- lung damage
Acute phase: edema with alveolar hemorrhage
Subacute or chronic phase: collagen and elastin deposition in alveolar walls
What does the lung damage in oxygen toxicity lead to?
Thickening of gas exchange area and fibrosis
Oxygen toxicity-course
+/- improvement in lung function
May see improvement months to years following exposure
