Drug induced pulmonary disease

1. DRUG INDUCED
PULMONARY DISEASES

2. DEFINITION:
Drug induced pulmonary disease is defined as any lung
disease caused by a drug or medication

3. DRUG INDUCED PULMONARY DISEASES
1) Bronchospasm, wheezing and cough
2) Pulmonary edema
3) Pulmonary hypertension
4) Interstitial lung disease
* Interstitial pneumonia/infiltrates
* Pulmonary fibrosis

4. * Bronchiolitis obliterans organizing pneumonia (BOOP)
5) Pulmonary eosinophillia
6) Pleural inflammation
7) Diffuse alveolar hemorrhage / vasculitis
8) Diffuse alveolar damage (DAD)
9) Drug hypersensitivity syndrome
10) Amiodarone induced pulmonary toxicity

5. 1) BRONCHOSPASM
 Most common drug induced pulmonary adverse event
 Clinical presentation is the same as with non-drug
induced bronchospasm
 Risk factors include pre-existing
hyper reactive lung disease,
smoking, advanced age
and respiratory infections

6. DRUGS THAT INDUCE
BRONCHOSPASM
MECHANISM OF
ACTION
Penicillin, sulphonamides,
cephalosporin, cimetidine,
tetracycline, allergen extracts
Anaphylaxis- IgE mediated
Acetate, Bisulfite, Cromolyn ,
smoke, inhaled steroids, N- acetyl
cysteine
Direct airway irritation
Methydopa, carbamazepine,
spiramycin
Precipitating IgG antibodies
Aspirin, phenylbutazone,
acetaminophen
Cycloxygenase inhibition
Adrenergic receptor blockers Pharmacologic effects

7. Narcotic analgesics, ethylene
diamine, Local anaesthetics,
benzalkonium chloride
Anaphylactoid reaction
ACE inhibitor, Hydrocortisone,
piperazine, isoproterenol,
Losartan, Mono sodium glutamate
Unknown mechanism
MANAGEMENT
• Withdrawal and avoidance of causative agents
• Treat acute anaphylaxis with low doses of injectable
epinephrine
• Oxygen, corticosteroids, antihistamines
• Inhaled β2-agonists are useful for persistent
bronchospasm

8. ASPIRIN INDUCED BRONCHOSPASM
 It begins within minutes to hours following ingestion of
aspirin
 Clinical presentation includes rhinorrhea, flushing of
head and neck, conjuctivitis
 MOA is inhibition of cycloxygenase
 Definitive diagnosis is done by oral provocation test
 Treatment includes desensitization
or avoidance

9. 2)

10. PULMONARY EDEMA
• Cardiogenic and non cardiogenic
• Symptoms include dyspnea, chest discomfort, tachypnea,
hypoxemia, foamy tracheal exudates
• Management focuses on adequate life support and limit
the accumulation of extravascular water in the lungs.
a) CARDIOGENIC
• It have an insidious onset
• Symptoms are vague fatigue, mild pedal edema ,
exertional dyspnea

11. • Iatrogenic cause includes IV fluids with resultant
cardiovascular fluid overload
• Eg: IV fluids, contrast media, magnesium sulfate
b) NON- CARDIOGENIC
• It occurs via drug related increase in capillary pulmonary
permeability
• Eg: Antineoplastic agents, IV β2-agonist, cocaine,
hydrocholorothiazide, naloxone, opiates, salicylates

12. 3) PULMONARY HYPERTENSION
• It is rare, but life threatening
• Symptoms include exertional dyspnea, fatigue,
weakness, chest pain, syncope
DRUGS CAUSING PULMONARY HYPERTENSION
Appetite supressants
fenfluramine derivatives
Amphetamine derivatives
Serotonin specific reuptake inhibitors

13. MANAGEMENT
• Supplemental oxygen, diuretics, Inotropic agents,
Anticoagulants, Prostacyclin analogues, Endothelin
receptor antagonist, Calcium channel blocker

14. 4) INTERSTITIAL LUNG DISEASE (ILD)
• It can lead to respiratory failure
• Symptoms include non productive cough, dyspnea, low
grade fever
• Oxidant injury either through increased production of
oxidants or inhibition of antioxidant accounts for
majority of ILD

16. 4a) INTERSTITIAL INFILTRATES / PNEUMONIA
 Diseases involving the space between the alveolus and
capillary.
 The infiltrates consists of fluid and or cells that gather in
the areas of the lungs
Drugs causing interstitial pneumonia:
• Epidermal growth factor receptor antagonist
• Tyrosine kinase inhibitors
• Methotrexate
• Nitrofurantoin

17. 4b) PULMONARY FIBROSIS
• It is characterized by accumulation of excessive
connective tissue in the lungs
• Activation of coagulation cascade and generation of
coagulation proteases play a key role.
Drugs that causes pulmonary fibrosis:
 Cytotoxic drugs like bleomycin, busulfan, carmustine,
cyclophosphamide, mitomycin
 Non cytotoxic drugs like amiodarone, bromocryptine,
ergot derivatives, heroin, methysergide

19. 4C) BRONCHIOLITIS OBLITERANS ORGANIZING
PNEUMONIA
• It is an inflammation of the lungs characterized by
alveolar fibrosis
• Symptoms include dyspnea, low-grade fever, acute
pleuritic chest pain
• More than 20 medications are associated with BOOP
Drugs causing BOOP
• Antimicrobials, Amphotericin B, Cephalosporin,
Minocycline, Nitrofurantoin drugs, Cytotoxic drugs

20. Cardiovascular drugs(amiodarone), HMG COA
reductase inhibitors, anti inflammatory drugs ,
carbamazepine, coccaine.

21. 5) PULMONARY EOSINOPHILIA
• It is characterized by pulmonary infiltration of
eosinophils in alveolar spaces, the interstitium or
both
• Pulmonary infiltrates with eosinophilia (PIE)
• Diagnosis is done by lung biopsy
• Loeffler syndrome
• Churg – Strauss syndrome (CSS)

23. Drugs causing pulmonary eosinophilia:
• Antimicrobial agents
• NSAIDS
• Leukotriene antagonists
• Minocycline
• nitrofurantoin

24. 6) PLEURAL INFLAMMATION
• It range in presentation from asymptomatic effusion to
acute pleuritis to symptomatic pleural thickening
• Symptoms are pleuritic chest pain, dyspnea, and cough
• Mechanism include hypersensitivity or allergic reaction,
direct toxicity, increased production of oxygen-free
radicals, suppression of antioxidant defenses, and
chemically-induced inflammation

25. Drugs causing pleural inflammation includes:
• Dantrolene
• Ergot alkaloids
(Bromocryptine, methysergide, pergolide)
• nitrofurantoin

26. 7) DIFFUSE ALVEOLAR HEMORRHAGE (DAH)
AND VASCULITIS
• DAH is characterized by bleeding from pulmonary
capillaries, leading to the accumulation of red blood cells in
the alveolar spaces
• Symptoms include varying degrees of hemoptysis, cough,
and progressive dyspnea
• Drug-related pathogenic mechanisms include
hypersensitivity reaction, direct toxicity diffuse alveolar
damage (DAD), and coagulation defects

27. Drugs causing DAH
• Anticoagulants
• Dextran 70
• Platelet aggregation inhibitors
• Thrombolytic agents
• Chemotherapeutic agents
• Cocaine
• Hydralazine
• Nitrofurantoin
• Penicillin

28. 8) DIFFUSE ALVEOLAR DAMAGE (DAD)
• In DAD, the alveolar epithelial cells are sloughed, and
the lung interstitium becomes edematous.
• Chronic inflammation and fibroproliferation of the
alveolar walls can present early in the process
• DAD presents with dyspnea, diffuse pulmonary
infiltrates

29. Drugs causing DAD
• Alkylating agents
• Antibiotics
• Antimetabolites
• Aspirin
• Carbamazepine
• Chemotherapeutic agents
• Cocaine
• Narcotics
• Nitrofurantoin
• Nitrosoureas
• Penicillamine

30. 9) DRUG HYPERSENSITIVITY SYNDROME
(DHS)
• DHS is a systemic idiosyncratic reaction
• It is defined by the presence of fever, rash, and organ
involvement, including pneumonitis
• Clinical presentations may involve dermatologic,
hematologic, lymphatic, or internal organ systems.
• Management involves drug withdrawal, supportive care
and corticosteroid therapy

31. Drugs causing DHS
• Allopurinol
• Anticonvulsants
Carbamazepine
phenytoin
• Sulfonamides

32. 10) AMIODARONE INDUCED PULMONARY
TOXICITY (APT)
• APT has an average onset of 18-24 months
• It can present as various patterns of pulmonary toxicity
• Symptoms include fatigue, dyspnea, nonproductive
cough, pleuritic chest pain, crackles , weight loss
• MOA : During chronic therapy amiodarone and its
metabolic product DEAm accumulate in lungs which are
toxic to the lung cells

33. Management:
Corticosteroid therapy for 6 month or 1 year
Eg: 0.75 – 1 mg/kg of oral predinisolone

34. REFERENCES
1) Koda-Kimble M A, Young L Y, Williams B R, Corelli R
L, et al. Applied Therapeutics- The Clinical Use of Drugs.
In: Kubota D S, Chan J editor. Drug induced pulmonary
disorders.9th edition:25.1-25.13
2) Dipiro J T, Talbert R L, Yee G C, Matzke G R, et
al.Pharmacotherapy- A Pathophysiological Approach. In:
Raissy H H, Harkins M,editor.Drug induced pulmonary
diseases New York: Mc Graw Hill Professional.9th edition