PULMONARY DISEASES WITH A NOTE ON DRUGS THAT INDUCE PULMONARY DISEASES

1. Drug Induced
Pulmonary Diseases
KRVS Chaitanya

2. Definition:
• Drug induced pulmonary disease is defined as any
lung disease caused by a drug or medication
Drug Induced Pulmonary Diseases

3. Drug Induced Pulmonary Diseases
1. Bronchospasm, wheezing and cough
2. Pulmonary oedema
3. Pulmonary hypertension
4. Interstitial lung disease
– Interstitial pneumonia/infiltrates
– Pulmonary fibrosis
– Bronchiolitis Obliterans Organizing Pneumonia (BOOP)

4. 5. Pulmonary eosinophillia
6. Pleural inflammation
7. Diffuse alveolar haemorrhage / vacuities
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
– respiratory infections

7. Drugs that induce Bronchospasm
S.N Drugs Mechanism Of Action
1
Penicillin, sulphonamides, cephalosporin,
cimetidine, tetracycline, allergen extracts
Anaphylaxis- IgE mediated
2
Acetate, Bisulfite, Cromolyn , smoke, inhaled
steroids, N- acetyl cysteine
Direct airway irritation
3 Methydopa, carbamazepine, spiramycin Precipitating IgG antibodies
4 Aspirin, phenylbutazone, acetaminophen Cycloxygenase inhibition
5 Adrenergic receptor blockers
Pharmacologic effects
6
Narcotic analgesics, ethylene diamine, Local
anaesthetics, benzalkonium chloride
Anaphylactoid reaction
7
ACE inhibitor, Hydrocortisone, piperazine,
isoproterenol, Losartan, Mono sodium glutamate
Unknown mechanism

8. 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

9. Ex. 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

10. 2. Pulmonary Oedema
1. Cardiogenic and non cardiogenic
2. Symptoms include
– Dyspnea,
– Chest Discomfort,
– Tachypnea,
– Hypoxemia,
– Foamy Tracheal Exudates
3. Management :
– focuses on adequate life support and limit the
accumulation of extra vascular water in the lungs.

12. A. Cardiogenic
• It have an insidious onset
• Symptoms are vague fatigue, mild pedal oedema , exertional
dyspnoea
• Iatrogenic cause includes IV fluids with resultant
cardiovascular fluid overload
• Eg: IV fluids, contrast media, magnesium sulphate

13. B. Non- Cardiogenic
• It occurs via drug related increase in capillary pulmonary
permeability
• Drug that induce
– Antineoplastic Agents
– Β2-agonist
– Cocaine
– Hydrochlorothiazide
– Naloxone
– Opiates
– Salicylates

14. 3. Pulmonary Hypertension
1. It is rare, but life threatening
2. Symptoms include exertional dyspnoea, fatigue,
weakness, chest pain, syncope
3. Drugs Causing Pulmonary Hypertension
– Appetite suppressants
– fenfluramine derivatives
– Amphetamine derivatives
– Serotonin specific reuptake inhibitors

16. Management:
– Supplemental oxygen
– Diuretics
– Inotropic agents
– Anticoagulants
– Prostacyclin analogues
– Endothelin receptor antagonist
– Calcium channel blocker

17. 4. Interstitial Lung Disease (ILD)
• It can lead to respiratory failure
• Symptoms include non productive cough, dyspnoea, low grade
fever
• Oxidant injury either through increased production of oxidants
or inhibition of antioxidant accounts for majority of ILD

18. 4a. Interstitial Infiltrates / Pneumonia:
1. Diseases involving the space between the alveolus and
capillary.
2. The infiltrates consists of fluid and or cells that gather in
the areas of the lungs
3. Drugs causing interstitial pneumonia:
• Epidermal growth factor receptor antagonist
• Tyrosine kinase inhibitors
• Methotrexate
• Nitrofurantoin

19. 4b. Pulmonary Fibrosis:
1. It is characterized by accumulation of excessive connective
tissue in the lungs
2. Activation of coagulation cascade and generation of
coagulation proteases play a key role.
3. Drugs that causes pulmonary fibrosis:
• Cytotoxic drugs: Bleomycin, Busulfan, Carmustine,
Cyclophosphamide, Mitomycin
• Non cytotoxic drugs: Amiodarone, Bromocryptine, Ergot Derivatives,
Heroin, Methysergide

21. 4c. Bronchiolitis Obliterans Organizing Pneumonia
– It is an inflammation of the lungs characterized by alveolar fibrosis
– Symptoms include dyspnoea, low-grade fever, acute pleuritic chest pain
– More than 20 medications are associated with BOOP Drugs causing
BOOP
– Antimicrobials, Amphotericin B, Cephalosporin, Minocycline,
Nitrofurantoin , Cytotoxic agents
– Cardiovascular drugs (Amiodarone), HMG COA reductase inhibitors,
anti inflammatory drugs , carbamazepine, coccaine.

22. 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, dyspnoea, and cough
• Mechanism:
– Hypersensitivity or allergic reaction
– Direct toxicity
– Increased production of oxygen-free radicals
– Suppression of antioxidant defences
– Chemically-induced inflammation

26. Drugs causing pleural inflammation includes:
1. Dantrolene
2. Ergot Alkaloids
– Bromocryptine
– Methysergide
– Pergolide
3. Nitrofurantoin

27. 7. Diffuse Alveolar Haemorrhage (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 haemoptysis', cough, and
progressive dyspnoea
• Drug-related pathogenic mechanisms include hypersensitivity
reaction, direct toxicity diffuse alveolar damage (DAD), and
coagulation defects

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

29. 8. Diffuse Alveolar Damage (DAD)
• In DAD, the alveolar epithelial cells are sloughed, and the
lung interstitium becomes oedematous.
• Chronic inflammation and fibroproliferation of the alveolar
walls can present early in the process.
• DAD presents with dyspnoea, diffuse pulmonary infiltrates

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

31. 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

32. Drugs causing DHS
• Allopurinol
• Carbamazepine
• Phenytoin
• Sulfonamides

33. 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 accumulate in lungs which are toxic to the lung cells

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

35. Thank You