Drug Induced Pulmonary Diseases

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

1. DRUG INDUCED PULMONARY DISEASES By VISHWANATH GOUDA 1 st Year M.Pharm Dept. of Pharmacy Practice NGSMIPS, Nitte University Mangalore - 575018

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, s moking, 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 β 2-agonists are useful for persistent bronchospasm

8. APIRIN 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

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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. CARDIOGENIC It have an insidious onset Symptoms are vague fatigue, mild pedal edema , exertional dyspnea

11. Latrogenic 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 β 2-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

15. 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 N itrofurantoin

16. 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 , cyclo p hosphamide, mitomycin Non cytotoxic drugs like amiodarone , bromocryptine , ergot derivatives, heroin, methysergide

17. 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

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

19. 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)

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

21. 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

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

23. 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

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

25. 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

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

27. 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

28. Drugs causing DHS Allopurinol Anticonvulsants Carbamazepine phenytoin Sulfonamides

29. 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

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

31. 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.9 th 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