Drug induced pulmonary diseases

Dr.Sameera Fathima

1. DRUG INDUCED PULMONARY DISEASES PRESENTED BY UNDER THE GUIDANCE OF SAMEERA FATHIMA MR.MISBA ALI BAIG 170721883006 Associate Professor Pharm D (pb)-1 st year Department Of Pharmacy Practice

2. DEFINATION A number of medications are known to cause undesirable reactions and lead to changes in the lungs or alter respiratory function. These reactions are known as Drug-induced pulmonary diseases. They could include pneumonitis, pulmonary edema, fibrosis, and even lung failure. At times, effective medicaments have to be withdrawn due to serious or lethal adverse effects.

3.   Theoretic mechanisms include: cytotoxic effects on alveolar capillary endothelial cells direct oxidative injury amphophilic medications causing deposition of phospholipid within the cells—particularly the alveolar macrophage; and immune-mediated lung injury, either through drug-induced systemic lupus erythematosus (SLE) or via hypersensitivity reactions.  Pathogenesis of DIPD

4. The different types of lung or pulmonary diseases caused by drugs are: Bronchospasm, wheezing and cough Pulmonary edema Pulmonary hypertension Interstitial lung disease * Interstitial pneumonia/infiltrates * Pulmonary fibrosis *Bronchiolitis obliterans organizing pneumonia (BOOP) Pulmonary eosinophillia Pleural inflammation Diffuse alveolar hemorrhage / vasculitis Diffuse alveolar damage (DAD) Drug hypersensitivity syndrome Amiodarone induced pulmonary toxicity Types of Drug Induced Pulmonary Diseases

5. Most common drug induced pulmonary adverse event Risk factors include pre-existing hyper reactive lung disease, smoking, advanced age and respiratory infections BRONCHOSPASM

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 Narcotic analgesics, ethylene diamine , Local anaesthetics , benzalkonium chloride   Anaphylactoid reaction

7. Withdrawal and avoidance of causative agents Treat acute anaphylaxis with low doses of injectable epinephrine Oxygen, corticosteroids, antihistamines are used to treat bronchospasm Inhaled β2- agonists are useful for persistent bronchospasm MANAGEMENT OF BRONCHOSPASM

8. About 4% of the bronchial asthmatic patients, experience bronchospasm, which is produced by aspirin and other NSAID’S.24 Inhalers that are used by the asthmatic patients also produce bronchospasm, because the excipients that are used in production of inhalers may trigger bronchospasm. Bronchospasm generally occurs, after administration of aspirin, within minutes to hour and more often it is associated with rhinorrhea, flushing of neck, head and conjunctivitis. Aspirin hypersensitivity is chronic and it is more often life-threatening. MECHANISM OF ACTION : Arachidonic acid is metabolized by the 5-lipoxygenase pathway may lead to an increase in the production of leukotrienes that causes bronchospasm. DIAGNOSIS : It is done by oral provocation test TREATMENT : It includes desensitization or avoidance. Aspirin-induced bronchospasm

9. Bronchial asthma can be defined as the chronic inflammatory disease of air passages that cause hyper responsiveness, mucosal production and mucosal edema. RISK FACTORS : cold air, exercise, viral upper respiratory infection, cigarette smoke, and respiratory allergens. Example : ACETAMENOPHEN induced Bronchial Asthama The increased use of acetaminophen increases the prevalence of COPD and bronchial asthma is showed in an epidemiological study.Various study shows that there exists an relation between acetaminophen and bronchial asthma within the age of 12 months will lead to development of bronchial asthma. Drug Induced Bronchial Asthma

10. MECHANISM : It is due to reduction in the secretion of an endogenous antioxidant enzymes in the airways that lead to oxidant damage in lungs. DIAGNOSIS : It include allergy testing, chest X ray, lung function test, blood test, arterial blood gas, peek respiratory flow measurement.

11. PULMONARY EDEMA Cardiogenic and non cardiogenic Symptoms : include dyspnea, chest discomfort, tachypnea, hypoxemia, foamy tracheal exudates Management: 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 • Latrogenic cause includes IV fluids with resultant cardiovascular fluid overload • Eg : IV fluids, contrast media, magnesium sulfate

12. b) NON- CARDIOGENIC • It occurs via drug related increase in capillary pulmonary permeability • Eg : Antineoplastic agents, IV β2- agonist, cocaine, hydrocholorothiazide , naloxone, opiates, salicylates

13. 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 INTERSTITIAL INFILTRATES / PNEUMONIA

14. Methotrexate belongs to the class of anti metabolites. It is used in the treatment of rheumatoid arthritis and other tissue diseases, but its dose as an anti-inflammatory is very low, when compared to an antineoplastic agent. The major complications faced by the patients, who use Methotrexate are acute interstitial pneumonitis, interstitial fibrosis and bronchial asthma. About 1-5% of the patients with rheumatoid arthritis faces Methotrexate induced pulmonary disease.31 Symptoms may include a progressive cough, fever, difficulty in breathing, which is temporary. Diagnosis : pulmonary function test, high-resolution computed tomography scan shows pulmonary infiltrates. EX:METHOTREXATE INDUCED PNEUMONIA /INTERSTITIAL INFILTRATES

15. It is rare, but life threatening Symptoms : exertional dyspnea, fatigue, weakness, chest pain, syncope DRUGS CAUSING PULMONARY HYPERTENSION : Appetite supressants fenfluramine derivatives Amphetamine derivatives Serotonin specific reuptake inhibitors PULMONARY HYPERTENSION

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

17. https://www.everydayhealth.com/pulmonary-arterial-hypertension https://www.researchgate.net/publication/338145361_Drug_Induced_Pulmonary_Disease-A_Mini_Review . https://www.uspharmacist.com/article/therapeutic-update-on-drug-induced-pulmonary-disorders . https://www.slideshare.net/VishwanathAnkola/drug-induced-pulmonary-diseases . REFERENCES