DRUG INDUCED LUNG DRUG INDUCED LUNG DISEASESDISEASES

CHEMOTHERAPEUTIC AGENTSCHEMOTHERAPEUTIC AGENTS

1. CYTOTOXIC ANTIBIOTICS1. CYTOTOXIC ANTIBIOTICS2. ALKYLATING AGENTS2. ALKYLATING AGENTS3. ANTIMETABOLITES3. ANTIMETABOLITES4. BIOLOGIC RESPONSE MODIFIERS4. BIOLOGIC RESPONSE MODIFIERS

CYTOTXIC ANTIBIOTICSCYTOTXIC ANTIBIOTICSBLEOMYCINBLEOMYCIN

1.CHRONIC PNEUMONITIS/ PULM FIBROSIS1.CHRONIC PNEUMONITIS/ PULM FIBROSISMOST COMMON SYNDROMEMOST COMMON SYNDROMERADIATION RECALL EFFECTRADIATION RECALL EFFECTRISK FACTORS: cumulative dose> RISK FACTORS: cumulative dose> 400u400u

oxyoxygen therapygen therapythetherapeutic radiationrapeutic radiationrenrenal al insuffinsuffoldold age age

2.HYPERSENSTIVITY TYPE LUNG DISEASES2.HYPERSENSTIVITY TYPE LUNG DISEASESDyspneaDyspnea , cough , skin rash , , cough , skin rash , eosinophiliaeosinophiliamay not occur with may not occur with rechallangerechallange

3. CHEST PAIN SYNDROME3. CHEST PAIN SYNDROMEAssociated with iv infusion of the drugAssociated with iv infusion of the drug

MITOMYCIN CMITOMYCIN C1.CHRONIC PNEUMONITIS /PULMONARY FIBROSIS1.CHRONIC PNEUMONITIS /PULMONARY FIBROSIS

most common syndromemost common syndromerisk factors : oxygen therapyrisk factors : oxygen therapy

therapeutic radiationtherapeutic radiationconcurrent use of other cytotoxic concurrent use of other cytotoxic drugsdrugs

2.ACUTE DYSPNEA/ BRONCHOSPASM2.ACUTE DYSPNEA/ BRONCHOSPASMNON CARDIOGENIC PULMONARY EDEMANON CARDIOGENIC PULMONARY EDEMA

pts receiving pts receiving vincavinca alkaloidsalkaloids

3. HAEMOLYTIC UREMIC SYNDROME3. HAEMOLYTIC UREMIC SYNDROMEmicroangiopathicmicroangiopathic hemolytic anemia,hemolytic anemia,thrombocytopenia, renal thrombocytopenia, renal insuffieciencyinsuffieciency,,non non cardiogeniccardiogenic pumonarypumonary edemaedema

ACTINOMYCIN DACTINOMYCIN D1. EXACERBATION OF RADIATION INDUCED INJURY1. EXACERBATION OF RADIATION INDUCED INJURY

ALKYLATING AGENTSALKYLATING AGENTS

BUSULFANBUSULFAN1. CHRONIC PNEUMONITIS /PUMONARY 1. CHRONIC PNEUMONITIS /PUMONARY

FIBROSISFIBROSIStoxicity may occur after several years toxicity may occur after several years of treatmentof treatmentfibrosis may occur insidiouslyfibrosis may occur insidiously

CYCLOPHOSPHAMIDECYCLOPHOSPHAMIDE1. CHRONIC PNEUMONITIS /PULMONARY 1. CHRONIC PNEUMONITIS /PULMONARY FIBROSISFIBROSIS

risk factors: concurrent use of risk factors: concurrent use of other cytotoxic drugsother cytotoxic drugs

therapeutic radiationtherapeutic radiation

ANTIMETABOLITESANTIMETABOLITES

METHOTREXATEMETHOTREXATE1. CHRONIC PNEUMONITIS /PULMONARY FIBROSIS1. CHRONIC PNEUMONITIS /PULMONARY FIBROSIS2. HYPERSENSTIVITY TYPE2. HYPERSENSTIVITY TYPE3. ACUTE CHEST PAIN SYNDROME3. ACUTE CHEST PAIN SYNDROME

often assoc with pleural effusionsoften assoc with pleural effusions4. 4. NON CARDIOGENIC PULMONARY EDEMANON CARDIOGENIC PULMONARY EDEMA

assoc with assoc with intrathecalintrathecal routeroute

CYTOSINE ARABINOSIDECYTOSINE ARABINOSIDE1. 1. NON CARDIOGENIC PULMONARY EDEMANON CARDIOGENIC PULMONARY EDEMA

FLUDARIBINEFLUDARIBINE1. HYPERSENSTIVITY RXN1. HYPERSENSTIVITY RXN2. INTERSTITIAL PNEUMONITIS2. INTERSTITIAL PNEUMONITIS

BIOLOGIC RESPONSE MODIFIERSBIOLOGIC RESPONSE MODIFIERSALLTRANS RETINOIC ACIDALLTRANS RETINOIC ACID

1. retinoic acid syndrome1. retinoic acid syndrome

INTERLEUKIN 2INTERLEUKIN 21. pleural effusions1. pleural effusions

focal/ diffuse radiographic abnormalitiesfocal/ diffuse radiographic abnormalitiesrisk factors: increasing cumulative doserisk factors: increasing cumulative dose

admnadmn of LAof LAKK cellscellsIL 2 induced cardiac toxicityIL 2 induced cardiac toxicity

2. 2. NON CARDIOGENIC PULMONARY EDEMANON CARDIOGENIC PULMONARY EDEMA

NON CHEMOTHERAPEUTIC NON CHEMOTHERAPEUTIC AGENTSAGENTS

CARDIOVASCULAR DRUGSCARDIOVASCULAR DRUGSTOPICAL OPHTHALMIC AGENTSTOPICAL OPHTHALMIC AGENTSTOCOLYTICSTOCOLYTICSCORTICOSTEROIDSCORTICOSTEROIDSANTIBIOTICSANTIBIOTICSANTICONVULSANTSANTICONVULSANTSSALICYLATESALICYLATEGOLD & PENCILLAMINEGOLD & PENCILLAMINEILLICIT DRUG USAGEILLICIT DRUG USAGE

CARDIOVASCULAR DRUGSCARDIOVASCULAR DRUGSAMIODARONEAMIODARONEincidence of pulmonary toxicity 5%incidence of pulmonary toxicity 5%

1. 1. alveolitisalveolitis/ fibrosis / fibrosis sndromesndromea) chronic 2/3 rd casesa) chronic 2/3 rd casesb) b) subacutesubacute ––fever, chest pain, alveolar/mixedfever, chest pain, alveolar/mixed

infiltratesinfiltratesleucocytosisleucocytosis, raised ESR, raised ESR

2. 2. NON CARDIOGENIC PULMONARY EDEMANON CARDIOGENIC PULMONARY EDEMA

Daily dose < 400mg is assoc with lower riskDaily dose < 400mg is assoc with lower risk

PATHOLOGYPATHOLOGYaccumulation of foamy macrophagesaccumulation of foamy macrophagesacute acute intraalveolarintraalveolar hh’’ageagetype 2 cell proliferationtype 2 cell proliferationHyaline membrane formationHyaline membrane formation

on Electron on Electron mm’’scopyscopy cytoplasm of foamy macrophages cytoplasm of foamy macrophages has lamellar inclusions containing indigested has lamellar inclusions containing indigested phospholipidsphospholipids

PROCAINAMIDEPROCAINAMIDEDRUG INDUCED SLEDRUG INDUCED SLE

ANA +ANA +veve, , antihistoneantihistone AbAbSlow Slow acetylatorsacetylators develop ANA & clinical SLE rapidlydevelop ANA & clinical SLE rapidlycommon symptoms: common symptoms: arthralgiasarthralgias, fever, feverPleural effusions & Pleural effusions & pleuriticpleuritic chest pain (MC pulmonary chest pain (MC pulmonary

symptoms)symptoms)ParenchymalParenchymal infiltratesinfiltrates

ADENOSINEADENOSINEMC pulmonary side effect is acute MC pulmonary side effect is acute dyspneadyspnea during during infusioninfusion

Acute Acute bronhcospasmbronhcospasm in asthma & COPD ptsin asthma & COPD pts

ACE INHIBITORSACE INHIBITORSchronic nonproductive cough 5chronic nonproductive cough 5--15%15%angioneuroticangioneurotic edemaedema

BETA BLOCKERSBETA BLOCKERSpulmonary fibrosispulmonary fibrosisdrug induced SLEdrug induced SLEdose dependent decrease in FEV1dose dependent decrease in FEV1

TOPICAL OPTHALMIC AGENTSTOPICAL OPTHALMIC AGENTSSignificant decrease in FEV1 in asymptomaticSignificant decrease in FEV1 in asymptomatic

Acute Acute bronchospasmbronchospasm

Non specific agents Non specific agents –– timololtimolol

TOCOLYTIC AGENTSTOCOLYTIC AGENTS

ACUTE PULMONARY EDEMAACUTE PULMONARY EDEMA

BRONCHOSPASMBRONCHOSPASM

METABOLIC ACIDOSIS AND DYSPNEAMETABOLIC ACIDOSIS AND DYSPNEA

CORTICOSTEROIDSCORTICOSTEROIDS

LONE COUGHLONE COUGH

MEDIASTINAL FATTY DEPOSITS (LIPOMATOSIS)MEDIASTINAL FATTY DEPOSITS (LIPOMATOSIS)

THROMBOEMBOLIC DISEASETHROMBOEMBOLIC DISEASE

OPPORTUNISTIC INFECTIONSOPPORTUNISTIC INFECTIONS

ANTIBIOTICSANTIBIOTICSHYPERSENSTIVITY RXNHYPERSENSTIVITY RXN

PIE syndrome PIE syndrome -- beta beta lactamslactams, sulfa drugs, sulfa drugsMC is MC is loefflerloeffler’’ss syndromesyndromec/fc/f-- dyspneadyspnea cough fever cough fever

peripheral blood peripheral blood eosinophiliaeosinophilia of acute onsetof acute onsetspontaneous resolution on drug withdrawalspontaneous resolution on drug withdrawal

NITROFURANTOINNITROFURANTOINACUTE CHRONICACUTE CHRONIC

Onset <1 Onset <1 mthmth after 1after 1st st elderly pts undergoingelderly pts undergoingDose; recurs with challenge chronic oral therapyDose; recurs with challenge chronic oral therapyfever, fever, dyspneadyspnea , cough, cough, , cough, cough, dyspneadyspnea,,MaculopapularMaculopapular rash cyanosis, fatiguerash cyanosis, fatigueMixed infiltrates interstitial infiltratesMixed infiltrates interstitial infiltratesPFTPFT--restrictive defect with prognosis worserestrictive defect with prognosis worseDecrease DLCODecrease DLCO

INH INDUCED SLEINH INDUCED SLEfever anemia rash fever anemia rash arthralgiasarthralgiasPleural effusions & Pleural effusions & pleuriticpleuritic chest pain (MC pulmonary chest pain (MC pulmonary

symptoms)symptoms)ANA+veANA+ve, anti , anti histonehistone AbAb

ANTIBIOTIC ASSOCIATED ALVEOLAR ANTIBIOTIC ASSOCIATED ALVEOLAR HYPOVENTILATION AND HYPERCARBIC RESP HYPOVENTILATION AND HYPERCARBIC RESP FAILUREFAILUREAMINOGLYCOSIDES ( MC DRUGS)AMINOGLYCOSIDES ( MC DRUGS)seen in cases of:seen in cases of:

post operative pts.post operative pts.myasthenia like syndromesmyasthenia like syndromesunrecognized myasthenia gravisunrecognized myasthenia gravis

ANTICONVULSANTSANTICONVULSANTSDIPHENYLHYDANTOINDIPHENYLHYDANTOIN

1. asymptomatic physiological abnormalities1. asymptomatic physiological abnormalities

2. hypersensitivity syndrome2. hypersensitivity syndrome

3. 3. lymphocyticlymphocytic interstitial interstitial pneumonitispneumonitis

4. 4. pseudolymphomapseudolymphoma syndromesyndrome

SALICYLATESSALICYLATESASPIRIN INDUCED ASTHMAASPIRIN INDUCED ASTHMA

aspirin sensitivity seen in 5% asthmaticsaspirin sensitivity seen in 5% asthmaticsSAMPTERSAMPTER’’S TRIADS TRIAD-- nasal nasal polyposispolyposis, chronic , chronic

sinusitis, asthma sinusitis, asthma SALICYLATE INDUCED PULM EDEMASALICYLATE INDUCED PULM EDEMA1010--15% of 15% of salicylatesalicylate overdosingoverdosingmetabmetab acidosis with acidosis with respresp alkalosisalkalosisSignificant Significant proteinuriaproteinuriaCXRAYCXRAY-- perihilarperihilar alveolar infiltrates with pleural alveolar infiltrates with pleural

effusion and effusion and cardiomegalycardiomegaly

GOLDGOLDseen in treatment of osteoarthritis , seen in treatment of osteoarthritis , pemphiguspemphigusAssoc with HLAB 40 & HLAB 35Assoc with HLAB 40 & HLAB 35typically interstitial typically interstitial pneumonitispneumonitisc/f cough fever skin rash peripheral blood c/f cough fever skin rash peripheral blood eosinophiliaeosinophiliaLung biopsyLung biopsy-- alveolar alveolar septalseptal thickening thickening

interstitial fibrosisinterstitial fibrosismononuclear cell infiltratemononuclear cell infiltrate

PENCILLAMINEPENCILLAMINE

1. Interstitial Lung Diseases1. Interstitial Lung Diseases

2. 2. BronchiolitisBronchiolitis ObliteransObliterans

3. Pulmonary Renal Syndrome3. Pulmonary Renal Syndrome

COMPLICATIONS OF ILLICIT DRUG USECOMPLICATIONS OF ILLICIT DRUG USE

Alveolar hypoventilation & Alveolar hypoventilation & hypercarbichypercarbic respresp failurefailureEndocarditisEndocarditis , septic emboli, septic emboliHIV assoc infectionsHIV assoc infectionsTuberculosisTuberculosisComplications of central Complications of central cannulationcannulationpneumothoraxpneumothoraxintravascular infectionsintravascular infectionsarterial aneurysms and dissectionsarterial aneurysms and dissections

Foreign body Foreign body granulomatosisgranulomatosisOpiate induced pulmonary edemaOpiate induced pulmonary edemaCocaine crack lungCocaine crack lungbronchospasmbronchospasmpneumothoraxpneumothorax, , pneumomediastinumpneumomediastinumairway burnsairway burnsnon cardiac pulmonary edemanon cardiac pulmonary edemapulmonary infiltrates with pulmonary infiltrates with eosinophiliaeosinophiliaacute alveolar acute alveolar hh’’ageage syndromesyndrome

TREATMENTTREATMENTDRUG CESSATIONDRUG CESSATION

CORTICOSTEROIDSCORTICOSTEROIDS

EMPERICAL GUIDELINES FOR USE STEROIDS IN EMPERICAL GUIDELINES FOR USE STEROIDS IN DIRDDIRD’’ss

Pattern of Involvement Indication for Steroids Duration of Treatment Level of Scientific Evidence†

Laryngeal edema Y Days 1

Sudden severe asthma Y Weeks 1

Worsening of asthma Y As needed 2

Bronchiolitis obliterans Y‡ Months 2

Classic interstitial pneumonia (NSIP)

Y§ A few weeks or months™ 2

Pulmonary infiltrates and eosinophilia

Y§ A few weeks or months™ 2, 3

Amiodarone lung Y§ 6 to 18 mo¶ 3

Organizing pneumonia Y§ A few months™ 3

Desquamative interstitial pneumonia

Y A few months ? 1

Pulmonary fibrosis Y‡ Months 2, 3

Lipoid pneumonia N – 1

Pulmonary edema ? – –

Pulmonary hypertension N – –

Alveolar hemorrhage Y? Months 2

Hemolytic-uremic syndrome

Y? ? 2

Veno-occlusive disease N – –

All the best..All the best..