drug induced pulmonary disorders

presentation

nonspecific

• pleuritic chest pain, dyspnea, cough, wheezing, fever

• sx can be present at rest or during activity

• if it affects the vasculature, it often presents w pulmonary hemorrhage or vasculitis, hemoptysis, hematoma, or alveolar hemorrhage

dx of DIPD

dx of exclusion!!!

timeline and improvement of sx after drug withdrawal are most helpful!

can use radiographic imaging, including x rays + ct scans to help rule out other potential causes of pulmonary disease + establish the dx

types of drug induced lung disease (DIILD)

interstitial pneumonitis and fibrosis

organizing pneumonia

eosinophil pneumonia

hypersensitivity pneumonitis

others

interstitial pneumonitis and fibrosis presentation

non productive cough w demonstration of crackles upon expiration + sudden onset dyspnea over a period of hours

can also include fever, rash, eosinphilia

if it progresses through fibrosis → can cause pulmonary htn or cyanosis

diagnostic tools for interstitial pneumonitis and fibrosis

naranjo adverse drug reaction probability scale

grade 1 interstitial pneumonitis and fibrosis

asymptomatic; clinical or dx observations only, intervention not indicated

grade 2 interstitial pneumonitis and fibrosis

symptomatic; medical intervention indicated; limiting instrumental ADL

grade 3 interstitial pneumonitis and fibrosis

severe sxs, limiting self care ADL; o2 indicated

grade 4 interstitial pneumonitis and fibrosis

life threatening respiratory compromise; urgent intervention indicated (tracheotomy or intubation)

grade 5 interstitial pneumonitis and fibrosis

death

mech of toxicity of interstitial pneumonitis and fibrosis

oxidative stress + direct cellular injury

risk factors of interstitial pneumonitis and fibrosis

genetic susceptibility, extremes of age, radiation use, drug exposure, pre-existing lung disease, tobacco smoking

causative agents of interstitial pneumonitis and fibrosis

antimicrobials: nitrofurantoin, daptomycin

chemo!!!

transplant meds: everolimus, sirolimus, temsirolimus

cardio agents: amio

how do nitrofurantoin and daptomycin lead to interstitial pneumonitis and fibrosis

cause eosinophilic pneumonia through oxidant/antioxidant imbalances

how do chemos lead to interstitial pneumonitis and fibrosis

can cause cytokine release, free o2 radicals, alveolar injury, hypersensitivity, etc

• bleomycin → bbw: pulmonary tox

• busulfan → bbw: bone marrow suppression (BMS)

• carmustine → bbw: pulmonary tox/BMS

• cyclophosphamide

• tyrosine kinase inhibitors

• immune checkpoint inhibitors

• gemcitabine

• taxanes → bbw: hypersensitivity

bleomycin

can present weeks-mons after tx through induction of cytokines, free o2 radicals, inflammatory cells → can progress to fibrosis

max lifetime cumulative dose: 400 units

transplant meds

need immunosuppression to prevent rejection of organ

pneumonitis can occur and is thought to be d/t direct alveolar damage from autoimmune response or delayed hypersensitivity rxns

cardio meds

amio has many adrs!!! can cause excessive accumulation of intracellular phospholipids in tissues

most common rxn → subacute or chronic interstitial disease (pulm tox)

increased likelihood of drug induced adr: improvement following dc of amio

prevention

check contraindications, cautions etc, and limit exposure if pt needs the causative agent

monitoring for interstitial pneumonitis and fibrosis

baseline spirometry

diffusing capacity for carbon monoxide (DLCO)

chest radiography

for amio specifically: baseline chest radiography, PFTs (including DLCO), + chest radiograph + sx monitor every 3-6mon while on therapy

management and tx of interstitial pneumonitis and fibrosis

identify and d/c offending agent

initiate corticosteroids if necessary

supportive measures (supplemental o2, mechanical ventilation

lung transplant for severe cases

organizing pneumonia

results in an inflammatory response localized in the long parenchyma

present w nonprod cough, dyspnea, bilateral crackles, occasional fever + rash, rarely can have eosinophilia

causative agents of organizing pneumonia

antimicrobials (minocycline, nitrofurantoin)

chemo agents (bleomycin)

cardiac agents (amio)

anti inflammatory agents (gold, sulfasalazine)

others like interferon alpha, carbamazepine, L-tryptophan and cocaine

can be reversed by d/c agent or tx w corticosteroids

eosinophilic pneumonia

results from drug related chemoattractants through 5HT2A (response to antipsychs + anti epileptics) and oxidant injury (nitro and dapto)

presents w dry cough, dyspnea, chest pain fever, bronchoalveolar lavage (BAL) >25% eosinophils as a proportion of all white blood cells present), imaging w bilateral reticular ground-glass opacities

eosinophilic pneumonia management

use steroids to manage

acute: no statistical difference in recurrence rates w or wo steroid use

chronic: higher recurrence rates in pts who get steroids

hypersensitivity pneumonia

presentation: urticaria, angioedema, rhinitis, conjunctivitis, dyspnea, bronchospasm

hypersen can occur acutely or chronically

causative agents: NSAIDs and methotrexate

hypersen pneumonitis is managed by: d/c drug, supportive care w corticosteroids + antihistamines to blunt immune mediated + allergic response

conditions w indirect effect on lung fxn

drug induced cough

drug induced respiratory depression

drug induced cough

angiotensin II inhibitor induced cough (greater risk for females and non-smokers)

presentation: persistent dry cough, and tickle season throat

pathogenesis: accumulation of bradykinin or substance P

d/c and switch to arb!

ccbs → relaxation of LES

fentanyl iv bolus → increase vagal tone by decreasing central sympathetic outflow or induction of pulm chemoreflex

latanoprost→ upregulate cough reflex systemically

drug induced respiratory depression

occurs through cns depression → hypoventilation or neuromuscular blockade, completely blunting pt-initiated respirations

agents: opioids (unintentionally decreasing sensitivity of peripheral chemoreceptors to co2 and by decreasing neuronal activity in central respiratory centers)