Drug-Induced Lung Diseases

Question 1

drugs that can cause drug-induced lung disease

Answer 1

*oxygen
*bleomycin
*amiodarone
*methotrexate
*nitrofurantoin
*volatile inhalants
*nicotine & tobacco smoke
*vapes & ENDS
*cannabis/marijuana
*cocaine
*heroin

Question 2

oxygen & drug-induced lung disease - MOA & toxicity

Answer 2

*induces formation of free radicals
*direct injury to endothelial cells & type 1 alveolar cells (results in alveolar-capillary leak)

Question 3

oxygen & drug-induced lung disease - clinical manifestations

Answer 3

*typical patient: mechanical ventilation with high FiO2
*exudative phase (48-72h after exposure) = interstitial & alveolar edema, alveolar hemorrhage
*proliferative phase (days 4-7) = hyperplasia of type 2 alveolar cells, hyaline membrane deposition; INDISTINGUISHABLE FROM OTHER CAUSES OF ARDS

Question 4

oxygen & drug-induced lung disease - treatment/prevention

Answer 4

*minimize oxygen exposure (goal FiO2 < 0.60)

Question 5

bleomycin & drug-induced lung disease - MOA and toxicity

Answer 5

*an antibiotic chemotherapy drug
*20% of patients develop overt pulmonary disease
*cumulative toxicity from direct cytotoxic effects, GENERATION OF FREE RADICALS by binding to Fe2+ and O2
*bleomycin “blasts the lungs”

Question 6

bleomycin & drug-induced lung disease - clinical manifestations

Answer 6

*ARDS/pulmonary inflammation & PULMONARY FIBROSIS
*CUMULATIVE TOXICITY increases the risk
*oxygen-sensitive toxicity and “radiation recall”

Question 7

bleomycin & drug-induced lung disease - treatment

Answer 7

*discontinue the drug
*corticosteroids to reduce inflammation
*avoid high FiO2 and radiation during bleomycin treatment

Question 8

amiodarone & drug-induced lung disease - MOA and toxicity

Answer 8

*iodine-containing antiarrhythmic
*INTERSTITIAL PNEUMONITIS
*dose-related, > 1 month or even for years

Question 9

amiodarone & drug-induced lung disease - clinical manifestations

Answer 9

*SOB with INTERSTITIAL LUNG CHANGES in patients taking amiodarone
*FOAMY MACROPHAGES in bronchoalveolar lavage fluid only indicates EXPOSURE< not toxicity
*if biopsy done, cellular INTERSTITIAL PNEUMONITIS is seen

Question 10

amiodarone & drug-induced lung disease - treatment

Answer 10

*discontinue amiodarone
*systemic corticosteroids for 2-6 months to suppress inflammation
*avoid high FiO2

Question 11

methotrexate & drug-induced lung disease - MOA and toxicity

Answer 11

*antimetabolite that interferes with folic acid metabolism, used in malignancy and in many nonmalignant conditions (psoriasis, RA, sarcoidosis)
*10% of patients develop pulmonary toxicity (rarely fatal)
*poorly understood mechanism, suspected to be a type of hypersensitivity reaction

Question 12

methotrexate & drug-induced lung disease - clinical manifestations

Answer 12

*dyspnea, nonproductive cough, fever, that occurs a FEW DAYS OR WEEKS after starting MTX

Question 13

methotrexate & drug-induced lung disease - treatment

Answer 13

*discontinue methotrexate
*corticosteroids not always required

Question 14

nitrofurantoin & drug-induced lung disease - MOA & toxicity

Answer 14

*an oral antibiotic used frequently for UTI
*mechanism of toxicity is unknown

Question 15

nitrofurantoin & drug-induced lung disease - clinical manifestations

Answer 15

*typical patient: fever, dyspnea, and dry cough with eosinophilia a few hours to days after starting nitrofurantoin
*one of the most common drug-induced pulmonary diseases

Question 16

nitrofurantoin & drug-induced lung disease - treatment

Answer 16

*discontinue nitrofurantoin

Question 17

volatile inhalants & drug-induced lung disease - MOA and toxicity

Answer 17

*volatile liquids become gaseous at room temperature and are inhaled
*multitude of products (paint thinner, gasoline, glue, felt-tip markers)
*nearly all are CNS DEPRESSANTS when abused

Question 18

volatile inhalants & drug-induced lung disease - clinical manifestations

Answer 18

*typical scenario: a patient with a history of dug abuse found obtunded, with slurred speech, and hypoventilating (respiratory acidosis)
*inhalants will likely be mentioned in vignette
*may also see paint or other stains on face, clothing, or nearby rags

Question 19

volatile inhalants & drug-induced lung disease - treatment approach

Answer 19

*remove the patient from the source of the exposure
*supportive care for respiratory depression

Question 20

nicotine/tobacco & drug-induced lung disease - MOA and toxicity

Answer 20

*nicotine: rapidly absorbed and acts on nicotinic cholinergic brain receptors, acting as a stimulant; highly addictive
*combustion of tobacco: several thousand different chemicals, including nicotine, carbon monoxide, acrolein; all can cause illness through systemic absorption and/or local pulmonary oxidative injury

Question 21

nicotine/tobacco & drug-induced lung disease - clinical manifestations

Answer 21

*acute stimulant effects of nicotine: systemic hypertension, increased heart rate and myocardial work, relative hypoxemia (COHb of 10%)
*long term effects: cardiovascular disease, emphysema, COPD, asthma, CANCER

Question 22

nicotine/tobacco & drug-induced lung disease - treatment

Answer 22

*smoking cessation (difficult due to chemical + behavioral addiction)

Question 23

vapes/ENDS & drug-induced lung disease - MOA and toxicity

Answer 23

*use varying strengths of electric current to vaporize liquid; this is NOT water vapor and is NOT smoke
*liquid may contain nicotine, THC, flavorings, etc
*acute inhalation causes increased airway resistance and inflammation

Question 24

vapes/ENDS & drug-induced lung disease - clinical manifestations

Answer 24

*nicotine/THC effects
*EVALI: e-cigarette and vaping-associated lung injury

Question 25

vapes/ENDS & drug-induced lung disease - treatment

Answer 25

*cessation strategies as for tobacco/nicotine, marijuana/THC addiction
*not approved for use in tobacco cessation

Question 26

cannabis/marijuana (THC) & drug-induced lung disease - terminology

Answer 26

*cannabis sativa is the plant
*marijuana refers to the part of the plant with substantial amounts of tetrahydrocannabinol (THC)
*THC is the psychoactive constituent of marijuana
*cannabidiol (CBD) is another biologically active compound in Cannabis

Question 27

cannabis/marijuana (THC) & drug-induced lung disease - MOA and toxicity

Answer 27

*THC causes direct (sympathomimetic) and indirect (anxiety/hallucination) stress on the cardiovascular system, and varies with the amount inhaled
*COMBUSTION of cannabis results in a similar plume as tobacco containing many of the same carcinogens and toxicants
*method of inhalation for cannabis differs (longer breath holds) resulting in greater CARBOXYHEMOGLOBIN

Question 28

cannabis/marijuana (THC) & drug-induced lung disease - clinical manifestations

Answer 28

*hyperemesis syndrome
*emphysema, lung cancer risk is likely and yet to be proven

Question 29

cannabis/marijuana (THC) & drug-induced lung disease - treatment

Answer 29

*avoidance, behavioral cessation strategies

Question 30

cocaine & drug-induced lung disease - forms

Answer 30

*powdered cocaine
*“crack” freebase cocaine

Question 31

cocaine & drug-induced lung disease - MOA and toxicity

Answer 31

*SYMPATHOMIMETIC - vasoconstriction, tachycardia, hypertension through stimulation of beta adrenergic receptors
*can be inhaled nasally, injected, or smoked (crack)

Question 32

cocaine & drug-induced lung disease - clinical manifestations

Answer 32

*hemorrhagic alveolitis
*pulmonary edema
*pulmonary hypertension

Question 33

cocaine & drug-induced lung disease - treatment

Answer 33

*AVOID BETA BLOCKERS in acute toxicity
*cessation counseling and behavioral strategies

Question 34

heroin & drug-induced lung disease - MOA and toxicity

Answer 34

*synthetic derivative of morphine, opioid agonist
*direct toxic effect on the alveolar-capillary membrane, possible hypersensitivity reaction

Question 35

heroin & drug-induced lung disease - clinical manifestations

Answer 35

*HEROIN-INDUCED PULMONARY EDEMA
*obtundation -> hypoventilation -> hypercarbic respiratory failure
*bronchiectasis and necrotizing infection from aspiration
*vascular embolization of talcum or other fill material

Question 36

heroin & drug-induced lung disease - treatment

Answer 36

*NALOXONE opioid antagonist temporarily counters effects (nasal or IV administration)
*cessation requires intensive behavioral counseling and support
*meds exist to help with cessation (methadone, buprenorphine, naltrexone)