DRUG INDUCED PULMONARY

DISEASES

By,
WIONA DENITA MORAS
1ST Year M.Pharm
Dept. of Pharmacy Practice
NGSMIPS, Nitte University
DEFINITION

A number of medications are known to cause undesirable reactions and lead to changes in the lungs or alter respiratory functions. These reactions are known as Drug-induced pulmonary diseases.

It can be suspected if the patient has been exposed to the drug, develops new signs and symptoms, and has a remittance of these symptoms once the suspected drug is withheld
 ADVERSE DRUG
REACTION CAN INVOLVE

Pulmonary
Pleura Airways
parenchyma

Neuromuscular Pulmonary
Mediastinum
junction vascular system
 Etiology
• DIPD is caused by the use of certain medications/ drugs that are injurious to the
lungs. There are many different drugs that can cause the condition such as:

• Certain antibiotics that include sulfa medications and nitrofurantoin given for
UTI’s

• Medications to treat heart conditions, such as amiodarone, commonly prescribed

for rhythm abnormalities of the heart

• Recreational and illegal drugs such as heroin and cocaine

• Some chemotherapy drugs for cancer treatment such as bleomycin,

cyclophosphamide and methotrexate

• Based on the health condition of each individual, the severity of DIPD

can range from mild to causing extreme harm to the lungs. In some cases,
lung damage may be irreversible.
Pathogenesis of DIPD
Theortic mechanism 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
 TYPES OF DRUG INDUCED PULMONARY DISEASES

1) Bronchospasm, wheezing and cough

2) Pulmonary edema
3) Pulmonary hypertension
4) Interstitial lung disease
-Interstitial pneumonia/infiltrates
-Pulmonary fibrosis
5) Pumonary eosinophilia
6) Pleural inflammation
7) Diffuse alveolar hemorrhage/vasculitis
8) Diffuse alveolar damage
9) Drug hypersentivity syndrome
10) Amidarone induced pulmonary toxicity
1. Bronchospasm, wheezing, and cough

• Bronchospasm is the most common drug-induced pulmonary adverse event.

• Clinical presentation is the same as with nondrug-induced bronchospasms.
Risk factors :Pre-existing hyperreactive lung disease, smoking, advanced age and respiratory
infections.

Management :

• Withdrawal and avoidance of the causative agent

• Treat acute anaphylaxis with small doses
• Oxygen, corticosteroids and parenteral antihistamines
• Inhaled β2-agonists are useful for persistent bronchospasm
Aspirin induced Bronchospasm:

• Aspirin have the highest incidence of drug-induced bronchospasm.

• It begins within minute to hours following ingestion of aspirin.

• Clinical representation includes conjuctivities ,rhinorrhea ,flushing of head and

neck

• MOA -inhibition of cycloxygenase

• Treatment includes desensitization or avoidance .

2. Acute pulmonary edema

symptoms:
• dyspnea, chest discomfort, hypoxemia
• Acute Respiratory Distress Syndrome (ARDS)

Management:

specific therapy that targets the causes of the accumulation of extravascular water
in the lungs

a. Cardiogenic

pulmonary edema can have an insidious onset

Symptoms : mild pedal edema, and exertional dyspnea.

b. Noncardiogenic pulmonary edema (NCPE)

NCPE consist of most cases of drug-induced pulmonary edema via drug-related

increases in capillary pulmonary permeability.

treatment may require mechanical ventilatory support with positive pressure.

Drugs causing NCPE:

Antineoplastic agents,cytarabine,interleukin-2 (IL-2),mitomycin,vinca alkaloids

3. Pulmonary hypertension

It is rare, but life threatening.

symptoms: The most frequent presenting symptom is exertional dyspnea, fatigue,

weakness, chest pain.

Management :

diuretics, inotropic agents, anticoagulants, prostacyclin analogues (eg. epoprostenol),

an endothelin receptor antagonist (e.g., bosentan), and calcium channel blockers.

4. Interstitial lung disease(ILD)

It can lead to respiratory failure.

Symptoms: nonproductive cough, dyspnea, low-grade fever.

Diagnosis: based on temporal association between exposure and development of

pulmonary infiltrate with meticulous exclusion of other potential causative factors.

Management: drug withdrawal, respiratory failure is commonly treated with high-dose

methylprednisolone, Respiratory distress is commonly treated with low-dose
methylprednisolone.
 a. Interstitia infiltrates/pneumonia

The infiltrates consist of fluid and/or cells that gather in this area of the lung.

Drug causing Intestinal pneumonia :

• Epidermal growth factor receptor antagonist

• Methotrexate
• Nitrofurantoin
• Tyrosine kinase inhibitor

b. Pulmonary fibrosis

Pulmonary fibrosis is characterized by accumulation of excessive connective tissue in the

lung caused by prolonged exposure to certain drugs.

activation of the coagulation cascade and generation of coagulation proteases play a key role.

Drugs causing pulmonary fibrosis:

Cytotoxic drugs : bleomycin, busulfan ,cyclophosphamide

Non-cytotoxic drugs : amiodarone, bromocriptine, nitrofurantoin, heroin

c. Bronchiolitis obliterans organizing pneumonia(BOOP)

BOOP is an inflammation of the lungs characterized by alveolar fibrosis.

More than 20 medications are associated with BOOP

Symptoms : dyspnea, low-grade fever and acute pleuritic chest pain.

Dugs causing BOOP:

Antimicrobials : amphotericin B, cephalosporins,minocycline,nitrofurantoin

Cytotoxic drugs: bleomycin, doxorubicin

Cardiovascular drugs: acebutolol,amiodarone

5. Pulmonary eosinophilia

• characterized by pulmonary infiltration of eosinophils in alveolar space, the

interstitium or both.

• When found with peripheral eosinophilia it is called as pulmonary infiltrates

syndrome.

• Diagnosis is done lung biopsy

• Loeffler syndrome

Drugs causing Pulmonary eosinophilia:

NSAID ,Nitrofurantoin,Antimicrobial agents, minocyclin.

6. Pleural inflammation

Drug-induced pleural reactions are rare compared with those affecting the
parenchyma.

symptoms: pleuritic chest pain, dyspnea, and cough.

mechanisms for the development of drug-induced pleural disease:

hypersensitivity or allergic reaction, direct toxicity, increased production of
oxygen-free radicals, suppression of antioxidant defenses, and chemically-induced
inflammation.

Drugs causing pleural inflammation :

Dantrolene,Ergot alkaloid,Nitrofurantoin
7. Diffuse alveolar hemorrhage(DAH)

DAH is characterized by bleeding from pulmonary capillaries, leading to the

accumulation of red blood cells in the alveolar spaces.

Symptoms: varying degrees of hemoptysis, cough, and progressive dyspnea.

Drug-related pathogenic mechanisms: hypersensitivity reaction, direct toxicity

diffuse alveolar damage (DAD), and coagulation defects.

Drugs causing DAH:

Anticoagulant and thrombolytic,Chemotherapeutic agents,Cocaine

Hydralazine,Nitrofurantoin,Penicillin .
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.

• DAH can develop with resultant hemoptysis.

Dugs causing DAD:

Alkylating agents,Antibiotics,Antimetabolites,Aspirin,Carbamazepine,

Chemotherapeutic agents,Cocaine,Narcotics,Nitrofurantoin
9. Drug hypersensitivity syndrome (DHS)

• DHS is a systemic idiosyncratic reaction defined by the presence of fever, rash,

and organ involvement, including pneumonitis or pulmonary infiltrates.

• It is associated with aromatic anticonvulsants.

• Clinical presentations may involve dermatologic,hematologic, lymphatic or

internal organ systems.

• Management :drug withdrawal, supportive care and corticosteroid therapy.

Drugs causing DTH:

Allopurinol, Anticonvulsant, Sulfonamides

10. AMIODARONE INDUCED PULMONARY TOXICITY(APT )

APT has an average onset of 18-24 months

Symptoms include - fatigue, dyspnea, nonproductive cough, weight loss

MOA: During chronic theraphy amiodarone and its metabolic product DEAm accumulate in lungs which are
toxic to lung cells

Mangement- Corticosteroids theraphy for 6months or 1 year

Eg; 0.75-1mg/kg of oral predinisolone
 CONCLUSION
• About 1.3% of patients experiencing respiratory disorder are due
to drugs. Among this the most common side effect is
bronchospasm.
• Although the overall occurrence of DIPD is relatively rare,
physicians should be aware of these potential side effects and
adverse effects and should be trained to take appropriate measures
when the reactions occur.
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THANK YOU!