2. Drug-Induced Pulmonary Diseases
2
Manifestations of drug-induced pulmonary diseases
span the entire spectrum of pathophysiologic
conditions of the respiratory tract
The pathological changes are nonspecific
The true incidence of drug-induced pulmonary disease
is difficult to assess as a result of the pathological non-
specificity and the interaction between the underlying
disease state and the drugs.
3. Drug-Induced Apnea
3
Apnea may be induced by CNS depression or
respiratory neuromuscular blockade
Combining intravenous diazepam with phenobarbital to
stop seizures in an emergency department frequently
results in admissions to an intensive care unit for a short
period of assisted mechanical ventilation, regardless of
the drug administration rate.
Too rapid intravenous administration of any of the
benzodiazepines, even without coadministration of other
respiratory depressants, will result in apnea
4. Drugs causing apnea
4
Relative Frequency of Reactions
Central nervous system depression
Narcotic analgesics
Barbiturates
Benzodiazepines
Other sedatives and hypnotics
Tricyclic antidepressants
Phenothiazines
Ketamine
Promazine
Anesthetics
Antihistamines
Alcohol
Fenfluramine
L-Dopa
Oxygen
F
F
F
I
R
R
R
R
R
R
I
R
R
R
Respiratory muscle dysfunction
Aminoglycoside
antibiotics
Polymyxin
antibiotics
Neuromuscular
blockers
Quinine
Digitalis
I
I
I
R
R
Myopathy
Corticosteroids
Diuretics
Aminocaproic
acid
Clofibrate
F
I
R
R
F, frequent; I, infrequent; R, rare.
5. Drug-Induced Bronchospasm
5
Bronchospasm can be induced by a wide variety of
drugs through a number of disparate
pathophysiologic mechanisms
Drug-induced bronchospasm is almost exclusively a
problem of patients with preexisting bronchial
hyperreactivity (e.g., asthma, COPD)
Beta Blockers comprise the other large class of
drugs that can be hazardous to a person with
asthma
Aspirin-Induced Bronchospasm
Aspirin sensitivity or intolerance occurs in 4% to 20% of all
asthmatics.
frequency increases with age.
6. ACE Inhibitor—Induced Cough
6
Cough has become a well-recognized side effect of
ACEIs
The cough is typically dry and nonproductive, persistent,
and not paroxysmal.
The severity of cough varies from a "tickle" to a debilitating
cough with insomnia and vomiting
The cough can begin within 3 days or have a delayed onset
of up to 12 months following initiation of ACE inhibitor
therapy
The cough remits within 1 to 4 days of discontinuing therapy
but (rarely) can last up to 4 weeks and recur with
rechallenge.
7. Narcotic-Induced Pulmonary Edema
7
The most common drug-induced noncardiogenic
pulmonary edema is produced by the narcotic
analgesics
Cardiogenic pulmonary edema
• Excessive intravenous fluids
• Blood and plasma transfusions
• Corticosteroids
• Phenylbutazone
• Sodium diatrizoate
• Hypertonic intrathecal saline
• Beta 2-Adrenergic agonists
F
F
F
R
R
R
I
Noncardiogenic pulmonary edema
• Heroin
• Methadone
• Morphine
• Oxygen
F
I
I
I
8. Pulmonary Fibrosis
8
A large number of drugs are associated with chronic
pulmonary fibrosis with or without a preceding acute
pneumonitis
The cancer chemotherapeutic agents make up the
largest group and have been the subject of numerous
reviews
Drugs Associated with Pulmonary Fibrosis
Antineoplastics : bleomycin, busulfan, and carmustine
(BCNU).
BCNU is associated with the highest incidence of
pulmonary toxicity (20% to 30%)
Alkylating Agents: Mitomycin, Chlorambucil, melphalan
Antimetabolites : Methotrexate
9. Drugs Associated with Pulmonary
Fibrosis
9
Noncytotoxic Drugs
Pulmonary fibrosis associated with the ganglionic-blocking
agent hexamethonium was first reported in 1954
Amiodarone
Acute pleuritis with pleural effusions and fibrosis is a
prominent manifestation of drug-induced lupus
syndrome.
Procainamide is associated with the largest number of
pulmonary reactions, with 46% of patients with the
lupus syndrome developing pulmonary complications
Hydralazine is the next most common cause of lupus
syndrome
