Transcript Blue Water Flow

Drug induced airways diseases
Dr. Mohammed Hussain Kamel
MBBCH. MSC. MD.
Ass.professor of chest disease
Benha University
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Background
More than 600 drugs are known to cause pulmonary toxicity. This number
will undoubtedly continue to increases as new therapeutic agents and
illicit drugs are developed. Because the medications that cause
respiratory diseases are used by a variety of healthcare providers,
including generalists, specialists, and subspecialists, virtually no area of
medicine is free from encounters of patients experiencing adverse drug
reactions.
To minimize the potential morbidity and mortality from drug – induced
respiratory diseases, health care providers should be familiar with the
possible adverse effects of the medications they prescribe, Recognition
of drug – induced lung disease is difficult because the clinical,
radiological, and histological findings are nonspecific. Instead, health
care providers can make a correct diagnosis only if they are aware of the
drugs that have been identified to cause pulmonary reactions and their
specific manifestation. (Tamura M, et al, 2013).
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Pathophysiology
Medications can elicit a wide variety of thoracic tissue effects and
responses. The adverse reactions can involve the pulmonary
parenchyma, the pleura, the airways, the pulmonary vascular system,
the mediastinum, and neuromuscular system. The clinical and
histopathological entities reported as drug – induced pulmonary
toxicities are listed below. (Tamura M, et al, 2013).
Adverse reactions involving the airways are as follows:
- Bronchospasm, bronchoconstriction, asthma.
- Bronchiolitis obliterans.
- Cough
- Dysphonia or hoarseness.
- Calcification of cartilaginous rings
- Eosinophilic granulomatosis with polyangiitis (Churg- Strauss
syndrome)
- Cryptogenic organizing pneumonia. ( Tamura M, et al, 2013).
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Mechanisms of pulmonary injury:
Pulmonary toxicity secondary to drugs may
be due to a variety of mechanisms, which
are as follows
oxidant injury
Pulmonary vascular damage.
Deposition of phospholipids within cells.
Immune system- mediated injury.
Central nervous system (CNS) depression.
Direct toxic effect.(De Vuyst P, et al.1997).
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Risk factors
-Adveanced age.
- Cumulative dose.
- Simultaneous oxygen therapy.
- Combination therapy.
- Radiation therapy.
- Occupational factors.
- Underlying lung disease.
- Genetic factors. (Hillerdal G, et al,1997).
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Bronchospasm
Anti – inflammatory drugs
Aspirin
Aspirin – induced asthma (AIA) occurs in less than 1% of healthy individuals and
up to 20% of asthmatic individuals.
The pathogensis of AlA is mediated by the production of potent inflammatory and
bronchoconstrictor leukortiene (LT) mediatiors such as LTC4, LTD4 , and LTE4 via
activation of the 5- lipoxygenase pathway.
In addition to whezzing, reactions are usually accompanied by nasal and ocular
sympthoms. Including congestion. Rhinorrhea, and tearing. Facial flushing,
angioedema, and gastrointestinal symptoms can also occur. The Samter triad is
asthama, nasal polyps, and aspirin sensitivity. The treatment of AIA is streroid
therapy and discontinuation of aspirin and NSAIDs.
Of elderly patients on long –term aspirin therapy, 10-15% develop NCPE. It usually
occurs when the serum salysalate level is greater than 40 mg/dl. Treatment is
usually supportive, but some patients require Hemo dialysis. Long – term
salicylate ingestion can manifest as pseudoseptic syndrome (fever, tachycardia,
elvated white blod cell count, hypotension, ARDS, and altered mental status).
Elevated salicylate levels are Helpful in diagnosing this condition (Meune, et al.,
2000).
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Penicillamine
Penicillamine is an anti- inflammatory agent mostly used in the treatment
of rheumatoid arthristis. It can cause bronchiolitis obliterans,
penicillamine - inuced systemic lupus erythmatosus, pulmonary – renal
syndrome, and pneumonitis. Management includes withdrawal of the
drug. Supportive therapy, and consideration of a trial of corticosteroids.
In general, the prognosis is poor (Fisma et al.,2002).
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Bronchospasm has also been reported with the use of the
following agents:
- inhaled pentamidine.
- Amphotericin B .
- Amiodarone
- Angiotensin- converting enzyme (ACE) inhibitors.
- Dipyridamole.
- Nitrofurantion
- Beta- blockers
- Penicillamine.
Because HIV infection is now better controlled and patients are
treated for many years. Further study of antiretroviral therapy
(ARVT) and lung function will determine whether bronchospasm
reverses after cessation of ARVT. In one study of pulmonary
function abnormalities in patients with HIV receiving ARVT.
University analysis demonstrated the ARVT is a risk factor for
airway obstruction unresponsive to bronchodilator treatment.
With an odds ratio of 4.71. (Gingu et al., 2010).
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ACE inhibitors :
Up to 20% of patients develop a dry cough after talking ACE inhibitor. The exact
mechanism of ACE inhibitor Cough is unknown. But it is thought to be linked to
the accumulation of substances normally metabolized by ACEI Theses substances
include bradykinin or tackykinins (with the consequent stimulation of vagal
afferent nerve fibers) and substance P.
Resolution of ACE inhibitor – induced cough usually occurs within 1-4 days but
may take weeks to months. Patients can be switched to an Anegiotensine receptor
blocker. Which rarely induces cough. Salindac has been reported to be benefit in
the management of ACE inhibitor – induced cough. Studies have also suggested
that intermediate doses of aspirin (500mg/d) , but not low doses (100mg/d), can
suppress ACE inhibitor cough.
Although ACE inhibitors are generally safe in most patients with obstructive
airways disease, Case reports suggest that in a subpopulation of patients, these
agents can increase bronchial reactivity, asthma symptoms, or exacerbations.
Another symptom of ACEI therapy is angioneuotic edema (0.68% of patients). It
manifests as swelling of the tongue. Lips, and mucous membranes within hours or
weeks after initiating treatment and can rapidly evolve in to respiratory distress.
This complication can be treated with a subcutaneous injection of epinephrine
every 15-20 minutes, diphenhydramine, and steroid therapy.(Skotis et. al., 2004) .
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Beta – Blockers
Beta – blockers can precipitate bronchospasm in patients with
asthma or chronic obstructive pulmonary disease (COPD). The
benefits of using beta – blockers Like any other drug Must be
weighed on a case – by – case basis against the risk of adverse
effects.
In patients with stable COPD or asthma, beta – blockers can be
started at low doses, with careful monitoring for adverse effects,
Because of its cardioselecitvity, atenolol is the drug of choice for
an individual with obstructive airways disease who needs a beta –
adrenergic antagonist.
Esmolol is the drug of choice in critically ill patients with asthma
or COPD who require a beta- blocker (unstable angina), owing to
its beta 1 selectivity and extremely short half – life (9 min).
Importantly, ophtalmic beta – blockers, such as timolol, which are
used in the tratement of glaucoma have produces a number of
deaths secondary to exacerbation of COPD and asthma. Betaxolol
ophthalnmic may be a safer altermative to timolol (Dunn et al.,
1986).
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Cocaine
Cocaine is one of the most frequently used illicit drugs in the
United State. Inhalation of Cocaine may result in
pneumomediastinum and pneumothorax. Smoking of cocaine is
associated with the following effects.
Acute exacerbations of asthma.
Bronchiolitis obliterans.
Cardiogenic pulmonary edema.
NCPE. (Donnel et al.,1991).
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Diagnosis :
Correct identification of the drug, its dose, and its duration of
administration.
Exclusion of other primary or secondary lung diseases.
Temporal eligibility – Appropriate latent period (exposure to
toxicity).
Recurrence with rechallenge (a practice not commonly
performed).
Singularity of drug (ie, other drugs the patient is taking).
Remission of symptoms with removal of the drug.
Characteristic pattern of reaction to a specific drug (perhaps
previous documentation).
Quantification of drug levels that confirm abnormal levels
(especially for overdoses).
Degree of certainty of drug reaction (ie, causative, probable, or
possible) (Tamera et al., 2013). .
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Management
The treatment of drug – induced lung disease consists of
immediately discontinuing the offending drug and appropriately
managing the pulmonary symptoms. Acute episodes of drug –
induced pulmonary disease ofen remit 24-48 hours after the drug
has been discontinued. Chronic syndromes may take a month or
months to resolve.
General supportive measures include the following:
Smoking cessation.
Control of other chronic underlying lung disease.
Prompt treatment of concomitant respiratory infections.
Anecdotal reports indicate that glucocorticoid therapy has been
associated with rapid improvement in gas exchange and reversal
of radiographic abnormalities in some drug – induced pulmonary
toxicities (Iry et al., 1976)
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References
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resolution computed tomography findings for patients with drug – induced
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patterns in gemcitabine – induced cases. Oncologist. 2013; 18 (4): 454- 9.
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