Respiratory drugs
د.جمال
1
DRUGS FOR DISORDERS OF THE
RESPIRATORY SYSTEM
Asthma, chronic obstructive pulmonary disease (COPD), and allergic rhinitis are commonly encountered
respiratory disorders.
DRUGS USED TO TREAT ASTHMA
Asthma is a chronic inflammatory disease of the airways characterized by episodes of acute
bronchoconstriction causing shortness of breath, cough, chest tightness, wheezing, and rapid
respiration.
Pathophysiology of asthma
Airflow obstruction in asthma is due to bronchoconstriction that results from contraction of bronchial
smooth muscle, inflammation of the bronchial wall, and increased secretion of mucus
Asthma attacks may be triggered by exposure to allergens, exercise, stress, and respiratory infections.
Goals of therapy
Quick-relief medication to treat acute asthma symptoms
Longterm control of asthma to reverse and prevent airway inflammation.
β2-Adrenergic agonists
Inhaled β2-adrenergic agonists directly relax airway smooth muscle.
They are used for the quick relief of asthma symptoms, as well as adjunctive therapy for long-term
control of the disease.
1. Short-acting β2 agonists (SABAs)
Members: albuterol (salbutamol) and levalbuterol
Onset & duration: rapid onset of action (5 to 30 minutes) and provide relief for 4 to 6 hours.
Use:
o They provide a quick relief of acute bronchoconstriction.
o All patients with asthma should be prescribed a SABA inhaler.
o They should never be used as the sole therapeutic agents except in patients with
intermittent asthma or exercise-induced bronchospasm.
Action:
o These agents provide significant bronchodilation with little of the undesired effect of α
or β1 stimulation.
o β2 agonists have no antiinflammatory effects,
Adverse effects: tachycardia, hyperglycemia, hypokalemia, and hypomagnesemia (minimized
with inhaled delivery). These agents can cause β2-mediated skeletal muscle tremors.
2. Long-acting β2 agonists (LABAs)
Members: salmeterol, formoterol,
arformoterol &
indacaterol
They have a long duration of action, providing bronchodilation for at least 12 hours
Uses:
o Used only in combination with inhaled corticosteroids (ICS) in long-term control.
o Use of LABA monotherapy is contraindicated
o They shouldnot be used for quick relief of an acute asthma attack.
Adverse effects of LABAs are similar to quick-relief β2 agonists
Respiratory drugs
د.جمال
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Corticosteroids
ICS (inhaled corticosteroids) are the drugs of choice for long-term control in patients with any degree of
persistent asthma.
To be effective in controlling inflammation, glucocorticoids must be used regularly.
Severe persistent asthma may require the addition of a short course of oral glucocorticoid
treatment.
They include (inhaled corticosteroids)
Beclomethasone
Fluticasone
Mometasone
Triamcinolone
Budesonide
Ciclesonide
Actions on lung:
ICS therapy directly targets underlying airway inflammation by decreasing the inflammatory cascade,
reversing mucosal edema, decreasing the permeability of capillaries, and inhibiting the release of
leukotrienes.
After several months of regular use, ICS reduce the hyperresponsiveness of the airway smooth muscle to
a variety of bronchoconstrictor stimuli, such as allergens, irritants, cold air, and exercise.
Routes of administration
a. Inhalation:
Used to decrease the systemic side effects
Appropriate inhalation technique is critical to the success of therapy
b. systemic (Oral or parenteral): Patients with a severe exacerbation of asthma (status asthmaticus)
may require intravenous steroids (hydrocortisone or methylprednisolone) or oral prednisone to reduce
airway inflammation.
Chronic maintenance with systemic administration of corticosteroids should be reserved for patients
who are not controlled on an ICS.
Adverse effects:
Oral or parenteral glucocorticoids have a variety of potentially serious side effects, whereas ICS,
particularly if used with a spacer, have few systemic effects.
ICS: deposition on the oral and laryngeal mucosa can cause adverse effects, such as
oropharyngeal candidiasis (due to local immune suppression) and hoarseness. Patients should
be instructed to rinse the mouth in a “swish-and-spit” method with water following use of the
inhaler to decrease the chance of these adverse events.
ALTERNATIVE DRUGS USED TO TREAT ASTHMA
These drugs are useful for treatment of asthma in patients who are poorly controlled by conventional
therapy or experience adverse effects secondary to corticosteroid treatment.
These drugs should be used in conjunction with ICS therapy for most patients, not as monotherapy.
Respiratory drugs
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A. Leukotriene modifiers
Leukotrienes (LT) B4 and the cysteinyl leukotrienes, LTC4, LTD4, and LTE4, are products of the
arachidonic acid metabolism and part of the inflammatory cascade.
LTB4 is a potent chemoattractant for neutrophils and eosinophils, whereas the cysteinyl leukotrienes
constrict bronchiolar smooth muscle, increase endothelial permeability, and promote mucus secretion.
Action:
Zileuton prevent the formation of both LTB4 and the cysteinyl leukotrienes.
Zafirlukast and montelukast are selective antagonists of the cysteinyl leukotriene-1 receptor.
All three drugs are approved for the prevention of asthma symptoms.
They should not be used in situations where immediate bronchodilation is required.
Pharmacokinetics:
Orally active
Highly protein bound.
Metabolized extensively by the liver.
Zileuton and its metabolites are excreted in urine, whereas zafirlukast, montelukast, and their
metabolites undergo biliary excretion.
Adverse effects:
Elevations in serum hepatic enzymes
Headache
Dyspepsia.
B. Cromolyn
Cromolyn is a prophylactic anti-inflammatory agent that inhibits mast cell degranulation and release of
histamine.
It is not useful in managing an acute asthma attack.
Adverse effects are minor and include cough, irritation, and unpleasant taste.
C. Cholinergic antagonists
MOA: The anticholinergic agents block vagally mediated contraction of airway smooth muscle
and mucus secretion.
Inhaled ipratropium has a much slower onset than inhaled SABAs.
Uses:
Useful in patients who are unable to tolerate a SABA or
Patients with concomitant COPD.
Used with a SABA for the treatment of acute asthma exacerbations in the emergency
department.
Adverse effects such as xerostomia and bitter taste.
D. Theophylline
Theophylline is a bronchodilator that relieves airflow obstruction in chronic asthma and decreases its
symptoms.
Theophylline has been largely replaced with β2 agonists and corticosteroids due to its narrow
therapeutic window, adverse effect profile, and potential for drug interactions.
Overdose may cause seizures or potentially fatal arrhythmias.
Respiratory drugs
د.جمال
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E. Omalizumab
Omalizumab is a recombinant DNA-derived monoclonal antibody that selectively binds to human
immunoglobulin E (IgE). This leads to decreased binding of IgE to its receptor on the surface of mast cells
and basophils. Reduction in surface-bound IgE limits the release of mediators of the allergic response.
Omalizumab is indicated for the treatment of moderate to severe persistent asthma in patients who are
poorly controlled with conventional therapy.
Adverse effects include serious anaphylactic reaction (rare), arthralgias, fever, and rash. Secondary
malignancies have been reported.
DRUGS USED TO TREAT CHRONIC OBSTRUCTIVE
PULMONARY DISEASE
COPD is a chronic, irreversible obstruction of airflow that is usually progressive.
Smoking is the greatest risk factor for COPD
Drug therapy for COPD is aimed at relief of symptoms and prevention of disease progression.
A. Bronchodilators
Inhaled bronchodilators, including the β2-adrenergic agonists and anticholinergic agents
(ipratropium and tiotropium), are the foundation of therapy for COPD.
These drugs increase airflow, alleviate symptoms, and decrease exacerbation rates.
B. Corticosteroids
The addition of an ICS to a long-acting bronchodilator may improve symptoms, lung function
and quality of life in COPD patients.
The use of an ICS is associated with an increased risk of pneumonia, and therefore, use should
be restricted to COPD patients with FEV1 of less than 60% predicted these patients.
Oral corticosteroids are not recommended for long-term treatment but can be used for short
period in acute exacerbations.
C. Other agents
Roflumilast is an oral phosphodiesterase-4 inhibitor used to reduce exacerbations in patients
with severe chronic bronchitis by reducing the inflammation. Roflumilast is not a
bronchodilator and is not indicated for the relief of acute bronchospasm.
Its use is limited by common side effects including nausea, vomiting, diarrhea, and
headache.
Theophylline has largely been replaced by the long-acting bronchodilators.
Respiratory drugs
د.جمال
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DRUGS USED TO TREAT ALLERGIC RHINITIS
Rhinitis is an inflammation of the mucous membranes of the nose and is characterized by
sneezing, itchy nose/eyes, watery rhinorrhea, nasal congestion, and sometimes, a
nonproductive cough.
Antihistamines and/or intranasal corticosteroids are preferred therapies for allergic rhinitis.
A. Antihistamines (H1-receptor blockers)
Antihistamines are useful for the management of symptoms of allergic rhinitis. However, they
are more effective for prevention of symptoms, rather than treatment once symptoms have
begun.
First-generation antihistamines, such as diphenhydramine and chlorpheniramine, are usually
not preferred due to adverse effects, such as sedation, performance impairment, and other
anticholinergic effects.
The second-generation antihistamines (for example, fexofenadine, loratadine, desloratadine,
cetirizine, and intranasal azelastine) are generally better tolerated.
B. Corticosteroids
Intranasal corticosteroids, such as beclomethasone, budesonide, fluticasone, and triamcinolone,
are the most effective medications for treatment of allergic rhinitis.
Systemic absorption is minimal, and side effects of intranasal corticosteroid treatment are
localized. These include nasal irritation, nosebleed, sore throat, and, rarely, candidiasis.
To avoid systemic absorption, patients should be instructed not to inhale deeply while
administering these drugs because the target tissue is the nose, not the lungs or the throat. For
patients with chronic rhinitis, improvement may not be seen until 1 to 2 weeks after starting
therapy.
C. α-Adrenergic agonists
Constrict dilated arterioles in the nasal mucosa and reduce airway resistance.
Short-acting α-adrenergic agonists (“nasal decongestants”), such as phenylephrine,
Longer-acting oxymetazoline is also available.
When administered as an aerosol, these drugs have a rapid onset of action and show
few systemic effects.
Unfortunately, the α-adrenergic agonist intranasal formulations should be used no
longer than 3 days due to the risk of rebound nasal congestion (rhinitis medicamentosa).
For this reason, the α-adrenergic agents have no place in the long-term treatment of
allergic rhinitis.
D. Other agents
Intranasal cromolyn.
LT antagonists
An intranasal ipratropium
Respiratory drugs
د.جمال
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DRUGS USED TO TREAT COUGH
Coughing is an important defense mechanism of the respiratory system to irritants & before
treating cough, identification of its cause is important to ensure that antitussive treatment is
appropriate.
The
priority
should
always
be
to
treat
the
underlying
cause of cough when possible.
A. Opioids
Codeine, an opioid,
o Decreases the sensitivity of cough centers in the central nervous system to
peripheral stimuli and decreases mucosal secretion.
o Effects occur at doses lower than those required for analgesia.
o Side effects: constipation, dysphoria, fatigue, and addictive potential.
Dextromethorphan is a synthetic derivative of morphine that
o Has no analgesic effect in antitussive doses.
o Has a low addictive profile.
o Has a significantly safer side effect profile than codeine and is equally effective
for cough suppression.
Guaifenesin, an expectorant
B. Benzonatate
Unlike the opioids, benzonatate suppresses the cough reflex through peripheral action. It
anesthetizes the stretch receptors located in the respiratory passages, lungs, and pleura.
Side effects include dizziness, numbness of the tongue, mouth, and throat.