1 Drugs Acting on the Respiratory System. 2 Introduction The respiratory system is subject to many...

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Drugs Acting on the Respiratory System

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Introduction The respiratory system is subject to

many disorders that interfere with respiration and other lung functions, including Respiratory tract infections Allergic disorders Inflammatory disorders Conditions that obstruct airflow (e.g.

asthma and chronic obstructive pulmonary disease, COPD)

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Introduction (Cont’d)

Drugs that act on the respiratory system include Bronchodilators Corticosteroids Cromoglycates Leukotriene receptor antagonists Antihistamines Cough preparations Nasal decongestants

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Drugs acting on the respiratory system, especially for asthma, can be administered by inhalation, the advantages are: Enhance therapeutic effects Minimize systemic effects Rapid relief of acute attacks


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Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular, mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, and epithelial cells. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The inflammation also causes an associated increase in the existing bronchial hyperresponsiveness to a variety of stimuli.

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The condition of a patient’s asthma may change depending on the environment, activities, and other factors. When the patient is well, monitoring and treatment are still needed to maintain control.

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There are various types of inhalation devices: Metered-dose inhalers (MDIs)

Pressurized devices that deliver a measured dose of drug with each activation

With CFC or non-CFC propellant Hand-mouth coordination is required


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Spacers: Use with MDIs Increase delivery of drug to the lungs & decre

ase deposition of drug on the oropharyngeal mucosa

Especially important for inhaled corticosteroids


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Dry-powder inhalers (DPIs) Include Turbuhalers & Accuhalers Drugs are in the form of dry, micronized powd

er No propellant is employed Breath activated, much easier to use


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Nebulizers Small machine to convert a drug solution into

mist Droplets in the mist are much finer than those

produced by inhalers Through face mask or mouth piece held betw

een the teeth Take several minutes to deliver the same am

ount of drug contained in 1 puff from an inhaler


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Bronchodilators

Drugs used to relieve bronchospasms associated with respiratory disorders

Includes: Adrenoceptor agonists

Selective β2-agonists & other adrenoceptor agonists

Antimuscarinic bronchodilators Xanthine derivatives

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Bronchodilators (Cont’d)

Adrenoceptor agonists (i) Selective beta2 agonists

Stimulate beta2 receptors in smooth muscle of the lung, promoting bronchodilation, and thereby relieving bronchospasms

They are divided into short-acting & long acting types

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Drug Formulation Dosage

Adult Child

Salbutamol Oral tablet (C.R) 8 mg twice daily 4 mg twice daily

Inhaler (MDI), 100mcg/dose 100-200mcg up to three to four times daily

Same as adult

Syrup, 2mg/5ml 4 mg three to four times daily

1-2 mg three to four times daily (≥2 yr)

Terbutaline Oral tablet (S.R) 5-7.5 mg two times daily -

Inhaler 500mg / dose ( Turbuhaler)

500 mcg up to four times daily

-

Inhaler 250mg / dose (MDI) 250-500mcg up to 3-4 times daily

Same as adult

Short-acting β-2 agonists

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Bronchodilators (Cont’d)Long-acting β-2 agonists


Adult Child

Formoterol Inhaler 4.5mcg / dose (Turbuhaer)

4.5-9 mcg once or twice daily

Same as adult

Inhaler 9mcg / dose (Turbuhaer)

Salmeterol Inhaler 25mcg / dose (MDI)

50-100 mcg twice daily Same as adult

50 mcg / dose (Accuhaler)

50 mcg twice Same as adult

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Adverse effects Tachycardia and

palpitations Headache Tremor

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(ii) Other adrenoceptor agonists Less suitable & less safe for use as bronchod

ilators because they are more likely to cause arrhythmias & other side effects

Ephedrine Adults: 15-60 mg tid po Child: 7.5-30 mg tid po

Adrenaline (epinephrine) injection is used in the emergency treatment of acute allergic and anaphylactic reactions

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Bronchodilators (Cont’d) Nursing Alerts

When 2 or more puffs are needed, inform the patient that at least 1 minute should be allowed between puffs

Inform the patient that salmeterol and formoterol, and oral β-2 agonists should be taken on a fixed schedule, not on a prn basis

Instruct the patient to report chest pain and changes in heart rhythm or rate, because β-2 agonists can cause cardiac stimulation

Contact physician if symptoms such as nervousness, insomnia, restlessness and tremor become severe

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Antimuscarinic bronchodilators Blocks the action of acetylcholine in bro

nchial smooth muscle, this reduces intracellular GMP, a bronchoconstrictive substance

Used for maintenance therapy of bronchoconstriction associated with chronic bronchitis & emphysema

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Adult Child

Ipratropium Inhaler 20 mcg / dose (MDI)

20-80 mcg three to four times a day

20-40 mcg three to four times a day (≥6yrs)

Tiotropium Inhaler 18 mcg /dose 18 mcg daily Not recommended in children and adolescents

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Adverse effects: Dry mouth Nausea Constipation Headache


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Xanthine Derivatives Main xanthine used clinically is theophyllin

e Theophylline is a bronchodilator which rela

xes smooth muscle of the bronchi, it is used for reversible airway obstruction

One proposed mechanism of action is that it acts by inhibiting phosphodiesterase, thereby increasing cAMP, leading to bronchodialtion

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Bronchodilators (Cont’d)Drug Formulation Dosage

Adult Child

Theophylline Tablet 200 / 300 mg (S.R.)

200 – 300 mg twice daily 10 mg / kg ((≥2yrs) twice daily

Capsule 50 / 100 mg (Slow release)

7-12 mg/ kg / day in two divided doses

10-16 mg / kg / day in two divided doses (9–16yrs)

13-20 mg / kg / day in two divided doses (30 months – 8 yrs)

Syrup 80 mg / 15 ml 25 ml q6h 1 ml / kg (Max 25 ml) q6h (≥2yrs)

Aminophylline Injection 25 mg / ml

10 ml

500 mcg / kg / hr IV infusion, adjust when necessary

1 mg / kg /hr (6 months – 9 years)

800 mcg / kg /hr (10 – 16 yrs)

IV infusion, adjust when necessary

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Adverse effects: Toxicity is related to theophyline levels (usuall

y 5-15 µg/ml) 20-25 µg/ml : Nausea, vomiting, diarrhea, ins

omnia, restlessness >30 µg/ml : Serious adverse effects including

dysrhythmias, convulsions, cardiovascular collapse which may result in death

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Nursing alerts:

Plasma theophylline levels should be monitored to keep it in the therapeutic range, usually 5-15 µg/ml. Dosage should be adjusted to keep theophylline levels below 20 µg/ml

If patients miss a dose, the following dose should not be doubled

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Nursing alerts (Cont’d):

Instruct the patient that sustained-release formulations should be swallowed intact

Caution patients in consuming caffeine containing-beverages and other sources of caffeine. Caffeine can intensify the adverse effects and decrease the metabolism of theophylline


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Corticosteroids

Used for prophylaxis of chronic asthma Suppressing inflammation

Decrease synthesis & release of inflammatory mediators

Decrease infiltration & activity of inflammatory cells Decrease edema of the airway mucosa

Decrease airway mucus production Increase the number of bronchial beta2

receptors & their responsiveness to beta2 agonists

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Corticosteroids (Cont’d)


Adult Child

Beclomethasone Inhaler 50 mcg / dose

(MDI)

200 mcg twice daily / 100mcg three to fours times daily

Up to 800 mcg daily

50 – 100 mcg two to four times daily

Inhaler 250 mcg / dose

(MDI)

500 mcg twice daily / 250 mcg four times daily

Not recommended

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Corticosteroids (Cont’d)Drug (Cont’d) Formulation Dosage

Adult Child

Budesonide Inhaler 50 mcg / dose (MDI)

200 mcg twice daily

Up to 1.6 mg daily

50 – 400 mcg twice daily

Up to 800 mcg dailyInhaler 200mcg / dose (MDI)

Inhaler 100 mcg / dose (Turbuhaler)

200-800 mcg once daily in evening

Up to 1.6 mg daily in two divided doses

200-800 mcg daily in two divided doses / 200-400 mcg once daily in evening

(<12 yrs)Inhaler 200 mcg / dose (Turbuhaler)

Inhaler 400 mcg / dose (Turbuhaler)

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Corticosteroids (Cont’d)Drug (Cont’d) Formulation Dosage

Adult Child

Fluticasone Inhaler 25mcg / dose (MDI) 100 – 1000 mcg twice daily

50-100 mcg twice daily (4-16 yrs)

Inhaler 50 mcg / dose (MDI)



Inhaler 50 mcg / dose (Accuhaler)



Acute attacks of asthma should be treated with short courses of oral corticosteroids, starting with a high dose for a few days

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Adverse effects Inhaled corticosteroids:

Candidiasis of the mouth or throat Hoarseness Can slow growth in children Adrenal suppression may occur in long-term,

high dose therapy Increases the risk of cataracts

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Nursing alerts Rinse mouth with water without swallowing

after administration to reduce the risk of candidiasis

If taking bronchodilators by inhalation, use bronchodilators several minutes before the corticosteroid to enhance application of the corticosteroid into the bronchial tract

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Combination Products

May be appropriate for patients stabilised on individual components in the same proportion Muscarinic antagonist+β2 agonist

Combivent (20mcg Ipratropium & 100mcg salbutamol /dose, MDI)

Corticosteroid+β2 agonist Symbicort (160mcg Budesonide+4.5mcg Formoter

ol / dose, Turbuhaler) Seretide (Salmeterol+Fluticasone: MDi in Lite, Med

ium, Forte preparation & Accuhaler)

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Cromoglycates

Stabilise mast cells & prevent the release of bronchoconstrictive & inflammatory substances when mast cells are confronted with allergens & other stimuli

Only for prophylaxis of acute asthma attacks

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Cromoglycates (Cont’d)


Adult Child

Cromoglycate Na Inhaler (1 mg & 5mg/dose)

10 mg four times daily, may be increased to six to eight times daily

Same as adult

Nebuliser solution 10 mg / ml 2 ml

20 mg four times daily, may be increased six times daily

Same as adult

Nedocromil Sodium

Inhaler 2 mg / dose (MDI)

4 mg two to four times daily Sames as adult (>6 yrs)

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Adverse effects Nursing Alerts

Transient Bronchospasm A selective β2 agonist such as salbutamol or terbutaline may be inhaled a few minutes beforehand

Others: coughing, throat irritation

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Nursing Alerts (Cont’d) Cromoglycates are for long-term prophylaxi

s, patients should administer on a regular schedule & the full therapeutic effects may take several weeks to develop

They are contraindicated in patients who are hypersensitive to the drugs


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Leukotriene receptor antagonists

Act by suppressing the effects of leukotrienes, compounds that promote bronchoconstriction as well as eosinophil infiltration, mucus productions, & airway edema

Help to prevent acute asthma attacks induced by allergens & other stimuli

Indicated for long-term treatment of asthma

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Dosage: Montelukast (5 & 10 mg tablets)

Adult: 10 mg daily at bedtime Child:

(2-5yrs) 4 mg daily at bedtime (6-14yrs) 5 mg daily at bedtime

Leukotriene receptor antagonists (Cont’d)

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Adverse effects: GI disturbances Hypersensitivity reactions Restlessness & headache Upper respiratory tract infection Manufacturer advises to avoid these drugs

in pregnancy & breast-feeding unless essential

Leukotriene receptor antagonists (Cont’d)

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Management of Chronic Asthma for adults & schoolchildren above 5yrs

Step 1: Occasional relief short-acting

beta2 agonist

Step 2: Add regular preventer therapyStandard-dose inhaled corticosteroid

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Management of Chronic Asthma for adults & schoolchildren above 5yrs (Cont’d)

Step 3: Add long-acting inhaled beta2 agonist;

dose of inhaled corticosteroid may also be increased

Step 4: Add high dose of inhaled corticosteroids

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Step 5: Add regular oral corticosteroid

E.g. prednisolone

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Stepping down: Review treatment every 3 months If symptoms controlled, may initiate

stepwise reduction Lowest possible dose oral corticosteroid Gradual reduction of dose of inhaled

corticosteroid to the lowest dose which controls asthma


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Antihistamines

H1 receptor antagonists Inhibit smooth muscle constriction in blood

vessels & respiratory & GI tracts Decrease capillary permeability Decrease salivation & tear formation

Used for variety of allergic disorders to prevent or reverse target organ inflammation

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All antihistamines are of potential value in the treatment of nasal allergies, particularly seasonal allergic rhinitis (hay fever)

Reduce rhinorrhoea & sneezing but are usually less effective for nasal congestion

Are also used topically in the eye, in the nose, & on the skin

Antihistamines (Cont’d)

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First-generation H1 receptor antagonists Non-selective/sedating Bind to both central & peripheral H1 recepto

rs Usually cause CNS depression (drowsines

s, sedation) but may cause CNS stimulation (anxiety, agitation), especially in children

Also have substantial anticholinergic effects


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Drug Dosage

Adult Child

Chorpheniramine (4 mg tablet, 2mg/ml Elixir & expectorant)

4 mg q4-6hr, max: 24 mg daily

1-2yrs: 1 mg twice daily

2-12yrs: 1- 2 mg q4-6h, Max:12 mg daily

Hydroxyzine (25 mg tablet)

25 mg at night; 25mg three to four times daily when necessary

6 months-6yrs: 5-15 mg daily; 50 mg daily in divided dose if needed

>6yrs: 15-25 mg daily; 50-100 mg daily in divided dose if needed

Diphendramine (10 mg/5ml Elixir)

25-50 mg q4-6h 6.25-25 mg q4-8 hr ( >1 yr)

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Drug (Cont’d) Dosage

Adult Child

Promethazine (10 & 25 mg tablets, 5mg/5ml Elixir)

25 mg at night; 25 mg twice daily if needed

2-10yrs: 5-25 mg daily in 1 to 2 divided dose

Azatadine (1 mg tablet)

1 mg twice daily 1-12 yrs: 0.25-1 mg twice daily

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Adverse effects: Sedation Dry mouth Blurred vision GI disturbances Headache Urinary retention Hydroxyzine is not recommended for pregn

ancy & breast-feeding

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Second-generation H1 receptor antagonists Selective/non-sedating Cause less CNS depression because they are

selective for peripheral H1 receptors & do not cross blood-brain barrier

Longer-acting compared to first-generation antihistamines


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Antihistamines (Cont’d)Drug Dosage

Adult Child

Acrivastine (Semprex)

8 mg three times daily Not recommended

Cetirizine (Zyrtec)

10 mg daily 5 mg daily / 2.5 mg twice daily (2-6 yrs)

Desloratadine (Aerius)

5 mg daily 1.25 mg daily (2-5 yrs)

2.5 mg daily (6-11yrs)

Fexofenadine (Telfast)

120-180 mg daily Not recommended

Loratadine (Clarityne)

10 mg daily` 5 mg daily (2-5 yrs)

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Adverse effects: May cause slight sedation Some antihistamines may interact with anti

fungal, e.g. ketoconazole; antibiotics, e.g. erythromycin; prokinetic drug-- cisapride or grapefruit juice, leading to potentially serious ECG changes e.g. Terfenadine

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Cough preparations

There are three classes of cough preparations: Antitussives Expectorants Mucolytics

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Antitussives Drugs that suppress cough Some act within the CNS, some act periph

erally Indicated in dry, hacking, nonproductive co

ugh that interfere with rest & sleep

Cough preparations (Cont’d)

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Drug Dosage

Codeine phosphate 25mg/5ml syrup 15-30 mg three to four times daily

Pholcodine 5mg/5ml Elixir 5-10 mg three to four times daily

Dextromethorphan 10mg/5ml in Promethazine Compound Linctus

10-30 mg q4-8h

Diphenhydramine 10 mg/ 5ml 25 mg q4h, Max:150 mg daily

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Adverse effects: Drowsiness Respiratory depression (for opioid antitussi

ves) Constipation (for opioid antitussives) Preparations containing codeine or similar

analgesics are not generally recommended in children & should be avoided altogether in those under 1 year of age


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Nursing Alerts: Observe for excessive suppression of the c

ough reflex (inability to cough effectively when secretions are present). This is a potentially serious adverse effect because retained secretions may lead to lungs collapse, pneumonia, hypoxia, hypercarbia, and respiratory failure


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Expectorants Render the cough more productive by stim

ulating the flow of respiratory tract secretions

Guaifenesin is most commonly used Available alone & as an ingredient in many

combination cough & cold remedies


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Dosage Guaifenesin

100-400 mg q4h po Ammonia & Ipecacuaha Mixture

10-20 ml three to four times daily po


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Mucolytics Reacts directly with mucus to make it more

watery. This should help make the cough more productive


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Dosage Acetylcysteine

100 mg two to four times daily 200 mg two to three times daily 600 mg once daily

Bromhexine 8-16 mg three times daily po

Carbocisteine 750 mg three times daily, then 1.5 g daily in d

ivided doses


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Sympathomimetics are used to reduce nasal congestion

Stimulate alpha1-adrenergic receptors on nasal blood vessels, which causes vasoconstriction & hence shrinkage of swollen membranes

Nasal Decongestants

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Topical administration: Response is rapid & intense

Oral administration: Response are delayed, moderate &

prolonged

Nasal Decongestants (Cont’d)

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Nasal Decongestants (Cont’d)Drug Formulation Dosage

Adult Child

Oxymetazoline Nasal Drops 0.025% 20 ml - 2-3 drops q12h (2-5 yrs)

Nasal Spray 0.05% 15 ml 2-3 sprays q12h Same as adults for children >6 yrs

Phenylephrine Nasal Drops 0.5% 10 ml Several drops q2-4h -

Xylometazoline Nasal Drops 0.05% / 0.1% 2-3 drops q8-10h (0.1%) 2-3 drops q8-10h (2-12 yrs) (0.05%)

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Adverse effects: Rebound congestion develops with topical a

gents when used for more than a few days CNS stimulation (such as restlessness, irrita

bility, anxiety and insomnia) occurs with oral sympathomimetics

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Adverse effects (Cont’d): Sympathomimetics can cause vasoconstric

tion by stimulating α-1 adrenergic receptors. More common with oral agents

Sympathomimetics cause CNS stimulation, and can produce effects similar to amphetamine. Hence, these drugs are subject to abuse


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Nursing alerts: Overuse of topical nasal decongestants ca

n cause rebound congestion, meaning that the congestion can be worse with the use of drug. To minimise this, drug therapy should be discontinued gradually.

The use of topical agents is limited to no more than 3 to 5 days

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Nursing alerts (Cont’d): The patient’s blood pressure and pulse sho

uld be assessed before a decongestant is administered

Inform the patient that nasal burning and stinging may occur with topical decongestants

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Intranasal Corticosteroids

Intranasal Corticosteroids Most effective for treatment of seasonal

and perennial rhinitis Have inflammatory actions and can

prevent or suppress all major symptoms of allergic rhinitis including congestion, rhinorrhea, sneezing, nasal itching and erythema

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Intranasal Corticosteroids (Cont’d)


Adult Child

Beclomethasone Dipropionate

Nasal Spray 50 mcg / dose

1 spray in each nostril four times daily

Max. 10 sprays / day

4-6 sprays / day

Nasal Spray 50 mcg dose (Aqueous)

2 applications into each nostril twice to four times daily

Max. 400 mcg daily

Same as adult (>6 yrs)

Not recommended in children <6yrs

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Drug (Cont’d) Formulation Dosage

Adult Child

Budesonide Nasal Spray 50 mcg / dose (Aqueous)

1-2 sprays into each nostril twice daily; after 2-3days: 1 spray into each nostril twice daily

Not recommended for age 12 yrs or below

Turbuhaler 100mcg / dose

400 mcg in the morning given as 2 applications into each nostril; then reduce to the smallest amount necessary

-

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Drug (Cont’d) Formulation Dosage

Adult Child

Fluticasone Nasal Spray 50 mcg / dose (Aqueous)

2 sprays into each nostril in the morning

Max: 8 sprays/day

1 spray into each nostril in the morning (4-11yrs)

Max: 4 sprays/day

Mometasone Nasal Spray 50 mcg / dose

2 sprays in each nostril once daily; 1spray in each nostril as maintenance

Max: 8 sprays/day

1 spray in each nostril once daily

(3-11yrs)

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Adverse effects: Mild Most common effects are drying of nasal

mucosa & sensations of burning or itching


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Chronic Obstructive Pulmonary Disease (COPD)

Umbrella term for various conditions characterized by limitation of airflow that is not fully reversible

Chronic airflow limitation caused by a mixture of small airway disease and parenchymal destruction

Airflow limitation is often progressive Associated with an abnormal inflammatory

response of lungs to noxious substances PREVENTABLE and TREATABLE disease

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Relationship between COPD and emphysema/chronic bronchitis

Emphysema Destruction of the gas exchanging surfaces of the lung

(alveoli) Pathological term that describes only one of several

structural abnormalities present in patients with COPD Chronic bronchitis

Presence of cough and sputum production for at least 3 months in each of two consecutive years

Remains a clinically and epidemiologically useful term, but does not reflect the major impact of airflow limitation on morbidity and mortality in COPD patients

The emphasis on these conditions are not included in the definition of COPD in current relevant clinical guidelines

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Mechanisms of COPD

Ref: Global Initiative for Chronic Obstructive Lung Disease (GOLD), National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.] World Health Organization - International Agency. 2001 (revised 2006).

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Risk factors

Genes Exposure to particles

Tobacco smoke Occupational dusts, organic and inorganic Indoor air pollution from heating and cooking with biomass in p

oorly vented dwellings Outdoor air pollution

Lung Growth and Development Oxidative stress Gender (appears to be related to cigarette use?) Respiratory infections Socioeconomic status Nutrition Comorbidities (e.g. asthma)

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GOLD report COPD Staging System

Stage / Severity

Postbronchodilator

FEV1/ FVC and FEV1 pred.

Characteristics

Stage I: Mild

FEV1/FVC < 0.70

FEV1 ≥ 80% predicted

chronic cough and sputum production may be present, but not always

Stage II: Moderate

FEV1/FVC < 0.70

50% ≤FEV1 < 80% predicted

shortness of breath typically developing on exertion and cough and sputum production sometimes also present

Stage III: Severe

FEV1/FVC < 0.70

30% ≤FEV1 < 50% predicted

greater shortness of breath, reduced exercise capacity, fatigue, repeated exacerbations that almost always have an impact on patients’ quality of life

Stage IV: Very severe

FEV1/FVC < 0.70

FEV1 < 30% predicted or FEV1 < 50% predicted plus chronic respiratory failure

quality of life is very appreciably impaired and exacerbations may be life threatening

FEV1: forced expiratory volume in one second

FVC: forced vital capacity

Respiratory failure: arterial partial pressure of oxygen (PaO2) less than 8.0 kPa (60 mm Hg) with or without arterial partial pressure of CO2 (PaCO2) greater than 6.7 kPa (50 mm Hg) while breathing air at sea level

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Asthma and COPD

Underlying cause is different Asthma: eosinophilic inflammation COPD: neutrophilic inflammation

COPD can coexist with asthma While asthma can usually be

distinguished from COPD, in some individuals with chronic respiratory symptoms and fixed airflow limitation it remains difficult to differentiate the two diseases

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Differences in causes of COPD and asthma

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Clinical features in COPD and asthma

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Pharmacotherapy

None of the current available medications can alter the natural course of COPD or modify the rate of decline in lung function

Aims (as per GOLD report) Relieve symptoms Prevent disease progression Improve exercise tolerance Improve health status Prevent and treat complications Prevent and treat exacerbations Reduce mortality

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Bronchodilators

Bronchodilator medications are central to symptom management in COPD

Inhaled therapy is preferred The choice between beta agonist, antich

olinergic, theophylline, or combination therapy depends on availability and individual response in terms of symptom relief and side effects

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Bronchodilators are prescribed on an as-needed or on a regular basis to prevent or reduce symptoms

Long-acting inhaled bronchodilators are more effective and convenient

Combining bronchodilators may improve efficacy and decrease the risk of side effects compared to increasing the dose of a single bronchodilator

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Corticosteroids

Effects of oral and inhaled corticosteroids in COPD are much less dramatic than in asthma, and their role in the management of stable COPD is limited to specific indications

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Oral corticosteroids

Use of a short course (two weeks) of oral corticosteroids to identify COPD patients who might benefit from long-term treatment with oral or inhaled corticosteroids is recommended

Due to lack of evidence of benefit, and the issue of side effects, long-term treatment with oral corticosteroids is not recommended in COPD

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Inhaled corticosteroids

Regular treatment is appropriate for symptomatic Stage III and Stage IV CPOD and repeated exacerbations (for example, 3 in the last 3 years)

Treatment has been shown to reduce the frequency of exacerbations and thus improve health status

More effective when combined with a long-acting beta agonist

1 Drugs Acting on the Respiratory System. 2 Introduction The respiratory system is subject to many...

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