Professional Documents
Culture Documents
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)
Introduction (Contd)
Drugs that act on the respiratory
system include
Bronchodilators Corticosteroids Cromoglycates Leukotriene receptor antagonists Antihistamines Cough preparations Nasal decongestants
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Introduction (Contd)
Drugs acting on the respiratory system,
Enhance therapeutic effects Minimize systemic effects Rapid relief of acute attacks
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 patients 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.
Introduction (Contd)
There are various types of inhalation
devices:
devices that deliver a measured dose of drug with each activation With CFC or non-CFC propellant Hand-mouth coordination is required
Introduction (Contd)
Spacers:
Use with MDIs Increase delivery of drug to the lungs & decrease deposition of drug on the oropharyngeal mucosa Especially important for inhaled corticosteroids
Introduction (Contd)
Turbuhalers & Accuhalers Drugs are in the form of dry, micronized powder No propellant is employed Breath activated, much easier to use
Introduction (Contd)
Nebulizers
Small
mist Droplets in the mist are much finer than those produced by inhalers Through face mask or mouth piece held between the teeth Take several minutes to deliver the same amount of drug contained in 1 puff from an inhaler
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Bronchodilators
Drugs used to relieve bronchospasms
Adrenoceptor agonists
Selective
agonists
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Bronchodilators (Contd)
Adrenoceptor agonists
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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Bronchodilators (Contd)
Short-acting -2 agonists
Drug Formulation Adult Salbutamol Oral tablet (C.R) Inhaler (MDI), 100mcg/dose Syrup, 2mg/5ml Terbutaline Oral tablet (S.R) Inhaler 500mg / dose ( Turbuhaler) Inhaler 250mg / dose (MDI) 8 mg twice daily 100-200mcg up to three to four times daily 4 mg three to four times daily 5-7.5 mg two times daily 500 mcg up to four times daily 250-500mcg up to 3-4 times daily Dosage Child 4 mg twice daily Same as adult 1-2 mg three to four times daily (2 yr) Same as adult
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Bronchodilators (Contd)
Long-acting -2 agonists
Drug Formulation Dosage
Adult Formoterol Inhaler 4.5mcg / dose (Turbuhaer) Inhaler 9mcg / dose (Turbuhaer) Salmeterol Inhaler 25mcg / dose (MDI) 50-100 mcg twice daily 4.5-9 mcg once or twice daily
Same as adult
Same as adult
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Bronchodilators (Contd)
Adverse effects
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Bronchodilators (Contd)
suitable & less safe for use as bronchodilators because they are more likely to cause arrhythmias & other side effects
Adrenaline
(epinephrine) injection is used in the emergency treatment of acute allergic and anaphylactic reactions
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Bronchodilators (Contd)
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 -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 -2 agonists can cause cardiac stimulation Contact physician if symptoms such as nervousness, insomnia, restlessness and tremor become severe
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Bronchodilators (Contd)
Antimuscarinic bronchodilators
Blocks the action of acetylcholine in bronchial smooth muscle, this reduces intracellular GMP, a bronchoconstrictive substance Used for maintenance therapy of bronchoconstriction associated with chronic bronchitis & emphysema
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Bronchodilators (Contd)
Drug Formulation Adult Ipratropium Inhaler 20 mcg / dose (MDI) 20-80 mcg three to four times a day Dosage Child 20-40 mcg three to four times a day (6yrs)
Tiotropium
18 mcg daily
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Bronchodilators (Contd)
Adverse effects:
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Bronchodilators (Contd)
Xanthine Derivatives
Main xanthine used clinically is theophylline Theophylline is a bronchodilator which relaxes 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 (Contd)
Drug Formulation Dosage Adult Theophylline Tablet 200 / 300 mg (S.R.) Capsule 50 / 100 mg (Slow release) 200 300 mg twice daily 7-12 mg/ kg / day in two divided doses Child 10 mg / kg ((2yrs) twice daily 10-16 mg / kg / day in two divided doses (916yrs) 13-20 mg / kg / day in two divided doses (30 months 8 yrs) 1 ml / kg (Max 25 ml) q6h (2yrs) 1 mg / kg /hr (6 months 9 years) 800 mcg / kg /hr (10 16 yrs) IV infusion, adjust when necessary
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Syrup 80 mg / 15 ml
25 ml q6h
Aminophylline
Injection 25 mg / ml 10 ml
Bronchodilators (Contd)
Adverse effects:
Toxicity
is related to theophyline levels (usually 5-15 g/ml) 20-25 g/ml : Nausea, vomiting, diarrhea, insomnia, restlessness >30 g/ml : Serious adverse effects including dysrhythmias, convulsions, cardiovascular collapse which may result in death
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Bronchodilators (Contd)
Nursing alerts:
Plasma
theophylline levels should be monitored to keep it in the therapeutic range, usually 5-15 g/ml. Dosage should be adjusted to keep theophylline levels below 20 g/ml If patients miss a dose, the following dose should not be doubled
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Bronchodilators (Contd)
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
Corticosteroids (Contd)
Drug
Formulation Adult
Beclomethasone
200 mcg twice daily / 100mcg three to fours times daily Up to 800 mcg daily 500 mcg twice daily / 250 mcg four times daily
Not recommended
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Corticosteroids (Contd)
Drug (Contd) Formulation Dosage Adult Budesonide Inhaler 50 mcg / dose (MDI) Inhaler 200mcg / dose (MDI) Inhaler 100 mcg / dose (Turbuhaler) Inhaler 200 mcg / dose (Turbuhaler) Inhaler 400 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) 200 mcg twice daily Up to 1.6 mg daily Child 50 400 mcg twice daily Up to 800 mcg daily
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Corticosteroids (Contd)
Drug (Contd) Formulation Dosage Adult Child
Fluticasone
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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Corticosteroids (Contd)
Adverse effects
Inhaled corticosteroids:
Candidiasis 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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Corticosteroids (Contd)
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
Corticosteroid+2 agonist
Symbicort
(160mcg Budesonide+4.5mcg Formoterol / dose, Turbuhaler) Seretide (Salmeterol+Fluticasone: MDi in Lite, Medium, 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 (Contd)
Drug Formulation Dosage Adult Cromoglycate Na Inhaler (1 mg & 5mg/dose) Nebuliser solution 10 mg / ml 2 ml Nedocromil Sodium Inhaler 2 mg / dose (MDI) 10 mg four times daily, may be increased to six to eight times daily 20 mg four times daily, may be increased six times daily Child Same as adult
Same as adult
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Cromoglycates (Contd)
Adverse effects Nursing Alerts
Transient Bronchospasm
A selective 2 agonist such as salbutamol or terbutaline may be inhaled a few minutes beforehand
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Cromoglycates (Contd)
Nursing Alerts (Contd)
Cromoglycates are for long-term prophylaxis, 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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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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10 mg daily at bedtime
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GI disturbances Hypersensitivity reactions Restlessness & headache Upper respiratory tract infection Manufacturer advises to avoid these drugs in pregnancy & breast-feeding unless essential
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Step
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Management of Chronic Asthma for adults & schoolchildren above 5yrs (Contd)
3: Add long-acting inhaled beta2 agonist; dose of inhaled corticosteroid may also be increased
Step
Step
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Management of Chronic Asthma for adults & schoolchildren above 5yrs (Contd)
Step
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Management of Chronic Asthma for adults & schoolchildren above 5yrs (Contd)
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
Antihistamines (Contd)
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
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Antihistamines (Contd)
First-generation H1 receptor antagonists Non-selective/sedating Bind to both central & peripheral H1 receptors Usually cause CNS depression (drowsiness, sedation) but may cause CNS stimulation (anxiety, agitation), especially in children
Antihistamines (Contd)
Drug Chorpheniramine (4 mg tablet, 2mg/ml Elixir & expectorant) Dosage Adult 4 mg q4-6hr, max: 24 mg daily Child 1-2yrs: 1 mg twice daily 2-12yrs: 1- 2 mg q4-6h, Max:12 mg daily
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
6.25-25 mg q4-8 hr ( >1 yr)
25-50 mg q4-6h
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Antihistamines (Contd)
Drug (Contd) Dosage Adult Promethazine (10 & 25 mg tablets, 5mg/5ml Elixir) 25 mg at night; 25 mg twice daily if needed Child 2-10yrs: 5-25 mg daily in 1 to 2 divided dose
Azatadine (1 mg tablet)
1 mg twice daily
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Antihistamines (Contd)
Adverse effects:
Sedation Dry mouth Blurred vision GI disturbances Headache Urinary retention Hydroxyzine is not recommended for pregnancy & breast-feeding
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Antihistamines (Contd)
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 (Contd)
Drug Dosage Adult Acrivastine (Semprex) 8 mg three times daily Child Not recommended
10 mg daily
5 mg daily
120-180 mg daily
10 mg daily`
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Antihistamines (Contd)
Adverse effects:
May cause slight sedation Some antihistamines may interact with antifungal, 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:
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Drugs that suppress cough Some act within the CNS, some act peripherally Indicated in dry, hacking, nonproductive cough that interfere with rest & sleep
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10-30 mg q4-8h
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Drowsiness Respiratory depression (for opioid antitussives) 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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Observe for excessive suppression of the cough 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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Render the cough more productive by stimulating 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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Guaifenesin
100-400
mg q4h po
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Reacts directly with mucus to make it more watery. This should help make the cough more productive
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Acetylcysteine
100
mg two to four times daily 200 mg two to three times daily 600 mg once daily
Bromhexine
8-16
Carbocisteine
750
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Nasal Decongestants
Sympathomimetics are used to reduce
nasal congestion Stimulate alpha1-adrenergic receptors on nasal blood vessels, which causes vasoconstriction & hence shrinkage of swollen membranes
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Oral administration:
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Phenylephrine
Xylometazoline
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Rebound congestion develops with topical agents when used for more than a few days CNS stimulation (such as restlessness, irritability, anxiety and insomnia) occurs with oral sympathomimetics
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Sympathomimetics can cause vasoconstriction by stimulating -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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Overuse of topical nasal decongestants can 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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The patients blood pressure and pulse should 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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Adult 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 400 mcg in the morning given as 2 applications into each nostril; then reduce to the smallest amount necessary
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Mometasone
2 sprays in each nostril once daily; 1spray in each nostril as maintenance Max: 8 sprays/day
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Mild Most common effects are drying of nasal mucosa & sensations of burning or itching
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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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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 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
Chronic bronchitis
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 poorly 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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greater shortness of breath, reduced exercise capacity, fatigue, repeated exacerbations that almost always have an impact on patients quality of life
quality of life is very appreciably impaired and exacerbations may be life threatening
FEV1/FVC < 0.70 FEV1 < 30% predicted or FEV1 < 50% predicted plus chronic respiratory failure
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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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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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, anticholinergic, theophylline, or combination therapy depends on availability and individual response in terms of symptom relief and side effects
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Bronchodilators (Contd)
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
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