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Drugs Acting on the Respiratory System

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1 Drugs Acting on the Respiratory System

2 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)

3 Introduction (Cont’d)
Drugs that act on the respiratory system include Bronchodilators Corticosteroids Cromoglycates Leukotriene receptor antagonists Antihistamines Cough preparations Nasal decongestants

4 Introduction (Cont’d)
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

5 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.

6 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.

7 Introduction (Cont’d)
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

8 Introduction (Cont’d)
Spacers: Use with MDIs Increase delivery of drug to the lungs & decrease deposition of drug on the oropharyngeal mucosa Especially important for inhaled corticosteroids

9 Introduction (Cont’d)
Dry-powder inhalers (DPIs) Include Turbuhalers & Accuhalers Drugs are in the form of dry, micronized powder No propellant is employed Breath activated, much easier to use

10 Introduction (Cont’d)
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 between the teeth Take several minutes to deliver the same amount of drug contained in 1 puff from an inhaler

11 Bronchodilators Drugs used to relieve bronchospasms associated with respiratory disorders Includes: Adrenoceptor agonists Selective β2-agonists & other adrenoceptor agonists Antimuscarinic bronchodilators Xanthine derivatives

12 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

13 Bronchodilators (Cont’d)
Short-acting β-2 agonists Drug Formulation Dosage Adult Child Salbutamol Oral tablet (C.R) 8 mg twice daily 4 mg twice daily Inhaler (MDI), 100mcg/dose mcg 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) mcg up to 3-4 times daily

14 Bronchodilators (Cont’d)
Long-acting β-2 agonists Drug Formulation Dosage 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) mcg twice daily 50 mcg / dose (Accuhaler) 50 mcg twice

15 Bronchodilators (Cont’d)
Adverse effects Tachycardia and palpitations Headache Tremor

16 Bronchodilators (Cont’d)
(ii) Other adrenoceptor agonists Less suitable & less safe for use as bronchodilators because they are more likely to cause arrhythmias & other side effects Ephedrine Adults: mg tid po Child: mg tid po Adrenaline (epinephrine) injection is used in the emergency treatment of acute allergic and anaphylactic reactions

17 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

18 Bronchodilators (Cont’d)
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

19 Bronchodilators (Cont’d)
Drug Formulation Dosage 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

20 Bronchodilators (Cont’d)
Adverse effects: Dry mouth Nausea Constipation Headache

21 Bronchodilators (Cont’d)
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

22 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

23 Bronchodilators (Cont’d)
Adverse effects: Toxicity is related to theophyline levels (usually 5-15 µg/ml) 20-25 µg/ml : Nausea, vomiting, diarrhea, insomnia, restlessness >30 µg/ml : Serious adverse effects including dysrhythmias, convulsions, cardiovascular collapse which may result in death

24 Bronchodilators (Cont’d)
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

25 Bronchodilators (Cont’d)
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

26 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

27 Corticosteroids (Cont’d)
Drug Formulation Dosage 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 500 mcg twice daily / 250 mcg four times daily Not recommended

28 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 daily Inhaler 200mcg / dose (MDI) Inhaler 100 mcg / dose (Turbuhaler) mcg once daily in evening Up to 1.6 mg daily in two divided doses mcg daily in two divided doses / mcg once daily in evening (<12 yrs) Inhaler 200 mcg / dose (Turbuhaler) Inhaler 400 mcg / dose (Turbuhaler)

29 Corticosteroids (Cont’d)
Drug (Cont’d) Formulation Dosage Adult Child Fluticasone Inhaler 25mcg / dose (MDI) 100 – 1000 mcg twice daily mcg twice daily (4-16 yrs) Inhaler 50 mcg / dose (MDI) Inhaler 125 mcg / dose (MDI) Inhaler 250 mcg / dose (MDI) Inhaler 50 mcg / dose (Accuhaler) Inhaler 100 mcg / dose (Accuhaler) Inhaler 250 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

30 Corticosteroids (Cont’d)
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

31 Corticosteroids (Cont’d)
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

32 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 Formoterol / dose, Turbuhaler) Seretide (Salmeterol+Fluticasone: MDi in Lite, Medium, Forte preparation & Accuhaler)

33 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

34 Cromoglycates (Cont’d)
Drug Formulation Dosage 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 Nedocromil Sodium Inhaler 2 mg / dose (MDI) 4 mg two to four times daily Sames as adult (>6 yrs)

35 Cromoglycates (Cont’d)
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

36 Cromoglycates (Cont’d)
Nursing Alerts (Cont’d) 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

37 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

38 Leukotriene receptor antagonists (Cont’d)
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

39 Leukotriene receptor antagonists (Cont’d)
Adverse effects: GI disturbances Hypersensitivity reactions Restlessness & headache Upper respiratory tract infection Manufacturer advises to avoid these drugs in pregnancy & breast-feeding unless essential

40 Management of Chronic Asthma for adults & schoolchildren above 5yrs
Step 1: Occasional relief short-acting beta2 agonist Step 2: Add regular preventer therapy Standard-dose inhaled corticosteroid

41 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

42 Step 5: Add regular oral corticosteroid
Management of Chronic Asthma for adults & schoolchildren above 5yrs (Cont’d) Step 5: Add regular oral corticosteroid E.g. prednisolone

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

44 BREAK

45 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

46 Antihistamines (Cont’d)
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

47 Antihistamines (Cont’d)
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 Also have substantial anticholinergic effects

48 Antihistamines (Cont’d)
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: mg daily; mg daily in divided dose if needed Diphendramine (10 mg/5ml Elixir) 25-50 mg q4-6h mg q4-8 hr ( >1 yr)

49 Antihistamines (Cont’d)
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: mg twice daily

50 Antihistamines (Cont’d)
Adverse effects: Sedation Dry mouth Blurred vision GI disturbances Headache Urinary retention Hydroxyzine is not recommended for pregnancy & breast-feeding

51 Antihistamines (Cont’d)
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

52 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) mg daily Loratadine (Clarityne) 10 mg daily` 5 mg daily (2-5 yrs)

53 Antihistamines (Cont’d)
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

54 Cough preparations There are three classes of cough preparations:
Antitussives Expectorants Mucolytics

55 Cough preparations (Cont’d)
Antitussives Drugs that suppress cough Some act within the CNS, some act peripherally Indicated in dry, hacking, nonproductive cough that interfere with rest & sleep

56 Cough preparations (Cont’d)
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

57 Cough preparations (Cont’d)
Adverse effects: 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

58 Cough preparations (Cont’d)
Nursing Alerts: 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

59 Cough preparations (Cont’d)
Expectorants 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

60 Cough preparations (Cont’d)
Dosage Guaifenesin mg q4h po Ammonia & Ipecacuaha Mixture 10-20 ml three to four times daily po

61 Cough preparations (Cont’d)
Mucolytics Reacts directly with mucus to make it more watery. This should help make the cough more productive

62 Cough preparations (Cont’d)
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 divided doses

63 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

64 Nasal Decongestants (Cont’d)
Topical administration: Response is rapid & intense Oral administration: Response are delayed, moderate & prolonged

65 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%)

66 Nasal Decongestants (Cont’d)
Adverse effects: 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

67 Nasal Decongestants (Cont’d)
Adverse effects (Cont’d): Sympathomimetics can cause vasoconstriction 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

68 Nasal Decongestants (Cont’d)
Nursing alerts: 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

69 Nasal Decongestants (Cont’d)
Nursing alerts (Cont’d): The patient’s 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

70 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

71 Intranasal Corticosteroids (Cont’d)
Drug Formulation Dosage 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

72 Intranasal Corticosteroids (Cont’d)
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 -

73 Intranasal Corticosteroids (Cont’d)
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 1 spray in each nostril once daily (3-11yrs)

74 Intranasal Corticosteroids (Cont’d)
Adverse effects: Mild Most common effects are drying of nasal mucosa & sensations of burning or itching

75 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

76 Relationship between COPD and emphysema/chronic bronchitis
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

77 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). 

78 Risk factors Genes Exposure to particles Lung Growth and Development
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)

79 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 50% ≤ FEV1 < 80% predicted shortness of breath typically developing on exertion and cough and sputum production sometimes also present Stage III: Severe 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 < 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 Stage I: Mild COPD - Characterized by mild airflow limitation (FEV1/FVC < 0.70; FEV1 ≥ 80% predicted). Symptoms of chronic cough and sputum production may be present, but not always. At this stage, the individual is usually unaware that his or her lung function is abnormal. Stage II: Moderate COPD - Characterized by worsening airflow limitation (FEV1/FVC < 0.70; 50% ≤ FEV1 < 80% predicted), with shortness of breath typically developing on exertion and cough and sputum production sometimes also present. This is the stage at which patients typically seek medical attention because of chronic respiratory symptoms or an exacerbation of their disease. Stage III: Severe COPD - Characterized by further worsening of airflow limitation (FEV1/FVC < 0.70; 30% ≤ FEV1 < 50% predicted), greater shortness of breath, reduced exercise capacity, fatigue, and repeated exacerbations that almost always have an impact on patients’ quality of life. Stage IV: Very Severe COPD - Characterized by severe airflow limitation (FEV1/FVC < 0.70; FEV1 < 30% predicted or FEV1 < 50% predicted plus the presence of chronic respiratory failure). Respiratory failure is defined as an arterial partial pressure of O2 (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. Respiratory failure may also lead to effects on the heart such as cor pulmonale (right heart failure). Clinical signs of cor pulmonale include elevation of the jugular venous pressure and pitting ankle edema. Patients may have Stage IV: Very Severe COPD even if the FEV1 is > 30% predicted, whenever these complications are present. At this stage, quality of life is very appreciably impaired and exacerba-tions may be life threatening.

80 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

81 Differences in causes of COPD and asthma

82 Clinical features in COPD and asthma

83 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

84 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

85 Bronchodilators (Cont’d)
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

86 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

87 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

88 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

89

90 END


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