Drugs Acting on the Respiratory System

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

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

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: 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

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)

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)

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)

28. Corticosteroids (Cont’d)

29. Corticosteroids (Cont’d) 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)

35. Cromoglycates (Cont’d)

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. 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)

49. Antihistamines (Cont’d)

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