1. 1 DRUGS AFFECTING RESPIRATORY SYSTEM

2. 2 ASTHMA chronic inflammatory airway disease excessive tracheobronchial reactivity SYMPTOMS wheezing, chest tightness, restlessness cough, dyspnea Mostly in night / early morning

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5. 5 ASTHMA – 5% POPULATION ALLERGIC FAMILY HISTORY HYPERSENSITIVITY Ig E MEDIATED RESP INFECTIONS DRUGS CHEMICAL IRRITANTS

6. 6 TRIGGERING FACTORS RESPIRATORY INFECTIONS Cold Air Fog Wood smoke; tobacco smoke Emotions Stress Laughter Anxiety Exercise (dry, cold weather especially ) OCCUPATION

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8. 8 DRUGS ASPIRIN NSAIDS BETA – BLOCKERS PRESERVATIVES – Sulfites – Benzalkonium chloride

9. 9 CONCEPT CONTINUAL AIRWAY INFLAMMATION EXACERBATED BY TRIGGERING FACTORS

10. 10 INTERACTIONS Airway inflammatory cells, Inflammatory mediators, Cytokines, Surface epithelium.

11. 11 CELLS INVOLVED Mast cells, Eosinophils, T-lymphocytes, Macrophages, Neutrophils, Epithelial cells

12. 12 CHEMICAL MEDIATORS HISTAMINE LEUKOTRIENE BRADYKININ PLATELET ACTIVATING FACTOR PROSTAGLANDIN E2, F2, D2

13. 13 Rationale for Pharmacological Intervention Reduction of mast cell degranulation – Sympathomimetic agents – Cromolyn / Nedocromil

14. 14 Rationale for Pharmacological Intervention Reduction of cholinergic influence from vagal motor nerves – Antimuscarinic agents Direct relaxation of airway smooth muscle – Sympathomimetic drugs – Theophylline

15. 15 Agents acting on Beta Adrenergic Receptors Albuterol Bitolterol Pirbuterol Salmeterol Terbutaline Ephedrine Epinephrine Ethylnorepinephrine Isoetherine Isoproterenol Metaproterenol

16. 16 Sympathomimetic Drugs ACTIONS Relax airway smooth muscle May Inhibit release of some mast cell bronchoconstrictive mediators May inhibit microvascular leakage May increase mucociliary transport

17. 17 ß 2 receptor activation Relaxation of airway smooth muscle Skeletal muscle tremor (toxicity)

18. 18 Beta 2 agonists Short acting Albuterol, Pirbuterol, Epinephrine, Terbutaline. Route : Inhalational Uses : Acute conditions & Symptomatic treatment of asthma No anti inflammatory action Never used as sole agent Side effects : Tachycardia, Hyperglycemia, tremors.

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21. 21 Beta 2 agonists Long acting : SALMETEROL SLOW ONSET OF ACTION LONG DURATION OF ACTION : 12 hrs NOT FOR ACUTE ASTHMATIC ATTACK USED for Maintainance

22. 22 Anticholinergic Agent – Ipratropium bromide – Competitive blocker of muscarinic receptors – prevents bronchoconstriction.

23. 23 Ipratropium DOC for beta-blocker-induced bronchospasm USEFUL FOR Pt. INTOLERANT TO BETA 2 AGONISTS MORE USEFUL IN ELDERLY

24. 24 MAST CELL STABILIZERS CROMOLYN, NEDOCROMIL Chloride-mediated channel effects: Inhibition of cough Inhibition of early response to antigens (mast cells) Inhibition of late response to antigens (eosinophils)

25. 25 CROMOLYN, NEDOCROMIL PROPHYLACTIC ANTI INFLAMMATORY NO DIRECT ACTION ON AIRWAYS NOT USEFUL IN ACUTE. ASTHMATIC ATTACK

26. 26 USES : PROPHYLACTIC AGENT FOR – EXERCISE INDUCED ASTHMA – ALLERGEN INDUCED ASTHMA SIDE EFFECTS : THROAT IRRITATION, COUGH

27. 27 METHYLXANTHINES THEOPHYLLINE ( AMINOPHYLLINE ) ACTION : DIRECT BROCHODILATOR Mech :??

28. 28 Central Nervous System Effects Increased alertness; reduced fatigue In more sensitive individuals: nervousness/insomnia Very high methylxanthine doses: medullary stimulation, convulsions Primary side effect in patients requiring aminophylline (large doses) for control of asthma: nervousness & tremor

29. 29 Cardiovascular Effects: – direct positive chronotropic – direct enhanced myocardial contractility GIT Effects: – enhanced secretion of gastric acid and digestive enzymes Renal Effects: – weak diuretics-- not therapeutically important

30. 30 THEOPHYLLINE - USE Relieves airway obstruction: – In acute asthma – Reduces symptoms severity – In chronic asthma

31. 31 THEOPHYLLINE – SIDE EFFECTS Nausea, Headache, Insomnia, Nervousness Seizures, Neuromuscular irritability, Tremor, Arrhythmias, hypokalemia, hyperglycemia, vomiting IV push - seizures/cardiac arrhythmias

32. 32 Corticosteroids NO DIRECT ACTION OVER AIRWAYS INHIBIT INFLAMMATION DECREASE ACTIVITY OF CELLS DECREASES RELEASE OF MEDIATORS DECREASE HYPERRESPONSIVENESS OF AIR WAYS DECREASES MUCOSAL EDEMA

33. 33 Beclomethasone Prednisone Fluticasone Flunisolide Triamcinolone

34. 34 CORTICOSTEROIDS - USES Status asthmaticus (Combination with Beta 2 agonists) For management of acutely ill patients Patients not adequately maintained with bronchodilators Patients whose symptoms are worsening, despite reasonable maintenance treatment

35. 35 ROUTES ORAL PARENTERAL INHALATIONAL

36. 36 ADVERSE EFFECTS Inhaled topical corticosteroids: oropharyngeal candidiasis Hoarseness: local effect -- vocal cords Suppression of hypothalamic-pituitary-adrenal axis Decreased bone density, delayed puberty Cataract formation High doses: – dermal thinning – glaucoma

37. 37 Other drugs Interruption of leukotriene pathways Inhibition of 5-lipoxygenase-- Zileuton Rationale: Prevents leukotriene synthesis Effective for maintenance treatment of asthma Requires monitoring for hepatic toxicity

38. 38 Inhibition of leukotriene D4 receptor binding Zafirlukast Montelukast Less effective than steroids SIDE EFFECT : BLEEDING COMPLICATIONS Monitor hepatic function

39. 39 Drugs to Treat Cough What causes a cough? – Irritation of mucosal surface Inflammation, hypersecretion Solutions: – Decrease sensitivity of CNS cough center, decrease secretions Codeine, Hydrocodone, Hydromorphone Dextromethorphan

40. 40 Drugs for Allergic Rhinitis The Problem: – Inflammation of mucous membranes – IgE-mediated – Mast cell degranulation The solution: – Antihistamines (eg: Diphenhydramine) – α-adrenergic agents (eg: Phenylephrine) – Steroids (eg: Beclomethasone) – Cromolyn

41. 41 Presents mainly with sneezing, nasal itching, watery rhinorrhea and congestion. H/O – allergen will be there Rx - Oral antihistamines + decongestants. In the form of intranasal spray.

42. 42 ANTIHISTAMINES H1 receptor blocker Diphenhydramine Clorpheniramine Loratidine Terfenadine Astemizole Cetirizine

43. 43 Alpha adrenergic agonists Phenylephrine Oxymetazoline Ephedrine Phenylpropanolamine Tetrahydrozoline Naphazoline Xylometazoline

44. 44 Drugs to Treat COPD The Problem: – Chronic, irreversible airflow obstruction – Variety of causes The Solutions: – β 2 agonists – Theophylline – Glucocorticoids – Ipratropium

45. 45 Treatment mainly based on assessing any reversible component of the disease. To prevent the acute exacerbations. Symptomatic