BRONCHIAL ASTHMA

1. BRONCHIAL ASTHMA

2. HISTORICAL BACKGROUND OF ASTHMA • Referred to by Hippocrates (400 B.C.) • Described in detail in second century • “facial anxiety, rapid, noisy respirations, fear of suffocation, and scanty foamy expectoration” • From the Greek meaning “panting”

3. Asthma is a chronic lung disease that obstructs airflow The obstruction is reversible It involves difficulty in breathing due to Inflammation (swelling) Mucus in the airways Tightening of muscles around the airways Asthma – What is It?

4. OVERVIEW - ASTHMA • Chronic inflammatory disease of the airways (mast cells, lymphocytes, eosinophils, epith cells) leading to: HYPERRESPONSIVENESS Worsening on exposure to various stimuli OBSTRUCTION Variable and usually reversible SYMPTOMS Recurrent wheezing, shortness of breath, chest tightness, and/or cough

9. CLASSIFICATION BRONCHODILATORS Adrenergic agonists • Salbutamol, terbutaline,salmeterol,bambuterol,formoterol Anticholinergics • Ipratropiumbromide, tiotropiumbromide Methyxanthines • Theophylline MAST CELL STABILIZERS • Sodiumcromoglycate, ketotifen

10. CLASSIFICATION LEUKOTRIENE ANTAGONISTS Montelukast,zafirlukast LEUKOTRIENE SYNTHESIS INHIBITOR Zileuton CORTICOSTEROIDS • Systemic:- hydrocortisone, prednisolone • Inhalational:- beclomethasone, budesonide, fluticasone Anti-igE antibody:- Omalizumab

12. Adrenergic Agents • Salbutamol • Terbutaline • Salmeterol • Bambuterol • Formoterol • Adrenaline • Ephedrine Non-selective β2 selective

13. Adrenergic Agents Actions of β2 agonists • Relax airway smooth muscle • Inhibit release of bronchoconstricting substances from mast cells • increase mucociliary transport

14. β2 Agonists Methods of Delivery • Inhalation • Oral (tablets and liquid) • Subcutaneous Onset: 5 min Duration: 4-6 hrs

15. Sympathomimetics Adverse Effects • Headache • Tachycardia • Hypokalemia • Hyperglycemia • Tremors

16. Anticholinergics • MOA: • Inhibit the action of Ach on smooth muscle muscarinic receptors • Effects: • Decrease bronchospasm • Decrease mucous production • Decrease release of histamines

17. Ipratroprium Bromide • Indications: • Chronic bronchitis • Asthma • COPD • Methods of Delivery • inhalation • Onset: 30 min; Peak: 60-90 min • Duration: 4-6 hours • Side effects: dry mouth

18. Methylxanthines 􀁘 Sites of action CNS • cortical arousal • convulsions (toxicity) CVS • positive inotropic action • positive chronotropic action • relax vascular smooth musc

19. Methylxanthines (continued) 􀁘 Sites of action (continued) GI tract • stimulates secretions Renal • weak diuretic Bronchioles • dilates smooth muscle • inhibits antigen-induced release of smooth • muscle contracting substances from mastcells

20. Methylxanthines • Mechanism of action • inhibit phosphodiesterase • increasecAMP • antagonize adenosine

21. Methylxanthines Route of administration • Oral • I.V. 􀁘 Plasma levels • therapeutic  10-20 μg/ml • toxicity  greater than 20 μg/ml

22. Adverse Effects/Toxicity • Dose dependent • CNS: Headache, insomnia, nervousness, tremor, hyperactivity, seizures,convulsions • GIT: Gastric upset, ulcers • CVS: Tachycardia leads to arrhythmias

23. Methylxanthines • Bronchial asthma • COPD • Apnoea in premature infants

24. LEUKOTRIENE RECEPTOR ANTAGONISTS&LEUKOTRIENE SYNTHESIS INHIBITOR

25. 5-LO inhibitors - zileuton LT receptor antagonists zafirlukast montelukast

26. Leukotriene Receptor Antagonists Zafirlukast • pharmacological actions • decrease bronchoconstriction • decrease inflammatory cell infiltration • Route - oral (one hour beforeor two hours after meals) • Uses moderate asthma maintenance and prophylaxis

27. Zafirlukast Adverse effects • GI upset • Headache • Cancer in rodents Interactions • inhibits cytochrome P450 isoenzymes • warfarin levels increase

28. Leukotriene synthesis inhibitor Zileuton • action  inhibits 5-ipoxygenase,reversibly. • route - oral • use - maintenance and prophylaxis Adverse effects • dyspepsia • liver toxicity

29. Corticosteroids 􀁘 Action • modify inflammation in airways 􀁘 Effects • decreases severity of attacks • stabilize mast cells • decrease eosinophils • decreases hyperresponsiveness • epithelium heals • decrease in mast cells

30. Corticosteroids 􀁘 Route of administration and agents Inhalation • beclomethasone • triamcinolone • fluticasone • budesonide Oral • prednisone • cortisol I.V. - cortisol

31. CORTICOSTEROIDS • Local side effects: • Oral thrush • Cough/hoarseness • Can be reduced with use of spacer or rinsing mouth • Systemic side effects Infrequent at currently recommended doses • Mild adrenal suppression possible with higher doses • Cataract formation • decreased growth in children • purpura • interference with bone metabolism

32. Mast cell stabilizerSodiumcromoglycate 􀁘 Actions • prevent antigen-induced release of smooth muscle contracting substances from sensitized mast cells • Taken by inhalation • Use • Bronchial asthma • Allergic rhinitis • Allergic conjuctivitis 􀁘 Toxicity • local irritation, nasalcongestion, rashes

34. Virus? Adenosine Exercise Fog Sensory nerve activation Bronchoconstriction Plasma leak Mast cell Antigen Eosinophil Macrophage Airway hyper-responsiveness Virus? T- lymphocyte Cellular effects of the mono-components Mastcell stabilizers bronchodilators corticosteroids Modified from P J Barnes

35. Omalizumab • Monoclonal antibody IgE • IV, SC • Severe asthma • Very expensive