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BRONCHIAL ASTHMA

BRONCHIAL ASTHMA. 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”.

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BRONCHIAL ASTHMA

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  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

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

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

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

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

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

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

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

  12. 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

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

  14. 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

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

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

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

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

  19. LEUKOTRIENE RECEPTOR ANTAGONISTS&LEUKOTRIENE SYNTHESIS INHIBITOR

  20. 5-LO inhibitors - zileuton LT receptor antagonists zafirlukast montelukast

  21. 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

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

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

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

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

  26. 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

  27. 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

  28. 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

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

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