Bronchial Asthma Dr Iribhogbe (1).pptx

Bronchial Asthma by Dr Iribhogbe O.I. (Assoc. Prof) MBBS, MPH, PhD, Cert. Clin. Pharm Highlights: Introduction Pathophysiology Pharmacological Basis of Therapy Pharmacological Agents Status Asthmaticus Conclusion Sample MCQ  Introduction It is a clinical condition cha...

Bronchial Asthma by Dr Iribhogbe O.I. (Assoc. Prof) MBBS, MPH, PhD, Cert. Clin. Pharm Highlights: Introduction Pathophysiology Pharmacological Basis of Therapy Pharmacological Agents Status Asthmaticus Conclusion Sample MCQ  Introduction It is a clinical condition characterized by: Recurrent episode of coughing Difficulty with breathing Chest tightness Wheezing Due to airway hypereactivity following exposure to allergen resulting in widespread narrowing of the airway  Pathophysiology This involves a type 1 hypersensitivity response following the exposure to an allergen Initial exposure to the allergen triggers the synthesis and release of reaginic Ig E antibodies which are bound to mast cells on the surface of the airway mucosa On re-exposure an Ag-IgE complex is formed on the surface of the mast cell  Contd This triggers the release of primary inflammatory mediators stored in the mast cell granules and other secondary mediators The primary mediators responsible for the early reactions include: Histamine, tryptase, proteases, LC4&D4, PG The mediators cause bronchial smooth muscle contraction, and vascular leakage due to ↑sed vascular permeability  Contd The secondary inflammatory mediators are responsible for the late phase response. This include: IL 4&5, GM-CSF, and other inflammatory cytokines. They produced from TH2-LYMPH, and other pro-inflammatory cells They cause: Sustained bronchoconstriction Cellular infiltration Mucus hyper-secretion Stimulate IgE production from B-lymphocytes Contd Contd Contd Contd  Pharmacological Basis of Therapy Problems identified from the pathophysiology includes: Bronchial hypereactivity resulting in narrowing of the airway from smooth muscle contraction Inflammatory/pro-inflammatory activity resulting in: Bronchial oedema Mucus hypersecretion Airway narrowing  Contd Therefore, pharmacological therapy will target: Airway narrowing due to bronchial smooth muscle contraction: Bronchodilators Airway narrowing due to inflammatory/pro- inflammatory activity: Agents that control inflammation  Pharmacological Agents They are divided into two major categories: Drugs used to relieve (relievers) acute or immediate asthmatic attack: Bronchodilators Drugs used to prevent or control recurrent asthmatic attacks (preventers or controllers): Agents that control inflammation  Contd Bronchodilators: This include the β2 selective agonist such as albuterol, terbutalline, isoproterenol, metaproterenol, pirbuterol, and bitoterol SABA: e.g. salbutamol, albuterol, levalbuterol, metoproterenol, terbutalline, and pirbuterol used for acute Px LABA: e.g. salmeterol, and formoterol used in combination with steroids for long term Px of Asthma  Contd MOA: Selectively bind to β2 adrenoceptors and stimulate adenylyl cyclase: ↑c AMP, smooth muscle relaxation, may inhibit microvascular leakage inhibit inflammatory cell function Muscarinic Antagonist: e.g. Atropine sulfate aerosols and ipratropium bromide  Contd Competitively inhibit the effect of acetylcholine at the muscarinic receptor in the bronchial airway blocks the contraction of bronchial airway smooth muscles and decrease the secretion of mucus that occurs in response to vagal activity Methylxantine Agents: e.g. Aminophyline and theophyline  Contd Preventers/Controllers: Anti-inflammatory Drugs: grouped into Systemic glucocorticoids: prednisolone, prednisone, methylprednisolone, triamcinolone Inhalational: budesonide, beclomethasone dipropionate, fluticarsone MOA: inhibit eosinophilic airway mucosal inflammation inhibit release of arachidonic acid from cell membranes and cause a reduction in prostaglandin synthesis  Contd inhibit the production of cytokines involved in the initiation of the inflammatory response reduce bronchial reactivity and increase the airway caliber thereby reducing the frequency of asthmatic exacerbation due to the potentiating effect of β2 receptor agonist Leukotriene pathway inhibitors: This include 5 lipo-oxygenase inhibitors e.g. zileutine, and a LTD4 receptor antagonist e.g. zafirlukast and montelukast MOA: Competitive antagonist at the leukotriene receptor (LT1)  Contd Mast cell membrane stabilizers (Chromones): chromolyn or nedocromil MOA: Alteration in the function of delayed chloride channels in the cell membrane thereby inhibiting cellular infiltration. mast cell inhibition of early phase response to antigen challenge inhibition of eosinophils responsible for the late phase response  Contd Phophodiesterase Inhibitors (Methylxanthines): e.g. Theophylline and aminophylline. They cause smooth muscle relaxation by ↑sing c AMP levels and by blocking adenosine receptors. Adenosine modulates adenylyl cyclase Also ↓ the release of inflammatory mediators by blocking adenosine receptors Humanized IgG monoclonal antibodies e.g. mepolizumab, reslizumab, benralizumab, dupilumab They bind to IL5 and prevents it from binding to its receptor on the inflammatory cells  Contd Anti-IgE monoclonal antibodies e.g. omalizumab Other Agents K† openers such as chromakalin Ca2 † channel blockers, NO donors  Contd Combination Therapy Combination of inhalation drugs that contains LABA + inhaled steroids can be used in long term Px of Asthma Salmeterol + fluticarsone dipropionate Formoterol + budesonide Other combinations that can be used include; Leukotriene receptor antagonist + glucocorticoids  Status Asthmaticus It is an acute severe exacerbation of an acute asthmatic episode that is resistant to appropriate outpatient treatment It is a medical emergency that requires hospitalization  Contd Mgx modalities includes: Use of systemic and inhalational anti-asthmatic drugs Supportive therapy: Administration of oxygen to correct hypoxia and hypercapnoea Administration of intravenous fluids to correct dehydration Assisted ventilation is required in case of respiratory failure  Conclusion Pharmacological therapy in bronchial asthma targets 2 major underlying problems: Bronchoconstriction Inflammation Hence the understanding of the pharmacological basis of treatment is based on a sound understanding of the pathophysiology of bronchial asthma  Sample MCQ for CBE Adrenoceptor agonists: A. May cause bradycardia at lower doses B. Has intrinsic activity but no affinity at adrenoceptors C. Has negative dromotropic effect D. May be used in the treatment of glaucoma E. Can be used in the management of cardiogenic shock What is your answer, give reasons