19.bronchial asthma
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This document provides information on the treatment of bronchial asthma. It discusses the major classes of drugs used including bronchodilators like beta agonists, anticholinergics, and methylxanthines. It also covers corticosteroids, mast cell stabilizers, and leukotriene modulators. For each class the mechanism of action, administration route, indications, and potential adverse effects are outlined. Treatment of an acute asthma attack and contraindicated drugs are also summarized.
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19.bronchial asthma
- 2. LEARNING OBJECTIVES • To know the commonly used drugs in bronchial asthma • To understand the mechanism of action of the major classes of drugs used in bronchial asthma • To know the adverse effects of these drugs
- 3. BRONCHIAL ASTHMA • Chronic inflammatory disease • Reversible episodes of airway obstruction • Due to hyperresponsiveness of tracheobronchial smooth muscle to various stimuli, resulting in : -Bronchospasm -Narrowing of airtubes -Mucosal edema -Increased bronchial mucus secretion and mucus plugging
- 4. Cardinal symptoms • Breathlessness • Wheezing • Cough • Chest tightness
- 5. Trigger factors for asthma • Infection • Irritants (pollen, house dust mites, chemical etc.) • Pollutants • Exercise • Exposure to cold air • Psychogenic
- 6. Different types of asthma • Acute asthma • Chronic asthma • Extrinsic asthma • Intrinsic asthma Status asthmaticus
- 7. Pathophysiology Inflammation underlying hyperactivity • Early reaction – Reversible airway obstruction • Late reaction – Worsening of disease • Increased vagal discharge to bronchial muscle Bronchoconstriction and increased mucus secretion • Adenosine - bronchoconstriction
- 8. Approaches to treatment • Prevention of Ag-Ab reaction – avoidence of antigen • Suppression of inflammation and bronchial hyperactivity – corticosteroids • Prevention of release of mediators – mast cell stabilizers • Antagonism of released mediators – LT antagonists • Blockade of constrictor neurotransmitter – anticholinergics • Mimicking dilator neurotransmitter – sympathomimetics • Directly acting bronchodilators – methylxanthines
- 9. Classification A.Bronchodilators i. Non-selective sympathomimetics – Adrenaline, ephedrine, isoprenaline ii. Selective beta2 agonists - Salbutamol, terbutaline, salmeterol, formoterol iii.Anticholinergics – Ipratropium bromide, atropine methonitrate iv.Methylxanthines – Theophylline, aminophylline, choline theophyllinate
- 10. B. Corticosteroids i. Systemic – Oral: Prednisone Parenteral : Methylprednisolone, hydrocortisone ii. Non- systemic – Inhalational : Beclomethasone, fluticasone, budesonide C. Mast cell stabilizers – Nedocromil, ketotifen, sodium cromoglycate D.Leukotrine (LT) modulators i. 5’- lipoxygenase inhibitors – Zileuton ii. LT receptor antagonist – Zafirlukast, montelukast
- 12. Role of beta agonists in asthma MOA β2 agonists have other beneficial effects including inhibition of mast cell-mediator release, prevention of microvascular leakage and airway edema, and enhanced mucocillary clearance. The inhibitor effects on mast cell actions suggest that β2 agonists may modify acute inflammation.
- 13. Sympathomimetics Mode of administration • Inhalation – metered dose inhaler, nebulizer, spinhaler, rotahaler, spray • Oral • i.m. or i.v. injection
- 14. • Adrenaline – prompt but short-lasting action; rarely used because of adverse effects • Isoprenaline – prompt and marked bronchodilatation; disadvantage – tachycardia • Ephedrine – mild slowly developing bronchodilatation; used for mild to moderate asthma • Salbutamol – inhaled drug – rapid onset, short duration of action; used for acute attack A/E: tremors, tachycardia, palpitation, nervousness
- 15. • Terbutaline – can be used safely during pregnancy • Salmeterol – slow onset of action, long acting; used for maintenance therapy and nocturnal asthma • Formoterol – faster onset of action, long acting; used for acute attack and maintenance therapy
- 16. Limitations • Non-selective sympathomimetics – cardiac side effects (β1action) – not preferred in elderly or heart patients • Long term use of salbutamol and terbutaline – downregulation of receptors – diminished responsiveness – worsening of disease
- 17. Anticholinergics • MOA • Atropine and ipratropium antagonize the actions of Ach at parasympathetic, postganglionic, effector cell junctions by competing with Ach for M3 receptor sites. • This antagonism of Ach results in airway smooth muscle relaxation and bronchodilation.
- 18. Anticholinergics • Mode of administration - inhalation • Slow onset of action – better suited for regular prophylactic use • Indications – – Asthmatic bronchitis – Psychogenic asthma COPD Nebulized ipratropium + salbutamol – refractory asthma
- 19. Methylxanthines • MOA – i. Inhibition of phosphodiesterase – increased cAMP and cGMP level ii.Blockade of adenosine receptors • Mode of administration - oral, i.m., i.v. , rectal suppositories
- 20. Plasma therapeutic range – 5-20 µg/ml Side effects : • GIT: nausea, vomiting, gastritis, aggravation of peptic ulcer • CVS: tachycardis, palpitation, arrhythmias, hypotension • CNS: insomnia, headache, delirium, restlessness, tremor • Diuresis, flushing • Rapid i.v. – syncope and sudden death
- 21. Methylxanthines x Sympathomimetics potentiate the effects of sympathomimetics • Bronchodilatation – beneficial • Cardiac stimulation - harmful
- 22. Corticosteroids MOA: • Decreases the synthesis of inflammatory mediators • Prevent recruitment, proliferation and activation of leukocytes Systemic steroid therapy – • Severe chronic asthma • Status asthmaticus Inhaled steroids – Long term treatment of asthma
- 23. • Others Indications Rhinitis Nasal polyposis Adverse effects Inhaled steroids– drymouth, dysphonia, sore throat, oropharyngeal candidiasis Systemic steroids – mood changes, osteoporosis, hyperglycemia, hypertension, HPA axis suppression
- 24. • MOA – They block IgE-regulated calcium channels essential for mast cell degranulation – Prevent the release of histamine and related mediators. Mast cell stabilizers
- 25. Mast cell stabilizers Mode of administration - inhalation, oral Indications • Bronchial asthma • Allergic rhinitis – nasal spray • Allergic conjunctivitis – eye drops Adverse effects - irritation, cough, dry mouth, sedation, headache, rashes
- 26. Leukotriene modulators Indications Prophylactic treatment of mild to moderate asthma Adverse effects Hepatotoxicity, headache, GI distress, rashes Zafirlukast – Churg-Strauss syndrome
- 27. Treatment of status asthmaticus • Humidified oxygen inhalation • Nebulized salbutamol+ ipratropium • Systemic steroids – hydrocortisone,prednisolone i.v. • IV fluids – correct dehydration • Potassium supplements – correct hypokalemia • Sodium bicarbonate – treat acidosis • Antibiotics – treat infection
- 28. Drugs contraindicated in bronchial asthma • Beta blockers • Cholinergic drugs • NSAIDs ( expect paracetamol)
- 29. Recent advances Omalizumab - anti IgE antibody