Respiratory Pharmacology 2 PDF

Respiratory Pharmacology 2 Prof LJ Egan Outline of lecture  Anti-inflammatory drugs in asthma       Corticosteroids Cysteinyl leukotriene receptor antagonists Mast cell stabilizers Anti-IgE antibody therapy Step-wise therapeutic approach to asthma patients Acute severe asthma exacerbations Hi...

Respiratory Pharmacology 2 Prof LJ Egan Outline of lecture  Anti-inflammatory drugs in asthma       Corticosteroids Cysteinyl leukotriene receptor antagonists Mast cell stabilizers Anti-IgE antibody therapy Step-wise therapeutic approach to asthma patients Acute severe asthma exacerbations Historical treatment of asthma      Early 1900s: inhaled epinephrine (unselective agonist) 1940: inhaled isoprenaline (selective beta agonist) 1950s: oral corticosteroids 1960s: inhaled corticosteroids 1960s: inhaled salbutamol Inhaled salbutamol Peaks of asthma mortality    England and Australia 1966: excessive reliance on inhaled bronchodilators New Zealand 1977: excessive reliance on inhaled beta agonists (salbutamol) and oral theophylline – inadequate treatment Underlines the importance of anti-inflammatory therapy in asthma Patient  16 year old girl       Physical exam:   Asthma diagnosed age 7 Triggered by cold air and exercise Keen Gaelic footballer Recurrent wheeze and dyspnoea when playing and after sessions Using lots of salbutamol Chest hyperinflated, prolonged phase of expiration Spirometry  FEV1 60% of predicted CORTICOSTEROIDS Corticosteroid receptors Hydrocortisone Glucocorticoid Receptor Metabolic/Immune Effects S Aldosterone Mineralocorticoid Receptor Salt retention Corticosteroids: classic molecular mechanism Corticosteroids Corticosteroids Cellular targets  Many   Innate immune cells   Monocytes, macrophages Adaptive immune cells   Glucocorticoid receptors ubiquitously expressed T lymphocytes Non-immune cells  Endothelial cells Inhaled corticosteroid side effects  Local side effects   Dysphonia Oropharyngeal candidiasis Cough Systemic side effects  Adrenal suppression Growth suppression Bruising Osteoporosis Cataracts Glaucoma Metabolic abnormalities (glucose, insulin, triglycerides) Psychiatric disturbances Corticosteroid use in asthma and COPD  By inhalation   Often combined with inhaled 2-adrenoceptor agonist Slow onset of action (hours)     Not used for immediate symptom relief Use to prevent attacks Long duration of benefit (hours) Systemically   Oral or IV Used in more severe cases Inhaled corticosteroids      Provide immediate relief of acute asthmatic symptoms Act via the mineralocorticoid receptor Target the inflammatory phase of airflow limitation Cause no side effects Can be used in conjunction of Beta2 agonists CYSTEINYL LEUKOTRIENE RECEPTOR ANTAGONISTS Leukotrienes in asthma Effect of montelukast on FEV1 Lukasts       Inhibit receptors expressed on respiratory epithelium and infiltrating leukocytes Improve airflow in both early and late phases Orally administered Well tolerated Example: Montelukast Slow acting: used to prevent attacks Comparison of inhaled corticosteroid and montelukast on PEFR Anti-IgE therapy of asthma      In some patients asthma triggers are allergic Moderate-to-severe persistent asthma Asthma symptoms that are inadequately controlled with inhaled glucocorticoids A total serum IgE level between 30 1500 international units/mL, which is the range over which the drug can reduce enough free IgE to ensure a therapeutic effect Allergic sensitization demonstrated by positive skin testing or in vitro testing for allergen-specific IgE to an allergen that is present year-round (a perennial allergen), such as house dust mites, animal danders, cockroaches, or molds Omalizumab, anti-IgE     Recombinant humanized anti-IgE antibody Used in selected asthmatic patients Results in marked fall in serum IgE May be useful also in other IgEmediated diseases eg recurrent anaphylaxis Therapeutic approach to asthma patients An asthma action plan “Relievers and Preventers” Severe asthma attacks: status asthmaticus    Severe asthma attach which is unresponsive to initial treatment with bronchodilators Quite common especially when respiratory virus infections are abundant Severe airflow limitation       Lowers the delivery of inhaled drugs Systemic therapy necessary Hospital admission Oxygen Nebulized bronchodilators at high dose IV corticosteroids Summary  Important Lessons    Use of inhaled corticosteroids in chronically symptomatic patients Short acting Beta agonists used for symptomatic relief Systemic corticosteroids life saving in severe attacks