1. Management of COPD & Asthma Melissa Brittle & Jessica Macaro

2. Overview  Drugs used in airway disease  Bronchodilators A. β 2 Agonists B. Anti-cholinergics C. Methylxanthines D. Leukotriene antagonists  Anti-inflammatory agents A. Glucocorticoids B. Mast cell stabilisers  Monoclonal Antibodies  Asthma  Acute management  Long term management  COPD management

3. Bronchodilators

4. β 2 Agonists 1. β 2 agonist binds to GPCR 2. This leads to activation of Adenyl cyclase 3. Adenyl cyclase converts ATP to cAMP which activates Protein Kinase A (PKA) 4. PKA phosphorylates myosin light chain kinase (MLCK), inactivating it, and therefore reducing smooth muscle contraction in the airway. Short acting (SABA) = salbutamol, Terbutaline Long acting (LABA) = salmeterol, Formoterol. Side effects -Tremor -Tachycardia -Headache -Cardiac arrhythmia -Peripheral vasodilation -Hypokalaemia Can you name any? 1 2 3 4

5. Anti-cholinergics 1. Blockade of Muscarinic M3 receptors. 2. Reduces action of Phospholipase C (PLC) leading to a) A reduction in calcium release from endoplasmic reticulum (ER) b) A reduction in calcium uptake into the cell Normally, calcium binds to Calmodulin which activates MLCK, which in turn activates myosin leading to smooth muscle contraction. 3. Without Calcium, smooth muscle contraction (i.e. bronchoconstriction) is inhibited. Short acting (SAMA) = Ipratropium Long acting (LAMA) = Tiotropium Side effects everything dries up!! -Dry mouthNausea -ConstipationUrinary retention -CoughGlaucoma -Headache Can you name any? 1 2 a b 3

6. Methylxanthines 1. Methylxanthines inhibit phosphodiesterase (PDE) which normally breaks down cAMP into 5’AMP 2. This allows cAMP levels to rise thus promoting muscle relaxation Aminophylline Theophylline Small therapeutic window- take care with dose Multiple drug interactions Side effects… -Insomnia -Nausea and vomiting -Cardiac arrhythmias -Seizures Can you name any? What breaks cAMP down?

7. Leukotriene Antagonists Leukotrienes cause airway inflammation and bronchospasm 1. Leukotriene antagonists block cysteinyl leukotriene (Cys LT) receptors. 2. This leads to reduced inflammatory response and reduced exercise induced symptoms in asthma Montelukast Zafirlukast Side effects… -Abdominal pain -Headache -Thirst -Restlessness Can you name any?

8. Anti-inflammatory agents

9. Glucocorticoids 1. Glucocorticoids cause a) Expression of anti-inflammatory products b) Inhibition of pro-inflammatory products e.g. cytokines, vasodilators, leukotrienes etc 2. This results in reduced oedema and mucous production which contributes to narrowed airways in asthma and COPD. Inhaled- beclomethasone, fluticasone Oral- Prednisolone IV- hydrocortisone Side effects… -Cushings syndrome -Oral steroids have more effects than inhaled. Can you name any?

10. Mast cell stabilisers  Act by stabilising mast cell membranes therefore preventing histamine release  Unfortunately not very effective but have few side effects  Typically used in children with asthma  Useless in COPD or acute asthma because histamines have already been released. Sodium cromoglycate, nedocromil. Side effects… -Bitter taste -Paradoxical bronchospasm Can you name any? We can’t… What do mast cells release?

11. MONOCLONAL ANTIBODIES Anti-IgE antibodies form complexes with free IgE Useful to prevent allergic asthma Very expensive and not often prescribed Omalizumab Mast cell Can you name any?

12. ACUTE MANAGEMENT OF ASTHMA OSHIT… O – Oxygen S – Salbutamol H – Hydrocortisone (IV) (if in hospital) or Prednisolone (oral) (if in GP) I – Ipratropium T – Theophylline

13. Reliever Inhaled SABA e.g salbutamol Preventer Add inhaled steroid e.g. fluticasone Controller Add inhaled LABA e.g. salmeterol Higher dose inhaled steroid + Leukotriene antagonist, theophylline or β agonist Oral steroid e.g. prednisolone LONG TERM MANAGEMENT OF ASTHMA Step by step approach Reliever Inhaled SABA e.g salbutamol Preventer Add inhaled steroid e.g. fluticasone Controller Add inhaled LABA e.g. salmeterol Higher dose inhaled steroid + Leukotriene antagonist, theophylline or β agonist Oral steroid e.g. prednisolone

14. MANAGEMENT OF COPD Smoking cessation advice Oxygen Bronchodilator therapy o SABA e.g. salbutamol o SAMA e.g. ipratropium Combination therapy o LABA e.g. salmeterol o LAMA e.g. tiotropium o Inhaled steroid e.g. fluticasone Oral methylxanthines e.g. theophylline