Respiratory Pharmacology

1. Applied Clinical Sciences Lecture Programme Respiratory Pharmacology Dr Cathy Armstrong Anaesthetic SpR & Clinical Fellow in Undergraduate Medical Education April 2010

2. Aims & Objectives • Discuss Oxygen therapy • Discuss the pharmacological management of: • Asthma • COPD • Inhaler quiz

3. OXYGEN

4. Oxygen Therapy • Fixed performance devices • Fi02 constant despite change in inspiratory flow rate • Variable performance devices • Fi02 varies with inspiratory flow rate • Reservoir devices

5. This is a fixed performance oxygen delivery device? • True • False

6. This is a fixed performance oxygen delivery device? • True • False

7. This is a fixed performance oxygen delivery device? • True • False

8. Fixed performance devices Venturi HAFOE High flow oxygen enrichment devices

9. Variable performance devices 2 l/min = approx 25-30% 4 l/min = approx 30-40%

10. Reservoir devices 15 l/min

11. Humidification

12. Emergency Situation 15 l/min

13. Oxygen -Potential concerns • COPD patients dependent on hypoxic drive • Atelectasis • Retinopathy of prematurity

14. Inflammatory response Intitiated by trigger & mast cell degranulation Asthma • Reversible airways obstruction • Bronchoconstriction • Bronchial mucosal oedema • Mucus plugging

15. COPD • lung disease characterised by chronic obstruction of lung airflow that interferes with normal breathing and is not fully reversible. • main features include • Bronchoconstriction • Mucosal oedema • Mucosal hypersecretion

16. Bronchodilators • Anti-inflammatory drugs • Mucolytics

17. ATP AC Β2 agonists Xanthines + + + cAMP Salbutamol PDE AMP Aminophylline Anticholinergic drugs Ipratropium bromide Agents acting on bronchial smooth muscle Bronchodilation SNS Magnesium Resting Bronchial tone PNS Bronchoconstriction

18. Β2 agonists • Short acting • Salbutamol • Ventolin, airomir, salamol easi-breathe • Terbutaline • Bricanyl • Long acting • Salmeterol • Serevent • Formoterol • oxis

19. ATP AC Β2 agonists + + cAMP PDE AMP Β2 agonists Bronchodilation SNS Resting Bronchial tone PNS Agonists at β2 adrenoceptors → activate second messenger system (adenyl cyclase) Bronchoconstriction

20. Β2 agonists • Side effects • Tachycardia • Arrythmias • Myocardial ischaemia • Tremor • Paradoxical bronchospasm • Hypokalaemia

21. Anticholinergic drugs • Short acting • Ipratropium bromide • Atrovent • Long acting • Tiotropium • spiriva

22. Anticholinergic drugs Anticholinergic drugs Bronchodilation Antagonise muscarinc receptors SNS Resting Bronchial tone PNS Bronchoconstriction

23. Anticholinergic drugs • Side Effects • Dry mouth • Nausea • Headache • Cautions • Pts with prostatic hyperplasia & bladder outflow obstruction • Pts susceptible to glaucoma

24. Xanthines • Theophylline • Nuelin SA • Slo-phyllin • Uniphyllin continus • Aminophylline • Theophylline + ethylenediamine • Increased water solubility allowing IV preparation • Phyllocontin Continus • Modified release tablet Modified release tablets

25. ATP AC Xanthines + + cAMP PDE AMP Xanthines Bronchodilation SNS Resting Bronchial tone PNS Phosphodiesterase inhibitors Bronchoconstriction

26. Xanthines • Side effects • Toxicity can occur • Tachycardia • Arrythmias • Agitation • Convulsions • Hypokalaemia • Levels can increase in sepsis & viral infections • Drug interactions (hepatic metabolism) • E.g ciprofloxacin & OCP reduce clearance • E.g. anticonvulsants increase clearance

27. Anti-inflammatory agents • Corticosteroids • Leukotriene receptor antagonists • Sodium cromoglycate

28. Corticosteroids • Broad anti-inflammatory effect • Inhibition of production of inflammatory cytokines • Inhaled • Beclomethasone • becotide • Fluticasone • Flixotide • Budesonide • Pulmicort • Oral • Prednisolone • IV • Hydrocortisone

29. Corticosteroids • Side effects • Inhaled fewer systemic effects than oral • Candidiasis • Hoarseness • Adrenal suppression • Osteoporosis • Growth restriction in children

30. Corticosteroids • Combined therapies (with LABA) • Seretide • Salmeterol & fluticasone • Symbicort • Budesonide & formoterol

31. Leukotriene Receptor antagonists • Leukotrienes are synthesized by a variety of inflammatory cells in the airways • E.g. eosinophils, mast cells, macrophages & basophils • Leukotriene receptor antagonists block the binding of LTD4 to its receptor on target tissues • Montelukast • singulair

32. Sodium cromoglycate • Mode of action not completely understood • May inhibit degranulation of mast cells • Less effective than inhaled corticosteroids

33. Omalizumab • Monoclonal antibody that binds IgE • Add on therapy in severe persistent allergic asthma • Fortnightly SC injection • If no response after 16 weeks then discontinued

34. BTS Guidelines Management of chronic asthma • Step 1 • Prn inhaled β2 agonist • Step 2 • Add inhaled steroid (200 – 800mcg/day) • Step 3 • Add LABA, +/- ↑ steroid dose to 800mcg/day • Consider leukotriene receptor antagonist or SR theophylline • Step 4 • Further ↑ inhaled steroid to up to 2000mcg/day • Add 4th drug (leukotriene receptor antagonist, SR theophylline or β2 agonist tablets) • Step 5 • Daily low dose oral steroid • Continue high dose inhaled steroid • Refer to specialist

35. NICE Guidelines Management of chronic COPD • Breathlessness & exercise limitation • Short-acting bronchodilator • Combined therapy (short acting β2 agonist & short acting anticholinergic) • Add longer acting bronchodilator • Consider combination of long acting bronchodilator & inhaled corticosteroid • Add theophylline salbutamol Combivent Tiotropium salmeterol Seretide symbicort

36. In a patient having an acute exacerbation of asthma which of the following features would most concern you? • RR 28 • Sats 93% on 15 L/min oxygen • Exhaustion • Unable to talk in full sentences

37. BTS Guidelines Moderate exacerbation Acute severe Life threatening Near Fatal Assessment of an acute exacerbation of asthma

38. Assessment of an acute exacerbation of asthma • Life threatening • PEF < 33% best or predicted • SpO2 < 92% • PaO2 < 8 Kpa • Silent chest • Cyanosis • Poor resp effort • Arrythmia • Exhaustion, altered conscious level • Near Fatal • Raised PaCO2 and / or requiring mechanical ventilation

39. Management of an acute exacerbation of asthma • Intial • Sit patient up • Give High flow oxygen • Nebulised β2 agonists every 15 min • Nebulised ipratropium (repeat every 4 hours) • Steroids • Prednisolone 40mg • Hydrocortisone 100mg • If not reponding • Magnesium • 1.2 – 2g IV over 20 minutes • Consider IV aminophylline or β2 agonists

40. Any patient with acute severe or life threatening asthma who is not responding to therapy needs referral to Intensive Care

41. Inhaler quiz

42. What is this inhaler? • Salbutamol • Seretide • salmeterol

43. Long - acting Short - acting

44. What is this inhaler? • fluticasone • beclomethosone • symbicort

46. What is this inhaler? • Serevent • Seretide • combivent

48. Summary • Oxygen therapy • Management of asthma & COPD • Bronchodilators • Anti-inflammatory agents • Generic Vs Brand names

49. ? BTS Asthma guidelines www.brit-thoracic.org.uk/ClinicalInformation/Asthma/AsthmaGuidelines/tabid/83/Default.aspx NICE COPD Guidance http://guidance.nice.org.uk/CG12