Improving the Lives of Our Patients with Asthma Asthma Interventions for Busy Pharmacists

1. Improving the Lives of Our Patients with AsthmaAsthma Interventions for Busy Pharmacists Controlling Asthma in American Cities Project of Minneapolis & St Paul

2. Definition of Asthma • A chronic, non-contagious inflammatory disorder of the airways consisting of an infiltration of mast cells, eosinophils, lymphocytes, neutrophils, and epithelial cells • Recurrent episodes of wheezing, chest tightness, shortness of breath, and cough • Widespread, variable, and reversible (not always completely) airflow obstruction • Airway hyperresponsiveness

3. Pathologic Airway Changes Induced in Asthma Mucous gland hypertrophy Epithelial damage Airway smooth muscle Edema Inflammatory cell infiltration Mucus Vascular dilatation Thickening of basement membrane Adapted from National Asthma Education and Prevention Program. Expert Panel Report: Guidelines for the diagnosis and management of asthma. NHLBI, NIH. 1991.

4. Percent of US Population with Asthma Age (yrs) Source: Surveillance for Asthma – United States, 1980-1999. Morbidity and Mortality Weekly Report, 51(SS01): 1-13.

5. The Goals of Asthma Therapy: (Asthma Control) • Reducing impairment • prevent chronic and troublesome symptoms • require infrequent use (≤ 2 days a week) of inhaled SABA for symptoms • maintain (near) “normal” pulmonary function • maintain normal activity levels • meet patients’ and families’ satisfaction with care • Reducing risk • prevent recurrent exacerbations of asthma (ED/inpatient) • prevent progressive loss of lung function • provide optimal pharmacotherapy

6. Rationale for Pharmacologic Therapy • Underlying cause of asthma: inflammatory airway disorder • Key principle of therapy: regulation of chronic airway inflammation

7. Guidelines For The Diagnosis and Management of Asthma (EPR-3) released: August 28, 2007 • (Almost) no new medications • Restructuring into “severity” and “control” • Domains of “impairment” and “risk” • Six treatment steps (step-up/step-down) • More careful thought into the ongoing management issues • Summarizes the extensively-validated scientific evidence that the guidelines, when followed, lead to a significant reduction in the frequency and severity of asthma symptoms and improve quality of life

11. Classifying Severity for Patients Currently Taking Controller Medications

15. Medications • Controller Medications - Daily • Corticosteroids (inhaled and systemic) • Long-acting beta2-agonists • Leukotriene modifiers • Cromolyn sodium - Nedocromil sodium • Sustained-release theophylline • Allergy Immunotherapy • Reliever (or Rescue) Medications • Short acting beta2-agonists • Systemic corticosteroids: “Burst Therapy” • Anticholinergics (used with nebulizer in ER)

16. Methods of Medication Delivery • Metered-dose inhaler (MDI) • Spacer/holding chamber/face mask • Dry-powder inhaler (DPI) • Nebulizer • Oral Medication • Tablets, Liquids • Intravenous Medication • IV Corticosteroids, IV Aminophylline

20. Overview of Asthma Medications: Controllers • Prevent and treat inflammation • Corticosteroids (inhaled and systemic) • Prevent inflammation • Leukotriene modifiers • Cromolyn/Nedocromil sodium • Bronchodilators • Long-acting beta2-agonists • Theophylline

21. CONTROLLERSCorticosteroids • Inhaled • Beclomethasone (QVAR®) • Fluticasone (Flovent®) • Triamcinolone (Azmacort®) • Budesonide (Pulmicort®) • Flunisolide (AeroBid®)

22. CONTROLLERSCommon Steroid Inhalers Azmacort® Pulmicort® Flovent® QVAR®

23. CONTROLLERS Inhaled Corticosteroids • Most effective long-term control therapy for persistent asthma • Benefit of daily use: • Fewer symptoms • Fewer severe exacerbations • Reduced use of quick-relief medicine (albuterol) • Improved lung function

24. CONTROLLERSInhaled Corticosteroids • Reduced airway inflammation • Decreases airway hyperresponsiveness • Maximum Effects • Oral: 6 to 24 hours • Inhaled: Weeks (maybe months) • **NEVER FOR RESCUE PURPOSES**

25. CONTROLLERS Estimated Comparative Dosages of Inhaled Corticosteroids • Preparations not equivalent per puff/per microgram • Comparative doses estimated • Few studies directly compare preparations • Clinician judgment: most important determinant of dosing • Monitor clinical response to therapy • Adjust dose accordingly

28. CONTROLLERSSystemic Effects & Inhaled Steroids • Individuals might experience side effects at high doses • More susceptible individuals may experience side effects at medium doses • Potential Systemic Effects: • Adrenal suppression • Rare individuals more susceptible • Potential impaired growth velocity in children • Decreased bone density (adults) • Other (cataracts, etc. in adults)

29. Inhaled Corticosteroids and Effect on Linear Growth • Untreated or poorly treated asthma is detrimental to height growth • Long term studies using medium dose inhaled steroids had no adverse effect on ultimate adult height • There is some slowed growth in the first year after starting ICS(1 cm/yr) however “catch up” occurs despite continuing on the medication

30. Corticosteroid Systemic Effects • All inhaled corticosteroids exhibit dose-related systemic adverse effects, but much less than comparable doses of oral corticosteroids.

31. Inhaled Local Dysphonia Cough/throat irritation Thrush Impaired growth (high dose)? Systemic (oral, IV) Fluid retention Muscle weakness Ulcers Malaise Impaired wound healing Nausea/Vomiting, HA Osteoporosis (adults) Cataracts (adults) Glaucoma (adults) Corticosteroid Side Effects

32. CONTROLLERSLong-acting Beta2-agonists Serevent® Diskus Foradil® Aerolizer

33. CONTROLLERSLong-acting Beta2-agonists • Salmeterol (Serevent®), Formoterol (Foradil®) • Indication: Daily long-term control Bronchodilate by long-term stimulation of beta2 receptors • Advantages • Blunt exercise induced symptoms for longer time • Decrease nocturnal symptoms • Improve quality of life • Combination therapy beneficial when added to inhaled corticosteroids • May decrease the need to increase inhaled corticosteroid dose dose

34. CONTROLLERSLong-acting Beta2-agonists • NOT for acute symptoms or exacerbations • Onset of effect  30 minutes • Peak effect  1-2 hours • Duration of effect  up to 12 hours • NOTa substitute for anti-inflammatory therapy • NOT appropriate for monotherapy

35. Serevent® Black Box Warning WARNING: Data from a large placebo-controlled US study that compared the safety of salmeterol (SEREVENT® Inhalation Aerosol) or placebo added to usual asthma therapy showed a small but significant increase in asthma-related deaths in patients receiving salmeterol (13 deaths out of 13,176 patients treated for 28 weeks) versus those on placebo (3 of 13,179) (see WARNINGS and CLINICAL TRIALS: Asthma: Salmeterol Multi-center Asthma Research Trial). From Serevent® Inhalation Aerosol Package Insert

36. CONTROLLERS Leukotriene Modifiers • Indications • Long-term control therapy in mild persistent asthma • Improved lung function • Prevent need for short-acting beta2-agonists • Prevent exacerbations by preventing inflammation • Combination therapy with an inhaled corticosteroid in moderate persistent asthma

37. CONTROLLERSLeukotriene Modifiers • Cysteinyl Leukotriene Receptor Antagonists • Montelukast (Singulair®)– Once a day in PM – indicated at age 1 • Zafirlukast(Accolate®) – Twice daily – Empty Stomach • Many drug interactions • 5-Lipoxygenase inhibitors • Zileuton(Zyflo®) – Four times daily • Many drug interactions

38. CONTROLLERS Leukotriene Modifiers • Montelukast (Singulair®) • 4mg granules (in C.A.I.R), 4 mg, 5 mg chewable and 10 mg tablet • Once daily dosing (evening) • Pediatric indication > 1 year • No food restrictions

39. RELIEVERSShort-Acting Beta2-agonist • Albuterol (Proventil®, Ventolin®) • Pirbuterol (Maxair®) • Terbutaline (Brethaire®, Brethine® MDI)

40. RELIEVERSShort Acting Beta2-agonist Ventolin® Proventil® Proventil® HFA Maxair® Autohaler

41. RELIEVERSShort-Acting Beta2-Agonists • Most effective medication for relief of acute bronchospasm • Preferably use inhaled rather than oral preparations • Increased need for these medications indicates uncontrolled asthma (and inflammation) • Regularly scheduled use not generally recommended – use “as needed” • May lower effectiveness • May increase airway hyperresponsiveness

42. RELIEVERSNew Short-Acting Beta-Agonists • Levalbuterol (Xopenex®) • R-Isomer of albuterol (active molecule) • Only available as Nebulized Solution • Give 1/2 dose-because give active component • POSSIBLY less side effects • Marketed as 3 times a day neb

43. RELIEVERSShort-Acting Beta2-Agonists • Side Effects: • Increased Heart Rate • Palpitations • Nervousness • Sleeplessness • Headache • Tremor

44. RELIEVERSSystemic Corticosteroids “Burst Therapy” • Indication - quick (6-24 hours) relief of inflammation • Beta2 agonist unresponsiveness • Gradual deterioration • Yellow zone  48 hours • With or without prior therapy • Establish “control” • ER/Urgent Care visit NOTE: Will NOT stop a flare-up but is used to reduce inflammation after a flare-up

45. RELIEVERSSystemic Corticosteroids “Burst Therapy” • Dosing for 3 to 10 days: • 1-2 mg/kg/day (60mg/day max) • Once or twice daily dosing • < 1 year – 10 mg prednisone • 1-4 years – 20 mg prednisone • > 5 years – 30 mg prednisone • NO taper required

46. The Asthma Action Plan • Helps patients/caregivers manage asthma • Uses Peak Flows • Spells out medication instructions • Green Zone 80-100% Peak Flow • Yellow Zone 50-80% Peak Flow • Red Zone Below 50% Peak Flow

47. Indicators of Poor Asthma Control • Step up therapy if patient: • Awakens at night with symptoms • Has an urgent care visit • Has increased need for albuterol • Rules of “two”

48. Short Acting Beta2-Agonists Rules of Two • Do you use a quick relief inhaler more than 2 times per week? • Do you awaken at night due to asthma more than 2 times per month? • Do you refill your quick relief inhaler prescription more than 2 times per year? If you answer “YES” to any of these questions, it’s a sign your asthma may be poorly controlled. ® Baylor Healthcare System

49. Indicators of Poor Asthma Control • Before increasing medications, check: • Inhaler technique • Adherence to prescribed regimen • Environmental changes • Also consider alternative diagnoses

50. Monitoring Pharmacotherapy • Monitor: • Patient adherence to regimen • Inhaler technique • Frequency of albuterol use • Frequency of oral corticosteroid “burst” therapy • Side effects of medications