Stacie L. Penkova, PharmD, MHSA, BCPS Clinical Pharmacy Manager Critical Care Pharmacy Specialist Drug Information Coordinator Pharmacology Summit

Transcription

1 Stacie L. Penkova, PharmD, MHSA, BCPS Clinical Pharmacy Manager Critical Care Pharmacy Specialist Drug Information Coordinator Pharmacology Summit July 26, 2014

2 Objectives Classify asthma by severity Prescribe medication regimens by severity Identify medications for: Asthma in pregnancy Asthma in the elderly Exercise induced bronchoconstriction Asthma triggers Comorbities Manage asthma exacerbations Educate on medication therapy

3 Asthma Control & Classification Control determined by considering: Symptoms (nighttime awakenings, normal activity interferences, short-acting β2-agonist (SABA) use) Lung function (FEV 1 & FEV 1 /FVC) Questionnaires (ATAQ, ACT) Risk determined by considering: Exacerbations per year (oral corticosteroid use, hospitalization) Loss of lung function Treatment-related adverse effects (AEs)

4 Asthma Control & Classification

5 Asthma Control & Classification

6 Stepwise Approach

7 Management Components Routine monitoring of symptoms & lung function Patient education to create a partnership between clinical & patient Controlling environmental factors & comorbid conditions Pharmacologic therapy

8 Asthma Treatment Goals Reduce impairment Freedom from frequent/troublesome symptoms of asthma Minimal need of inhaled SABAs Few night-time awakenings Optimization of lung function Maintenance of normal daily activities Satisfaction with asthma care Reduce risk Prevention of recurrent exacerbations Prevention of reduced function Optimization of pharmacotherapy

9 Symptom assessment Monitoring Assessment of impairment Assessment of risk Pulmonary function Office Home

10 Metered-dose inhalers (MDIs) Valved holding chambers (VHCs) Dry powder inhalers (DPIs) Nebulizer Inhalation Devices

11 Treatment of Asthma Asthma Severity Intermittent Mild Persistent Preferred Alternatives Moderate Persistent Preferred Alternatives Severe Persistent Preferred Alternatives Recommended Regimen SABA PRN SABA PRN + Low-dose ICS Montelukast or Theophylline SABA PRN + Low-dose ICS + LABA or Medium-dose ICS Low-dose ICS + leukotriene modifier or theophylline SABA PRN + Medium- or high-dose ICS + LABA Medium-dose ICS + leukotriene modifier or theophylline

12 Short Acting β2 Agonists SABAs Albuterol (Ventolin HFA, ProAir HFA) Levalbuterol (Xopenex HFA) Pirbuterol (Maxair Autohaler) Place in therapy: rapid relief of asthma symptoms Mechanism of Action (MOA): bronchodilator that relaxes bronchial, uterine, and vascular smooth muscle by stimulating beta 2 receptors

13 Short Acting β2 Agonists Pharmacokinetics (PK) Onset - 5 minutes Peak effect minutes Duration hours AEs: paradoxical bronchospasm, tremor, tachycardia, QT prolongation, hyperglycemia, hypokalemia/magnesemia, tolerance Education: technique, adverse effects

14 Inhaled Corticosteroids ICSs Beclomethasone (Qvar) Budesonide (Pulmicort) Ciclesonide (Alvesco) Flunisolide (Aerospan HFA) Fluticasone (Flovent) Mometasone (Asmanex) Place in therapy: mild, moderate, & severe persistent

15 Inhaled Corticosteroids MOA: decreases inflammation by decreasing the number & activity of inflammatory cells, inhibiting bronchoconstrictor mechanisms producing direct smooth muscle relaxation & decreasing airway hyperactivity PK: Onset weeks Peak - unknown Duration - unknown

16 Inhaled Corticosteroids AEs: oral candidiasis, dysphonia, reflex cough, bronchospasm Education: technique, adverse effects, asthma action plan

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18 Oral Corticosteroids OCSs Methyprednisolone (Medrol) Prednisone (Rayos, Sterapred) Prednisolone (Millipred, Orapred) Hydrocortisone (Cortef) Dexamethasone (Decadron) Place in therapy: asthma exacerbations incompletely responsive to bronchodilators MOA: decreases inflammation, mainly by stabilizing leukocyte lysosomal membranes; suppresses immune response; stimulates bone marrow; influences protein, fat, and carbohydrate metabolism

19 Oral Corticosteroids PK: Onset - variable Peak - variable Duration - variable AEs: insomnia, hypertension, edema, GI irritation, hyperglycemia, osteoporosis, growth suppression, delayed wound healing, hirsutism, rebound inflammation Education: adverse effect, take with food, importance of not stopping medication abruptly

20 Long Acting β2 Agonists LABAs Salmeterol (Serevent) Formoterol (Foradil, Perforomist) Aformoterol (Brovana) Indacterol (Arcapta) Place in therapy: moderate, & severe persistent MOA: selectively activates beta 2 receptors, which results in bronchodilation; also, blocks the release of allergic mediators from mast cells lining the respiratory tract

21 Long Acting β2 Agonists PK: Drug Onset Peak Duration Salmeterol 20 minutes 2 hours 12 hours Formoterol N 5 minutes 15 minutes 12 hours Formoterol I 12 minutes 15 minutes 12 hours Aformoterol 15 minutes 30 minutes 12 hours Indacterol 5 minutes 15 minutes 24 hours AEs: tremor, hypokalemia, tachycardia, tolerance Education: technique, adverse effects, asthma action plan, storage

22 Leukotriene Modifiers Montelukast (Singulair) Zafirlukast (Accolate) Zileuton (Zyflo) Place in therapy: mild, moderate, & severe persistent MOA: reduces early & late phase bronchoconstriction from antigen challenge

23 Leukotriene Modifiers PK: Onset - unknown Peak hours Duration - 24 hours AEs: headache, dyspepsia, fatigue, dizziness, liver dysfunction (zafirlukast/zilueton), vasculitis (montelukast/zafirlukast) Education: storage & administration, asthma action plan, adverse effects

24 Combination Therapies LABAs/ICSs Fluticasone/salmeterol (Advair) Budesonide/formoterol (Symbicort) Mometasone/formoterol (Dulera) Fluticasone/vilanterol (Breo Ellipta) SABAs/AC Ipratropium/albuterol (DuoNeb, Combivent)

25 Other Asthma Medications Oral β-agonists Albuterol (VoSpire ER) Metaproterenol (Alupent) Terbutaline (Brethine) Inhaled Cromolyn (Intal) Acetylcysteine (Mucomyst) Racemic epinephrine (S2) Vaccinations Influenza Pneumococcal OTC Ephedrine/guaifenesin (Primatene, Bronkaid) Racepinephrine (Asthmanefrin)

26 Inhaled Anticholinergics Ipratropium (Atrovent) Tiotropium (Spiriva) Aclidinium (Tudorza) Place in therapy: Ipratropium - off label as an alternative reliever medication in patients who cannot take a SABA or in combination with a SABA for treatment of acute bronchoconstriction Tiotropium can be added to improve lung function & symptoms in patients uncontrolled on an ICS; can be added to an ICS and a LABA to improve lung function in poorly controlled severe asthma & increase time to the first severe exacerbation Aclidium - no clinical data are available in asthma

27 Inhaled Anticholinergics MOA: inhibits vagally mediated reflexed by antagonizing acetylcholine at muscarinic receptors on bronchial smooth muscle PK: Onset 5-15 minutes Peak 1-2 hours Duration 3-6 hours AEs: dizziness, headache, palpitations, blurred vision, pharyngitis, nausea, dry mouth, bronchospasm Education: technique, adverse effects

28 Theophylline Methylxanthine Place in therapy: persistent asthma, alone or concurrently with an ICS MOA: inhibits phosphodiesterase, the enzyme that degrades camp, resulting in relation of smooth muscle of the bronchial airways and pulmonary blood vessels

29 Theophylline PK: Route Onset Peak Duration PO IR minutes 1-2 hours Unknown PO ER minutes 4-7 hours Unknown IV 15 minutes minutes Unknown AEs: insomnia, seizures, headache, arrhythmias, nausea, vomiting, tachypnea, lab interactions Education: drug interactions, adverse effects, administration

30 Anti-IgE Antibody Omalizumab (Xolair) Place in therapy: patients 12 years old with moderate to severe persistent asthma not well controlled on an ICS who have well documented specific sensitization to a perennial airborne allergen MOA: inhibits binding of IgE to high affinity receptor on surface of mast cells and basophils, which limits release of allergic response mediators

31 Anti-IgE Antibody PK: Onset unknown Peak 7-8 days Duration unknown AEs: headache, dizziness, fatigue, arthralgia, injection site reactions Education: technique, Black Box Warning, patient medication guide

32 Other Therapies Immunotherapy: in patients with allergic asthma, specific immunotherapy with SQ injections may provide long lasting benefits in reducing asthma symptoms Bronchial thermoplasty: approved in 2010 for use in adults with severe persistent asthma not well controlled on an ICS and a LABA Fiberoptic bronchoscopy on 3 separate occasions 3 weeks apart Walls of the central airways are treated with radiofrequency energy that is converted to heat, resulting in ablation of airway smooth muscle

33 Treatment Failure Attributed to: Lack of adherence to prescribed medications Uncontrolled comorbid conditions Continued exposure to tobacco smoke and other airborne pollutants, allergens, or irritants Aspirin, NSAIDs Β-blockers (oral & ophthalmic) Trained asthma educators can: Improve inhaler technique Create a personalized asthma management plan

34 Exacerbation Management

35 Exercise Induced Bronchoconstriction SABAs Just before exercise Prevent EIB for 2-4 hours LABAs Salmeterol at least 30 minutes before exercise Formoterol at least 5 minutes before exercise Prevent EIB for up to 12 hours Montelukast 2 hours before exercise Prevents EIB in 50% of patients for up to 24 hours

36 Asthma in Pregnancy SABA Albuterol ICSs Budesonide LABAs Montelukast Immunotherapy Omalizumab

37 Asthma in Elderly ICSs adverse effects include skin bruising, cataracts, increased IOP, hyperglycemia, accelerated bone mass loss SABAs & LABAs reduced response if on β- blockers; increased incidence of tachycardia, arrhythmias, tremors Technique problems MDIs, DPIs

38 Triggers & Comorbidities Allergic rhinitis Up to 95% of patients with asthma also suffer from persistent rhinitis GERD Patients with poorly controlled asthma have a higher prevalence of GERD PPI improves pulmonary function and asthma-related QOL Obesity Has been associated with asthma persistence and severity Diminished response to ICSs Weight loss improves lung function and responsiveness to treatment

39 Questions