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Medications for the Acute Management of Asthma A. Shaun Rowe, Pharm.D., BCPS Risk Factors for Death • Social History – Low socioeconomic status or inner-city residence – Illicit drug use – Major psychosocial problems • Co-morbidities – Cardiovascular disease – Other chronic lung disease – Psychiatric disease Physical Exam • Shortness of breath • Accessory muscle use • Wheezing • Tachypnea • Cough • Tachycardia • Anxiety • Hypoxia Functional Assessment • FEV1 or PEF – Severity of airflow obstruction – Patient’s response to treatment • Oxygen Saturation – Pulse oximetry – SpO2 > 90% Goals of Treatment • Correction of significant hypoxemia • Rapid reversal of airflow obstruction • Reduction of the likelihood of recurrence Treatment • Beta2 agonists • Anticholinergics • Systemic corticosteroids • Adjunct therapies Therapies Not Recommended • Antibiotics • Aggressive hydration • Chest physical therapy • Mucolytics • Sedation Short-Acting Beta2-Agonists • Albuterol (Proventil HFA®) – Nebulizer solution & MDI • Levalbuterol (Xopenex HFA®) – Nebulizer solution & MDI • Pirbuterol (Maxair®) – MDI MOA & Indication • Stimulates beta adrenergic receptors causing bronchial smooth muscle dilation • Most potent and rapidly acting bronchodilators for relief of acute asthma symptoms • Adequacy of response related to contribution of bronchospasm in producing airway obstruction Albuterol (Proventil®) > 6 years old Albuterol 2.5-5mg q 20 min x nebulizer soln 3 doses, then 2.5(0.63mg/3ml, 10mg q 1-4 h prn 1.25mg/3ml, 2.5mg/3ml, 5mg/ml) 10-15mg/h continuously Albuterol MDI 4-8 puffs q 20 min (90mcg/puff) up to 4 h, then q 1-4 h prn < 6 years old 0.15mg/kg (min dose 2.5mg) q 20 min x 3 doses, then 0.150.3mg/kg up to 10mg q 1-4 h prn 0.5mg/kg/h continuously 4-8 puffs q 20 min x 3 doses, then q 1-4 h prn; use VHC; add mask in < 4 yo Levalbuterol (Xopenex®) Levalbuterol nebulizer soln (0.63mg/3ml, 1.25mg/0.5ml, 1.25mg/3ml) > 6 years old < 6 years old 1.25-2.5mg q 20 min x 3 doses, then 1.25-5mg q 1-4 h prn 0.075mg/kg (min dose 1.25mg) q 20 min x 3 doses, then 0.075-0.15mg/kg up to 5mg q 1-4 h prn 5-7.5 mg/h continuously 0.25 mg/kg/h continuously Levalbuterol MDI 4-8 puffs q 20 min (45 mcg/puff) up to 4 h, then q 1-4 h prn 4-8 puffs q 20 min x 3 doses, then q 1-4 h prn; use VHC; add mask in < 4 yo Albuterol Kinetics • Onset: 5 – 15 minutes • Peak effect: 30 – 60 minutes • Duration: 3 – 6 hours Albuterol Adverse Effects • Common • Less common – Tremor – Hypokalemia – Nervousness – Tachycardia – Palpitations – Dizziness – Insomnia – Headache – HTN – EKG changes Levalbuterol vs Albuterol • Levalbuterol is R-isomer of albuterol • Administered in one-half the mg dose of albuterol • Provides comparable efficacy and safety • Significant cost difference Anticholinergics • Ipratropium (Atrovent®) – Nebulizer solution & MDI • Ipratropium with albuterol (Combivent® Respimat®, DuoNeb®) – Nebulizer solution & MDI MOA & Indication • Relaxes smooth muscles of bronchi and bronchioles through competitive inhibition of cholinergic receptors • Does not inhibit release of anti-inflammatory mediators • Used with albuterol for relief of acute asthma symptoms Ipratropium (Atrovent®) > 6 years old < 6 years old Ipratropium 0.5mg q 20 min x nebulizer soln 3 doses, then prn (0.25mg/ml) 0.25mg q 20 min x 3 doses, then prn Ipratropium 8 puffs q 20 min prn up to 3 hours MDI (18mcg/puff) 4-8 puffs q 20 min prn up to 3 hours Ipratropium with Albuterol ® ® (Duoneb , Combivent ) > 6 years old < 6 years old Ipratropium with albuterol nebulizer soln (3ml vial; 0.5mg ipratropium & 2.5mg albuterol) 3ml q 20 min x 3 doses, then prn 1.5ml q 20 min x 3 doses, then prn Ipratropium with albuterol MDI (18mcg ipratropium; 90mcg albuterol/puff) 8 puffs q 20 min 4-8 puffs q 20 prn up to 3 min prn up to 3 hours hours Ipratropium Kinetics • Onset: 5 – 30 minutes • Peak effect: 1 – 2 hours • Duration: 4 – 5 hours Ipratropium Adverse Effects • Limited adverse effects due to limited systemic absorption • Most common – Blurred vision – Tachycardia – Headache – Dry mouth Inhaled Ipratropium • Not recommended for monotherapy due to more gradual bronchodilation • Addition of ipratropium to a selective SABA produces additional bronchodilation • Results in fewer hospital admissions, particularly in patients with severe airflow obstruction • May be used up to 3 hours in initial management of severe exacerbations Systemic Corticosteroids • Prednisone (Deltasone®) – Oral tablets • Methylprednisolone (Solu-Medrol®, Medrol®) – Injection – Oral tablets • Prednisolone (Prelone®) – Oral solution MOA & Indication • Decreases inflammation and reduces inflammatory response to cytokines released during inflammation • Component of treatment for acute asthma exacerbation • Also used for prevention of acute asthma exacerbation Systemic Corticosteroids > 6 years old Prednisone 40-80 mg/day in 1 or 2 divided doses until PEF reaches Methylprednisolone 70% predicted < 6 years old 1 mg/kg in 2 divided doses (max 60mg/d) until PEF 70% predicted Prednisolone “Burst”: 40-60 mg in single or 2 divided doses x 5-10 days “Burst”: 1-2 mg/kg/d (max 60 mg/d) x 3-10 days Corticosteroid Kinetics • Onset: ~ 3 hours for oral prednisone & 1 hour for intravenous methylprednisolone • Peak effect: 12 hours for oral & 5 hours for intravenous Corticosteroid Adverse Effects • Acute – Hypertension – Fluid retention – Hyperglycemia • Chronic – Cushing’s syndrome – Osteoporosis – Leukocytosis – Peptic ulcer disease – Depression – Adrenal suppression – Euphoria – Impaired wound healing – Stunted growth Role of Systemic Corticosteroids in ED • Moderate or severe exacerbations or incomplete response to initial SABA • Oral equivalent to IV • 5 – 10 day course following d/c from ED • IM depot injections for nonadherence • Supplemental doses to pts who take corticosteroids regularly, even in mild exacerbations Pediatric Status Asthmaticus • Beta-adrenergic agonists – Albuterol – Bind to beta2-adrenergic receptors in the airway smooth muscle to produce bronchodilation – Start with intermittent nebulizations and switch to continuous if inadequate response – May need 20 – 30 mg/hr – Tachycardia and hypertension • Corticosteroids – Systemic not inhaled in this case – Give oral if they can tolerate but IV if not – High dose Beta agonists can impair gut absorption – Early administration improves outcomes – 2mg/kg/day of prednisone or methylprednisolone – No evidence that higher doses are better Carroll CL, Sala KA. Pediatric Status Asthmaticus. Critical Care Clinics. 2013:153-66. Pediatric Status Asthmaticus • Second line treatments – Magnesium • Causes bronchodialation through calcium inhibition in the smooth muscle • Weakness, respiratory depression, and cardiac arrhythmias – Anticholinergics • Ipratropium • Works well as an adjunct when added to albuterol – Terbutaline • IV beta-agonist • Good for those that can’t inhale enough albuterol to be effective • cardiotoxicity