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 Wheezing Cough Anxiety Accessory muscle use Tachypnea Tachycardia Hypoxia

Functional Assessment FEV 1 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 Beta 2 agonists Anticholinergics Systemic corticosteroids Adjunct therapies

Therapies Not Recommended Antibiotics Aggressive hydration Chest physical therapy Mucolytics Sedation

Short-Acting Beta 2 -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< 6 years old Albuterol nebulizer soln (0.63mg/3ml, 1.25mg/3ml, 2.5mg/3ml, 5mg/ml) 2.5-5mg q 20 min x 3 doses, then mg q 1-4 h prn 10-15mg/h continuously 0.15mg/kg (min dose 2.5mg) q 20 min x 3 doses, then mg/kg up to 10mg q 1-4 h prn 0.5mg/kg/h continuously Albuterol MDI (90mcg/puff) 4-8 puffs q 20 min 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

Levalbuterol (Xopenex ® ) > 6 years old< 6 years old Levalbuterol nebulizer soln (0.63mg/3ml, 1.25mg/0.5ml, 1.25mg/3ml) mg q 20 min x 3 doses, then mg q 1-4 h prn mg/h continuously 0.075mg/kg (min dose 1.25mg) q 20 min x 3 doses, then mg/kg up to 5mg q 1-4 h prn 0.25 mg/kg/h continuously Levalbuterol MDI (45 mcg/puff) 4-8 puffs q 20 min 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 – Tremor – Nervousness – Tachycardia – Palpitations Less common – Hypokalemia – 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 nebulizer soln (0.25mg/ml) 0.5mg q 20 min x 3 doses, then prn 0.25mg q 20 min x 3 doses, then prn Ipratropium MDI (18mcg/puff) 8 puffs q 20 min prn up to 3 hours 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 prn up to 3 hours 4-8 puffs q 20 min prn up to 3 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< 6 years old Prednisone40-80 mg/day in 1 or 2 divided doses until PEF reaches 70% predicted “Burst”: mg in single or 2 divided doses x 5-10 days 1 mg/kg in 2 divided doses (max 60mg/d) until PEF 70% predicted “Burst”: 1-2 mg/kg/d (max 60 mg/d) x 3-10 days Methylprednisolone Prednisolone

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 – Leukocytosis – Depression – Euphoria – Impaired wound healing Chronic – Cushing’s syndrome – Osteoporosis – Peptic ulcer disease – Adrenal suppression – 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:

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