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The goal is rapid reversal of airflow obstruction by repetitive or continuous administration of inhaled β2-agonists, ensuring adequate oxygenation, and relieving inflammation.7,8,9,10 Figure 69-1 shows the National Asthma Education and Prevention Program Expert Panel ED treatment algorithm.10 The following categories of medications are used in the treatment of acute asthma: β-adrenergic agonists, anticholinergics, and glucocorticoids. Treatments for impending or actual respiratory arrest are discussed below in "Status Asthmaticus."
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β-Adrenergic agonists with rapid onset are the preferred initial rescue medication for acute bronchospasm (Table 69-5). Stimulation of β1-receptors increases rate and force of cardiac contraction and decreases small intestine motility and tone, whereas β2-adrenergic stimulation promotes bronchodilation, vasodilation, uterine relaxation, and skeletal muscle tremor.
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β-Adrenergic drugs cause bronchodilation by stimulation of the enzyme adenyl cyclase, which converts intracellular adenosine triphosphate into cyclic adenosine monophosphate. This action enhances the binding of intracellular calcium to cell membranes, reducing the myoplasmic calcium concentration, and results in relaxation of bronchial smooth muscle. β-Adrenergic drugs also inhibit mediator release and promote mucociliary clearance.
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The most common side effect of β-adrenergic drugs is skeletal muscle tremor. Patients also may experience nervousness, anxiety, insomnia, headache, hyperglycemia, palpitations, tachycardia, and hypertension. Clinical toxicity is rare and less common than undertreatment complications. Provoking dysrhythmias or myocardial ischemia is rare, especially in those without a prior history of coronary artery disease. The older catecholamine bronchodilators, such as epinephrine, are not β2 specific and have a short duration of action.
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Albuterol is a 50:50 racemic mixture (equal amounts of left and right isomers); it is now available in the hydrofluoroalkane formulation, which has increased the cost and the effectiveness. The R isomer has great binding affinity for the β2-receptor and is responsible for bronchodilation. The S isomer has no bronchodilatory effect but has a long half-life (12 hours); this isomer may be responsible for late paradoxical bronchospasm in some patients. Levalbuterol (Xopenex®) is the pure R isomer form of the drug, intended to improve effectiveness and limit side effects such as tachycardia and rhythm change. Both racemic albuterol and levalbuterol can be given as intermittent or continuous nebulizations. Levalbuterol costs 5 to 25 times more than albuterol, and it has no clear advantage over albuterol regarding symptom change, admission, or tachycardia.15,16,17
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Nonprescription racemic epinephrine (Asthmanefrin®) replaced Primatene® as an over-the-counter medication, and the cost is less than for prescription β2-adrenergics. Asthmanefrin® contains 11.25 milligrams of racemic epinephrine/0.5 mL. In one study, subjects recruited through local pharmacies reported no worse asthma outcomes than individuals treated with prescription β-agonists.18 No other data exist to guide use of Asthmanefrin® versus prescribed agents.
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Aerosol therapy with β2-adrenergic drugs produces excellent bronchodilation and is favored over oral or parenteral routes. The aerosol route achieves topical administration of a relatively small dose of drug, thereby producing local effects with minimum systemic absorption and fewer side effects. Aerosol delivery occurs with a metered-dose inhaler coupled to a spacing device or with a compressor-driven nebulizer.20 A spacing device attached to the inhaler improves drug deposition; when optimally used, metered-dose inhaler therapy delivers the most drug to target airways, better than nebulized therapy. Even with optimum technique, a maximum of 15% of the drug dose is retained in the lungs, regardless of the aerosol method used.
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Aerosol treatments may be administered every 15 to 20 minutes or on a continuous basis.21 Subcutaneous epinephrine and terbutaline are options for patients unable to coordinate aerosolized or metered-dose inhaler treatments, seen often in severe airflow-limited states. IV β-agonist infusions offer no advantage over aerosolized or metered-dose inhaler–delivered agents and carry increased risk.22
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Salmeterol xinafoate and formoterol are β2-adrenoreceptor agonists that bind with greater affinity to the β2-receptor site than albuterol. They are indicated for twice-daily maintenance therapy. Neither drug should be used for acute asthma exacerbations. Bronchodilator effects last at least 12 hours, and tachyphylaxis has not been reported with long-term use. The number of asthma-related deaths among patients receiving salmeterol, especially in African Americans, has increased for unknown reasons, although this may be due to failure to recognize the need for or use rescue short-acting agents and to seek care appropriately. Long-acting β2-adrenoreceptor agonists are an effective treatment for long-term control of asthma, especially in conjunction with inhaled corticosteroids. Short-acting β2-adrenoreceptor agonists are used for infrequent or breakthrough symptoms that occur despite the use of long-acting β2-adrenoreceptor agonists.7,8,9,10,21
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Corticosteroids are a cornerstone of asthma treatment. Steroids produce beneficial effects by restoring β-adrenergic responsiveness and reducing inflammation. The peak anti-inflammatory effect occurs at least 4 to 8 hours after IV or PO administration, but early use is wise to enhance care quickly; corticosteroids given within 1 hour of arrival in the ED reduce the need for hospitalization.23 Although there is disagreement over the optimal dose in acute asthma, an initial dose of PO prednisone of 40 to 60 milligrams or IV methylprednisolone of 1 milligram/kg is sufficient, and higher-dose corticosteroid therapy offers no advantage.24 Admitted patients should receive additional daily corticosteroids until subjective and objective improvements are achieved. Patients who are being discharged home with an FEV1 or PEF of <70% predicted after aggressive ED treatment should be prescribed a 5- to 10-day nontapering course of prednisone (40 to 60 milligrams/d in a single daily dose or its equivalent) or a 2-day course of oral dexamethasone (16 milligrams/d in a single daily dose).7,8,9,10,19,25,26 A single dose of depot methylprednisolone, 150 milligrams IM, is another option if compliance is a concern.27
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Current recommendations favor inhaled corticosteroids for all patients with mild persistent asthma or more severe asthma.7,8,9,10 This means discharging patients with mild persistent or more severe asthma on maintenance inhaled corticosteroids in addition to any systemic bursts.28,29,30,31 Inhaled corticosteroid options are beclomethasone, 80 to 240 micrograms/d; budesonide, 180 to 600 micrograms/d; flunisolide, 500 to 1000 micrograms/d; fluticasone, 88 to 264 micrograms/d; mometasone, 200 micrograms/d; and triamcinolone acetonide, 300 to 750 micrograms/d.
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The effects of anticholinergics used in combination with β-adrenergic agents are additive. Anticholinergics affect large, central airways, whereas β-adrenergic drugs dilate smaller airways. Anticholinergic drugs competitively antagonize acetylcholine at the postganglionic junction between the parasympathetic nerve terminal and effector cell. This process blocks the bronchoconstriction induced by vagal cholinergic-mediated innervation to the larger central airways. In addition, anticholinergics reduce concentrations of cyclic guanosine monophosphate in airway smooth muscle, further promoting bronchodilation.
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The anticholinergic commonly used is inhaled ipratropium bromide. Ipratropium is available as a nebulized solution and a metered-dose inhaler or in combination with albuterol7,8,9,10 (Table 69-5). Use an aerosolized ipratropium bromide solution, 0.5 milligrams, in patients with moderate to severe exacerbation.7,8,9,10 Adding multiple doses of ipratropium bromide to a short-acting selective β-agonist may improve bronchodilation and decrease the need for hospitalization among severely obstructed asthmatics,32 although this benefit is not universal.33 Potential side effects with anticholinergics include dry mouth, thirst, and difficulty swallowing. Less commonly, tachycardia, restlessness, irritability, confusion, difficulty in micturition, ileus, blurring of vision, or an increase in intraocular pressure can occur. Long-acting anticholinergic agents have no role in acute care.