Asthma Medication

Updated: Nov 19, 2017
  • Author: Michael J Morris, MD, FACP, FCCP; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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Medication

Medication SummaryQuick reliefLong-term control

Asthma medications are generally divided into two categories:

  • Quick relief (also called reliever medications)

  • Long-term control (also called controller medications)

Quick relief medications are used to relieve acute asthma exacerbations and to prevent exercise-induced bronchoconstriction (EIB) symptoms. These medications include short-acting beta agonists (SABAs), anticholinergics (used only for severe exacerbations), and systemic corticosteroids, which speed recovery from acute exacerbations.

Long-term control medications include inhaled corticosteroids (ICSs), [94, 95] , long-acting beta agonists (LABAs), long-acting anticholinergics, combination inhaled corticosteroids and long-acting beta agonists, methylxanthines, and leukotriene receptor antagonists. Inhaled corticosteroids are considered the primary drug of choice for control of chronic asthma, but unfortunately the response to this treatment is characterized by wide variability among patients. A study by Tantisira et al showed the glucocorticoid-induced transcript 1 gene (GLCCI1) to be the cause of this decrease in response. [107]

In a study by Peters et al, the use of the anticholinergic agent tiotropium in 210 asthmatic patients resulted in a superior outcome compared with a doubling of the dose of an inhaled glucocorticoid, as assessed by measuring the morning peak expiratory flow and other secondary outcomes. The addition of tiotropium in this study was also shown to be noninferior to the addition of salmeterol. [108]

Kerstjens et al evaluated 912 patients already taking an ICS/LABA combination who were randomized to 48 weeks of tiotropium versus placebo in two replicate, randomized, controlled trials. The patients had a mean baseline FEV1 of 62% of the predicted value. The use of tiotropium compared to placebo increased the time to first exacerbation (282 versus 226 days) and resulted in a higher peak change in FEV1 from baseline of 86 ± 34 mL (Trial 1) and 154 ± 32 mL (Trial 2) for those patients taking tiotropium. [109]

In a cross-sectional population-level comparison study of asthmatics from 1997-1998 and 2004-2005, researchers evaluated controller-to-total asthma medication ratio (greater than 0.5) with asthma exacerbation rates (dispensing of systemic corticosteroid or emergency department visit/hospitalization for asthma). They were able to demonstrate an increased use of asthma controllers based on a 16% increase in controller-to-total asthma medication ratio. However, there was no change in annual asthma exacerbation rates (0.27/year to 0.23/year) despite this improvement in controller use. [110]

Two systematic reviews indicate that the regular use of ICSs for the treatment of pediatric asthma may suppress linear growth in the first year of treatment, but lower ICS doses may minimize such effects. [1, 2, 111] The investigators of both reviews also noted that head-to-head comparison trials are needed to assess the effects of different ICSs, ICS doses, inhalation devices, and patient ages on growth suppression over time.

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Beta2-adrenergic agonist agents

Class Summary

Beta2 agonists (albuterol sulfate [Proventil HFA, Ventolin HFA, ProAir HFA; pirbuterol acetate [Maxair Autohaler]; levalbuterol [Xopenex]) relieve reversible bronchospasm by relaxing the smooth muscles of the bronchi. These agents act as bronchodilators and are used to treat bronchospasm in acute asthmatic episodes and to prevent bronchospasm associated with exercise-induced asthma or nocturnal asthma.

Albuterol sulfate (Proventil HFA, Ventolin HFA, ProAir HFA)

This beta2-agonist is the most commonly used bronchodilator that is available in multiple forms (eg, solution for nebulization, metered-dose inhaler, oral solution). This is most commonly used in rescue therapy for acute asthmatic symptoms and is used as needed. Prolonged use may be associated with tachyphylaxis due to beta2-receptor down-regulation and receptor hyposensitivity.

Pirbuterol (Maxair Autohaler)

This agent is available as a breath-actuated or ordinary inhaler. The ease of administration with the breath-actuated device makes it an attractive choice in the treatment of acute symptoms in younger children, who otherwise may not be able to use a metered-dose inhaler. The Autohaler delivers 200 mcg per actuation.

Levalbuterol (Xopenex)

A nonracemic form of albuterol, levalbuterol (R isomer), is effective in smaller doses and is reported to have fewer adverse effects (eg, tachycardia, hyperglycemia, hypokalemia). The dose may be doubled in acute severe episodes when even a slight increase in the bronchodilator response may make a big difference in the management strategy (eg, in avoiding patient ventilation).

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Anticholinergic Agents

Class Summary

The long-acting anticholinergic agent, tiotropium, may be considered for long-term maintenance therapy, but not for acute treatment of asthma exacerbations.

Tiotropium (Spiriva Respimat)

Tiotropium is a long-acting antimuscarinic agent, often referred to as an anticholinergic. It inhibits M3-receptors at smooth muscle, leading to bronchodilation. It is indicated for long-term, once-daily, maintenance treatment of asthma in patients aged 6 years or older.

Ipratropium (Atrovent)

Ipratropium is chemically related to atropine. It has antisecretory properties and, when applied locally, inhibits secretions from serous and seromucous glands lining the nasal mucosa. It is approved for COPD, but off-label use for acute exacerbations of asthma in addition to beta2-agonist therapy has been described in the literature. It is a short-acting anticholinergic agent with an onset of 15 minutes.

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Anticholinergic agent combinations

Class Summary

Combination agents with ipratropium and albuterol. A test spray of 3 sprays is recommended before using this combination for the first time and when the aerosol has not be used for more than 24 hours. Ipratropium is chemically related to atropine. It has antisecretory properties and, when applied locally, inhibits secretions from serous and seromucous glands lining the nasal mucosa. Albuterol is beta-agonist for bronchospasm refractory to epinephrine. It relaxes bronchial smooth muscle by action on beta2-receptors, with little effect on cardiac muscle contractility.

Ipratropium and albuterol (Combivent, DuoNeb)

Ipratropium is chemically related to atropine. It has antisecretory properties and, when applied locally, inhibits secretions from serous and seromucous glands lining the nasal mucosa. Albuterol is beta-agonist for bronchospasm refractory to epinephrine. It relaxes bronchial smooth muscle by action on beta2-receptors, with little effect on cardiac muscle contractility.

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Corticosteroid, oral

Class Summary

Oral steroids (prednisone [Deltasone, Orasone]; prednisolone [Pediapred, Prelone, Orapred]; methylprednisolone [Solu-Medrol]) are used for short courses (3-10 d) to gain prompt control of inadequately controlled acute asthmatic episodes. They are also used for long-term prevention of symptoms in severe persistent asthma as well as for suppression, control, and reversal of inflammation. Frequent and repetitive use of beta2 agonists has been associated with beta2 -receptor subsensitivity and down-regulation; these processes are reversed with corticosteroids.

Prednisone (Deltasone, Orasone)

Prednisone is an immunosuppressant for the treatment of autoimmune disorders; it may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity.

Methylprednisolone (Solu-Medrol, Medrol)

Methylprednisolone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity.

Prednisolone (Pediapred, Prelone, Orapred)

This glucosteroid occurs naturally and synthetically. It is used for both acute and chronic asthma. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity.

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Long-acting beta2 agonists

Class Summary

Long-acting bronchodilators are not used for the treatment of acute bronchospasm. They are used for the preventive treatment of nocturnal asthma or exercise-induced asthmatic symptoms, for example. Currently, 2 LABAs are available in the United States: salmeterol (Serevent) and formoterol (Foradil). Salmeterol and formoterol are available as combination products with inhaled corticosteroids in the United States.

Salmeterol (Serevent)

Salmeterol can relieve bronchospasm by relaxing the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis. The effect also may facilitate expectoration. Adverse effects are more likely when salmeterol is administered at high doses or more frequent doses than recommended.

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Beta2-Agonist/Corticosteroid Combinations

Class Summary

These combinations (budesonide and formoterol [Symbicort]; fluticasone and salmeterol [Advair HFA, Advair Diskus]; mometasone and formoterol [Dulera]) may decrease asthma exacerbations when inhaled short-acting beta2 agonists and corticosteroids have failed.

Budesonide/formoterol (Symbicort)

Formoterol relieves bronchospasm by relaxing the smooth muscles of the bronchioles in conditions associated with asthma. Budesonide is an inhaled corticosteroid that alters the level of inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing the production of cytokines and other mediators involved in the asthmatic response.

Mometasone and formoterol (Dulera)

Combination corticosteroid and long-acting selective beta-2 agonist (LABA) metered-dose inhaler. Mometasone elicits local anti-inflammatory effects to respiratory tract with minimal systemic absorption. Formoterol elicits bronchial smooth muscle relaxation. Indicated for prevention and maintenance of asthma symptoms in patients inadequately controlled with other asthma controller medications (eg, low- to medium-dose inhaled corticosteroids) or whose disease severity clearly warrants initiation of treatment with 2 maintenance therapies, including a LABA. Available in 2 strengths; each actuation delivers mometasone/formoterol 100 mcg/5 mcg or 200 mcg/5 mcg.

Salmeterol/fluticasone inhaled (Advair)

Fluticasone inhibits bronchoconstriction mechanisms, produces direct smooth muscle relaxation, and may decrease the number and activity of inflammatory cells, in turn decreasing airway hyperresponsiveness. It also has vasoconstrictive activity. Salmeterol relaxes the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis, and can relieve bronchospasms. Its effects may also facilitate expectoration. Adverse effects are more likely to occur when the agent is administered at high or more frequent doses than recommended.

Vilanterol/fluticasone furoate inhaled (Breo Ellipta)

Indicated for once-daily treatment of asthma for adults not adequately controlled on a long-term asthma control medication (eg, inhaled corticosteroid), or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a long-acting beta agonist (LABA). Use prescribe strength (25 mcg/100 mcg or 25 mcg/200 mcg per actuation) once daily via oral inhalation. Fluticasone furoate is a corticosteroid with anti-inflammatory activity. Vilanterol is a long-acting beta agonist (LABA) that stimulates intracellular adenyl cyclase (catalyzes the conversion of ATP to cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.

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Methylxanthines

Class Summary

These agents are used for long-term control and prevention of symptoms, especially nocturnal symptoms.

Theophylline (Theo-24, Theochron, Uniphyl)

Theophylline is available in short- and long-acting formulations. Because of the need to monitor the drug levels, this agent is used infrequently. The dose and frequency of administration depend on the particular product selected.

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Mast cell stabilizers

Class Summary

These agents (cromolyn sodium [Intal]) block early and late asthmatic responses, interfere with chloride channels, stabilize the mast cell membrane, and inhibit the activation and release of mediators from eosinophils and epithelial cells. They inhibit acute responses to cold air, exercise, and sulfur dioxide.

Cromolyn sodium (Intal)

Cromolyn sodium inhibits the release of histamine, leukotrienes, and other mediators from sensitized mast cells exposed to specific antigens. It has no intrinsic anti-inflammatory, antihistamine, or vasoconstrictive effects.

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Corticosteroid, Inhalant

Class Summary

Inhaled steroids include ciclesonide (Alvesco), beclomethasone (QVAR), triamcinolone, flunisolide (Nasalide), fluticasone (Flovent Diskus, Flovent HFA), budesonide (Pulmicort Flexhaler or Respules), and mometasone furoate inhalation powder (Asmanex Twisthaler). Steroids are the most potent anti-inflammatory agents. Inhaled forms are topically active, poorly absorbed, and least likely to cause adverse effects.

Ciclesonide (Alvesco)

Ciclesonide is an aerosol inhaled corticosteroid indicated for maintenance treatment of asthma as prophylactic therapy in adult and adolescent patients aged 12 years and older. It is not indicated for relief of acute bronchospasm. Corticosteroids have a wide range of effects on multiple cell types (eg, mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (eg, histamines, eicosanoids, leukotrienes, cytokines) involved in inflammation.

Beclomethasone (QVAR, Beclovent)

This agent inhibits bronchoconstriction mechanisms; causes direct smooth muscle relaxation; and may decrease the number and activity of inflammatory cells, which, in turn, decreases airway hyperresponsiveness. It is available as a 40- or 80-mcg/actuation.

Fluticasone inhaled

Fluticasone has extremely potent vasoconstrictive and anti-inflammatory activity. It has a weak HPA-axis inhibitory potency when applied topically. It is available as a metered-dose inhaler aerosolized product (HFA) or DPI (Diskus).

Budesonide inhaled (Pulmicort Flexhaler or Respules)

Fluticasone has extremely potent vasoconstrictive and anti-inflammatory activity. It has a weak HPA-axis inhibitory potency when applied topically. It is available as a DPI in 90-mcg/actuation (delivers about 80 mcg/actuation) or 180-mcg/actuation (delivers about 160 mcg/actuation). A nebulized suspension (ie, Respules) is also available for young children.

Mometasone (Asmanex Twisthaler)

Mometasone is a corticosteroid for oral inhalation. It is indicated for asthma as prophylactic therapy.

Triamcinolone inhaled (Azmacort)

Triamcinolone alters the level of inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing the production of cytokines and other mediators involved in the asthmatic response.

Flunisolide inhaled (Aerospan HFA)

Flunisolide inhibits bronchoconstriction mechanisms, produces direct smooth muscle relaxation, and may decrease the number and activity of inflammatory cells, in turn decreasing airway hyperresponsiveness. It decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability. It does not depress the hypothalamus. AeroBid (flunisolide CFC) delivers about 250 mcg per actuation. AeroSpan (flunisolide HFA) delivers about 80 mcg per actuation.

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Leukotriene Receptor Antagonist

Class Summary

Knowledge that leukotrienes cause bronchospasm, increased vascular permeability, mucosal edema, and inflammatory cell infiltration leads to the concept of modifying their action by using pharmacologic agents. These are either 5-lipoxygenase inhibitors or leukotriene-receptor antagonists (zafirlukast [Accolate]; montelukast [Singulair]).

Zafirlukast (Accolate)

Zafirlukast is a selective competitive inhibitor of LTD4 and LTE4 receptors.

Montelukast (Singulair)

Montelukast is the last agent introduced in its class. The advantages are that it is chewable, it has a once-a-day dosing, and it has no significant adverse effects.

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Monoclonal Antibodies, Anti-asthmatics

Class Summary

Monoclonal antibody effects vary depending on their receptor target. Omalizumab binds to IgE on the surface of mast cells and basophils. It reduces the release of these mediators that promote an allergic response. Mepolizumab inhibits IL-5 binding to eosinophils and results in reduced blood, tissue, and sputum eosinophil levels. Benralizumab binds to basophils and eosinophils.

Omalizumab (Xolair)

Omalizumab is a recombinant, DNA-derived, humanized IgG monoclonal antibody that binds selectively to human IgE on the surface of mast cells and basophils. It reduces mediator release, which promotes an allergic response. It is indicated for moderate-to-severe persistent asthma in patients who react to perennial allergens in whom symptoms are not controlled by inhaled corticosteroids.

Mepolizumab (Nucala)

Mepolizumab is a humanized IgG1 kappa monoclonal antibody specific for IL-5. Mepolizumab binds to IL-5 and therefore stops IL-5 from binding to its receptor on the surface of eosinophils. It is indicated for add-on maintenance treatment of patients with severe asthma aged 12 years or older and with an eosinophilic phenotype.

Reslizumab (Cinqair)

Reslizumab is an IL-5 antagonist monoclonal antibody (IgG kappa). It is indicated for add-on maintenance treatment of patients with severe asthma aged 18 years and older with an eosinophilic phenotype.

Benralizumab (Fasenra)

Benralizumab is a humanized monoclonal antibody (IgG1/kappa-class) selective for the IL-5 alpha subunit of basophils and eosinophils. It is indicated for add-on maintenance treatment of severe asthma in patients aged 12 years or older who have an eosinophilic phenotype.

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