In this 2023 update of one of RT’s most popular online articles, “Pharmacological Treatment of Respiratory Disorders”, the most commonly administered classes of pulmonary medications will be reviewed.
By Bill Pruitt, MBA, RRT, CPFT, AE-C
Over the past 50 years there has been a revolution in medications to treat respiratory disorders such as chronic obstructive pulmonary disease (COPD), asthma, prematurity, bronchiectasis, and other pulmonary issues. Most of the new medications are designed to be inhaled, but several of the newer medications are injected. In the 1970s and into the 1980s, the medications had to be administered every four to six hours as the duration of the medications were short-acting. Now, many inhaled drugs last 12 to 24 hours, and the injectables are needed only once a week or longer. There has also been a revolution in the delivery of these medications by new, innovative devices.
This article will review the major medications seen today, touch on the use of various devices, and discuss some of the new medications that may be coming.
Why Are Inhaled Medications a Preferred Route?
The airways are often involved in lung disorders such as bronchospasm, excess mucus production, and inflammation that reduce the airway lumen and increase work of breathing, dyspnea, cough, sputum production, and may be clogged with mucus plugs. Delivery of medications directly to the airways can speed up delivery and allow for a reduced dose of the medication compared to the oral or intravenous routes (referred to as systemic routes).1 Some of the issues with systemic include: they may not be able to reach a high enough concentration to be effective in the pulmonary system, they have toxic side effects when given at the required systemic doses, and/or a rapid effect of the medications is needed which is not reachable if given systemically.1
However, there are problems with the inhaled route that need to be considered. A major issue involves poor technique if using an inhaler (ie, omission of priming the inhaler, improper timing of activation, lack of breath-hold at the end of inspiration, inhaling too rapidly). Patient noncompliance with the treatment plan is often encountered with inhaled medications while taking oral medications may not involve this issue. Another problem is that some inhaled medications can trigger a cough which may limit the needed dose. Regardless, if taken properly, inhaled medications can bring about effective, timely improvement in symptoms.
Classification of Inhaled Respiratory Medications
The two main respiratory disorders seen worldwide are COPD and asthma. The most frequently cited guidelines for diagnosing and treating these diseases are the Global Initiative for Chronic Obstructive Lung Disease (GOLD) for COPD, and Global Initiative for Asthma (GINA). Both of these guidelines have been updated in 2023 and provide evidence-based approaches to these diseases. Many of the medications used to treat COPD are also found in the treatment of asthma. For this article, the framework used for medication classification is based mainly on the GOLD 2023 guidelines, with some crossover into GINA 2023. (See Table 1: Frequently Used Medications for Respiratory Disorders, online at www.respiratory-therapy.com.)2-3
Note that, through the years of developing these inhaled medications, the pharmaceutical companies are trying to find better, more appropriate drugs. In particular, work is being done to produce those that are more specific in targeting certain receptors to achieve their purposes without affecting other receptors, to find those that last longer and reduce the frequency of administration, to uncover those with fewer adverse side effects, and to find new, novel approaches/pathways to relieve symptoms or treat the disease. With this background in mind, we have an expanding number of new medications coming on the market and will likely see more in the future.
|Table 1. Some Frequently Administered Inhaled Medications for Respiratory Disorders
|Short-Acting β2-Agonists (SABAs)
|• Albuterol (salbutamol)
|• ProAir, Ventolin
• Brethaire, Brethine
|Long-Acting β2-Agonists (LABAs)
• Perforomist, Foradil
• Arcapta Neohaler
• Striverdi Respimat
• Serevent Diskus
|Short-Acting Muscarinic Antagonists (SAMAs)
|• Ipratropium bromide
• Oxitropium bromide
• Oxivent, Tersigan
|• Aclidinium bromide
• Glycopyrronium (glycopyrrolate) bromide
• Glycopyrrolate (see above)
• Spiriva Respimat
• Incruse Ellipta (See above)
|Combination SABA + SAMA
in One Device
|• Berodual N
• Duoneb, Combivent
|LABA + LAMA Combination
in One Device
|• Duaklir Pressair
• Bevespsi Aerosphere
• Ultibron Neohaler
• Breztri Aerosphere
|Inhaled Corticosteroids (ICS)
|• Beclomethasone dipropionate
• Flucticasone furoate (long-acting)
• Fluticasone propionate (short-acting)
• Mometasone furoate
• Pulmicort, Entocort EC, Uceris
• Arnuity Ellipta
|LABA + ICS
Combination in One Device
• Salmeterol/flucticasone propionate
• Vilanterol/flucticasone furoate
• Fostair, Modulite
• Advair Diskus
• Breo Ellipta
|LABA + LAMA + ICS
Combination in One Device
• Trelegy Ellipta
• Breztri Aerosphere
Short and Long-Acting β2 Agonists
The β2 agonists are bronchodilators which act on the airway smooth muscles. They stimulate the β2 receptors in the sympathetic pathway, causing the muscles to relax (this is active bronchodilation or bronchorelaxation). This opens the narrowed lumen of the airway and relieves shortness of breath caused by bronchoconstriction. SABA medications have a rapid onset (< 5 minutes) and the effect lasts from four to six hours. Being short acting, they are often administered up to six times in a 24-hour period. LABA medications have a much longer effect, some lasting 12 and some 24 hours. With this longer effect, administration is only once or twice a day.
Note, it is not recommended to use LABA medications as a monotherapy. These medications should be in combination with an inhaled corticosteroid (ICS), such as a LABA+ICS combination, or in combination with a long-acting muscarinic antagonist (LAMA), such as a LAMA+LABA combo (most are only available in a fixed combination with the ICS or LAMA). The SABA and LABA medications play a major role in treating COPD, asthma, and other lung diseases where the patient benefits from immediate relief (and prolonged relief with the long-acting medications) from bronchoconstriction.
Short and Long-Acting Muscarinic Antagonists
Muscarinic antagonist medications are also called anti-cholinergic medications or cholinergic antagonists. These drugs block the signal coming through the parasympathetic pathway from reaching the muscarinic receptors (in particular, the M3 receptors—out of the five muscarinic receptor subtypes M1 to M5).1 Stimulation of the muscarinic receptors contributes to muscle tone and reduces airway diameter. Blocking this transmission results in bronchodilation by preventing bronchoconstriction signals from coming through (consider this as passive bronchodilation). Much of the early research, as well as FDA approvals, were focused on treating COPD; however, further research supported approvals for SAMA and LAMA medications in asthma, as well.
Inhaled Corticosteroids (ICS)
ICS medications are effective in reducing inflammation and decreasing symptoms, and in preventing the inflammatory cascade involving many pathways in order to provide maintenance of control of symptoms.4 The onset of action takes a few hours, so these are not considered quick-relief medications. Thus, ICS prevent exacerbations and reduce symptoms in both COPD and asthma cases. They are recommended in COPD when regular bronchodilator therapy is ineffective in controlling symptoms. In asthma, ICS are first-line controller medications. Each ICS comes in two or three doses and the particular dose must be specified in the prescription. More frequent or more severe symptoms call for higher dose or more frequent use of ICS. The GINA 2023 guidelines have an excellent table showing the low, medium, and high doses with recommendations based on age for the available ICS medications. (See reference 3, Box 3-14.)
There are very few adverse side effects when using ICS for long-term control of inflammation, in contrast to the many adverse side effects found in systemic administration of corticosteroids. Systemic ICS issues include increased incidence/risk of lower extremity edema, elevated blood pressure, mood swings, increased appetite and weight gain, glaucoma, cataracts, cushingoid appearance (“moon” face), elevated blood sugar and risk of diabetes, increased risk of infection, osteoporosis, fatigue, thinning of skin, suppression of the adrenal gland, growth suppression in children, and delayed wound healing. On the other hand. ICS has mainly two side effects; risk of oral thrush (fungal infection) and hoarseness.5-6
In asthma diagnosis and management, the fractional concentration of exhaled nitric oxide (FeNO) has been used to uncover those who would benefit from ICS therapy, and to monitor the effectiveness in controlling inflammation—particularly in patients with allergic or eosinophilic asthma.3 Although FeNO is being studied in COPD cases and not mentioned in the GOLD 2023 guidelines, it is found some 56 times in the GINA guidelines.
Combination Inhaled Medications
Combination therapies offer the advantages of reducing the number of inhalers needed, increased patient compliance/acceptance with the plan of care, plus the benefits of each medication in its own right. For example, the SABA/SAMA combinations provide both active and passive bronchodilation while the SABA/ICS and LABA/ICS combinations provide active bronchodilation with anti-inflammatory action.
The next step up in combination drugs moves to the LABA/LAMA and LABA/ICS or LAMA/ICS inhalers to give long-term action in bronchodilation and anti-inflammation. Triple therapy, found in LAMA/LABA/ICS inhalers, provides all three components of long-term active and passive bronchodilation with anti-inflammatory activity. Triple therapy is utilized for moderate to severe respiratory disease states. Combinations of the medications mentioned often result in a synergistic effect: the cumulative effect of two or more drugs show increased positive results (ie, increased FEV1 or FEV1/FVC) compared to each drug individually.
Both the COPD and asthma guidelines recommend the use of combination therapies. These documents also describe the progression of therapy based on relief and control of symptoms. Recommendations start with the short-acting medications (sometimes using a solo medication), then move to a combination of short-acting drugs, then stepping up to longer acting agents, and/or adding on ICS. The final steps move to triple therapy and, if appropriate, addition of biologics to target specific phenotypes of the disease (especially in asthma). These progressions are driven by relief and control of symptoms. Both GOLD 2023 and GINA 2023 have an underlying foundational recommendation of using a SABA (with COPD), or rapid-onset or LABA/ICS (with asthma) on an as-needed basis for quick relief of symptoms and adding the other long-acting β2 agonists, anti-muscarinics, and long-acting ICS medications if the short-acting approach is being called on too often (with the intent that SABA or LABA/ICS relief therapy should be infrequent).
Devices for Inhalation of Medications
Many of the medications mentioned above are provided only in product-specific inhalers. Some are available for nebulization only. A few are available in both inhaler and nebulizer products. The GOLD 2023 guidelines offer a good reference for which medications are available in inhalers—either metered-dose inhaler, dry-powder inhaler, soft-mist inhaler—or nebulizer, or both. (For more details see GOLD 2023 Table 3.3 from reference 2.)
The full range of inhalers and nebulizers used for inhaled medication therapy are beyond the scope of this article, but it is an important topic for which respiratory therapists should be well-versed. UpToDate provides a good resource for this, as well as the American Association for Respiratory Care (AARC), and the Association of Asthma Educators (AAE).7-9
For patients with difficult-to-treat asthma or severe asthma, ongoing symptoms and exacerbations may persist despite use of the aforementioned pharmacotherapies. Biologics—the newest class of pulmonary medications—may be beneficial to some of these patients. For example, use of biologics is indicated in Type 2 high-inflammatory asthma patients who have elevated blood eosinophil counts or elevated FeNO levels. Biologics, including monoclonal antibodies, target specific inflammatory pathways mediated by such entities as Immunoglobulin E (IgE) and the inflammatory cytokines Interlukin-4 (IL-4), IL-5, and IL-13.11 Another pathway that is being challenged involves thymic stromal lymphopoietin (TSLP).
Each biologic has particular indications, specific dosing, and side effects that need to be monitored. Biologics are mentioned in the GINA 2023 guidelines and research for use of biologics in COPD is promising. It is expected that this strategy will be appearing in the toolbox for treating certain COPD patients, although use of biologics in COPD is not mentioned in GOLD 2023.10 Patients who begin biologic therapy may be able to reduce or eliminate use of systemic and inhaled corticosteroids. The biologics are administered by injection so they are more often administered by nurses, but respiratory therapists need to be aware of these medications and be an advocate for their patients who qualify for this approach and be a resource for the providers who may not have expertise in managing the more difficult asthma (and COPD) patients. (See Table 2: Biologics for Use to Reduce Inflammation, online at www.respiratory-therapy.com.)
|Table 2. Biologics for Use to Reduce Inflammation
• IL-4, IL-13
Other Medications in the Treatment of Respiratory Disorders
There are several more classifications of medications and agents available for treating respiratory disorders. Some are over-the-counter medications while others are by prescription only. These include medications that are leukotriene antagonists, antihistamines, respiratory stimulants, pulmonary surfactants, antivirals, and expectorants. (See references 12 and 13 for a closer look at these medications.)12-13
Possibilities for the Future
Work is continuing to develop medications that affect specific pathways of inflammation, are more specific in targeting certain receptors in the pulmonary system, have prolonged effectiveness, and fewer side effects. In addition, research is continuing in the development of new, more effective, or easier to use devices to deliver the inhaled medications to help in compliance and adherence to the treatment plan. Bringing a new medication through the entire process and gaining approval for use is difficult. According to a recent review of respiratory drugs published in 2022, “Even once the product enters phase 1, the failure rate is over 90%, and it remains over 30% from phase 3 to approval.”1 The COVID-19 pandemic brought about a burst of activity in developing inhaled medications to prevent and treat the virus or its pathologic consequences, and work continues in uncovering new agents to use in cases of idiopathic pulmonary fibrosis, cystic fibrosis, respiratory syncytial virus, and other diseases.
Bill Pruitt, MBA, RRT, CPFT, FAARC, is a writer, lecturer, and consultant. Bill has over 40 years of experience in respiratory care in a wide variety of settings and has over 20 years teaching at the University of South Alabama in Cardiorespiratory Care. Now retired from teaching, Bill continues to provide guest lectures, participates in podcasts, and writes professionally. For more info, contact [email protected].
- Anderson S, Atkins P, Bäckman P, Cipolla D, Clark A, et. al. Inhaled medicines: past, present, and future. Pharmacological Reviews. 2022 Jan 1;74(1):48-118.
- Global Initiative for Chronic Lung Disease. GLOBAL STRATEGY FOR PREVENTION, DIAGNOSIS AND MANAGEMENT OF COPD: 2023 Report. Accessed August 8, 2023. https://goldcopd.org/2023-gold-report-2/
- Global Initiative for Asthma. 2023 GINA MAIN REPORT. July 2023. Accessed August 8, 2023. https://ginasthma.org/2023-gina-main-report/.
- Wadsworth SJ, Sin DD, Dorscheid DR. Clinical update on the use of biomarkers of airway inflammation in the management of asthma. Journal of asthma and allergy. 2011 Jun 30:77-86.
- Prednisone and other corticosteroids. Mayo Clinic. https://www.mayoclinic.org/steroids/art-20045692
- Saag K, Furst D. Major side effects of systemic glucocorticoids. UpToDate. Published July 2022. Accessed August 10, 2023. https://www.uptodate.com/contents/major-side-effects-of-systemic-glucocorticoids.
- Hess D, Dhand R. Delivery of inhaled medication in adults. UpToDate. Published August 3, 2023. Accessed August 15, 2023. https://www.uptodate.com/contents/delivery-of-inhaled-medication-in-adults
- Gardenhire DS, Burnett D, Strickland S, Myers TR. Aerosol delivery devices for respiratory therapists. Irving, TX: American Association for Respiratory Care. 2017.
- Various educational materials from the Association of Asthma Educators website. Accessed August 15, 2023. https://asthmaeducators.org/patient-and-educator-materials/#1583521776810-788a59db-f058
- Agusti A. Biologics for COPD—Finally Here. J Med. 2023;389:205-14.
- Brusselle GG, Koppelman GH. Biologic therapies for severe asthma. New England Journal of Medicine. 2022 Jan 13;386(2):157-71.
- Pruitt B. Pharmacological treatment of respiratory disorders: respiratory therapists are often some of the few resources to offer expert help in finding alternative respiratory medications for patients who experience side effects. RT for Decision Makers in Respiratory Care. 2007 May 1;20(5):36-40.
- Asthma medications: Know your options. Mayo Clinic. Accessed August 16, 2023. https://www.mayoclinic.org/diseases-conditions/asthma/in-depth/asthma-medications/art-20045557