Continuing Education Activity

Bronchodilators are indicated for individuals that have lower than optimal airflow through the lungs. The mainstay of treatment is beta-2 agonists that target the smooth muscles in the bronchioles of the lung. Various respiratory conditions may require bronchodilators, including asthma and chronic obstructive pulmonary disease. They are used to either reverse asthma symptoms or improve lung function in patients with chronic obstructive pulmonary disease. This activity reviews the mechanism of action, adverse event profile, toxicity, dosing, pharmacodynamics, and monitoring of bronchodilators, pertinent for interprofessional team members to treat patients with obstructive lung pathology.

Objectives:

• Summarize the different classes of bronchodilator drugs.
• Identify the various mechanisms of action of the bronchodilator drug classes.
• Describe the adverse event profile and interactions of bronchodilator class medications.
• Review interprofessional team strategies for improving care coordination and communication to advance the use of bronchodilating medications and improve outcomes in obstructive lung disease treatment.

Indications

Bronchodilators are indicated for individuals that have lower than optimal airflow through the lungs. The mainstay of treatment is beta-2 agonists that target the smooth muscles in the bronchioles of the lung. Various respiratory conditions may require bronchodilators, including asthma and chronic obstructive pulmonary disease. They are used to either reverse asthma symptoms or improve lung function in patients with chronic obstructive pulmonary disease. Pulmonary function tests assess lung function. Thus, bronchodilators play an essential role in diagnosing and treating lung conditions based on their effect on pulmonary function tests. The FEV1/FVC ratio compares how much air flows during the first second of exhalation (forced expiratory volume) to the theoretical amount of air someone can push out in a maximum exhalation (forced vital capacity). A typical ratio is 0.7. In reversible increased airway resistance like asthma, pre-bronchodilator pulmonary function tests will typically be lower than 0.7. However, after the administration of a short-acting bronchodilator, the ratio may normalize. In nonreversible conditions like chronic obstructive pulmonary disease, giving a short-acting bronchodilator may not normalize pulmonary function test levels in patients.[1][2]

Commonly, inhaled corticosteroids are added to beta-2 agonists to reduce inflammation and pro-inflammatory agents that will further constrict airways. Beta-2 agonist class bronchodilators do not affect the underlying pathology of lung disease; they are only symptomatic treatments. Therefore, adding inhaled corticosteroids to the regimen has been the mainstay of mild to moderate reversible lung diseases with or without long-acting beta-2 agonists. Anticholinergics are the final class of medicine considered bronchodilators. This class's mechanism inhibits the effects of the parasympathetic nervous system mediated by the vagus nerve. A hyperactive parasympathetic nervous system causes bronchial secretions and narrowing of the airways. Medicines that inhibit the actions of the parasympathetic nervous system at the level of the airways will then generate a bronchodilatory effect. These medicines include ipratropium bromide, which is a short-acting medicine (4 to 6 hours), and tiotropium bromide, which is longer-acting (24 hours). Anticholinergics primarily function in the setting of chronic obstructive pulmonary disease. Patients with asthma can usually control their symptoms with the combination of a beta-2 agonist and corticosteroid.[1]

The step theory in managing reversible lung diseases like asthma incorporates both short- and long-acting bronchodilators. Those with intermittent asthma should receive a short-acting bronchodilator such as albuterol as needed. Adding a low-dose, inhaled corticosteroid is the next step to more symptomatic disease, followed by adding a long-acting bronchodilator with the inhaled steroid. Increasingly aggressive treatment should defer to those who specialize in asthma and allergy treatment. After achieving control, the patient will consult with their doctor to wean them off these medicines to a smaller dose with fewer adverse effects. Failure to control symptoms with short or long-acting bronchodilators and corticosteroids can cause irreversible lung injury. Frequent monitoring by pulmonary function tests and peak airway flow is the mainstay of treatment success.[3]

Mechanism of Action

The mechanism of action of bronchodilators includes targeting the beta-2 receptor, which is a G-protein coupled receptor, in the lung airways. When the beta-2 receptor is activated, the smooth muscle of the airway relaxes. Subsequently, the patient experiences better airflow for a period. Consistent use of beta-2 agonists for an extended amount of time reduces their efficacy due to the down-regulation of the beta-2 receptor in the airways. As such, a higher dose of medicine is necessary to achieve the same result. Bronchodilator metabolism occurs in the gastrointestinal tract by cytochrome P-450 enzymes. About 80% to 100% is excreted in the urine, and less than 20% is excreted in feces. Short-acting bronchodilators have a half-life of 3 to 6 hours, while longer-acting bronchodilators have a half-life of 18 to 24 hours.[4][5]

Anticholinergics target parasympathetic nervous system receptors in the airways and inhibit their function. Since the parasympathetic nervous system is responsible for increased bronchial secretions and constriction, reversing those should provide bronchodilation and fewer secretions.[6]

Administration

The administration of bronchodilators is primarily through inhalation devices to deliver the drug to the lung's bronchioles. Inhalation devices come in all shapes and sizes, but the critical factor is to maximize the amount of drug reaching the bronchioles. Even when used with a perfect technique, the bioavailability of this class of medications remains very low. The best way to achieve maximum bioavailability is by fully exhaling, placing the inhaler in the mouth, and taking a full inhalation. After the patient has inhaled completely, it is followed by 10 seconds of no breathing to wait for the medicine to dissipate into the lung space. Then, a slow exhalation back to normal breathing is advised.[7]

Failure to follow the correct steps risks not maximizing the full potential of the inhaled medicines. Patients taking short-acting bronchodilators should benefit from the medication's effects quickly, within seconds to minutes, and should have the clinical benefit for around 4 hours. These are sometimes called emergency inhalers due to their immediate impact on bronchodilation. Long-acting bronchodilators do not typically work as quickly and are not helpful in an emergency setting.[8]

Adverse Effects

The adverse effects of bronchodilators are due to sympathetic system activation. The most frequent and common adverse effects include trembling, nervousness, sudden, noticeable heart palpitations, and muscle cramps. More severe effects include sudden constriction of the bronchial airways, paradoxical bronchospasm, hypokalemia, and in rare cases, myocardial infarction. A patient should talk to their primary care physician if they have any comorbidities.[9] For anticholinergics, side effects include symptoms caused by a decrease in vagal tone. These can include dry mouth, urinary retention, tachycardia, constipation, and an upset stomach. Caution is always necessary when administering an anticholinergic agent to older patients due to the possibility of acute delirium.[5]

Contraindications

If a patient has a known hypersensitivity to the drug, then physicians should not prescribe it. These hypersensitivities include severe allergic reactions that can cause hemodynamic instability or loss of a patent airway. Use caution when treating patients with ischemic heart disease, arrhythmias, or hypokalemia, as bronchodilators have demonstrated worsening of the effects of these conditions.[1] Exercising care with this class of medication is also essential during labor and delivery and when treating elderly patients. In very high doses, caution is also necessary for patients with renal impairment.[10]

Monitoring

Clinicians should advise the patient on how to take the drug with the correct dosage. There are no recommended routine monitoring tests with this class of medications. Serious adverse effects of bronchodilators include bronchospasm, hypersensitivity reactions, hypertension, hypotension, cardiac arrest, hypokalemia, and hyperglycemia. Anticholinergics have correlated with dry mouth, constipation, urinary retention, and delirium. If a patient believes they are experiencing any of these symptoms or general discomfort after taking this medicine, they should be seen by emergency personnel quickly. In particular, patient chronically on short-acting beta-2 agonists patient risks not achieving the same relief from their medicine as they once did. This phenomenon is called receptor downregulation. It happens because a portion of the receptors targeted end up being inactivated by the body due to overuse. Since fewer receptors are available to be targeted by this medication class, a less than adequate relief of symptoms occurs. Higher dosages are then required to achieve the same result.[9]

Toxicity

If a patient uses a bronchodilator and experiences any of the adverse effects described, they should promptly seek medical attention. These effects include difficulty breathing, fever/chills, decreased urinary output, nausea or vomiting, tremors, or convulsions, among others. A doctor can measure the patient's vitals in an emergency room and take a blood sample to detect any electrolyte abnormalities.[11] From there, the patient can have conservative management. If more invasive interventions are needed, patients may be started on a standard saline drip or given potassium to replenish reserves. In severe cases, they may require intubation to protect and control the airway. 

Enhancing Healthcare Team Outcomes

Bronchodilators are prescribed by nurse practitioners, physician assistants, primary care providers, internists, emergency department clinicians, and others. Anyone who prescribes these agents must educate the patient on the potential adverse effects, which can include anticholinergic symptoms as well as cardiac symptoms. Patients must be informed when to return to their provider when these symptoms appear. Overall, bronchodilators are safe when prescribed and administered correctly and can significantly improve asthma patients' quality of life.

Review Questions

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References

1.

Perez-Padilla R, Menezes AMB. Chronic Obstructive Pulmonary Disease in Latin America. Ann Glob Health. 2019 Jan 22;85(1) [PMC free article: PMC7052319] [PubMed: 30741508]

2.

Almeshari MA, Alobaidi NY, Sapey E, Usmani O, Stockley RA, Stockley JA. Small Airways Response to Bronchodilators in Adults with Asthma or COPD: A Systematic Review. Int J Chron Obstruct Pulmon Dis. 2021;16:3065-3082. [PMC free article: PMC8593205] [PubMed: 34795479]

3.

Corhay JL. [IMPACT study in COPD]. Rev Med Liege. 2019 Jan;74(1):54-60. [PubMed: 30680975]

4.

Drugs for cough. Med Lett Drugs Ther. 2018 Dec 17;60(1562):206-208. [PubMed: 30625123]

5.

Sharma S, Hashmi MF, Chakraborty RK. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jun 20, 2023. Asthma Medications. [PubMed: 30285350]

6.

Maes A, DePetrillo P, Siddiqui S, Reisner C, Dorinsky P. Pharmacokinetics of Co-Suspension Delivery Technology Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate (BGF MDI) and Budesonide/Formoterol Fumarate Dihydrate (BFF MDI) Fixed-Dose Combinations Compared With an Active Control: A Phase 1, Randomized, Single-Dose, Crossover Study in Healthy Adults. Clin Pharmacol Drug Dev. 2019 Feb;8(2):223-233. [PMC free article: PMC6585691] [PubMed: 29901860]

7.

Hanania NA, Sethi S, Koltun A, Ward JK, Spanton J, Ng D. Long-term safety and efficacy of formoterol fumarate inhalation solution in patients with moderate-to-severe COPD. Int J Chron Obstruct Pulmon Dis. 2019;14:117-127. [PMC free article: PMC6311322] [PubMed: 30643398]

8.

Feng JF, Ding GR, Xie YZ, Zhao D, Wang X. Efficacy of budesonide/formoterol and tiotropium combination for the treatment of Chinese patients with chronic obstructive pulmonary disease. Medicine (Baltimore). 2018 Jun;97(22):e10841. [PMC free article: PMC6393098] [PubMed: 29851792]

9.

Nanda A, Baptist AP, Divekar R, Parikh N, Seggev JS, Yusin JS, Nyenhuis SM. Asthma in the older adult. J Asthma. 2020 Mar;57(3):241-252. [PubMed: 30656998]

10.

Chung KF. Managing severe asthma in adults: lessons from the ERS/ATS guidelines. Curr Opin Pulm Med. 2015 Jan;21(1):8-15. [PubMed: 25405672]

11.

Hahn B, Hull M, Blauer-Peterson C, Buikema AR, Ray R, Stanford RH. Rates of escalation to triple COPD therapy among incident users of LAMA and LAMA/LABA. Respir Med. 2018 Jun;139:65-71. [PubMed: 29858004]

Disclosure: Khaled Almadhoun declares no relevant financial relationships with ineligible companies.

Disclosure: Sandeep Sharma declares no relevant financial relationships with ineligible companies.