NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-.

Bronchodilators
Authors
Khaled Almadhoun1; Sandeep Sharma2.

Affiliations
1
West Virginia School of Osteopathic Med
2
Mery Fitzgerald Hospital

Last Update: March 16, 2020.

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 the symptoms
of asthma or improve lung function in patients with chronic obstructive
pulmonary disease. Pulmonary function tests assess lung function. Thus,
bronchodilators have an essential role in the diagnosis and treatment of 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.
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 treatment. 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.
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.[1][2]

Mechanism of Action
Bronchodilators' mechanism of action 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.
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.[3][4][5]

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 what is critical is maximizing 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. 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 effects of the medication very
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 effect on bronchodilation. Long-acting bronchodilators do not
typically work as quickly and are not useful in an emergency setting.[6][7]

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, or
paradoxical bronchospasm, hypokalemia, and in rare cases, myocardial
infarction. A patient should talk to their primary care physician if they have
any comorbidities. 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 to elderly patients due to the
possibility of acute delirium.[8][4]

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. 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.[1][9]

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, someone who is chronically on short-acting beta-2
agonists 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 receptors targeted end up being inactivated by the body due to
overuse. Since fewer receptors are available to be targeted by this class of
medicine, a less than adequate relief of symptoms occurs. Higher dosages are
then required to achieve the same result.[8]

Toxicity
If someone uses a bronchodilator and experiences any of the adverse effects
described, they should seek medical attention promptly. These effects include
difficulty breathing, fever/chills, decrease urine output, nausea or vomiting,
tremors, or convulsions, among others. In an emergency room, a doctor can
measure the patient's vitals and take a blood sample to detect any electrolyte
abnormalities. 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. If a patient is
suspected of having a toxic episode caused by an anticholinergic,
physostigmine salicylate is an option to reverse the
symptoms rapidly.[10][11]

Enhancing Healthcare Team Outcomes

Bronchodilators are prescribed by the nurse practitioner, primary care
provider, internist, the emergency department physician, 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.

Questions
To access free multiple choice questions on this topic, click here.

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.
Corhay JL. [IMPACT study in COPD]. Rev Med Liege. 2019
Jan;74(1):54-60. [PubMed: 30680975]
3.
Drugs for cough. Med Lett Drugs Ther. 2018 Dec 17;60(1562):206-
208. [PubMed: 30625123]
4.
Sharma S, Hashmi MF, Chakraborty RK. StatPearls
[Internet]. StatPearls Publishing; Treasure Island (FL): Jan 28, 2020.
Asthma Medications. [PubMed: 30285350]
 5.
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]
6.
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]
7.
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]
8.
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]
9.
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]
10.
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]
11.
Kann L, McManus T, Harris WA, Shanklin SL, Flint KH, Queen B,
Lowry R, Chyen D, Whittle L, Thornton J, Lim C, Bradford D,
 Yamakawa Y, Leon M, Brener N, Ethier KA. Youth Risk Behavior
Surveillance - United States, 2017. MMWR Surveill Summ. 2018 Jun
15;67(8):1-114. [PMC free article: PMC6002027] [PubMed:
29902162]
Copyright © 2020, StatPearls Publishing LLC.

This book is distributed under the terms of the Creative Commons Attribution 4.0 International License

(http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution, and reproduction in

any medium or format, as long as you give appropriate credit to the original author(s) and the source, a link is provided to

the Creative Commons license, and any changes made are indicated.

Bookshelf ID: NBK519028PMID: 30085570