Bronchodilators


Article Author:
Khaled Almadhoun


Article Editor:
Sandeep Sharma


Editors In Chief:
Kranthi Sitammagari
Mayank Singhal


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
3/13/2019 4:01:44 PM

Indications

Bronchodilators are indicated for individuals that have lower than optimal air flow 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 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 is 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 are primarily used 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 is deferred to those who specialize in asthma and allergy treatment. Once control is achieved, 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 down-regulation of the beta-2 receptor in the airways. As such, a higher dose of medicine is required to achieve the same result. Bronchodilators are metabolized 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 should not be used in an emergency setting.[6][7]

Adverse Effects

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 a 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 should always be given to elderly patients whenever an anticholinergic is administered 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 been shown to worsen the effects of these conditions. Exercising care with this class of medication is also important during labor and delivery and when treating elderly patients. In very high doses, caution is also warranted for patients with renal impairment.[1][9]

Monitoring

A clinician should advise the patient on how to take the drug with the correct dosage. No routine monitoring tests are recommended with this class of medications. Serious adverse effects of bronchodilators include bronchospasm, hypersensitivity reactions, hypertension, hypotension, cardiac arrest, hypokalemia, and hyperglycemia. Anticholinergics have been associated 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 that are being 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 are advised to seek medical attention quickly. 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 be managed conservatively. 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 be intubated to protect and control the airway. If a patient is suspected to have a toxic episode caused by an anticholinergic, physostigmine salicylate may be administered 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.


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Bronchodilators - Questions

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A 10-year-old female presents with recurrent episodes of shortness of breath. She states that when she exerts herself or performs any physical activity, her airways seem to "tighten up." She is prescribed albuterol to take as needed. Albuterol stimulates what class of receptors?



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An anxious 27-year-old male presents to the office with shortness of breath. He states that for the past couple years, he has had difficulty breathing after exercise or hard labor. He has a father who is diagnosed with asthma. How much should inspiratory flow increase after a pre- and post-bronchodilator spirometry study to determine a positive response in a patient with reversible airway disease?



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A 17-year-old male comes to the emergency department with shortness of breath. He states he has had a long history with asthma, and forgot to take his medicine before playing basketball. Which of the following drug classes is the first line agent to reverse his breathing difficulty?



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A 68-year-old male presents to the primary care office for his annual check-up. He has been diagnosed with chronic obstructive pulmonary disease and has been hospitalized a few times this past year for its complications. He asks the doctor about his condition and asks for the first line medication. He is told to monitor his potassium levels. How does this class of medicine affect potassium levels in the body?



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A 33-year-old woman diagnosed with severe persistent asthma presents to the office with shortness of breath. He is using accessory muscles of respiration to breathe. Past medical history includes using her short-acting inhaler for ten years 4 to 6 times per day and recently has complained that her symptoms do not subside like they once did. She denies smoking or illicit drug use. What is the mechanism for his decreased responsiveness to the medicine?



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Bronchodilators - References

References

Rates of escalation to triple COPD therapy among incident users of LAMA and LAMA/LABA., Hahn B,Hull M,Blauer-Peterson C,Buikema AR,Ray R,Stanford RH,, Respiratory medicine, 2018 Jun     [PubMed]
Efficacy of budesonide/formoterol and tiotropium combination for the treatment of Chinese patients with chronic obstructive pulmonary disease., Feng JF,Ding GR,Xie YZ,Zhao D,Wang X,, Medicine, 2018 Jun     [PubMed]
Youth Risk Behavior Surveillance - United States, 2017., 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,, Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002), 2018 Jun 15     [PubMed]
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., Maes A,DePetrillo P,Siddiqui S,Reisner C,Dorinsky P,, Clinical pharmacology in drug development, 2018 Jun 14     [PubMed]
Perez-Padilla R,Menezes AMB, Chronic Obstructive Pulmonary Disease in Latin America. Annals of global health. 2019 Jan 22;     [PubMed]
Corhay JL, [IMPACT study in COPD]. Revue medicale de Liege. 2019 Jan;     [PubMed]
Drugs for cough. The Medical letter on drugs and therapeutics. 2018 Dec 17;     [PubMed]
Sharma S,Chakraborty RK, Asthma Medications 2018 Jan;     [PubMed]
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. International journal of chronic obstructive pulmonary disease. 2019;     [PubMed]
Nanda A,Baptist AP,Divekar R,Parikh N,Seggev JS,Yusin JS,Nyenhuis SM, Asthma in the older adult. The Journal of asthma : official journal of the Association for the Care of Asthma. 2019 Jan 18;     [PubMed]
Chung KF, Managing severe asthma in adults: lessons from the ERS/ATS guidelines. Current opinion in pulmonary medicine. 2015 Jan;     [PubMed]

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