Beta agonists: Uses, common brands, and safety information

Bronchospasm is a phenomenon in which the bronchial tubes in our lungs tighten down, limiting airflow and producing wheezing and shortness of breath. This uncomfortable and potentially dangerous airway event is typical in asthma and chronic obstructive pulmonary disease (COPD). The beta agonist drug class is the pharmacologic counterpunch to bronchospasm, and therefore, these drugs are an essential element in the treatment of asthma and COPD. Members of the class, their mechanism and use, possible adverse effects, and associated costs will be detailed here. 

Other beta agonists

• Brovana (arformoterol) nebulizer solution

• Ipratropium-albuterol nebulizer solution

• Combivent Respimat (ipratropium-albuterol)

• Bevespi Aerosphere (glycopyrrolate-formoterol)

• Breztri Aerosphere (budesonide-glycopyrrolate-formoterol)

• Terbutaline tablets

• Perforomist (formoterol)

• Airduo Respiclick (fluticasone-salmeterol)

• Airduo Digihaler (fluticasone-salmeterol)

• Wixela Inhub (fluticasone-salmeterol)

• Dulera (mometasone-formoterol)

• Striverdi Respimat (olodaterol)

• Stiolto Respimat (olodaterol-tiotropium)

• Primatene mist (epinephrine)

• Asthmanefrin (racemic epinephrine) nebulizer solution

What are beta agonists?

Beta agonists (β-agonists) are bronchodilators, meaning they relax and open tightened bronchial tubes. Administration is almost always by the inhaled route. Handheld inhalers are a common and convenient option for delivery of beta agonist drugs to the airways. A hydrofluoroalkane (HFA) propellant is used to propel the active ingredient from the inhaler to the airways. 

When used with a spacer device, inhalers result in more deposition of the drugs in the bronchial tubes and less in the mouth. A different inhaler variety is the dry powder inhaler (DPI), which delivers an ultrafine powder of the active ingredient using only a quick and deep inspiration by the user. Alternatively, nebulizer machines use pressurized air to aerosolize medications such as β-agonists in order to allow them to be inhaled easily. Oral and injectable beta agonist options exist as well, but based on slower onset time and more adverse effects, they are not preferred.

RELATED: Can you use an expired inhaler?

How do beta agonists work?

Beta-2 agonists attach to the beta-2 receptor in the smooth muscle that lines the bronchial tube. Unlike their parent compound epinephrine, they have much less effect on the beta-1 receptors in the heart and consequently produce less tachycardia (fast heart rate). Activation of the beta adrenoreceptors results in a domino effect, first triggering adenylyl cyclase to make cyclic adenosine monophosphate, which then initiates protein kinase A effects on cellular calcium levels. In the airway, the result of this molecular chain reaction is bronchodilation.

Short-acting beta-adrenergic receptor agonists (SABAs) can produce symptomatic relief from wheezing, cough, and shortness of breath within five to 20 minutes and continue to do so for two to six hours. 

By adding a lipophilic chain to their molecular structure, long-acting adrenergic receptor agonists (LABAs) can stay attached to the bronchial smooth muscle cell membrane and continue to provide bronchodilator effects for 12 to 24 hours. However, the onset of action is not always as quick with long-acting beta-adrenoceptor agonists. For example, formoterol acts as quickly as albuterol, but salmeterol can take 30 to 45 minutes for bronchodilation.

What are beta agonists used for?

• Bronchospasm

• Exercise-induced bronchospasm

• Asthma

• COPD, including emphysema and chronic bronchitis

Types of beta agonists

Short-acting beta agonists

Albuterol, in the form of Proair, Proventil, or Ventolin, is the primary SABA used in asthma and other conditions associated with bronchospasm. Albuterol is also known as salbutamol. Delivered by inhaler or nebulizer, the drug asks within a few minutes. The quick symptom relief is what qualifies albuterol as a rescue inhaler for COPD and asthma exacerbations. It can be used on an as-needed basis when COPD or asthma symptoms like cough, wheeze, or shortness of breath are experienced. Alternatively, it can be used preemptively prior to exposure to bronchospasm triggers, such as exercise or allergens.

Xopenex is an alternative SABA. While albuterol is a racemic mixture of isomers, levalbuterol consists of only one albuterol isomer. The intended advantage is to lessen adverse effects such as tachycardia, although this is not always the case.

Epinephrine is a SABA, but it is not beta-2 selective, meaning that stimulation of beta-1 receptors in the heart may lead to tachycardia. Epinephrine is available as an over-the-counter (OTC) inhaler, Primatene Mist, and as a nebulized racemic solution, Asthmanefrin or S2. The nebulized form is used off-label for treatment of croup, an upper airway condition in children. Injectable epinephrine is used in the setting of anaphylactic allergic reactions, which can include bronchospasm.

Terbutaline is an oral beta-2 receptor agonist. This SABA is rarely used in asthma management due to slow onset of action and more side effects.

Long-acting beta agonists

Formoterol, salmeterol xinafoate, and olodaterol are the LABAs that are available as inhaler products, Perforomist, Serevent, and Striverdi Respimat respectively, without being combined with other agents. They can be used alone in COPD management, but they are to be combined with inhaled corticosteroids when used for asthma. Perforomist and Serevent can both provide bronchodilation for 12 hours, compared to 24 hours with Striverdi Respimat. The extended action classifies them as maintenance or controller agents, meant to prevent symptoms before they start. 

Combination agents

More commonly, LABAs are combined with other inhaled medications. Anti-inflammatory corticosteroids are available in inhaled forms, and these drugs lessen the swelling within bronchial tubes. Airway inflammation is one of the problems, other than bronchoconstriction, in asthma and COPD. Combining the bronchodilating effects of a LABA with the antiinflammatory effects of an inhaled glucocorticoid steroid provides a useful duo for disease maintenance therapy, controlling symptoms and preventing flares. 

Salmeterol is combined with fluticasone propionate in multiple products, Advair, Airduo, and Wixela. Likewise, Symbicort combines formoterol with budesonide, and Dulera combines formoterol with mometasone. Another LABA, vilanterol, has a notable advantage of having a 24-hour duration of action, enabling once daily dosing; it is available in combination with fluticasone as the Breo Ellipta inhaler.

While all glucocorticoid-LABA products are useful as maintenance medications for asthma and COPD, the glucocorticoid-formoterol products (Symbicort and Dulera) have a unique role for some asthmatics. The fast onset of long-acting formoterol, when coupled with an inhaled steroid, permits these products to be used as a single maintenance and rescue therapy (SMART), as opposed to regimens which use a glucocorticoid-LABA for maintenance and a SABA for rescue use. The SMART therapeutic option is not FDA-approved.

Muscarinic antagonists (also known as anticholinergics) are another prime drug class to integrate with β-agonists. By blocking muscarinic receptors, specifically the M1 and M3 varieties, in the smooth muscle of the bronchial tubes, muscarinic antagonists produce bronchodilation by a different mechanism than beta agonists. Achieving the dual, complimentary effect has proven useful in the treatment of COPD. The short-acting antimuscarinic ipratropium combines with the SABA albuterol in the inhaler Combivent Respimat and in a nebulizer solution. For COPD maintenance therapy, a long-acting muscarinic antagonist (LAMAs) is paired with a LABA for Anoro Ellipta (umeclidinium with vilanterol), Stiolto Respimat (tiotropium with olodaterol), and Bevespi Aerosphere (glycopyrrolate with formoterol). 

For some people with COPD, adequate control of their symptoms and prevention of disease exacerbations requires all three long-acting inhaled drug varieties, LABA, LAMA, and steroid. Trelegy Ellipta (fluticasone-umeclidinium-vilanterol) and Breztri Aerosphere (budesonide-glycopyrrolate-formoterol) provide this triad in a single inhaler.

Who can take beta agonists?

Can both men and women take beta agonists?

Men and women can take β-agonists. The exceptions would be individuals who have class or product-specific contraindications to their use.

Can you take beta agonists while pregnant or breastfeeding?

The decision on whether to use beta agonists during pregnancy or breastfeeding must take into account the risks of untreated bronchospasm, which often outweigh some unknowns of beta agonist use in these circumstances. Clinical trial data on use in pregnancy and breastfeeding is limited. A potential alteration in uterine contractions is noteworthy in pregnancy. In general, SABAs are often preferred over LABAs if possible. Ask a healthcare provider about which medications are safe to take during pregnancy and lactation.

Can children take beta agonists?

Most children can take SABAs. FDA approval extends to different ages for different products. For example, nebulized albuterol is approved for children aged 2 years and older, compared to age 4 for albuterol inhalers, but both are used off-label for even younger ages. 

LABAs are not approved for use on their own in children. Among LABA combination products, the lower age limit of FDA approval varies from 5 years for Dulera to 12 years for Advair. Breo Ellipta is not approved for use in children. 

Ipratropium-albuterol combinations are not approved either for children, but they are used off-label in some cases of asthma. LAMA-LABA products are not approved for children.

Can seniors take beta agonists?

As long as there are no contraindications, seniors can use beta agonists. Based on a higher rate of cardiovascular disease, a tachycardia side effect may need to be monitored for in this demographic group.

Are beta agonists safe?

Black box warning

The FDA has placed its highest level of warning label on LABAs regarding two concerns. First, clinical trials have indicated an increased risk of asthma-related deaths when LABAs are used as monotherapy, without concurrent inhaled corticosteroids. 

Second, studies in pediatric and adolescent asthmatics show a higher risk of asthma-related hospitalizations when LABAs are used as monotherapy. 

The recommendations from the FDA are to not use LABA monotherapy for asthma treatment, not use LABAs if asthma is controlled with inhaled glucocorticoids alone, and use LABA only in conjunction with an inhaled glucocorticoid, preferably with a combination glucocorticoid-LABA inhaler.

Recalls

No beta agonists have current recalls, but the FDA’s database should be searched for updated listings.

Restrictions

Contraindications to β-agonists include a history of hypersensitivity allergic reactions to the drug or drug class. DPI inhalers should also be avoided in those with a history of severe milk protein allergy. LABAs are contraindicated in the setting of acute bronchospasm, acute asthma, and acutely deteriorating COPD.

Are beta agonists controlled substances?

The Drug Enforcement Agency (DEA) does not list beta agonists as controlled substances.

Common beta agonists side effects

• Tachycardia, chest pain, or heart palpitations

• Tremor or nervousness

• Throat irritation, hoarseness, upper respiratory infection symptoms, or cough

• Nausea, vomiting, or diarrhea

• Bad taste or dry mouth

• Hyperlactatemia (elevated blood lactate levels)

• Headache or pain

• Urticaria (hives) or rash

• Insomnia

• Oral candidiasis (thrush) with combination products containing glucocorticoids

RELATED: Albuterol side effects

How much do beta agonists cost?

The cost of beta agonist drugs spans a wide range and depends on a number of factors—brand name or generic status, nebulizer or inhaler format, HFA or DPI inhaler style, and single agent or combination product. For example, generic albuterol solution vials for nebulizer use can be $30 for a box, a Proair HFA albuterol inhaler may run almost $100, and a Proair Digihaler DPI albuterol inhaler may be $200. Combination products carry a variable expense as well. A Symbicort inhaler may cost $460, while an Advair HFA inhaler costs $500 and a Trelegy Ellipta inhaler costs $800. The prices of beta agonists can seem intimidating, but the SingleCare discount card can be used at your pharmacy to make the cost much more reasonable.