What to Know About Beta2-Agonists for Asthma

SABAs, LABAs, and Their Role in Treatment

Beta2 (ß2)-agonist medications are a type of inhaled bronchodilator used to treat asthma. In the pathophysiology of asthma, tightened airways cause wheezing, chest tightness, shortness of breath, and chronic cough. ß2-agonists relax the smooth muscles of your airways to reduce these symptoms.

Both short-acting ß2-agonists (SABAs) and long-acting ß2-agonists (LABAs) play important—but different—roles in asthma management.

Pediatrician explaining inhaler to patient and mother
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What Do ß2-Agonists Do?

SABAs work quickly and are used to halt asthma attacks and other asthma symptoms right away. The most common SABA is albuterol. SABAs are often called rescue inhalers.

LABAs are daily medications used to control chronic symptoms and prevent asthma attacks. Studies show they can:

  • Improve lung function
  • Decrease asthma symptoms
  • Increase the number of symptom-free days
  • Reduce the number of asthma attacks
  • Decrease rescue-inhaler use

LABAs are also used to prevent exercise-induced asthma.

LABAs aren't used alone, though. They come in combination medications that also include an inhaled corticosteroid (ICS).

In addition to asthma, both SABAs and LABAs are used to treat chronic obstructive pulmonary disorder (COPD).

Drug Names

The U.S. Food and Drug Administration (FDA) has approved two SABAs for use in asthma, both of which are available in generic form as well as under brand names:

FDA-approved LABAs on the market include:

  • Serevent (salmeterol)
  • Foradil (formoterol)

ICS/LABA combination inhalers include:

  • Advair (fluticasone and salmeterol)
  • Symbicort (budesonide and formoterol)
  • Dulera (mometasone and formoterol)

How They Work

ß2-agonists mimic two hormones—epinephrine and norepinephrine—and attach to ß2 receptors in the muscles of your airways. These receptors are found in your lungs, as well as your digestive tract, uterus, and some blood vessels.

When this occurs, it starts a chemical chain reaction that ends with the smooth muscles relaxing. For those with asthma, this means less bronchoconstriction.

ß2-agonists open your airways, but they don't address the inflammation that's at the root of asthma symptoms and exacerbations (attacks). ICSs, however, are powerful anti-inflammatories.

Interestingly, the Chinese appear to have used beta-agonists to relax airways about 5,000 years ago, when they discovered that a plant called ma huang improved breathing. Scientists later found that the plant contains epinephrine.

Effectiveness

ß2-agonists medications are considered highly effective at relieving symptoms of asthma. Modern ß2-agonists are the result of more than a century of intensive research into asthma treatments.

SABAs provide almost instant relief of symptoms, but the effect only lasts for between four and six hours.

LABAs are able to keep the muscles relaxed for longer (between five and 12 hours, depending on frequency of use), but they are considered less effective than ICSs.

Side Effects

Side effects of the various ß2-agonists are similar and include:

  • Increased heart rate
  • Headache
  • Dizziness
  • Anxiety
  • Rash
  • Tremors
  • Nervousness
  • Shakiness
  • Upset stomach (rare)
  • Insomnia (rare)

More serious side effects of ß2-agonists include:

  • Allergic reactions such as rash, hives, difficulty breathing, swelling of the mouth, face, lips, or tongue
  • Chest pain
  • Ear pain
  • Fast or irregular heartbeat
  • Hoarseness
  • Pounding in the chest
  • Red, swollen, blistered, or peeling skin
  • A severe headache or dizziness
  • Trouble breathing

Warning Removed

From 2011 to 2017, LABAs carried a black-box warning about their ability to increase the risk of asthma-related death. However, the FDA rescinded that warning after reviewing data from four large clinical trials that showed LABAs didn't increase the risk of serious side effects over treatment with ICS alone.

Guidelines for Use

Standard asthma treatment involves a step-wise approach to medication use:

  1. SABA: When first diagnosed with asthma, most people are given a rescue inhaler to help stop asthma attacks. If you need your rescue inhaler frequently (more than twice a week) or your symptoms are severe, it's time for the next step up in treatment.
  2. Inhaled corticosteroids: An ICS, by itself, helps many people get better control of their symptoms than a SABA alone. The inhaled corticosteroid is a daily preventive treatment, and you'll still need your rescue inhaler for asthma attacks. If control isn't achieved, other medications are then considered.
  3. ICS+LABA: Using a combination inhaler helps many people finally achieve good control of their asthma symptoms. With this treatment approach, you use the ICS+LABA inhaler daily for prevention and still use a SABA inhaler when symptoms are exacerbated.

LABAs are typically avoided until after you've tried an ICS because they are less effective. The fact that LABAs are believed to have a greater risk of side effects than ICSs plays a part in this as well.

Updated Recommendations

In 2019, The Global Initiative for Asthma (GINA) released revised guidelines recommending a single inhaler—ICS or combination ICS+LABA—serve as both preventive treatment and a rescue inhaler for most people with asthma.

The guidelines say that the organization no longer recommends treatment with SABA alone because:

  • A SABA does not protect you from severe exacerbations (asthma attacks).
  • Frequent use of SABAs may increase the risk of exacerbations.
  • ICS and ICS+LABA inhalers are effective both for prevention and short-term symptom relief.

In more practical terms, GINA is saying that you no longer have to juggle a rescue inhaler and your preventive medication. If symptoms flare, you simply need to take an additional dose of the ICS or ICS+LABA.

Some doctors employ these new guidelines now, but others question them and continue to use the traditional step-wise approach.

The United States medical community is unlikely to adopt these recommendations for a few reasons:

  • The FDA hasn't approved these medications for as-needed use.
  • Pharmacies and insurance companies would need to adjust policies to allow earlier refills of daily-use inhalers to account for the extra doses you'd be using under the new guidelines.
  • Most importantly, some doctors argue there's not nearly enough evidence to support this new stance. (The recommendation change is largely based on a single trial demonstrating that ICS-LABA is effective as a rescue inhaler.)

Criticism has also focused on the timing of the advice to phase out SABAs in light of findings that people with asthma are at greater risk of severe symptoms of COVID-19. In 2020, SABAs quickly became the first line of defense in people with asthma and other lung problems who contracted COVID-19.

Research into and debate over the new guidelines and the science behind them is ongoing, and it's far from certain whether the updated guidelines will be widely adopted in the U.S.

How to Take and Store

It's important to make sure you're using your asthma inhaler(s) properly.

When using a new inhaler, or one that's gone unused for a while, you'll need to prime it first to ensure you get the proper dosage:

  1. Remove the cap.
  2. Shake for 5 seconds.
  3. Spray a short burst away from your face.
  4. Repeat once.

If you've used the inhaler recently, you shouldn't need to do this. Just follow the steps recommended for use of all bronchodilators, which include ensuring your lungs are empty before you inhale the medication, holding it in for 10 seconds before exhaling, and rinsing your mouth out with water when you're done.

Once a week, rinse your inhaler's plastic case and allow it to dry completely. Don't submerge the cartridge in water or use cleaning products on your inhaler.

For safety purposes:

  • Store your inhaler at room temperature (ideally between 68 and 77 degrees F).
  • Keep your inhaler away from high heat and open flames, as these situations can cause the cartridge to burst.
  • Keep your inhaler in a place where children and pets don't have access to it.

Make sure you request a refill from your pharmacy or doctor's office before your inhaler expires or runs out so you can treat your next asthma attack right away. If your inhaler (or any medication) is expired, don't use it.

Treatment Additions and Alternatives

SABAs are first-line treatments when it comes to rescue inhalers. However, if they don't provide you with enough relief, a couple of other options are available:

  • Inhaled anticholinergics: These may be added to SABAs to get control of lengthy, severe asthma attacks. They're sometimes used in the home but are more often given in the emergency room or hospital.
  • Oral steroids: You ingest these drugs in pill or liquid form for moderate and severe asthma attacks. They can have significant side effects and, thus, are used only after several other drugs have failed.

Other than ICSs and LABAs, classes of medications used for long-term asthma control include:

  • Long-acting muscarinic antagonists (LAMAs)
  • Leukotriene receptor antagonists (LTRAs)

Because inhaled corticosteroids are considered the most effective due to their anti-inflammatory effects, the other types of drugs are all used as add-on therapies in people already taking an ICS.

A 2020 study comparing the add-on medications concluded that:

  • LAMAs appear to be an effective alternative to LABAs.
  • LAMAs may be associated with greater improvements in lung function than LABAs.
  • Both LABAs and LAMAs appear to improve lung function more than LTRAs.

A Word From Verywell

If your asthma is not adequately managed on your current treatment plan, even if it has already been modified, speak with your doctor.

Remember that your asthma isn't well controlled if:

  • You use your relief inhaler more than twice a week
  • You wake up with asthma symptoms more than twice a month
  • You refill your rescue inhaler more than twice a year

Discuss whether you need to add another medication to your asthma-control regimen, such as a beta2-agonist.

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Article Sources
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