Short-Acting Beta Agonists (SABAs) for Asthma

Short-acting beta-agonists (SABAs) are a class of prescription drugs used to provide quick relief of shortness of breath and wheezing in people with asthma. SABAs work by relaxing the smooth muscles of the lungs, alleviating spasms, and constriction (narrowing) of the airways. Although most SABAs are delivered via a rescue inhaler, there are some that are taken in pill or syrup form and even by injection.

Unlike long-acting beta-agonists (LABAs) that are used on a daily basis, SABAs are used as needed to treat acute asthma attacks.

What They Are

SABAs are considered the frontline defense for acute asthma symptoms. They are most often inhaled via a metered-dose inhaler (using a pressurized canister) or a dry powder inhaler (which you simply breathe in) but are also available as tablets, syrups, nebulized solutions, injectable solutions, and even intravenous solutions.

When used as a rescue inhaler, SABAs can relieve dyspnea (shortness of breath) and wheezing within minutes. After one to two puffs, the drug will remain active for around four to six hours and can be used anywhere from three to six times daily depending on the formulation.

There are two SABAs approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute asthma symptoms:

• Albuterol, also known as salbutamol and marketed under the brand names ProAir, Proventil, Ventolin, and others
• Levalbuterol, marketed under the brand name Xopenex and others

Other older-generations SABAs like Alupent (metaproterenol), Maxair (pirbuterol), and Bricanyl (terbutaline) have been discontinued by their manufacturers or pulled from the market due to safety concerns.

How SABAs Work

SABAs, along with closely related LABAs, belong to a larger class of drugs known as beta₂ (β₂)-adrenergic receptor agonists. By definition, agonists are drugs that bind to a cell receptor to trigger a specific reaction.

The receptor, in this case, is the beta₂-adrenergic receptor, which relaxes smooth muscles. Smooth muscles are those found in the walls of hollow organs that contract and relax involuntarily to, among other things, move food through the intestines, regulate blood pressure and circulation, or—as is relevant to asthma—open and close airways in the lungs.

The receptors are considered adrenergic because they respond to the hormone epinephrine (adrenaline) that helps regulate smooth muscle function. By mimicking epinephrine, beta-agonists can bind to adrenergic receptors and trigger a chain reaction in which calcium is quickly released from channels within smooth muscles, causing them to relax.

When applied to the lungs, this effect will cause the bronchi and bronchioles to quickly dilate, allowing more air to enter. It also alleviates bronchospasms that cause chest tightness and coughing during an asthma attack.

Although SABAs and LABAs have similar mechanisms of action, they differ by their half-life (the time it takes to clear 50% of the drug from the body). As per their name, SABAs have a short half-life (around three to six hours), while newer LABAs have a half-life closer to 36 hours.

Indications for Use

The use of SABAs can vary by the frequency or severity of asthma symptoms:

• Mild intermittent asthma: SABAs are often used on their own as needed.
• Persistent asthma: SABAs are typically used to relieve acute symptoms; inhaled LABAs and/or corticosteroids are also taken on a daily basis to provide long-term control.
• Exercise-induced asthma: SABAs can be taken five to 30 minutes in advance of exercise to reduce the risk of an attack.
• Asthma emergency: Albuterol is sometimes delivered intravenously (into a vein) by emergency department personnel.

Off-Label Uses

SABAs are frequently used off-label to treat respiratory distress in people with severe lower respiratory infections, although their usefulness in this respect has yet to be proven.

Albuterol is sometimes used off-label as a tocolytic (a drug that suppresses contractions to prevent or delay preterm birth). Depending on the severity of the contractions, the drug may be given intravenously or by mouth.

Precautions and Contraindications

There are few absolute contraindications to SABAs other than a known allergy to the drug or any inactive ingredient in the formulation. If you are allergic to albuterol, you should not use levalbuterol (or vice versa).

SABAs are known to affect pulse rate, blood pressure, blood sugar, and thyroid hormone production and, on rare occasions, induce seizures. While not contraindicated for use, SABAs should be used with caution in people with:

• Coronary artery disease (CAD)
• Cardiac arrhythmias
• Uncontrolled hypertension
• Diabetes
• Convulsive disorders, including epilepsy
• Hyperthyroidism

Albuterol and levalbuterol are both classified as Pregnancy Category C drugs, meaning that animal studies suggest a potential for fetal harm but no well-controlled trials in humans are available.

Based on the statistical risk, the drugs are unlikely to pose any harm. Even so, it is important to speak to your doctor if you are pregnant, planning to get pregnant, or breastfeeding so that you can weight the benefits and risks of use.

Dosage

The recommended dosage of albuterol and levalbuterol varies by the drug formulation as well as the user's age. Among the approved formulations:

• Albuterol is available as a metered-dose inhaler (MDI), dry powder inhaler (DPI), nebulized solution, immediate-release (IR) tablet, extended-release (ER) tablet, syrup, and intravenous solution.
• Levalbuterol is available as an MDI or nebulized solution.

Tablets and syrups are less commonly used but may be appropriate for children and adults who are unable to tolerate or properly use inhaled medications.

How to Take and Store

SABAs should never be used in excess of the recommended dose. Overuse can lead to premature drug tolerance and treatment failure.

Of the three inhaled formulations, MDIs need to be primed before use if not recently used. This involves shaking and spraying the inhaler away from your face in two short bursts to ensure that the aerosol valve is clear. (DPIs and nebulizers can be used as needed.)

The various inhalers also need to be regularly cleaned to avoid clogging and insufficient dosing:

• Metered-dose inhalers, which deliver the medications using an aerosolized propellant, should be cleaned once weekly by removing the canister and running water through the mouthpiece for 30 to 60 seconds. The canister should never be submerged in water.
• Dry powder inhalers, which have no propellant and are breath activated, simply need to be wiped off between use. The unit should never be washed or submerged in water.
• Nebulizers, which deliver the medications using an inhaled mist, should be cleaned after every use and disinfected once weekly with either a steam sterilizer, an approved disinfecting solution, or a complete dishwasher cycle.

The medications can be safely stored at room temperature (ideally between 68 and 77 degrees F). Keep the drug in its original packaging away from direct sunlight and out of the reach of children.

Do not use a SABA after its expiration date.

Side Effects

The side effects of the different SABA formulation are largely the same. However, because inhaled SABAs are delivered locally, they tend to have milder and shorter-lasting side effects than their oral or intravenous counterparts.

When to Call 911

On rare occasions, SABAs can cause paradoxical bronchospasm in which breathing symptoms get worse rather than better. The cause of this is unclear, but it seems to occur more frequently in people with allergic asthma who have severely inflamed airways.

SABA-induced paradoxical bronchospasm should always be considered a medical emergency.

Allergies to SABAs are rare but can occur. Call 911 or seek emergency care if you develop hives or rash, difficulty breathing, abnormal heartbeats, confusion, or the swelling of the face, throat, tongue, or throat. These are signs of a potentially life-threatening, whole-body allergy known as anaphylaxis.

Warnings and Interactions

The routine monitoring of heart function, blood glucose, or thyroid function is recommended if albuterol is used in any at-risk groups. The treatment may need to be stopped if symptoms worsen or diagnostic test results fall well outside of the acceptable range of values.

Because of their effect on heart rhythms, SABAs should never be overused. The overuse of albuterol or levalbuterol has been known on rare occasions to cause myocardial infarction (heart attack) or stroke.

Beta₂-agonists are known to interact with certain classes of drugs. In some cases, the interaction may increase the activity of a drug (raising the risk of side effects). In others, it may decrease the blood concentration of a drug (reducing its effectiveness).

Among the drugs that may interact with SABAs are:

• Anti-arrhythmia drugs like Multaq (dronedarone) or digoxin
• Antifungals like Diflucan (fluconazole), Noxafil (posaconazole), or ketoconazole
• Anti-malaria drugs like chloroquine or piperaquine
• Antipsychotics like Orap (pimozide), Mellaril (thioridazine), Serentil (mesoridazine), amisulpride, or ziprasidone
• Beta-blockers like Inderal (propranolol) or Lopressor (metoprolol)
• HIV protease inhibitors like Viracept (nelfinavir) or Fortovase (saquinavir)
• Monoamine oxidase inhibitor (MAOI) antidepressants like Parnate (tranylcypromine) or Marplan (isocarboxazid)
• Potassium-sparing diuretics like Aldactone (spironolactone) or Inspra (eplerenone)

A Word From Verywell

Though rescue inhalers like albuterol and levalbuterol are safe and effective in relieving acute asthma symptoms, it is important not to overuse them. Some people will do out so of panic if the drug is "not working fast enough," while others will overuse SABAs to avoid having to take other longer-acting drugs. Both of these are signs that your condition is not being well controlled.

As a rule of thumb, if you need to use a rescue inhaler more than twice weekly, your asthma is being poorly controlled. By speaking with your doctor and being honest about your inhaler use, you should be better able to find the right combination of drugs to control your asthma symptoms.