Bronchodilator

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [2]

Overview

A bronchodilator is a substance that dilates the bronchi and bronchioles, increasing airflow and relieving bronchial obstruction. Bronchodilators may be endogenous (originating naturally within the body), or they may be medication administered for the treatment of breathing difficulties. Bronchial asthma is the most common application of these drugs. They are also intended to help improve the breathing capacity of patients with emphysema, pneumonia and bronchitis.

Pharmaceutically bronchodilators belong to β2 mimetics as they act on β2 receptors present in the bronchial smooth muscle and bronchial mucous membranes. Bronchodilators, particularly non-prescription ones, are often misused as stimulants. A common side effect of these medications is desensitization, which may produce refractory bronchospasm.

Bronchodilators are either short-acting or long-acting. Short-acting medications (also known as SABA) provide quick or rescue relief from acute bronchoconstriction. Long-acting bronchodilators (known as LABA) help to control and prevent symptoms. The three types of prescription bronchodilator drugs are β2-agonists (short- and long-acting), anticholinergics (short-acting), and theophylline (long-acting).

Short-acting β2-agonists

Examples

Mechanism of Benefit

  • Beta-2 receptor is a G protein-coupled transmembrane receptor that is widely distributed in the respiratory tract and activates the enzyme adenylyl cyclase that produces cAMP to cause bronchial smooth muscle relaxation.[1]
  • Short-acting beta agonists provide immediate symptomatic benefit; however, are unsuccessful in inhibiting chronic inflammatory responce. Thereby, provide no benefit for prophylactic use.[4][5]

Duration of Action

These medications usually take effect within 20 minutes or less, and can last from four to six hours.

Mode of administration

  • Albuterol by metered dose inhaler provided similar bronchodilation to that achieved by wet nebulization in patients with acute asthma. No significant difference in the effectiveness of albuterol administered by nebulizer or the inhaler system.[6][7]
  • Oral beta agonists have a delayed therapeutic effect and peak bronchodilation occurs only two hours after ingestion; hence, making it suitable for the treatment of mild to moderate asthma and not for acute exacerbation.[8]
  • Inhaled medications are best for treating sudden and severe or new asthma symptoms. In patients with severe asthma, only after a failed or absent response observed with inhaled beta agonist, is parenteral administration indicated; as the nebulized route is associated with a greater efficacy and fewer side effect.[9][10][11][12][13]

Uses in Asthma

  • Quick-relief or rescue medications that provide fast, temporary relief from asthma symptoms or flare-ups.[14]
  • Short-acting β2-agonists (SABA) along with ipratropium may be administered within the first three hours of acute severe exacerbation.[14]
  • Taken 15 to 20 minutes ahead of time, these medications can also prevent asthma symptoms triggered by exercise or exposure to cold air.
  • Few patients may require higher-dose of nebulized beta-2 agonist to provide effective treatment of acute severe asthma.[15][16][17][18][19]

Caution/Contra-indication

  • Patients who chronically or frequently take short-acting β2-agonists, may be subjected to resistance secondary to the down-regulation of beta receptor and may indicate towards uncontrolled asthma.[20]
  • Intravenous administration of beta agonists is associated with the development systemic adverse effects.[12][11][21]
  • Intravenous isoproterenol is not used as it is associated with severe cardiac toxicity.[21]

Adverse Effects

Long-acting β2-agonists

Examples

Mechanism of Benefit

  • Beta-2 receptor is a G protein-coupled transmembrane receptor that is widely distributed in the respiratory tract and activates the enzyme adenylyl cyclase that produces cAMP to cause bronchial smooth muscle relaxation.[1]

Duration of Action

These medications take longer to begin working, but relieve airway constriction for up to 12 hours.

Mode of administration

  • Inhaled: Commonly taken twice a day with an anti-inflammatory medication, they maintain open airways and prevent asthma symptoms, particularly at night.
  • Oral: Long-acting albuterol is available in pill or syrup form. Effective for 12 hours, albuterol is particularly helpful for nighttime asthma symptoms.

Uses in Asthma

  • These are long-term medications taken routinely in order to control and prevent bronchoconstriction. They are not intended for fast relief.
  • Formoterol has been shown to be effective as a rescue medication for the immediate relief of asthma symptoms similar to albuterol.[28][29] However, formoterol has not been approved as a quick relief medication.[14]
  • Salmeterol, has shown to block both the immediate and late phase bronchospastic responses; however, has no anti-inflammatory properties.[30]

Caution

Because this medication requires high dosing, there tend to be increased side effects. Therefore, long-acting β2-agonists (LABA) are never prescribed as monotherapy.[37][38]

Adverse Effects

Anticholinergics

Examples

Mechanism of Benefit

Muscarinic-1 receptor facilitates neurotransmission through parasympathetic ganglia and enhances the cholinergic reflexes, and are also localized to alveolar walls. Muscarinic-3 receptors mediate contractile responses in the airway smooth muscle via phosphoinositide hydrolysis, and are the predominant receptors on submucosal glands and airway vascular endothelium.[40][41][42] M3-receptor activation results in bronchospasm secondary to decrease in intracellular cAMP.[43]

Anticholinergic drugs such as ipratropium, selectively block M3 and M1-receptors; thereby, causing bronchial smooth muscle relaxation and reducing the bronchial submucosal gland secretions.[40][44]

Duration of Action

Slow-onset of action but longer duration of action [45][46]

Mode of administration

Only available as an inhalant, ipratropium bromide relieves acute or new asthma symptoms with less than 1% systemic absorption and therefore, reduced risk of systemic toxicity.[47][48]

Uses in Asthma

Ipratropium is not the first drug of choice for asthma; however, it is extensively used in conjunction with short-acting β2-agonist for the treatment of acute exacerbations.[49][50]

Adverse Effects

  • Dry throat is the most common side effect.
  • If the medication gets in contact with the eyes, it may cause blurred vision for a brief time.[51]

Theophylline

Mechanism of Benefit

Duration of Action

It must be taken 1-4 times daily and doses cannot be missed.

Mode of administration

Available in oral and injectable form, theophylline is a long-acting bronchodilator that prevents asthma episodes.

Caution

Blood tests are required to monitor therapy and to indicate when dosage adjustment is necessary.

Uses in Asthma

It is prescribed in severe cases of asthma or those that are difficult to control.

Adverse Effects

  • It may promote acid reflux, also known as GERD, by relaxing the lower esophageal sphincter muscle.

Drug Interactions

  • Some medications, such as seizure and ulcer medications and antibiotics containing erythromycin, can interfere with the way theopylline works.
  • Coffee, tea, colas, cigarette smoking, and viral illnesses can all affect the action of theophylline and change its effectiveness.

Brand names of common bronchodilators

Following the standard convention of medicine, the capitalized brand name is followed by the lowercased generic name in parentheses.

References

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