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Beta-2 Adrenergic Agonists

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Information about Beta-2 Adrenergic Agonists

The beta-2 adrenergic agonists are a large group of drugs that mimic the actions of naturally occurring catecholamines such as norepinephrine, epinephrine and dopamine.

Mechanism of action of Beta-2 Adrenergic Agonists

Direct agonists directly interact with the adrenergic receptors, whereas indirect agonists typically stimulate the release of endogenous catecholamines. The beta-2 adrenergic agonists act mainly on the smooth muscle of the vasculature, bronchial tree, intestines and uterus. These agents also act on the liver stimulating glycogenolysis and release of glucose from the liver and muscle (particularly if used in high doses). The beta-2 adrenergic agonists are used largely as bronchodilators in the management of asthma, both in control of acute symptomatic attacks as well as chronic, long term prevention and management. These agents are some of the most commonly prescribed drugs for asthma and are widely used and proven to be well tolerated and safe.

Liver toxicity of Beta-2 Adrenergic Agonists

The use of beta adrenergic agonists in asthma has not been associated with elevations in serum aminotransferase or alkaline phosphatase levels or in causing clinically apparent liver disease. When given in large doses or after intentional overdose, beta adrenergic agonists can cause liver injury. Most case reports of liver damage from these agents have been associated with their use in control of premature labor (for their effects on relaxation of uterine smooth muscle). The liver injury typically arises within a few days of starting high dose intravenous beta adrenergic agonists, is usually asymptomatic, not associated with jaundice, and rapidly reversed once the medication is stopped.

Commonly used beta adrenergic drugs include albuterol, bitolterol, metaproterenol, pirbuterol, salmeterol and terbutaline. These agents share structural similarity and are discussed together.

Beta Adrenergic Agonists Used for asthma Bitolterol, Formoterol, Metaproterenol, Pirbuterol, Salbutamol (Albuterol), Salmeterol, Terbutaline

The beta adrenergic agonists act on bronchial smooth muscle inducing bronchodilation and relieving bronchospasm in asthma and chronic obstructive pulmonary disease with asthmatic features. Their use in asthma has not been associated with liver injury.

Clinical use of Beta-2 Adrenergic Agonists

The beta adrenergic agonists are potent bronchodilators that are widely used in the management of bronchial asthma. These agents act by engaging the beta-2 adrenergic receptors on smooth muscle of bronchial tissue, relieving bronchospasm and reducing airway resistance. They also act on smooth muscle of the vascular system, intestines and uterus. Common forms of beta adrenergic agonists include albuterol, bitolterol, fenoterol, formoterol, levalbuterol, metaproterenol, salmeterol, pirbuterol and terbutaline, which all have similar mechanisms of action, chemical structure, side effects and efficacy, but somewhat different pharmacokinetics allowing for differences in dosing regimens and duration of action. Most of these agents are administered by inhalation (alone or in combination with other bronchodilators or corticosteroids), with only albuterol and terbutaline being available in oral forms in the United States.

Types of Beta-2 Adrenergic Agonists

Albuterol (also known as salbutamol) is available in generic forms and under the brand names of Proventil and Ventolin as 2 and 4 mg tablets as well as in aerosol and syrup solutions.

Dosage and administration for Beta-2 Adrenergic Agonists

The recommended regimen of albuterol is 2 to 4 mg orally 3 to 4 times a day. Sustained release formulations are available for twice daily dosing (4 and 8 mg). Salmeterol is available as an inhalation powder in generic forms and under the brand name of Serevent Diskus. The typical dosage is one inhalation (50 mcg) twice daily and it is recommended to be given with corticosteroids only. Systemic absorption is minimal. Terbutaline is available in generic forms and under the brand name of Brethine in tablets of 2.5 and 5 mg, the usual adult dosage being 5 mg three times daily. These oral forms of beta adrenergic agonists are approved as means of prevention and reversal of bronchospasm and are used largely in the therapy of asthma. Terbutaline is also available in parenteral formulations for use in acute bronchospasm and has also been used as therapy of premature labor.

Side effects of Beta-2 Adrenergic Agonists

Common side effects of the beta adrenergic agonists include dizziness, headache, nervousness, tachycardia, palpitations, nausea and diaphoresis, largely due to their beta adrenergic effects on other organs. Rare, potentially severe adverse events include cardiovascular events, paradoxical worsening of asthma and acute hypersensitivity reactions.

Beta-2 Adrenergic Agonists

Albuterol, Bitolterol, Formoterol, Metaproterenol, Pirbuterol, Salbutamol, Salmeterol, Terbutaline

Leukotriene Receptor Antagonists

Montelukast, Zafirlukast

Monoclonal Antibodies

Benralizumab, Mepolizumab, Omalizumab, Reslizumab

Xanthine Derivatives

Theophylline Zileuton

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