What is the mechanism of action and effects of terbutaline (beta-2 adrenergic agonist) in asthma management?

From the Guidelines

Terbutaline is a beta-2 adrenergic agonist that effectively treats asthma by selectively binding to beta-2 receptors in bronchial smooth muscle, causing bronchodilation, and is typically administered as a short-acting rescue medication at doses of 0.25-0.5 mg via subcutaneous injection or 2.5-5 mg orally every 6 hours as needed. When terbutaline binds to these receptors, it activates adenylyl cyclase, increasing intracellular cyclic AMP levels, which leads to smooth muscle relaxation and airway opening 1. This mechanism provides rapid relief of bronchospasm and wheezing in asthma patients.

Key Points

• Terbutaline is used for acute symptom relief, but not recommended for long-term control due to potential side effects including tremor, tachycardia, and hypokalemia 1.
• The dose of subcutaneous terbutaline is 0.25 mg, which can be repeated every 20 minutes for 3 doses 1.
• There is no evidence that subcutaneous terbutaline has advantages over inhaled β2-agonists 1.
• Patients should be monitored for cardiovascular effects, especially those with heart conditions, as beta-2 receptors are present not only in the lungs but also in the heart, blood vessels, and skeletal muscle.
• Unlike newer beta-2 agonists such as albuterol, terbutaline is less commonly used today but remains an option when other medications are unavailable or ineffective.

Administration and Monitoring

• Terbutaline can also be used as a nebulized solution at 0.1-0.3 mg/kg/dose.
• Increasing the use of short-acting beta2 agonists or using them more than two days per week for symptom relief generally indicates inadequate control of asthma and the need to initiate or intensify anti-inflammatory therapy 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Terbutaline sulfate injection is a beta-adrenergic receptor agonist. In vitro and in vivo pharmacologic studies have demonstrated that terbutaline exerts a preferential effect on beta2‑adrenergic receptors The pharmacologic effects of beta-adrenergic agonists, including terbutaline, are at least in part attributable to stimulation through beta-adrenergic receptors of intracellular adenyl cyclase, the enzyme which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic 3’,5’-adenosine monophosphate (cAMP) Increased cAMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. Controlled clinical studies have shown that terbutaline sulfate injection relieves bronchospasm in acute and chronic obstructive pulmonary disease by significantly increasing pulmonary flow rates (e.g., an increase of 15% or more in FEV1).

The mechanism of action of terbutaline in asthma management is through its preferential effect on beta2-adrenergic receptors, which leads to:

• Stimulation of intracellular adenyl cyclase
• Increase in cyclic 3’,5’-adenosine monophosphate (cAMP) levels
• Relaxation of bronchial smooth muscle
• Inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells The effects of terbutaline in asthma management include:
• Relief of bronchospasm
• Increase in pulmonary flow rates (e.g., an increase of 15% or more in FEV1) 2

From the Research

Mechanism of Action

• Terbutaline is a beta-2 adrenergic agonist that works by stimulating beta-2 receptors in the lungs, leading to relaxation of airway smooth muscle and bronchodilation 3, 4, 5.
• The relaxation of airway smooth muscle is caused by an increase in intracellular cAMP and activation of protein kinase A (PKA), which phosphorylates several cellular proteins, resulting in relaxation 5.
• Terbutaline also influences membrane K+ channels and induces smooth muscle relaxation without a rise in cAMP, which appears to be the major feature of bronchodilatation in asthma 5.

Effects on Asthma

• Terbutaline is an effective bronchodilator drug in subjects with acute asthma, with significant improvements in spirometric measurements and subjective responses 3.
• However, long-term administration of terbutaline can lead to subsensitivity and a decrease in peak response and duration of action 6.
• Terbutaline has an anti-cholinergic effect that can relieve asthmatic symptoms, and it can inhibit electrical field stimulation (EFS) induced spike contraction in tracheal smooth muscle 4.
• The combination of terbutaline with inhaled corticosteroids can improve asthma symptoms and lung function, and reduce exacerbations, although it is less effective than inhaled corticosteroids as monotherapy 7.

Cardiovascular Effects

• Terbutaline can cause an increase in heart rate, with a maximal increase of 25 percent above control, due to stimulation of beta 1-adrenergic receptors in the heart 3.
• The cardioaccelerator effect of terbutaline is more pronounced than that of epinephrine, although the latter can also cause an increase in heart rate 3.

Other Effects

• Terbutaline can modulate neurotransmission in airways via prejunctional receptors on airway nerves, both sensory and motor, and can inhibit the release of histamine from mast cells in vitro 5.
• However, terbutaline has little or no effect on the chronic inflammatory response that underlies chronic airway hyper-responsiveness, and it has little or no inhibitory action on the activities of eosinophils, macrophages, lymphocytes, and neutrophils due to rapid tachyphylaxis 5.