A 64-year-old patient with frequent wheezing and shortness of breath is started on a new inhaled medication, with significant relief of symptoms. The medication has a long lipophilic side chain that allows attachment to the plasma membrane. The side chain also binds to an auxiliary, deeper site different from the one that binds epinephrine, helping to tether the molecule near the beta-2 adrenergic receptor. Which of the following medications did this patient most likely receive?
Beta-2 agonists are bronchodilators frequently used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). They can be categorized by their duration of action, which is largely due to drug lipophilicity.
Long-acting beta-2 agonists (eg, salmeterol, formoterol) are typically used for maintenance therapy in COPD or with inhaled corticosteroids in asthma. These drugs have a lipophilic side chain, which allows them to attach to the plasma membrane and diffuse laterally across to the beta-2 receptor. As a result, they have an extended duration of action (≥12 hours) but slow onset of action. Salmeterol has a slightly longer duration of action than formoterol due to its ability to bind a secondary exosite within the beta-2 receptor, which serves as an anchor to prevent active site dissociation.
Short-acting beta-2 agonists (eg, albuterol, levalbuterol) are typically used for acute symptom relief. These drugs are relatively hydrophilic, interact minimally with the plasma membrane, and are rapidly metabolized, explaining their rapid onset (minutes) and short duration of action (4-6 hours) (Choices A and C).
(Choice B) Isoproterenol is a nonselective beta agonist used primarily for its chronotropic effects in patients with bradycardia or heart block.
(Choice E) Terbutaline is a short-acting beta-2 agonist administered via intravenous or subcutaneous injection for very severe asthma exacerbations (ie, those requiring intubation). It does not have a long lipophilic side chain.
Educational objective:
Short-acting beta-2 agonists (eg, albuterol, levalbuterol) are hydrophilic and are rapidly metabolized, explaining their rapid onset and short duration of action. Long-acting beta-2 agonists (eg, salmeterol, formoterol) have a prolonged duration of action due to their lipophilic side chain, which allows them to attach to the cell plasma membrane. Salmeterol also binds to a secondary exosite within the beta-2 receptor, anchoring the molecule and further prolonging its action.