From the Guidelines
Yes, inhaled beta agonists do shift potassium into cells, as evidenced by a decrease in serum potassium concentrations, typically by less than 1 mmol/L, as reported in recent studies 1.
Mechanism of Action
Medications such as albuterol (salbutamol), levalbuterol, formoterol, and salmeterol activate beta-2 adrenergic receptors, which stimulate the sodium-potassium ATPase pump in cell membranes. This activation causes potassium to move from the extracellular space into the intracellular compartment, resulting in a decrease in serum potassium levels.
Clinical Implications
This effect occurs within 30 minutes of administration and can reduce serum potassium by approximately 0.5-1.0 mEq/L, with the maximum effect typically seen within 1-2 hours 1. This mechanism is clinically useful in the emergency treatment of hyperkalemia, where nebulized albuterol (10-20 mg) is often administered alongside other treatments. The potassium-lowering effect is temporary, lasting about 2-4 hours, so definitive treatment of the underlying cause of hyperkalemia is still necessary.
Side Effects
The same mechanism explains why patients using beta agonists for asthma or COPD may occasionally develop hypokalemia as a side effect, particularly with high doses or frequent use. Other side effects of inhaled beta agonists include tachycardia, arrhythmias, tremor, dizziness, and palpitations, as reported in studies 1.
Treatment of Hyperkalemia
In the treatment of severe hyperkalemia, therapies that shift potassium into cells, such as sodium bicarbonate, are used to rapidly lower serum potassium levels, as recommended in guidelines 1. However, the use of inhaled beta agonists for this purpose is not explicitly mentioned in these guidelines, highlighting the need for further research on their efficacy and safety in this context.
From the FDA Drug Label
Beta-adrenergic agonists may produce significant hypokalemia in some patients, which has the potential to produce adverse cardiovascular effects The decrease in serum potassium is usually transient, not requiring supplementation.
The inhaled beta agonists can cause a shift of potassium into cells, but this is described as producing hypokalemia, which implies that potassium is moving out of the blood, not into cells. However, the mechanism of beta agonist-induced hypokalemia is by shifting potassium into cells.
- Key point: Inhaled beta agonists can cause potassium to shift into cells, leading to hypokalemia 2.
From the Research
Inhaled Beta Agonists and Potassium Shift
- Inhaled beta agonists, such as salbutamol, fenoterol, and terbutaline, have been shown to decrease plasma potassium concentration in normal volunteers 3.
- The decrease in plasma potassium is dose-dependent and more pronounced for fenoterol and salbutamol than for terbutaline 3.
- The mechanism of this effect is thought to be related to the stimulation of beta-2 receptors, which leads to an increase in cAMP and the subsequent stimulation of the Na-K-ATPase, resulting in the shift of potassium into skeletal muscle cells 4.
Clinical Implications
- Salbutamol has been used to treat hyperkalemia in children and adults, with a significant decrease in plasma potassium concentration observed after administration 4, 5.
- The use of salbutamol for hyperkalemia has been shown to be safe and efficacious, with a predictable and long-lasting reduction in serum potassium 5.
- However, salbutamol-induced hypokalemia has been correlated with impaired cardiac repolarization, which could potentially trigger arrhythmias and sudden cardiac death in susceptible individuals 6.
Mechanism of Action
- The decrease in plasma potassium concentration induced by inhaled beta agonists is thought to be mediated by the beta-2 receptors, which stimulate the Na-K-ATPase and lead to the shift of potassium into skeletal muscle cells 4, 7.
- The same mechanism is involved in eliciting hypokalemia and bronchodilatation, suggesting a link between the two effects 7.