What is the mechanism by which albuterol (a β2‑adrenergic agonist) lowers serum potassium?

Mechanism of Albuterol-Induced Hypokalemia

Albuterol decreases serum potassium by stimulating β2-adrenergic receptors, which activates the Na+/K+-ATPase pump on cell membranes, causing an intracellular shift of potassium from the extracellular space into cells—this does not change total body potassium, only redistributes it temporarily. 1, 2

The Cellular Mechanism

• β2-receptor activation triggers the Na+/K+-ATPase pump, which actively transports potassium ions from the bloodstream into cells, particularly skeletal muscle cells 2, 3
• This represents an intracellular shunting mechanism rather than potassium elimination from the body 2, 4
• The effect occurs through intracellular shift, not through renal excretion or other elimination pathways 1, 5

Clinical Magnitude and Timing

• The onset of potassium-lowering occurs within 30 minutes of administration 1
• Mean decreases in serum potassium typically range from 0.52-0.54 mmol/L with standard doses 1
• In controlled studies, nebulized albuterol decreased potassium by 0.66-0.71 mmol/L at 60 minutes 6, 5
• Healthy volunteers receiving 10 mg nebulized albuterol showed a mean decrease of 0.5 mEq/L (95% CI: -0.72 to -0.28 mEq/L) 7
• The decrease is usually transient and typically does not require potassium supplementation 2

Important Clinical Context

• This mechanism is therapeutically exploited for acute hyperkalemia treatment, where albuterol (10-20 mg nebulized over 15 minutes) is used alongside insulin/glucose and calcium to rapidly lower dangerous potassium levels 1
• The hypokalemic effect is additive with insulin—combined therapy produces substantially greater potassium reduction (1.21 mmol/L) than either agent alone (0.65-0.66 mmol/L) 5
• Repeated dosing with 0.15 mg/kg in children has been associated with asymptomatic declines of 20-25% in serum potassium levels 2

Route-Dependent Effects

• Nebulized delivery produces more systemic absorption and greater potassium shifts compared to metered-dose inhalers 4, 3
• Nebulizer administration resulted in 7.8% decrease in skeletal muscle strength (related to hypokalemia) versus a 2.4% increase with metered-dose inhaler delivery 4
• Intravenous administration produces the most pronounced metabolic effects, including the most significant potassium decreases 3

Clinical Caveats

• While the potassium decrease is typically mild and of uncertain clinical significance in most patients 1, it can produce adverse cardiovascular effects in susceptible individuals 2
• The FDA label warns that albuterol "may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects" 2
• Patients with pre-existing cardiovascular disease, arrhythmias, or those on medications affecting potassium require closer monitoring 2
• The effect is dose-dependent—higher doses and continuous nebulization produce greater potassium shifts 8, 3