Salbutamol (Albuterol)

Mechanism

Mechanism of Action

Selective agonist of postsynaptic β₂ adrenergic receptors located predominantly in bronchial smooth muscle. Its binding to the receptor activates the α_s subunit of the G protein, stimulating adenylate cyclase to raise the intracellular concentration of cAMP. This activates protein kinase A (PKA), which phosphorylates and inactivates myosin light chain kinase and inhibits the release of intracellular calcium, inducing immediate and potent relaxation of bronchial smooth muscle. Likewise, it inhibits the release of inflammatory mediators by local bronchial mast cells and stimulates mucociliary clearance of the airway.

Pharmacokinetics

Key Pharmacokinetics

• Routes: Pressurized metered aerosol inhalation (MDI), nebulization, oral (tablets or syrup, not recommended due to a higher incidence of systemic ADRs), intravenous (restricted to refractory critical asthma attacks).
• Absorption: After inhalation, only 10-20% of the nominal dose reaches the lower bronchial tree; The rest is swallowed and absorbed through the gastrointestinal tract.
• Onset of action: Rapid, between 5 to 15 minutes post-inhalation, with a maximum bronchodilator effect at 60-90 minutes.
• Duration of effect: 3 to 6 hours.
• Metabolism: Mainly hepatic and gastrointestinal mucosa by conjugation with sulfate, converting into inactive metabolites.
• Excretion: Renal, eliminating more than 80% of the administered dose in the first 72 hours.

Indicators and dose

Approved and Off-label Indications

Approved: Relief and prevention of acute bronchospasm in bronchial asthma, chronic bronchitis and chronic obstructive pulmonary disease (COPD); prevention of bronchospasm induced by physical exertion induced by exercise.

Off-label: Severe acute hyperkalemia (stimulation of skeletal β₂ receptors activates the Na⁺/K⁺-ATPase pump, internalizing potassium to the intracellular compartment); Transient emergency tocolysis to delay premature birth.

Dosage and Adjustments

Acute Bronchospasm (MDI Inhaler): 100-200 µ g (1 to 2 inhalations) every 4-6 hours as needed. In severe asthma attacks, up to 4 to 10 inhalations can be administered every 20 minutes during the first hour.

Nebulization: 2.5 to 5.0 mg diluted in 3-4 mL of isotonic saline every 20-30 minutes in severe attacks.

Renal/hepatic adjustment: Does not require specific guidelines for preliminary quantitative adjustment, closely monitoring the plasma ionogram.

Security

Contraindications

Absolute: Known hypersensitivity to salbutamol or associated excipients (e.g., lactose in dry powder formulations).

Relative: Pre-existing tachycardia cardiac arrhythmias, ischemic heart disease, active decompensated thyrotoxicosis, uncontrolled diabetes mellitus (risk of ketoacidosis due to direct stimulation of glycogenolysis and lipolysis).

Adverse Effects (ADR)

Common: Fine tremor of the extremities (especially in the hands due to direct stimulation of β₂ receptors in skeletal muscle), sinus tachycardia, anxious palpitations, tension headache, muscle cramps.

Serious: Cardiac arrhythmias (atrial fibrillation, supraventricular tachycardia), refractory myocardial ischemia in coronary patients, severe paradoxical bronchospasm with immediate life threat (after initial inhalation, requires immediate cessation and therapeutic replacement), clinically relevant hypokalemia.

Interactions

Non-selective β-blockers (e.g., propranolol): They directly antagonize the bronchodilator effect of salbutamol, and can trigger severe bronchospasm with life-threatening consequences in asthmatic patients.

Non-potassium-sparing diuretics (e.g., furosemide, thiazides): Synergy in the hypokalemic effect, increasing the risk of serious ventricular arrhythmias.

Digoxin: May reduce plasma concentrations and the therapeutic effect of digoxin.

Pregnancy and Breastfeeding

FDA Classification: Category C. Parenteral or oral administration may delay active labor due to uterine relaxation (tocolytic effect). The inhaled route is preferred due to its minimal systemic absorption and low excretion in breast milk.