indication

For symptomatic relief and prevention of bronchospasm due to bronchial asthma, chronic bronchitis, and other chronic bronchopulmonary disorders such as COPD.

pharmacology

Salbutamol (INN) or albuterol (USAN), a moderately selective beta(2)-receptor agonist similar in structure to terbutaline, is widely used as a bronchodilator to manage asthma and other chronic obstructive airway diseases. The R-isomer, levalbuterol, is responsible for bronchodilation while the S-isomer increases bronchial reactivity. The R-enantiomer is sold in its pure form as Levalbuterol. The manufacturer of levalbuterol, Sepracor, has implied (although not directly claimed) that the presence of only the R-enantiomer produces fewer side-effects.

mechanism of action

Salbutamol is a beta(2)-adrenergic agonist and thus it stimulates beta(2)-adrenergic receptors. Binding of albuterol to beta(2)-receptors in the lungs results in relaxation of bronchial smooth muscles. It is believed that salbutamol increases cAMP production by activating adenylate cyclase, and the actions of salbutamol are mediated by cAMP. Increased intracellular cyclic AMP increases the activity of cAMP-dependent protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular calcium concentrations. A lowered intracellular calcium concentration leads to a smooth muscle relaxation and bronchodilation. In addition to bronchodilation, salbutamol inhibits the release of bronchoconstricting agents from mast cells, inhibits microvascular leakage, and enhances mucociliary clearance.

toxicity

LD₅₀=1100 mg/kg (orally in mice)

biotransformation

Hydrolyzed by esterases in tissue and blood to the active compound colterol. The drug is also conjugatively metabolized to salbutamol 4'-O-sulfate.

absorption

Systemic absorption is rapid following aerosol administration.

half life

1.6 hours

route of elimination

Approximately 72% of the inhaled dose is excreted in the urine within 24 hours, 28% as unchanged drug and 44% as metabolite.

drug interactions

Amitriptyline: The tricyclic antidepressant, amitriptyline, increases the sympathomimetic effect of salbutamol.

Amoxapine: The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of salbutamol.

Atenolol: Antagonism

Bisoprolol: Antagonism

Carvedilol: Antagonism

Clomipramine: The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of salbutamol.

Desipramine: The tricyclic antidepressant, desipramine, increases the sympathomimetic effect of salbutamol.

Doxepin: The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of salbutamol.

Esmolol: Antagonism

Imipramine: The tricyclic antidepressant, imipramine, increases the sympathomimetic effect of salbutamol.

Isocarboxazid: Increased arterial pressure

Labetalol: Antagonism

Linezolid: Possible increase of arterial pressure

Methyldopa: Increased arterial pressure

Metoprolol: Antagonism

Midodrine: Increased arterial pressure

Moclobemide: Moclobemide increases the sympathomimetic effect of salbutamol.

Nadolol: Antagonism

Nortriptyline: The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of salbutamol.

Oxprenolol: Antagonism

Phenelzine: Increased arterial pressure

Pindolol: Antagonism

Propranolol: Antagonism

Rasagiline: Increased arterial pressure

Reserpine: Increased arterial pressure

Timolol: Antagonism