Salbutamol

Salbutamol is a short-acting, selective beta-2 adrenoreceptor agonist used in the treatment of asthma and COPD. It is 29 times more selective for beta-2 receptors than beta-1 receptors, giving it greater specificity for receptors in the lung compared to beta-1 receptors in the heart. Salbutamol is generally used for bronchospasm caused by bronchial asthma, chronic bronchitis, and other chronic pulmonary diseases such as chronic obstructive pulmonary disease (COPD). It is also used prophylactically for exercise-induced asthma. Salbutamol is administered exclusively in the form of an aerosol for inhalation. Salbutamol is available only on prescription.

Pharmacodynamics

Salbutamol is a beta receptor agonist and is much more selective for β2 receptors, which are the predominant receptors on bronchial smooth muscle. Activation of these receptors causes adenylate cyclase to convert ATP to cAMP, which initiates a signaling cascade that lowers the intracellular concentration of calcium ions (necessary for muscle contractions). The increase in cAMP also inhibits the release of inflammatory mediators and cytokines by inflammatory cells in the respiratory tract, which further helps to relieve symptoms.

Pharmacokinetics

After inhalation, salbutamol acts topically on bronchial smooth muscle. The drug is initially undetectable in the blood. After 2 to 3 hours, low concentrations appear in plasma, probably due to the portion of the dose that is swallowed and absorbed in the intestine. Salbutamol is only weakly bound to plasma proteins. Salbutamol is not metabolized in the lungs but is converted in the liver to salbutamol 4'-O-sulfate, which has little pharmacologic activity. After oral administration, 58-78% of the dose is excreted in the urine within 24 hours, about 60% as metabolites. A small fraction is excreted in the feces.

Drug Interactions

Interactions may occur in combination with the following drugs:

• Xanthine derivatives, diuretics, and steroids may cause acute potassium deficiency
• simultaneous use with non-selective beta-blockers may lead to severe bronchoconstriction
• Salbutamol can weaken the effect of antidiabetic drugs.
• Together with other sympathomimetics, an undesired increase in effect may occur.
• Levodopa, L-thyroxine and alcohol may affect cardiovascular regulation
• MAO inhibitors and tricyclic antidepressants may increase the effect of salbutamol.
• halogenated anaesthetics can lead to severe cardiac arrhythmias

Side effects

The most common side effects are tremors, anxiety, headache, muscle cramps, dry mouth, and palpitations. Other symptoms may include tachycardia, cardiac arrhythmias, skin flushing, myocardial ischemia (rare), and sleep and behavioral disturbances. Rarely occurring but of importance are allergic reactions with paradoxical bronchospasm, urticaria (hives), angioedema, hypotension, and collapse. High doses or prolonged use may cause hypokalemia, which should be especially noted in patients with renal failure.

Toxicological Data

LD50 (rat, oral): 660 mg-kg-1