indication

For the treatment of asthma and chronic obstructive pulmonary disease (COPD).

pharmacology

Salmeterol is a long acting beta2-adrenoceptor agonist (LABA), usually only prescribed for severe persistent asthma following previous treatment with a short-acting beta agonist such as salbutamol and is prescribed concurrently with a corticosteroid, such as beclometasone. The primary noticable difference of salmeterol to salbutamol is that the duration of action lasts approximately 12 hours in comparison with 4-6 hours of salbutamol. When used regularly every day as presecribed, inhaled salmeterol decreases the number and severity of asthma attacks. However, it is not for use for relieving an asthma attack that has already started. Inhaled salmeterol works like other beta 2-agonists, causing bronchodilatation by relaxing the smooth muscle in the airway so as to treat the exacerbation of asthma. Salmeterol is similar in action to formoterol, however formoterol has been demonstrated to have a faster onset of action than salmeterol as a result of a lower lipophilicity, and has also been demonstrated to be more potent - a 12 µg dose of formoterol has been demonstrated to be equivalent to a 50 µg dose of salmeterol.

mechanism of action

Salmeterol's long, lipophilic side chain binds to exosites near beta(2)-receptors in the lungs and on bronchiolar smooth muscle, allowing the active portion of the molecule to remain at the receptor site, continually binding and releasing. Beta(2)-receptor stimulation in the lung causes relaxation of bronchial smooth muscle, bronchodilation, and increased bronchial airflow.

toxicity

Symptoms of overdose include angina (chest pain), dizziness, dry mouth, fatigue, flu-like symptoms, headache, heart irregularities, high or low blood pressure, high blood sugar, insomnia, muscle cramps, nausea, nervousness, rapid heartbeat, seizures, and tremor. By the oral route, no deaths occurred in rats at 1,000 mg/kg (approximately 81,000 times the maximum recommended daily inhalation dose in adults and approximately 38,000 times the maximum recommended daily inhalation dose in children on a mg/m² basis).

biotransformation

Hepatic, metabolized by hydroxylation via CYP3A4

absorption

Because of the small therapeutic dose, systemic levels of salmeterol are low or undetectable after inhalation of recommended doses.

half life

5.5 hours

drug interactions

Acebutolol: Antagonism

Atenolol: Antagonism

Bisoprolol: Antagonism

Carvedilol: Antagonism

Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. Concurrent use of salmeterol with strong inhibitors of CYP3A4 is not recommended according to salmeterol prescribing information.

Esmolol: Antagonism

Labetalol: Antagonism

Metoprolol: Antagonism

Nadolol: Antagonism

Oxprenolol: Antagonism

Pindolol: Antagonism

Propranolol: Antagonism

Quinupristin: This combination presents an increased risk of toxicity

Telithromycin: Telithromycin may reduce clearance of Salmeterol. Concomitant therapy is contraindicated.

Timolol: Antagonism

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor may increase the serum concentration of salmeterol by decreasing its metabolism. Consider alternate therapy.