Buventol Easyhaler Mechanism of Action

Pharmacotherapeutic group: Selective beta₂-adrenoreceptor agonists. ATC code: R03AC02.
PHARMACOLOGY: Pharmacodynamics: The pharmacologic effects of salbutamol are at least in part attributable to stimulation through beta-adrenergic receptors of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3', 5'-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels are associated with relaxation of bronchial smooth muscle. Bronchial effects of inhaled salbutamol can be detected after few minutes and duration of action is normally 4-6 hours.
Like other beta₂-adrenoceptor agonists also salbutamol has cardiovascular effects in some patients as measured by changes in pulse rate, blood pressure, symptoms and ECG changes. These effects can especially be detected after oral and intravenous administration of salbutamol. In addition, salbutamol has some metabolic effects. Especially intravenous and nebulized salbutamol decreases serum potassium concentrations although the effect is generally mild and transient.
Pharmacokinetics: After administration of salbutamol by the inhaled route between 10 and 25% of the dose reaches the lung. The remainder is retained in the delivery system or is deposited in the oropharynx from where it is swallowed. The fraction deposited in the airways is absorbed into the pulmonary tissues and circulation, but is not metabolised by the lung. On reaching the systemic circulation it becomes accessible to hepatic metabolism and is excreted primarily in the urine. The swallowed portion of an inhaled dose is absorbed from the gastrointestinal tract and undergoes considerable first-pass metabolism. Both unchanged drug and conjugate are excreted primarily in the urine. The elimination half-life of salbutamol is 2.7 to 5.5 hours after oral and inhaled administration.
Toxicology: Preclinical safety data: Acute toxicity of salbutamol is low in the mouse, rat and dog. LD50 values in these species have exceeded several thousand fold the intended human therapeutic doses. Reported findings in repeated dose studies such as tachycardia, increases in heart weights and hypertrophy of muscle fibres are common to all potent selective beta₂-agonists and are an expression of excessive beta-stimulant action. Cleft palate has been reported in mice but not in rats or rabbits after subcutaneous administration. Salbutamol is not mutagenic. Mesovarian leiomyomas, benign tumours of smooth muscle, occur particularly in Sprague-Dawley rats, but not in other species.