Ventolin Mechanism of Action

Pharmacotherapeutic group: Selective beta₂-adrenoceptor agonists. ATC Code: R03CC02.
Pharmacology: Pharmacodynamics: Salbutamol is a selective beta₂-adrenoreceptor agonist. At therapeutic doses, it acts on the beta₂-adrenoreceptors of bronchial muscle providing short-acting (4 to 6 hours) bronchodilation [with a fast onset within 5 minutes (for Evohaler)] in reversible airways obstruction.
Clinical Studies: Evohaler: Special Patient Populations: Children <4 years of age: Paediatric clinical studies conducted at the recommended dose (SB020001, SB030001, SB030002), in patients <4 years with bronchospasm associated with reversible obstructive airways disease, show that the Evohaler has a safety profile comparable to that in children ≥4 years, adolescents and adults.
Pharmacokinetics: Syrup/Infusion: Salbutamol administered intravenously has a half-life of 4 to 6 hours and is cleared partly renally and partly by metabolism to the inactive 4'-O-sulphate (phenolic sulphate) which is also excreted primarily in the urine. The faeces are a minor route of excretion. The majority of a dose of salbutamol given intravenously, orally or by inhalation is excreted within 72 hours. Salbutamol is bound to plasma proteins to the extent of 10%.
Syrup: After oral administration, salbutamol is absorbed from the gastrointestinal tract and undergoes considerable first-pass metabolism to the phenolic sulphate. Both unchanged drug and conjugate are excreted primarily in the urine. The bioavailability of orally administered salbutamol is about 50%.
Evohaler/Respirator Solution/Nebule: Absorption: After administration by the inhaled route, between 10 and 20% of the dose reaches the lower airways. 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.
Distribution: Salbutamol is bound to plasma proteins to the extent of 10%.
Metabolism: On reaching the systemic circulation, salbutamol becomes accessible to hepatic metabolism and is excreted, primarily in the urine, as unchanged drug and as the phenolic sulphate.
The swallowed portion of an inhaled dose is absorbed from the gastrointestinal tract and undergoes considerable first-pass metabolism to the phenolic sulphate. Both unchanged drug and conjugate are excreted primarily in the urine.
Elimination: Salbutamol administered intravenously has a half-life of four (4) to six (6) hours and is cleared partly renally and partly by metabolism to the inactive 4'-O-sulphate (phenolic sulphate) which is also excreted primarily in the urine. The faeces are a minor route of excretion. The majority of a dose of salbutamol given intravenously, orally or by inhalation is excreted within 72 hours.
Toxicology: Preclinical Safety Data/Non-Clinical Information: In common with other potent selective beta₂-receptor agonists, salbutamol has been shown to be teratogenic in mice when given subcutaneously. In a reproductive study, 9.3% of the foetuses were found to have cleft palate, at 2.5 mg/kg, four (4) times the maximum human oral dose. In rats, treatment at the levels of 0.5, 2.32, 10.75 and 50 mg/kg/day orally throughout pregnancy resulted in no significant foetal abnormalities. The only toxic effect was an increase in neonatal mortality at the highest dose level as the result of lack of maternal care. A reproductive study in rabbits revealed cranial malformations in 37% of foetuses at 50 mg/kg/day, 78 times the maximum human oral dose.
In an oral fertility and general reproductive performance study in rats at doses of 2 and 50 mg/kg/day, with the exception of a reduction in number of weanlings surviving to day 21 postpartum at 50 mg/kg/day, there were no adverse reactions/effects on fertility, embryofetal development, litter size, birth weight or growth rate.
Syrup: Reproductive studies in the rabbit at doses of 50 mg/kg/day orally (i.e much higher than the normal human dose) have shown foetuses with treatment related changes; these included open eyelids (ablepharia), secondary palate clefts (palatoschisis), changes in ossification of the frontal bones of the cranium (cranioschisis) and limb flexure.
Evohaler: HFA 134a has been shown to be non-toxic at very high vapour concentrations, far in excess of those likely to be experienced by patients, in a wide range of animal species exposed daily for periods of two years.