Ventolin Expectorant Mechanism of Action

Bronchodilator + Expectorant.
Pharmacology: Pharmacodynamics: Mechanism of action: Salbutamol is a selective beta-₂ adrenoceptor agonist. At therapeutic doses it acts on the beta-₂ adrenoceptors of bronchial muscle.
Guaifenesin can make the viscous mucus of the respiratory pathway more fluid and therefore expectoration and reduces cough.
Pharmacodynamic Effects: Salbutamol is a selective beta₂-adrenoceptor agonist. At therapeutic doses it acts on the beta₂-adrenoceptors of bronchial muscle providing short acting (4 to 6 hour) bronchodilation in reversible airways obstruction.
Pharmacokinetics: Absorption: After oral administration, salbutamol is absorbed from the gastrointestinal tract and undergoes considerable first-pass metabolism to the phenolic sulfate. Both unchanged drug and conjugate are excreted primarily in the urine.
Guaifenesin is well-absorbed after oral administration. After the administration of 600 mg guaiphenesin in healthy adult volunteers the Cmax was approx 1.4 micrograms/ml with Tmax about 15 minutes after drug administration.
Distribution: The bioavailability of orally administered salbutamol is about 50%. Salbutamol is bound to plasma proteins to the extent of 10%.
Metabolism: 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-sulfate (phenolic sulfate) which is also excreted primarily in the urine.
Guaifenesin has a plasma half-life of approx 1 hour and was not detectable in the blood after 8 hours. Guaifenesin appears to undergo both oxidation and demethylation.
Elimination: The majority of a dose of salbutamol given intravenously, orally or by inhalation is excreted within 72 hours. The faeces are a minor route of excretion.
Guaifenesin is excreted in urine.
Toxicology: Non-clinical Information: In common with other potent selective beta-₂ receptor agonists, salbutamol has been shown to be teratogenic in mice when given subcutaneously. In a reproductive study, 9.3% of foetuses were found to have cleft palate, at 2.5 mg/kg, 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.
Reproduction studies in rats demonstrated no evidence of impaired fertility at oral doses of salbutamol up to 50 mg/kg.
Animal studies on guaifenesin to assess carcinogenicity, genotoxicity, or effects on fertility or embryo-fetal development have not been performed.