Ventolin Expectorant Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Salbutamol is a selective beta₂-adrenoceptor agonist. At therapeutic doses it acts on the beta₂-adrenoceptors of bronchial muscle.
Guaifenesin can make the viscous mucus of the respiratory pathway more fluid and therefore facilitates 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 guaifenesin in healthy adult volunteers the C_max was approx 1.4 micrograms/mL with T_max 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 beta₂-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.
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 post partum at 50 mg/kg/day, there were no adverse effects on fertility, embryofetal development, litter size, birth weight or growth rate.
Animal studies on guaifenesin to assess carcinogenicity, genotoxicity, or effects on fertility or embryo-fetal development have not been performed.