Mucocystein Mechanism of Action

Pharmacology: Acetylcysteine reduces the viscosity of mucus and other secretions, in vitro. It is thought to act by reducing disulfide bonds in proteins and altering their configuration to improve flow characteristics. It is readily converted to cysteine in vivo; and by stimulating hepatic glutathione synthesis, it effectively prevents acute acetaminophen-induced hepatotoxicity. By virtue of its free thiol group, acetylcysteine can form stable thiolates with heavy metals and has had limited use in the treatment of poisoning with these agents. As a nucleophile, it can protect against the effects of ionizing radiation and the toxicity of agents such as alkylating cytotoxic drugs and some halogenated hydrocarbons. Inorganic nitrates deplete vascular thiols, and this probably explains the development of tolerance to their hemodynamic effects. Acetylcysteine potentiates the vasodilator action of nitroglycerin and can reverse tolerance to nitrates.
Pharmacokinetics: Acetylcysteine is rapidly absorbed from the gastrointestinal tract and peak plasma concentrations occur about 0.5 to 1 hour after oral doses of 200 to 600 mg. Some studies indicate dose-dependent pharmacokinetics with peak concentrations, the time taken to reach peak concentrations, and bioavailability increasing with increasing doses. Acetylcysteine may be present in plasma as the parent compound or as various oxidized metabolites such as N-acetylcysteine, N,N-diacetylcysteine, and cysteine either free or bound to plasma proteins by labile disulfide bonds or as a fraction incorporated into protein peptide chains. In a study, about 50% was in a covalently protein-bound from 4 hours after a dose. Oral bioavailability is low and mean values have ranged from 4 to 10% depending on whether total acetylcysteine or just the reduced forms are measured. It has been suggested that acetylcysteine's low oral bioavailability may be due to metabolism in the gut wall and first-pass metabolism in the liver. Renal clearance may account for about 30% of total body clearance. On intravenous dosage, mean terminal half-lives have been calculated to be 1.95 and 5.58 hours for reduced and total acetylcysteine, respectively; the terminal half-life of total acetylcysteine was 6.25 hours after oral doses.