Fluimucil Mechanism of Action

Pharmacology: Pharmacodynamics: Acetylcysteine, active ingredient of FLUIMUCIL, exerts an intensive mucolytic-fluidifying action on the mucous and mucopurulent secretions by depolymerizing the mucoproteic complexes and the nucleic acids which confer viscosity to the vitreous and purulent component of the sputum and other secretions.
Furthermore, acetylcysteine exerts a direct antioxidant action, having a free thiol (-SH) nucleophilic group which is able to interact directly with the electrophilic group of the oxidant radicals. Of particular interest is the recent finding that acetylcysteine protects α1-antitrypsin enzyme inhibiting elastase from the inactivation by hypochlorous acid (HOCl), a powerful oxidant agent produced by the myeloperoxidase enzyme of activated phagocytes.
These features make Acetylcysteine (Fluimucil) particularly suitable for the treatment of acute and chronic affections of the respiratory system, characterized by thick, viscous mucous and mucopurulent secretions. In addition, due to its molecular structure, acetylcysteine can easily cross the cellular membranes. Inside the cell, acetylcysteine is deacetylated to L-cysteine, an amino acid indispensable for the glutathione synthesis (GSH).
GSH is a highly reactive tripeptide found ubiquitously in the various tissues of animal and is essential for the maintenance of functional capacity as well as cellular morphological integrity. It represents the most important protective endocellular mechanism against oxidant radicals, either of external or internal nature, as well as toward numerous cytotoxic substances.
Acetylcysteine plays a role of primary importance in the maintenance of adequate GSH levels contributing to the cellular protection from harmful agents which, through progressive GSH depletion, would be able to express their cytotoxic action as in the case of paracetamol poisoning.
Due to this mechanism of action, acetylcysteine is also indicated as a specific antidote in paracetamol poisoning and in the course of treatment of cyclophosphamide-induced hemorrhagic cystitis, in the latter case, it provides the -SH groups necessary to inactivate acrolein, a toxic metabolite that affects the urinary mucosa, whilst not interfering with chemotherapy.
Pharmacokinetics: Absorption: In humans, acetylcysteine is completely-absorbed after oral administration. Because of the gut wall metabolism and first pass effect, the bioavailability of acetylcysteine taken orally is very low (approximately 10%). No differences were reported for the various pharmaceutical forms. In patients with various respiratory or cardiac diseases, the maximum plasma concentration is obtained between two and three hours after administration and the levels remained high over a period of 24 hours.
Distribution: Acetylcysteine is distributed both in the non-metabolized (20%) and the metabolized (active) (80%) form, and can mainly be found in the liver, kidneys, lungs, and bronchial secretions. The volume of distribution of acetylcysteine ranges from 0.33 to 0.47 L/kg. Protein binding is about 50% four hours after the dose and decreases to 20% at 12 hours.
Biotransformation: Acetylcysteine undergoes rapid and extensive metabolism in the gut wall and liver following oral administration. The resulting compound, cysteine, is considered to be an active metabolite. Following this stage of transformation, acetylcysteine and cysteine share the same metabolic route.
Elimination: Renal clearance may account for about 30% of the total body clearance. Following oral administration the terminal half-life of total acetylcysteine is 6.25 (4.59-10.6).