Hidonac Mechanism of Action

Pharmacology: Mechanism of Action: In toxic pathology, N-acetylcysteine (NAC) exerts its effects on multiple mechanisms. The best-known effect regards its action as precursor of glutathione. N-acetylcysteine acts as precursor of cysteine needed for GSH synthesis (by deacetylation with formulation of free cysteine and by reduction of plasma cystine to cysteine with formation of oxidized NAC); increases the total amount of glutathione (GSH + GSSG), if depleted and facilitates conversion of glutathione from the oxidized form (GSSG) to the biologically active, reduced form (GSH).
Furthermore, in paracetamol poisoning, NAC acts by: Reducing the reactive metabolites (eg, NAPQI) to atoxic compounds; conjugating itself directly with the said metabolites; in a specific manner, as antioxidant agent and as precursor of sulfates necessary for the metabolism of paracetamol by sulfation.
These mechanisms justify the need of early treatment (within 10 hrs) in paracetamol poisoning, to prevent or minimize with maximum efficacy the occurrence of hepatic damage.
Likewise, important is the capacity of NAC to improve peripheral utilization of O₂, increasing delivery and peripheral extraction. In intoxications with severe hepatic insufficiency, this makes it possible to prevent or correct tissular hypoxia, which represents one of the main factors responsible for the genesis of multiple organ insufficiency. This effect is evident even in the event of delayed treatment.
Pharmacokinetics: After oral administration of 100 mg/kg, NAC is completely absorbed and undergoes rapid and extensive metabolism in the intestinal wall and liver. The elimination half-life was 5-6 hrs after IV administration. N-acetylcysteine is mainly excreted in the urine. The main urinary metabolite of NAC is the inorganic sulfate. However, during the acute paracetamol intoxication, the urinary metabolite of NAC may differ, being at least partially represented by complexation products of NAC or its derivatives with the toxin.
Teratogenicity: Evaluation of experimental animal studies does not indicate teratogenic effects.