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Acetylcysteine
- indication:Used mainly as a mucolytic and in the management of paracetamol (acetaminophen) overdose.
- pharmacologypharmacology:
- mechanism: Acetylcysteine may protect against acetaminophen overdose-induced hepatotoxicity by maintaining or restoring hepatic concentrations of glutathione. Glutathione is required to inactivate an intermediate metabolite of acetaminophen that is thought to be hepatotoxic. In acetaminophen overdose, excessive quantities of this metabolite are formed because the primary metabolic (glucuronide and sulfate conjugation) pathways become saturated. Acetylcysteine may act by reducing the metabolite to the parent compound and/or by providing sulfhydryl for conjugation of the metabolite. Experimental evidence also suggests that a sulfhydryl-containing compound such as acetylcysteine may also directly inactivate the metabolite. Inhalation - Acetylcysteine exerts its mucolytic action through its free sulfhydryl group, which opens the disulfide bonds and lowers mucus viscosity. This action increases with increasing pH and is most significant at pH 7 to 9. The mucolytic action of acetylcysteine is not affected by the presence of DNA.
- toxicity: Single intravenous doses of acetylcysteine at 1000 mg/kg in mice, 2445 mg/kg in rats, 1500 mg/kg in guinea pigs, 1200 mg/kg in rabbits and 500 mg/kg in dogs were lethal. Symptoms of acute toxicity were ataxia, hypoactivity, labored respiration, cyanosis, loss of righting reflex and convulsions.
- absorprion: Bioavailability is 6–10% following oral administration and less than 3% following topical administration.
- halflife: 5.6 hours (adults), 11 hours (neonates)
- roouteelimination:
- volumedistribution:
- clearance: