Pneumotyl Mechanism of Action

Pharmacotherapeutic group: mucolytics. ATC code: R05CB01.
Pharmacology: Pharmacodynamics: Acetylcysteine is a derivative of the amino acid cysteine. The efficacy of acetylcysteine is secretolytic and secretomotoric in the area of the respiratory tract. It is discussed that it splits off the interconnecting disulphide bonds between the mycopolysaccharide chains and that it has depolymerizing effect on DNA-chains (in purulent mucus). Due to these mechanism, the viscosity of mucus should be reduced.
An alternative mechanism of acetylcysteine is meant to be based on the capacity of its reactive SH group to bind chemical radicals and detoxify them in this way.
Furthermore, acetylcysteine contributes to an increase in glutathione synthesis, which is important for the detoxifcation of noxae. This provides the explanation for its antidotal effect in paracetamol intoxication.
Pharmacokinetics: Absorption: Following oral administration, acetylcysteine is rapidly and almost completely absorbed and metabolized in the liver to cysteine, the pharmacologically active metabolite, as well as diacetylcystine, cystine and further mixed disulphides.
Distribution: Due to high first-pass effect, the bioavailability of orally administered acetylcysteine is very low (approx. 10%). In humans, the maximum plasma concentrations are achieved after 1-3 hours with the maximum plasma concentration of the metabolite cysteine in the range of approx. 2 μmol/L. The protein binding of acetylcysteine was determined to be about 50%.
Biotransformation: Acetylcysteine and its metabolites occur in three different forms in the organism: partially in free form, partially bound to proteins via labile disulphide bonds and partially as incorporated amino acid. Acetylcysteine is excreted almost exclusively in the form of inactive metabolites (inorganic sulphates, diacetylcysteine) via the kidneys. The plasma half-life of acetylcysteine is approximately 1 hour and is mainly determined by the rapid hepatic biotransformation. Impaired hepatic function therefore leads to prolonged plasma half-lives up of up to 8 hours.
Elimination: Pharmacokinetic studies with intravenous administration of acetylcysteine revealed a distribution volume of 0.47 L/kg (in total) or 0.59 L/kg (reduced); the plasma clearance was determined to be 0.11 L/h/kg (in total) and 0.84 L/h/kg (reduced), respectively.
The elimination half-life after intravenous administration is 30-40 minutes while excretion follows three-phase kinetics (alpha, beta, and terminal gamma phase).
Acetylcysteine crosses the placenta and is detected in cord blood. No information is available regarding excretion into breast milk.
No knowledge is available concerning the behaviour of acetylcysteine at the blood-brain barrier in humans.
Toxicology: Preclinical safety data: Acute toxicity: The acute toxicity in animal experiments is low. For the treatment of overdoses, see Overdosage.
Chronic toxicity: Studies in various animal species (rat, dog) with duration of up to one year did not show any pathological alterations.
Tumorigenic and mutagenic potential: No mutagenic effects of acetylcysteine are to be expected. An in vitro test was negative.
No studies of a tumorigenic potential of acetylcysteine have been carried out.
Reproductive toxicology: No malformations were detected in embryotoxicity studies in rabbits and rats. Studies of fertility and perinatal or postnatal toxicity were negative.
Acetylcysteine passes the placenta in rats and was detected in amniotic fluid. The concentration of the metabolite L-cysteine is above the maternal plasma concentration in placenta and foetus for up to 8 hours after oral administration.