2 sources
Collated from PsychonautWiki, Pharmacology. Where sources differ (e.g. dosing), Compare shows them side by side.
Also known as N-AcetylcysteinePW
Oral
Route dataPsychonautWiki
| Threshold | Light | Common | Strong | Heavy |
|---|---|---|---|---|
| 100 mg | 400–600 mg | 600–1000 mg | 1000–1500 mg | 1500 mg+ |
| Onset | 20–60 minutes |
|---|---|
| Total | 3–6 hours |
🧬 Receptor activityPH
Mechanism of actionPH
A number of possible mechanisms for the mucolytic activity of acetylcysteine have been proposed. Acetylcysteine's sulfhydryl groups may hydrolize disulfide bonds within mucin, breaking down the oligomers, and making the mucin less viscous. Acetylcysteine has also been shown to reduce mucin secretion in rat models. It is an antioxidant in its own right but is also deacetylated to cysteine, which participates in the synthesis of the antioxidant glutathione. The antioxidant activity may also alter intracellular redox reactions, decreasing phosphorylation of EGFR and MAPK, which decrease transcription of the gene MUC5AC which produces mucin. In the case of acetaminophen overdoses, a portion of the drug is metabolized by CYP2E1 to form the potentially toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). The amount of NAPQI produced in an overdose saturates and depletes glutathione stores. The free NAPQI promiscuously binds to proteins in hepatocytes, leading to cellular necrosis. Acetylcysteine can directly conjugate NAPQI or provide cysteine for glutathione production and NAPQI conjugation.
Acetylcysteine exerts its mucolytic action through its free sulfhydryl group, which opens the disulfide bonds and lower the viscosity of the mucus. 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.
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 directly inactivate the metabolite.
PharmacodynamicsPH
Acetylcysteine is indicated for mucolytic therapy and in the management of acetaminophen overdose. It has a short duration of action as it is given every 1-8 hours depending on route of administration, and has a wide therapeutic window. Patients should be counselled regarding diluting oral solutions in cola for taste masking, the risk of hypersensitivity, and the risk of upper gastrointestinal hemorrhage.
Pharmacokinetics
Half-lifePH
The mean terminal half life of acetylcysteine in adults is 5.6 hours and in pre-term neonates is 11 hours.
Following IV administration of acetylcysteine, mean elimination half lives of 5.6 and 11 hours have been reported in adults and in neonates, respectively. The mean elimination half life was increased by 80% in patients with severe liver damage (i.e., alcoholic cirrhosis (Child-Pugh score of 7-13) or primary and/or secondary biliary cirrhosis (Child-Pugh score of 5-11)).
AbsorptionPH
An 11 g dose in the form of an effervescent tablet for solution reaches a mean Cmax of 26.5 µg/mL, with a Tmax of 2 hours, and an AUC of 186 µg\*h/mL.
An oral dose of radiolabelled acetylcysteine is 13-38% recovered in the urine in the first 24 hours, while 3% is recovered in the feces.
The volume of distribution of acetylcysteine is 0.47 L/kg.
Acetylcysteine has a mean clearance of 0.11 L/hr/kg.
Following oral administration (e.g., when used as an antidote for acetaminophen overdosage), acetylcysteine is absorbed from the GI tract.
Oral acetylcysteine is rapidly absorbed, but the bioavailability is low (10-30%) due to significant first-pass metabolism. Intact acetylcysteine has a relatively small volume of distribution (0.5 L/kg). Serum concentrations after intravenous administration of an initial loading dose of 150 mg/kg over 15 minutes are about 500 mg/L. A steady state plasma concentration of 35 mg/L (10-90 mg/L) was reached in about 12 hours following the loading dose with a continuous infusion of 50 mg/kg over 4 hours and 100 mg/kg over the next 16 hours.
MetabolismPH
Acetylcysteine can be deacetylated by aminoacylase 1 or other undefined deacetylases before undergoing the normal metabolism of cysteine.
Following oral inhalation or intratracheal instillation, most of the administered drug appears to participate in the sulfhydryl-disulfide reaction; the remainder is absorbed from the pulmonary epithelium, deacetylated by the liver to cysteine, and subsequently metabolized.
Acetylcysteine undergoes rapid deacetylation in vivo to yield cysteine or oxidation to yield diacetylcystine.
Protein bindingPH
Acetylcysteine is 66-97% protein bound in serum, usually to albumin.
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External links
Fact-sheets from PsychonautWiki. Harm-reduction reference only — not medical advice.