Browsing Pathways

Acetylcysteine is a medication that can be used as a mucolytic in patients with certain lung conditions and as an antidote for acetaminophen overdose. 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 Acetaminophen (APAP) is metabolized in 3 main ways: glucuronidation, sulfation and oxidation. Glucuronidation and sulfation of acetaminophen produces non-toxic acetaminophen conjugates (APAP-glucuronide and APAP-sulfate). 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. Acetylcysteine can directly conjugate NAPQI or provide cysteine for glutathione production and NAPQI conjugation. Acetylcysteine can also provide sulfur for the sulfate conjugation of acetaminophen. Therefore, acetylcysteine aims to prevent formation of toxic NAPQI and detoxify NAPQI that has already been formed. NAPQI can cause mitochondrial dysfunction and leading to necrotic cell death. Acetylcysteine may prevent cellular toxicity by increasing oxygen delivery to tissues, increasing mitochondrial ATP production, and altering the microvascular tone to increase the blood flow and oxygen delivery to the liver and other vital organs. Oral NAC may cause nausea, vomiting, diarrhea, flatus, and gastroesophageal reflux. IV NAC can cause rate related anaphylactoid reactions in up to 18% of patients, which is not an issue with the oral route. Most of the anaphylactoid reactions are mild (6%) or moderate (10%) with severe reactions like bronchospasm and hypotension rare at 1%.