![]() ![]() NAC by itself also binds to the toxic metabolites and scavenges free radicals. NAC repletes glutathione reserves by providing cysteine, which is an essential precursor in glutathione production. In APAP overdose, glucuronidation and sulfation pathways are saturated, and the CYP450 pathway takes more significance, producing more toxic metabolites that deplete the glutathione reserves, leading to their accumulation and hence tissue injury by binding to cellular macromolecules. Glutathione in the liver can normally detoxify these minuscule quantities of NAPQI and prevent tissue damage. APAP metabolism in therapeutic dosing primarily occurs through glucuronidation and sulfation(>90%), with less than 5% being oxidized by CYP450 isoform (predominately CYP2E1) to produce a toxic metabolite called N-acetyl-p-benzoquinone imine (NAPQI), which is the precursor to cellular injury. NAC exerts its therapeutic effect in APAP overdose through several mechanisms. There are case reports of NAC helping with improving neurological status in patients comatose with carbon monoxide poisoning. Other potential applications, but still in the experimental stage, include NAC being used as an antineoplastic agent as well as for psychiatric conditions like schizophrenia, bipolar disorder, depression, gastrointestinal conditions like hepatorenal syndrome, Helicobacter pylori infections, necrotizing enterocolitis, critical care patients like lung injury, cardiac injury, multiorgan dysfunction, sepsis and hematological conditions like sickle cell disease. NAC may also have therapeutic application in chronic valproate hepatotoxicity and acute pennyroyal or clove oil ingestion-induced hepatotoxicity There are animal and human tissue studies showing its use in decreasing cisplatin-induced nephrotoxicity, although clinical evidence is minimal. NAC has also been investigated for use in xenobiotics with free radical or reactive metabolite toxicity. There is good evidence to show it is of benefits in acute exposures to cyclopeptide containing mushrooms and carbon tetrachloride. Off-label indications include acute hepatic failure, prevention of contrast-induced nephropathy, and topical treatment of keratoconjunctivitis sicca. It is also approved for use in conditions with abnormal, viscid or inspissated mucous secretions such as pneumonia, bronchitis, tracheobronchitis, cystic fibrosis, tracheostomy patients, postoperative pulmonary complications, posttraumatic chest conditions and before diagnostic bronchoscopy to help with mucous plugging. NAC has Federal and Drug Administration (FDA) approval for the treatment of potentially hepatotoxic doses of acetaminophen (APAP), and it is almost 100% effective if given within 8 hours post-ingestion. N-acetylcysteine (NAC) is the mainstay of therapy for acetaminophen toxicity. This activity outlines the indications, mechanism of action, methods of administration, important adverse effects, contraindications, monitoring, and toxicity of NAC, so providers can direct patient therapy to optimal outcomes where NAC is indicated. Off-label indications include acute hepatic failure, prevention of contrast-induced nephropathy and topical treatment of keratoconjunctivitis sicca. ![]() It is also approved for use in conditions with abnormal, viscid or inspissated mucous secretions such as pneumonia, bronchitis, tracheobronchitis, cystic fibrosis, tracheostomy patients, postoperative pulmonary complications, posttraumatic chest conditions and before diagnostic bronchoscopy to help with mucous plugging. NAC has FDA approval for the treatment of potentially hepatotoxic doses of acetaminophen (APAP), and it is almost 100% effective if given within 8 hours post-ingestion. ![]()
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