Acetylcysteine

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acetylcysteine (A-seh-til-SIS-teh-een) is a drug usually used to reduce the thickness of mucus and ease its removal. It is also used to reverse the toxicity of high doses of acetaminophen. Also called N-acetyl-L-cysteine and N-acetylcysteine.

Information about Acetylcysteine

Acetylcysteine, also known as N-acetylcysteine (NAC), is a modified amino acid that is used as an antidote for acetaminophen overdose to prevent hepatic injury.

Liver safety of Acetylcysteine

Acetylcysteine is a hepatoprotective agent and has not been linked to significant serum enzyme elevations during therapy or to instances of clinically apparent acute liver injury.

Mechanism of action of Acetylcysteine

Acetylcysteine (a seet" il sis' teen) is a modified amino acid that is used to reverse the toxic effects of acetaminophen overdose and prevent acute liver failure. The amino acid cysteine has a thiol side chain that can undergo redox reactions and thus has antioxidant activity. Importantly, cysteine is required for synthesis of glutathione (a tripeptide of cysteine, glycine and glutamic acid) that is an essential intracellular antioxidant, providing protection against free radicals and other intracellular toxins including intermediates of drug metabolism.

Glutathione

Cysteine itself has a disagreeable odor and taste, while acetylated cysteine is more palatable and maintains the ability to support glutathione synthesis. Glutathione can become depleted in patients with malnutrition, chronic debilitating illnesses and chronic alcoholism, and becomes acutely depleted in patients with acetaminophen overdose leading to formation of toxic adducts of acetaminophen metabolites with essential intracellular molecules. Restoration of glutathione stores ameliorates the cell injury from acetaminophen. In multiple clinical trials, administration of acetylcysteine (also referred to as N-acetylcysteine or NAC) within 10 hours of an acetaminophen overdose effectively prevented serious liver injury. Subsequent studies suggested that administration even after 10 hours was partially effective and may also be beneficial in other, non-acetaminophen causes of acute liver failure, including drug induced liver injury.

FDA approval information for Acetylcysteine

Acetylcysteine also has mucolytic activity and was initially approved for use in humans in 1963 as Mucomyst, a solution for inhalation that helps to emulsify respiratory secretions in patients with pulmonary infections or chronic bronchitis.

Dosage and administration for Acetylcysteine

An oral form of acetylcysteine was approved for use as an acetaminophen antidote in 1978, and an intravenous formulation in 2004. Acetylcysteine is available as effervescent tablets of 500 and 2500 mg (Cetylev) for oral use and as a solution for injection in single dose vials of 200 mg/mL (Acetadote). The dose of acetylcysteine should be calculated based upon body weight and estimated time and acetaminophen ingestion. A nomogram (Rumack-Matthew Nomogram) to calculate the likelihood of liver injury form acetaminophen is available that plots acetaminophen plasma concentrations against time after ingestion that the sample was taken. It is typically given as a loading dose, followed by maintenance dosing every 4 hours for several days. Dosing recommendations are available in the product label and from the U.S. National Poison Center: 1-800-222-1222.

Side effects of Acetylcysteine

Side effects are generally dose related and can include disagreeable taste, diarrhea, nausea and vomiting from the oral formulation and mild-to-moderate hypersensitivity reactions (urticaria, rash, angioedema, wheezing) from the intravenous form. hypersensitivity reactions can generally be treated satisfactorily with antihistamines.


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