N Acetylcysteine
It is also used post-operatively, as a diagnostic aid, and in tracheotomy care. When paracetamol is taken in large quantities, a minor metabolite called N-acetyl-p-benzoquinone imine (NAPQI) builds up.
It is normally conjugated by glutathione, but when taken in excess, the body's glutathione reserves are not sufficient to inactivate the toxic NAPQI. This metabolite is then free to react with key hepatic enzymes, therefore damaging hepatocytes.
This may lead to severe liver damage and even death by fulminant liver failure.
For this indication, acetylcysteine acts to augment the glutathione reserves in the body and, together with glutathione, directly bind to toxic metabolites. Studies conducted by Baker and Dilger suggest that the prior pharmacokinetic studies of N-acetylcysteine did not include Acetylation as a reason for the low bioavailability of N-acetylcysteine.
In the research conducted by Baker, it was concluded that oral N-acetylcysteine was identical in bioavailability to Cysteine precursors. Repeated overdoses will cause the allergic reaction to progressively worsen.)
Several studies have found this anaphylaxis-like reaction to occur more often in people given IV acetylcysteine despite serum levels of paracetamol not high enough to be considered toxic.
In some countries, a specific intravenous formulation does not exist to treat paracetamol overdose. Some studies show that prior administration of acetylcysteine markedly decreases (90%) radiocontrast nephropathy, whereas others appear to cast doubt on its efficacy. Worth considering is the newest data published in two papers in the New England Journal of Medicine and the Journal of the American Medical Association.
liquefaction and decontamination of sputum, in preparation for diagnosis of tuberculosis.
Interstitial lung disease
Acetylcysteine is used in the treatment of interstitial lung disease to prevent disease progression.
Investigational
The following uses have not been well-established or investigated:
NAC has been shown to reduce the symptoms of both schizophrenia and bipolar disorder in two placebo controlled trials.
Evidence that NAC and other antioxidants can exert beneficial effects on pancreatic b-cell function in diabetes was published in a 1999 study. The authors conclude that a sufficient supply of antioxidants (NAC, vitamin C plus vitamin E, or both) may prevent or delay b-cell dysfunction in diabetes by providing protection against glucose toxicity.
NAC is undergoing clinical trials in the United States for the treatment of obsessive-compulsive disorder. It is thought to counteract the glutamate hyperactivity in OCD.
NAC has been shown to reduce cravings associated with chronic cocaine use in a study conducted at the Medical University of South Carolina
It may reduce the incidence of chronic obstructive pulmonary disease (COPD) exacerbations
In the treatment of AIDS, NAC has been shown to cause a "marked increase in immunological functions and plasma albumin concentrations" Albumin concentration are inversely correlated with muscle wasting (cachexia), a condition associated with AIDS.
An animal study indicates that acetylcysteine may decrease mortality associated with influenza
Animal studies suggest that NAC may help prevent noise-induced hearing loss.
A clinical trial to determine efficacy in preventing noise-induced sensorineural hearing loss in humans is currently (2006) being jointly conducted by the US Army and US Navy.
A human study of 262 primarily elderly individuals indicates that NAC may decrease influenza symptoms. In the study, 25% of virus-infected subjects NAC treatment developed a symptoms, whereas 79% in the placebo group developed symptoms.
It has been suggested that NAC may help sufferers of Samter's triad by increasing levels of glutathione allowing faster breakdown of salicylates, though there is no evidence that it is of benefit
There are claims that acetylcysteine taken together with vitamin C and B1 can be used to prevent and relieve symptoms of veisalgia (hangover following ethanol (alcohol) consumption). The claimed mechanism is through scavenging of acetaldehyde, a toxic intermediate in the metabolism of ethanol.
It has been shown to help women with PCOS (polycystic ovary syndrome) to reduce insulin problems and possibly improve fertility.
The thiol (sulfhydryl) group confers antioxidant effects and is able to reduce free radicals.
Possible toxicity
Researchers at the University of Virginia reported in 2007 study using very large doses in a mouse model that acetylcysteine, which is found in many bodybuilding supplements, could potentially cause damage to the heart and lungs. They found that acetylcysteine was metabolized to S-nitroso-N-acetylcysteine (SNOAC), which increased blood pressure in the lungs and right ventricle of the heart (pulmonary artery hypertension) in mice treated with acetylcysteine. The effect was similar to that observed following a 3-week exposure to an oxygen-deprived environment (chronic hypoxia).
The authors also found that SNOAC induced a hypoxia-like response in the expression of several important genes both in vitro and in vivo.
The implications of these findings for long-term treatment with acetylcysteine have not yet been investigated.