Adverse effects for inhalational formulations of acetylcysteine include nausea, vomiting, stomatitis, fever, rhinorrhea, drowsiness, clamminess, chest tightness, and bronchoconstriction. Although infrequent, bronchospasm has been reported to occur unpredictably in some patients.Adverse effects for oral formulations of acetylcysteine have been reported to include nausea, vomiting, rash, and fever.Large doses in a mouse model showed that acetylcysteine 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. The dose used by Palmer and colleagues was dramatically higher than that used in humans, the equivalent of about 20 grams per day. Nonetheless, positive effects on age-diminished control of respiration (the hypoxic ventilatory response) have been observed previously in human subjects at more moderate doses.Although N-acetylcysteine prevented liver damage in mice when taken before alcohol, when taken four hours after alcohol it made liver damage worse in a dose-dependent fashion. Pharmacology
Pharmacodynamics
Acetylcysteine serves as a prodrug to L-cysteine, a precursor to the biologic antioxidant glutathione. Hence administration of acetylcysteine replenishes glutathione stores.
Research
While many antioxidants have been researched to treat a large number of diseases by reducing the negative effect of oxidative stress, acetylcysteine is one of the few that has yielded promising results, and is currently already approved for the treatment of paracetamol overdose. In mouse mdx models of Duchennes muscular dystrophy, treatment with 1–2% acetylcysteine in drinking water significantly reduces muscle damage and improves strength. It is being studied in conditions such as autism, where cysteine and related sulfur amino acids may be depleted due to multifactorial dysfunction of methylation pathways involved in methionine catabolism. Animal studies have also demonstrated its efficacy in reducing the damage associated with moderate traumatic brain or spinal injury, and also ischaemia-induced brain injury. In particular, it has been demonstrated to reduce neuronal losses and to improve cognitive and neurological outcomes associated with these traumatic events. It has been suggested that acetylcysteine may help people with Samters triad by increasing levels of glutathione allowing faster breakdown of salicylates, although there is no evidence that it is of benefit. Small studies have shown acetylcysteine to be of benefit to people with blepharitis. It has been shown to reduce ocular soreness caused by Sjögrens syndrome. It has been shown that N-acetylcysteine may protect the human cochlea from subclinical hearing loss caused by loud noises such as impulse noise. In animal models, it reduced age-related hearing loss. It has been shown effective in the treatment of Unverricht-Lundborg disease in an open trial in four patients.