Article: Acetylcysteine

Acetylcysteine
Systematic (IUPAC) name
(R)-2-acetamido-3-mercaptopropanoic acid
Identifiers
CAS number	616-91-1
ATC code	R05CB01 S01XA08 V03AB23
PubChem	12035
DrugBank	n/a
Chemical data
Formula	C5H9NO3S
Mol. weight	163.19
Pharmacokinetic data
Bioavailability	6–10% (oral) <3% (topical)
Metabolism	hepatic
Half life	5.6 hours (adults) 11 hours (neonates)
Excretion	renal
Therapeutic considerations
Pregnancy cat.	B2 (Aus)
Legal status	Schedule 4 (Aus) OTC or Rx (U.S.)
Routes	inhalation, IV, oral

Acetylcysteine (rINN) (IPA: [ˌæsɛtlˈsɪstin, əˌsɛtl-, ˌæsətaɪl-]), also known as N-acetylcysteine (abbreviated NAC), is a pharmacological agent used mainly as a mucolytic and in the management of paracetamol overdose. For these indications, acetylcysteine is available under the trade names Mucomyst (Bristol-Myers Squibb) and Parvolex (GSK).

Dosage forms

Acetylcysteine is available in different dosage forms for different indications:

• Solution for inhalation (Mucomyst, Mucosil) – inhaled for mucolytic therapy or ingested for nephroprotective effect
• IV injection (Parvolex) – treatment of paracetamol overdose
• Oral solution – various indications

The IV injection and inhalation preparations are generally prescription only, while oral solution is available over the counter in many countries.

Chemistry

Acetylcysteine is the N-acetyl derivative of the amino acid L-cysteine, and is a precursor in the formation of the antioxidant glutathione in the body. The thiol (sulfhydryl) group confers antioxidant effects and is able to reduce free radicals.

Clinical use

Mucolytic therapy

Inhaled acetylcysteine is indicated for mucolytic ("mucus dissolving") therapy as an adjuvant in respiratory conditions with excessive and/or thick mucus production. Such conditions include: emphysema, bronchitis, tuberculosis, bronchiectasis, amyloidosis, pneumonia. It is also used post-operatively, as a diagnostic aid, and in tracheostomy care. It is considered ineffective in cystic fibrosis (Rossi, 2006). Oral acetylcysteine may also be used as a mucolytic in less serious cases.

For this indication, acetylcysteine acts to reduce mucus viscosity by splitting disulfide bonds linking proteins present in the mucus (mucoproteins).

Paracetamol overdose

Intravenous acetylcysteine is indicated for the treatment of paracetamol (acetaminophen) overdose. Oral acetylcysteine for this indication is uncommon as it is poorly tolerated owing to the high doses required (due to poor oral bioavailability), unpleasant taste/odour and adverse drug reactions (particularly nausea and vomiting).

For this indication, acetylcysteine acts to augment glutathione reserves (depleted by toxic paracetamol metabolites) in the body and, together with glutathione to directly bind to toxic metabolites. These actions serve to protect hepatocytes in the liver from toxicity due to paracetamol overdose.

Nephroprotective agent

Oral acetylcysteine is used for the prevention of radiocontrast-induced nephropathy (a form of acute renal failure). Some studies show that prior administration of acetylcysteine markedly decreases (90%) radiocontrast nephropathy (Tepel et al 2000), while others appear to cast doubt on its efficacy (Hoffman et al., 2004; Miner et al., 2004) Nevertheless, acetylcysteine continues to be commonly used in individuals with renal impairment to prevent the precipitation of acute renal failure.

Other uses

The following uses have not been well-established or investigated:

• It may reduce the incidence of chronic obstructive pulmonary disease (COPD) exacerbations (Pela et al., 1999)
• It has been proposed as a supplement for patients with AIDS, who generally have decreased glutathione levels. However, it does not appear to be effective in restoring glutathione levels (Witschi et al., 1995).
• An animal study indicates that acetylcysteine may decrease mortality associated with influenza (Ungheri et al., 2000)
• Animal studies suggest that NAC may help prevent noise-induced hearing loss (Kopke et al., 2005)
• 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 (Bachert et al., 2003).
• 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.