Acetylcysteine

Also known as

N-acetylcysteine

 

Common indications

1. As the antidote for paracetamol poisoning. 
2. To help prevent renal injury due to radiographic contrast material (contrast nephropathy). 
3. To reduce the viscosity of respiratory secretions (acting as a mucolytic).

 

Mechanisms of action

• In therapeutic doses, paracetamol is metabolised mainly by conjugation with glucuronic acid and sulfate. 
• A small amount is converted to N-acetyl-p-benzoquinone imine (NAPQI), which is hepatotoxic. 
• Normally, this is quickly detoxified by conjugation with glutathione. However, in paracetamol poisoning, the body’s supply of glutathione is overwhelmed and NAPQI is left free to cause liver damage. 
• Acetylcysteine works mainly by replenishing the body’s supply of glutathione. 
• Acetylcysteine also has antioxidant effects, which may contribute to its effect in preventing contrast nephropathy, although this is not completely understood. 
• If acetylcysteine is brought into contact with mucus, it causes it to liquefy. 
• For patients who have tenacious respiratory secretions (e.g. in bronchiectasis), this may aid sputum clearance.

 

Important adverse effects

• When administered intravenously in large doses for paracetamol poisoning, acetylcysteine can cause an anaphylactoid reaction. 
• This is similar to an anaphylactic reaction (presenting with nausea, tachycardia, rash and wheeze), but involves histamine release independent of IgE antibodies. 
• Therefore, once the reaction has settled (by stopping the acetylcysteine and giving an antihistamine ± a bronchodilator), it is usually safe to restart acetylcysteine, but at a lower rate of infusion. 
• When administered in nebulised form as a mucolytic, acetylcysteine may cause bronchospasm. 
• Therefore, a bronchodilator (e.g. salbutamol) should usually be given immediately beforehand.

 

Warnings

• History of an anaphylactoid reaction to acetylcysteine does not contraindicate its use in future, if it is required. 
• It is important that such reactions are not labelled as ‘allergic,’ which may lead to effective treatment for paracetamol poisoning being inappropriately denied. 
• However, it is essential to obtain specialist advice if there is any doubt.

 

Important interactions

• There are no significant adverse drug interactions with acetylcysteine.