Acetylcysteine paracetamol overdose

Paracetamol overdose is most likely to cause hepatic necrosis and to a lesser extent renal necrosis. Hepatic necrosis is maximal within 3-4 hours of ingestion and may lead to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema and death. Acetylcysteine tends to protect the liver if given within 10-12 hours of paracetamol poisoning. The maximum adult dose of paracetamol is 4 g in 24 hours. 

Although the investigation of the mechanism underlying paracetamol hepatotoxicity has been of intrinsic toxicological interest, there has also been a particularly significant benefit that has arisen from this work. This is the development of an antidote that is now successfully used for the treatment of paracetamol overdose. The antidote now most commonly used is N-acetylcysteine, although methionine is also used in some cases, as it can be given orally. There are various mechanisms by which N-a cetyl cysteine may act ... 

Acetylcysteine is given as a glutathione precursor in paracetamol overdose and in many other liver failures, including septic shock. 

Despite case reports of hepatotoxicity in patients taking enzyme inducers and paracetamol concomitantly, there is currently no good evidence that the interactions are clinically significant when recommended doses of paracetamol are used [5]. However, because of the theoretical basis and the potentially severe outcome, patients taking enzyme-inducing drugs are treated with N-acetylcysteine at a reduced threshold in the event of paracetamol overdose. 

Acetylcysteine, a mycolytic agent that also is used as an antidote for paracetamol overdose, is available as an effervescent tablet. 

Acetylcysteine (A -acetylcysteine) is used as a mucolytic and to treat paracetamol overdose. 

Adding antidotes to oral formulations Because restricting the packet size cannot completely resolve the problem of paracetamol overdose, alternative measures have been proposed (SEDA-22, 114). Because of the beneficial effect of acetylcysteine in paracetamol overdose, it has been suggested that toxicity caused by paracetamol overdoses, whether intentional or not, could... 

Acetylcysteine is usually given intravenously, but a 20-hour treatment protocol for acute paracetamol overdose using oral acetylcysteine has also been proposed... 

However, if paracetamol is taken in overdose, the levels of quinoneimine exceed the ability of glutathione to convert it back to paracetamol and toxicity to the liver results. In some cases, if treatment is not initiated in time, severe toxicity results, leading to death by acute liver failure. Treatment of paracetamol overdose is by administration of N-acetylcysteine (Figure 5.8). This compound (the acetyl derivative of the essential amino acid cysteine) functions as an alternative source of thiol (—SH) groups, which act in a similar manner to glutathione to detoxify the quinoneimine. 

In substantial overdose, severe, life-threatening liver damage is likely to occur due to excessive production of a toxic metabolite. There is an antidote to paracetamol overdose (acetylcysteine) and provided it is given within eight hours a complete recovery can be made. In the liver, acetylcysteine is converted to glutathione, which forms a harmless conjugate with paracetamol (see Table 2.2, page 22). 

It is still prudent to consider patients who are alcoholics as being at high risk of hepatotoxicity after a paracetamol overdose, and to treat them with acetylcysteine. Some workers have questioned the use of a lower plasma-paracetamol concentration threshold for the treatment of paracetamol poisoning in alcoholics, but most advocate treatment at the lower threshold. Possible malnutrition and fasting in these patients would further support the need for such treatment. ... 

Activated charcoal may be given as first aid if the patient presents within an hour of ingestion. Antidotal treatment is almost universally effective if administered within 6 hours of overdose. The serum paracetamol concentration measured between 4 and 16 hours determines whether antidotal treatment with acetylcysteine is required, but if a significant overdose has been taken and no result is available by 6 hours after overdose, antidote should be... 

Owing to the theoretical risk of greater NAPQI formation when paracetamol is taken in overdose by alcoholics, they are administered N-acetylcysteine at a reduced threshold. 

Knowledge that paracetamol was detoxified by the thiol glutathione led the development of an antidote. Glutathione itself cannot be given to the patient after an overdose, so a number of similar substances were initially tried as possible antidotes. There was some success but some had unpleasant effects. It was then found that a substance called N-acetylcysteine would help to regenerate the glutathione in the liver. 

Ro. 17. Plasma GST B and B2 subunits and ALT activities in patients with paracetamol poisoning. The upper (a) figure shows enzyme levels in patients treated successfully with Af-acetylcysteine following the admission (first) blood sample and the lower (b) figure the enzyme levels in patients admitted too late after the overdose for effective treatment with Af-acetylcysteine. All data are expressed as multiples of the upper reference limit. 

Fig. 18. Schematic diagram of the plasma profile of GST Bj ( ) and ALT (A) following poisoning with paracetamol. The dashed lines represent the profiles if patients are treated with IV-acetylcysteine within 12-hr of the overdose. All data are expressed as multiples of the upper reference limit.

Brok J et al Interventions for paracetamol (acetaminophen) overdoses. Cochrane Database Syst Rev2002 (3) CD003328. [PMID 12137690 ] (There are few randomized controlled trials of treatment, but oral activated charcoal and use of ftf-acetylcysteine is recommended, with no NAC regimen proven more effective than any other.)... 

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