Evaluation of Differences Between the Standered NAC Regimen Protocol and the SNAP Regimen Protocol in the Treatment of Paracetamol Toxicity for Cases Presented Early and Late to Assiut University Hospitals in Terms of Safety and Efficiecy.

Acetamenphen is an analgesic and antipyretic drug . It is used as an active ingredient in many over-the-counter and prescription medications. It is generally considered safe at therapeutic doses. However, toxicity can be caused by multiple supratherapeutic doses or an acute, high overdose .

Acetaminophen is metabolized by the cytochrome P450 2E1 to N-acetyl para- benzoquinone-imine (NAPQI), a metabolit extremely toxic to the liver. This process depletes glutathione; thus, NAPQI binds to cellular and mitochondrial proteins to form adducts, impairing mitochondrial respiration and generating oxidative stress .

N-Acetylcysteine (NAC) is a 20-21-hour regimen which involves 3 weight related infusions. The first 150mg/kg is given over 1 hour, second 50mg/kg given over 4 hours and the last 100mg/kg given over 16 hours. This has been the optimal available therapy since 1980 .

Several evidence shows various adverse effect of this regimen which include anaphylactoid reaction, nausea, vomiting and medication error .

Recently the intravenous regimen has been simplified from a three-bag regimen to a two-bag regimen in many parts of the world, which has reduced the early very high concentrations and therefore adverse reaction rate .

Different clinical studies have been carried out to propose the adoption of a shorter regimen, the Scottish and Newcastle Antiemetic Pre-treatment (SNAP) 12-hours NAC regimen into clinical practice .

The SNAP is a two-bag regimen which involves giving 100mg/kg infusion over 2hours, then last 200mg/kg infusion giving over 10hours .

The SNAP regimen confirms that it produces fewer adverse drug reactions (ADRs) and has similar efficacy with regard to preventing liver injury when compared to the 21 h NAC regimen. Further clinical development and adoption of the SNAP regimen could improve treatment safety for this patient group, potentially shorten the length of treatment without compromising antidote effectiveness.

Inclusion criteria

• All cases admitted to Assiut University Hospitals with history of acute paracetamol overdose ingestion .

Exclusion criteria

• * Co-ingestion of other hepatotoxic drugs .

• Pre-existing liver diseases: Chronic hepatitis B or C, Autoimmune hepatitis, Wilson's disease, Known cirrhosis , Sepsis, shock, or hypoxic injury affecting the liver.
• Hemolytic disorders causing abnormal LFTs.
• Genetic or metabolic diseases that affect liver functions.