Paracetamol has become a  customary medicine in the everyday life .eventhough it is an otc  ( over the counter ), the consequences of consuming it needlessly over a long period of time can undeniably cause some grievous aftermath. To know in detail about the consequence first we need to know about the drug in deep.

WHAT IS PARACETAMOL?

Acetaminophen or more easily paracetamol is an over the counter drug to relieve pain and fever. It belongs to the class of analgesics and anti-inflammatory drugs. It is the first-line therapy for pain by World Health Organisation. Paracetamol is also used for reducing fever due to its antipyretic effects.

It can be taken either orally or rectally, it is also given as injected into the veins.

The recommended dose of paracetamol for healthy adults is 3-4 g, when taken in larger than the prescribed dose taking into consideration the patient’s health condition it can cause paracetamol toxicity.

PARACETAMOL POISONING

Acetaminophen or paracetamol poisoning is caused due to excessive unwanted use of the drug over the course of time. How is this toxicity is caused or what happens to our body when we take it in a larger quantity than prescribed ??

When taken in normal therapeutic doses it is transfigured into its non-toxic metabolites by Phase II metabolism by conjugation with glucuronide and sulfate conjugation, a small portion being oxidized via cytochrome P450 pathway and is converted into highly reactive intermediate metabolite  N-acetyl –p- benzoquinone imine (NAPQI), normally this NAPQI is detoxified by conjugation with glutathione to form cysteine and mercapturic acid conjugates.

In the case of paracetamol poisoning, this sulfate and glutathione pathways get swamped, and as a result of which more amount of paracetamol is propelled to the Cytochrome P450 system to produce more NAPQI.  Due to the imbalance between the demand and regeneration of glutathione its supply from the hepatic cells depletes.  This makes the produced NAPQI to reside in the hepatic cells and  reacts with the cellular membrane molecules and cause hepatocyte damage and death which leads to acute liver necrosis

MANAGEMENT

Principally 3 treatment techniques are there for paracetamol poisoning

  1. Gastric decontamination
  2. Acetylcysteine
  3. Liver transplant

GASTRIC DECONTAMINATION

Under normal situations within 2 hours, the absorption of paracetamol from the gastrointestinal tract is complete, so for effective gastric decontamination it is should be done within this time limit.

GASTRIC LAVAGE

If the amount of drug taken is potentially life-threatening and treatment can b provided within 60 mins of consumption then gastric lavage or stomach pumping is effective, where the contents in the stomach are cleaned. It involves the passage of a tube into the stomach through the nose or mouth and followed by the back to back administration and removal of small volumes of liquid.

ACTIVATED CHARCOAL

 It is one of the most common gastric decontamination techniques used as it adsorbs paracetamol reducing its absorption.

ACETYLCYSTEINE

N-ACETYLCYSTEINE or NAC or acetylcysteine acts by replenishing the body’s storage of glutathione which reacts with the toxic metabolite NAPQI and converts it into a form by which it does not damage the cells and can be safely excreted. Within 8 hours of ingestion if the patient is administered with acetylcysteine then it reduces the risk of serious hepatotoxicity and guarantees survival, whereas if the patient is administered with the acetylcysteine after 8 hrs of administration then the effectiveness of acetylcysteine decreases due to the toxic events that have already begun in the liver, as a result, the risk of liver necrosis and death increases significantly.

  Oral acetylcysteine is given as a 140 mg/kg loading dose followed by 70 mg/kg every four hours for 17 more doses, and if the patient vomits within 1 hour of dose, the dose must be repeated intravenous acetylcysteine is given as a continuous infusion over 20 hours for a total dose 300 mg/kg. Recommended administration involves infusion of a 150 mg/kg loading dose over 15 to 60 minutes, followed by a 50 mg/kg infusion over four hours; the last 100 mg/kg are infused.

LIVER TRANSPLANT

A liver transplant is done in case the patient reaches the stage of acute liver failure, it is used as the last resort. the most important criteria for liver transplant involves an arterial blood pH less than 7.3 after fluid resuscitation or prothrombin time greater than 100 seconds or serum creatinine greater than 300mmol/ L in 24 hrs or the patient has grade III or IV encephalopathy.

Partial liver transplants can also be used,  supporting the patient while their own liver regenerates,  when the liver function has returned, immunosuppressive drugs are prescribed for the rest of their lives.

The use of paracetamol both as an analgesic and antipyretic has increased significantly, but a majority of the people do not understand about the longterm side effects it can cause, one must have an in and out knowledge about the serious side effects of paracetamol overdose and how to manage it as it is a drug which has become an inevitable part of our daily lives…

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