Paracetamol Toxicity: An Overview.

Paracetamol Toxicity:
An Overview.

Author: Aalam Muntazim
(Karaganda Medical University)
Aim:
Make aware about overdose of paracetamol drug as it increases the cases of liver failure world-wide.
Abstract:
Acetaminophen (Paracetamol) is one of the most widely used as a medication worldwide.
In 1960, it was first noted with the toxicity 
Paracetamol which is commonly used as analgesic and antipyretic drug but it shows some strange and life threatening effects are like liver damage which actual leads to fulminant liver failure and also death.
As it is now the most common drug in self-poisoning, with a high rate of morbidity and mortality. Various steps has been taken by regulatory authorities across the world to reduce the drug related toxicity.
Keywords: liver failure, methionine, hepatocellular necrosis, 
Overview:
introduction
Paracetamol overdose is a now most common means  self-poisoning worldwide due its easy availability and accessibility. It is widely available as a single-component medication and also as a component of a excessive of combination over-the-counter and prescription medications. Rather its safety when used properly, Paracetamol poisoning is one of the more common overdoses reported to poison centers.
In 2009, An American Association of Poison Control Centers‘ National Poison Data System reported 401 deaths caused by Paracetamol or an Paracetamol combination product. liver failure is now the leading cause of acute liver failure and is the second most common cause of liver failure requiring transplantation in the United States induced by the paracetamol.
Accidental or intentional?.
Although  utmost paracetamol poisoning is due to the wilful ingestion of supratherapeutic doses with the intention of committing self-murder, a proportion of cases present with  toxin due to incorrect dosing for  remedial intent or accidental overdose. In children under 5 yr old, ingestion of  poisonous substances is  nearly always unintentional, and is  generally due to chemicals or  medicines belonging to other family members. 
Methionine‐paracetamol combination tablets
Methionine is a glutathione needed in the metabolism of paracetamol. The analgesic effectiveness of paracetamol has been shown in the combination  medicine, with a slight increase in minor adverse  efftects such as doziness, Other adverse  efftects of methionine are mild, and include nausea, flatulence and headache. As  utmost paracetamol overdoses are impulsive methionine would have to be added to all drugs containing paracetamol. This would mean that a lot of people would needlessly consume methionine, and the cure needed to be effective is unclear. 
Effects on Internal Organs
Pathologic evaluation of organs shows that the liver is the main target for toxin after paracetamol overdose because the hepatocytes elaborate NAPQI. As NAPQI has a short life span, it can damage only cells that  unfold it. Overdose of paracetamol may produce severe liver injury with hepato cellular necrosis. The important mechanisms of cell injury are metabolic activation of paracetamol, glutathione  reduction, alkylation of proteins, especially mitochondrial proteins, and  conformation of reactive oxygen/ nitrogen species. 
Treatment
The  aim of the  treatment of paracetamol  toxin focuses on the prevention of hepatotoxicity by appropriate line of treatment which is achieved by limiting the  immersion of the  medicine and by  dwindling the  poisonous impact of NAPQI through loss of glutathione store.  Specific treatment is carried out with N- Acetyl Cysteine( NAC). The treatment of paracetamol  toxin with NAC is  began in UK in the time 1970. The World Health Organization Model List of Essential Medicines and Model Formulary of 2006 lists Acetyl Cysteine( NAC) as an  cure for use in the treatment of paracetamol overdose. NAC is stylish given within the first 8 hours following an acute overdose for maximum hepato-defensive  goods. A study published in 1988  set up that NAC is slightly effective if given within eight hours of a single overdose, but  latterly its  efficacity falls. A controlled trial  handed  substantiation that NAC can ameliorate  outgrowth indeed in cases with encephalopathy, so those who present  further than eight hours after overdose are still treated with this  cure. 
Intravenous NAC is associated with advanced prevalence of adverse  goods  similar as rashes, pruritus(  dropped by givinganti-histaminic like Chlorpheniramine), nausea,  puking, hyponatremia and anaphylactoid  response. The anaphylactoid  response is  intermediated by histamine and depends on the blood  position of NAC. In the event of development of an anaphylactoid  response, the NAC  remedy has to be discontinued and treatment with adrenaline, corticosteroid andanti-histaminic has to be started  incontinently along with other  probative measures 
Alternative drugs
In adults there is the possibility of exchanging an alternative drug such as a non‐steroidal anti‐inflammatory drug. These have been shown to be at lesser as effective as paracetamol.
Conclusion:
Paracetamol is a generally used,  relatively effective analgesic and antipyretic. In overdose it causes significant morbidity and mortality. The burden to health care services is considerable, with a high  fiscal cost and  numerous sanitarium admissions. According to the Medicines Control Agency Medicines Act Leaflet( MAL 82, March 1996), which gives guidance on changing the legal bracket of a  drug to the General trade List, a criterion for addition on the General trade List is ‘ where the hazard to health, the  threat of abuse, is small and where wider  trade would be a convenience to the purchaser ’( our italics). It's surprising that paracetamol is available on the General trade List, as it appears to fail this criterion for an OTC  drug.  Present approaches to reduce  toxin have had variable and moderate  goods. Other  styles of reducing this burden must be considered. These could include public education on the  goods of overdose,  farther  exploration on  medicine ‐  cure combination tablets and changing the legal status of adult boluses from the General Deals List to the  tradition ‐ only  drugs list, or at least  confining it to  drugstore ‐ only deals. 
References:
UB Ghaffar & Naser Ashraf Tadvi Assistant Professor, College of Medicine, Majmaah University, Al-Majmaah, Saudi Arabia
 

Emergency Medicine: Open AccessIbrahim et al., Emergency Med 2013, 3:6
DOI: 10.4172/2165-7548.1000158
Tasneem Ibrahim1*, Smriti Agnihotri2 and Arun Kumar Agnihotri31.Lecturer, Department of Pharmacology, SSR Medical College, Mauritius 2.Professor, Department of Pathology, SSR Medical College, Mauritius 3.Department of Forensic Medicine & Toxicology, SSR Medical College, Mauritius
 

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