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The effect of paracetamol overdose on the liver and the standard method of treatment of paracetamol poisoning.
Drug induced liver injury is one of the widespread reason of acute liver failure. Paracetamol, is commonly used anti-pyretic drug that is from longtime known to cause toxicity and effect liver if consumed in amount more than the therapeutic doses. Paracetamol is easily accessible on purchase even without any prescription. It has outstanding safety profile when administered as recommended dosages (Ward et. al., 1999). However, overdoses of paracetamol is known to be hepatotoxic.  Hepatotoxicity is due to paracetamol overdosing whether taken accidentally or deliberately ,is the main reason behind it. Drug induced liver injury remains one of the main global concern throughout the world. Acute liver injury is a serious condition of liver dysfunction indicated by symptoms such as jaundice, encephalopathy and coagulopathy (Reuben et. al., 2010).
Paracetamol is one of the most common reason of drug induced liver injury in many western countries. On the basis of studies it is recommended, that consumption of paraetamol up to a maximum level of 4000 mg within in a day is safe (Herndon et. al., 2014) whereas experts suggest doses of 2000 mg or less in people who persistently use alcohol or those with liver disease (Bosilkovska et. al., 2012). Though, toxicity caused by paracetamol has become more challenging due to more use of combination drugs, like over-the-counter drugs for cold or prescribed pain relievers which also comprises paracetamol. Moreover lethal consumption with these drugs or in combination with alcohol may show slow appearance of hepatotoxicity (Dougherty et. al., 2012). Paracetamol was first discovered in the year 1878 from phenacetin. Only after 1950s it was extensive used medically as over-the-counter analgesic and antipyretic. Since then , various studies have been performed involving administration of paracetamol, its safe dosage, its effect on liver, use of drugs during chronic alcohol abuse, or coexisting infections.
Hepatocytes was known to
eak paracetamol into non-toxic by-product by microsomal cytochrome P450 or CYP450. This metabolic pathway  by microsomal cytochrome P450, mainly cytochrome P450 2E1 gives away reactive oxygen species (Wendel et. al,1981),
The metabolic pathway was first considered to be the eventual reason of liver failure in paracetamol overdose. It only after many cu
ent studies which proved mitochondrial dysfunction is thought to be the main cause of release of free radicals in paracetomol poisoning (Smith et. al., 1989) .
The development of drug-protein adducts between N-acetyl-p-benzoquinone imine, the reactive paracetamol metabolite and proteins that partake in electron transport chain leads to Mitochondrial dysfunction. In addition, elevated action of mitochondrial complex I, leads to more free radical production. This increased level of action was discovered to have link with higher risk of liver injury. Oxidative stress caused by paracetamol overdose is also recognized to be associated with peroxynitrite and mitochondrial superoxide. These superoxide along with nitric oxide generates extremely reactive peroxynitrite groups which is main cause behind nitrosative and oxidative stress (Ramachandran et. al., 2016)
.Paracetamol is easily abso
ed after ingestion with 80% of the medicine being abso
ed when administered though mouth. In a person with no liver injury, the half-life of the drug is around 2-3 hours. After being abso
ed, blood has about 90% of the drug which is metabolized into non-toxic products by glucuronidation and sulfidation pathways and later...