This animated video illustrates the mechanisms of Paracetamol (Acetaminophen) induce hepatotoxicity.
Paracetamol or acetaminophen hepatotoxicity and treatment paracetamol at therapeutic dose has very good safety profile however paracetamol overdose is the most common cause of acute hepatic failure but how paracetamol overdose induces such notorious fatal hepatic failure to answer this question we’ll go through the metabolism of paracetamol under both therapeutic
And overdose concentrations under recommended therapeutic doses 95% of paracetamol are conjugated in the liver into both sulphate and glue coronoid moieties which are non-toxic conjugates that can be readily excreted by the kidney however a small percentage around 5% of paracetamol is oxidized by cytochrome p450 isozymes system in the liver this oxidation process
Results in the production of n0p benzoquinone i mean molecule abbreviate as napkin napkin is a very toxic intermediate metabolite it can induce severe acute hepatic necrosis fortunately the glutathione molecules in our liver rapidly conjugate napkin molecules to produce non toxic metabolites that can be peacefully excreted by the kidney thank you very much
Glutathione however when large amount of paracetamol is ingested either as suicidal at or accidental overdose the conjugation machines even at their maximum capacities cannot safely process the flooding of paracetamol molecules therefore large percentage of paracetamol molecules are directed toward cy p450 isozymes oxidation system which sadly results in the
Production of massive amounts of the severely toxic napkin molecules surely our glutathione friends will do their maximum efforts to neutralize the evolving toxic napkin but unfortunately we have limited storage of the precious glutathione and as expected huge amount of toxic nap ki will accumulate in the liver inducing acute hepatic necrosis the question which
Confused the scientists over long years is why paracetamol induces hepatotoxicity even at therapeutic doses in a very small percentage of population to answer this question we must go back to the paracetamol metabolic pathways under therapeutic concentrations there are two explanations for this rare phenomena either abnormalities in the cytochrome p450 oxidation
System or abnormalities include a scion conjugation system let’s start with the cy p450 isozymes oxidation system indeed many cy p450 isozymes have been involved in oxidation of parasurama and production of napkin it has been discovered that one of these eyes designs specifically cyp2d6 has genetic polymorphism and as a result few percentages of population have
Ultra rapid and extensive cyp2d6 activities therefore these unfortunate people produce large amount of napkin even as therapeutic doses of paris in a ball to clarify this tricky point we will compare the metabolism of therapeutic paracetamol doses in both normal people and those with extensive and ultra-fast cyp2d6 eyes design in the hepatocytes of the unlucky
People the very active cyp2d6 isozymes will vacuum up large percentage of paracetamol molecules towards the oxidation system where they produce huge amount of the toxic napkin molecules in as usual our glutathione friends will work hard to divert napkin molecules toward much safer pathways but unfortunately the amount of nap keep reduced by oxidation system exceeds
The detoxification capacity of glutathione conjugation system thus huge amount of na ki will find their way to destroy our lovely liver it is worthy notice that alcohol enhanced the activities of cy p450 isozymes therefore alcohol produces larger amount of napkin even a therapeutic concentration of parasurama now we will go to other explanation for the weird toxic
Potentials of paracetamol even at therapeutic doses in some unfortunate people and this time it is attributed to glutathione conjugation system it has been reported that the precious glutathione storage is low in infants malnourished alcoholics malabsorption and in some elderly in these people the not ki detoxification ability is low therefore as you can see from
The diagram to the left more nap key are accumulated in the liver even at therapeutic concentrations of paracetamol paracetamol acetaminophen hepatotoxicity is an emergency and if we don’t intervene promptly within first hours the liver might be irreversibly damaged among the suggested measures to save the liver of the intoxicated patient is to give the paris serum
Old antidote which is an acetylcysteine abbreviated as nac nac is a precursor of glutathione therefore intravenous administration of nac will reinstate the storage of glutathione the evolving level of glutathione will vacuum up the nap key towards the safe conjugation pathway which produced non-toxic conjugates that are peacefully excreted by the kidney and hopefully
Far less amount of nadki will remain available to induced hepatic city additionally nac enhanced the sulfate conjugation pathway which direct more paracetamol from the toxic oxidation pathway toward the safer conjugation pathway hopefully you find this video helpful my best wishes from dr. jihad hamid this video was narrated by hannah judah medical student at islamic university of gaza
Transcribed from video
Paracetamol (Acetaminophen) hepatotoxicity and its management. By Pharmacology Animation
