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Mastering the mechanism of acetaminophen toxicity

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After completing this course, you will be prepared to evaluate and treat common poisonings in the acute care setting with confidence. The use of decontamination, toxin removal, and antidote therapies will become second nature.

Acetaminophen also known as paracetamol is the most common cause of acute liver failure in several countries it’s found in many over-the-counter products used for relieving pain and fever but it can be dangerous if used incorrectly for example in suicide attempts in this medmastery lesson we’ll cover the mechanism of acetaminophen toxicity let’s begin with the

Story of one of my patients that represents a problem we see on a regular basis in the emergency department a sixteen-year-old girl was brought in by her parents after she took an overdose of acetaminophen her parents determined that she took six thousand milligrams about eight hours ago on physical examination the patient appeared confused she was vomiting and

Complaining of pain in her right upper abdomen so what happened to this patient well acetaminophen undergoes a few chemical reactions in the liver and its non-toxic byproducts get sent to the kidneys where they leave the body through the urine this occurs through a direct and indirect route the direct route is how approximately 90 percent is processed the liver

Metabolizes acetaminophen in a single step by swapping one chemical part for another and this non-toxic byproduct goes straight to the kidney the indirect route is how up to eight percent is processed the liver uses a special enzyme system known as p450 that creates a toxic byproduct called n-acetyl p-benzoquinonamine or napke the liver then performs a second

Chemical reaction to protect itself specifically glutathione changes napke into a non-toxic byproduct and this is sent to the kidney for completeness about two percent doesn’t get processed and travel straight to the kidney so how does acetaminophen overdose cause liver damage well think of this process as a mass transit system like a train in this analogy the

Stations represent the organs the passengers represent acetaminophen and its byproducts the train represents the chemical reactions that break the drug down into its by-products and the train tracks represent the different routes those by-products take imagine it’s rush hour and people are trying to get to work most passengers prefer to take the express train

Directly from the liver station to the kidney station a few passengers take the slow train that requires them to make a stop between the liver and kidney stations this step represents napke so the passengers have to get on a connecting train to avoid getting stuck at the station the connecting train represents glutathione which we just reviewed is necessary to

Create a non-toxic byproduct from napki finally a small number of people don’t take the train at all and drive themselves directly to the kidney station let’s apply some numbers say that 100 people are on their way to work so 90 get on the express train 8 take the slow train and successfully get on the connecting train at the napkey stop and two drive themselves

Now let’s see what happens during an overdose using our train analogy instead of 100 let’s say there are 300 people on their way to work about 2 percent so six people drive themselves so now we’re left with 294 people in a hurry to get to work but the express train can only carry 100 passengers so once those 100 people get on what happens to the remaining 194

Well their only option is to get on the slow train so the slow train starts dropping people off at the napki stop but because it’s so crowded and there aren’t enough connecting trains 100 passengers get left behind at the stop and don’t make it to the kidney station this is analogous to napkin building up and not getting changed into its non-toxic byproduct which

Is very dangerous because napkin is toxic to liver cells when there is too much napkin inside liver cells it attaches itself to proteins and doesn’t let go as a result these proteins can’t do their usual jobs like making blood clotting proteins so the liver cells start to die and patients start to experience upper right abdominal pain nausea vomiting bleeding

And confusion some of which our patient complained of the inflamed liver starts to release aspartate amino transferase or ast and alanine aminotransferase or alt which can be detected in blood tests and because the liver can no longer make blood clotting proteins the prothrombin time increases if the liver damage is left untreated the liver becomes permanently

Scarred and no longer works so patients will require a liver transplant and without it they may not survive so i hope you liked this video absolutely make sure to check out the course this video was taken from and to register for a free trial account which will give you access to selected chapters of the course if you want to learn how medmastery can help you

Become a great clinician make sure to watch the about mastery video so thanks for watching and i hope to see you again soon

Transcribed from video
Mastering the mechanism of acetaminophen toxicity By Medmastery