March 22, 2023

In this video, I will be presenting on Acetaminophen, a very common non-opioid analgesic mainly uses to alleviate fever and pain.

In this video we are going to talk about a very popular drug known as paracetamol the other name for this drug is acetaminophen or acetaminophen and the other name also which is very popular particularly in the u.s is tenello or tiny law right so before we talk more about this drug let’s review a basic pathway uh of arachidonic acid right so in in the cell

Membrane you find phospholipids right these phospholipids are cleaved by an enzyme called phospholipase a to form arachidonic acid right so arachidonic acid is then cleaved by cyclooxygenase enzyme or cox right so this is an enzyme that converts arachidonic acid to prostaglandins right another pathway of our lip oxygenase will give us a locotrines but we’ll

Talk about that in a separate video in this video i just want you to focus on cox1 and cox2 right so cox1 is constitutive it means it’s always present but cox 2 is induced it means it’s only active when there is a tissue injury that’s where this enzyme will be present right but both of them will give us a prostaglandins and particularly in the cox one pathway

We have a gi protection that’s gastrointestinal tract protection and a platelet functioning like adhesion etc right on cox2 uh you need to remember like a induction of pain and inflammation so if we give a patient paracetamol this paracetamol will inhibit both cox-1 and cox-2 right one more time what is the mechanism of action of paracetamol it reversibly

Inhibits cyclooxygenase both of them are particularly in the central nervous system it is inactivated peripherally what are the effects of uh this drug right so it’s antipyretic does reducing fever is analgesic thus are using pain here uh and you need to remember this point is not an anti-inflammatory drug paracetamol does not have and inflammatory effect

Side effects of paracetamol this drug is minimal gastric side effects and the most dangerous one is hepato toxicity due to acetaminophen overdose right it’s drug induced hepatitis the minimum toxic dose for adults is 7.5 grams per day and acetaminophen or paracetamol is the leading cause of acute hepatic failure in the united states let’s talk about the

Pathophysiology of acetaminophen overdose so this is a basic pathway that you need to know right so here is the drug acetaminophen right so it’s acted upon by cytochrome p450 is an oxidation reaction and will get a compound and known as uh n acetyl p benzoquinone amine right or nap qi right nep qi right so uh under normal conditions uh this compound is acted

Upon by glutathione right this is a conjugation reaction uh then this will lead to detoxification and elimination uh of this product of acetaminophen right but if there is overdose this compound will be high right so it will build up leading to irreversible oxidative hepatocyte injury that’s leading to uh hepatic necrosis that’s a necrosis of the hepatocytes

Themselves leading to um clinical symptoms right so what are the clinical features of acetaminophen overdose right so there are four phases phase one phase two phase three to phase four right so this is a basically or depending on time right so from zero to 24 hours that’s phase one and the patient will have a nausea vomiting nothing phase two is 24 to 48

Hours and in this phase the patient we have a right upper quadrant pain elevated liver enzymes and are prolonged pt that’s a pro thrombin time right liver enzymes who talk about uh s-t-a-l-a-t etc in the third phase which is 72 to 96 hours this patient will have hepatic necrosis enzyphalopathy called gelopathy or acute tubular necrosis in the fourth phase

That’s four days to two weeks right so this this is the outcome right if the damage is not irreversible there will be complete resolution of hepatic dysfunction but if the damage is irreversible this is dead that’s the bad news right so management of overdose right so firstly activated charcoal right this is administered like um not in not more than four

Hours after ingestion and we measured acetaminophen levels four hours after ingestion or immediately if ingestion occurred more than four hours prior to the presentation of our symptoms and what is the antidote this is very important yeah it is either oral that’s per oral or iv uh n acetylcysteine knack and access to sustain you can’t forget this one even if

You forget everything that i said so far just you know overdose of acetaminophen and asset of sustain you can’t possibly forget this right so this is administered 4 to 24 hours after ingestion so knack or n-acetyl sustain will replenish glutathione stores in the leave right so this will enable it this glutathione to start degrading that dangerous compound

Nab qi right so we also need to treat liver failure and in severe cases liver transplant can be indicated right so what are the basic indications for paracetamol or acetaminophen right so firstly you have fever and pain right this drug is good tolerability is preferred it’s a preferred analgesic or antipyretic drug during pregnancy is not teratogenic it’s

Not associated with any uh danger to the fetus again this drug is a more preferred over aspirin in pediatrics because if you give a aspirin to someone with a viral infection for example influenza if you give a spring the person will have rare syndrome which is again very dangerous to the liver right so this drug is contraindicated in severe liver impairment

Is contraindicated you can give this drug to a patient with a problem points to take home please don’t forget this the toxic dose will be like more than 7.5 grams per day in adults and the antidote is an acetylcysteine knack and acetylsystem don’t forget that thank you so much if you like this video please make sure you give it a thumbs up and don’t forget

To leave a comment in the comment section you

Transcribed from video
Acetaminophen (Paracetamol/ Tylenol) – mechanism of action, indications & management of overdose By Nexus Medical MedialiveBroadcastDetails{isLiveNowfalsestartTimestamp2022-06-01T212358+0000endTimestamp2022-06-01T213537+0000}