Created by world-class clinical faculty, Learning in 10 (LIT) Reviews covers topics in the United States Medical Licensing Exam (USMLE) Step 2CK examination.
This lecture will cover acetaminophen toxicity by the end of this lecture you should be able to describe the new towell ism of acetaminophen identify the key toxic metabolites describe the clinical presentation of acetaminophen toxicity and discuss the treatment and antidote or acetaminophen toxis we’ll start with a general discussion about acetaminophen and
Then talk about its pharmacology and metabolism and how this applies to acetaminophen toxicity will then discuss the clinical presentation and finally the treatment for acetaminophen toxicity see dominican is one of the most commonly used analgesics in antipyretics today it is in many over-the-counter medications as well as in many prescription medications in
Combination with various opioids because of this in addition to acetominophen toxicity you must consider toxicity from other medications in keeping chronic congestion x’ consider acetaminophen to be a benign medication however it is the most common cause of acute fulminant liver failure in the united states today in overdose it can be fatal cause paddock necrosis
In fulminant liver failure that requires transplantation acetominophen is rapidly absorbed by the gi tract percent is metabolized by deliver and the remaining 3% is excreted unchanged in the urine of the 97% metabolized by the liver 94% goes through either glucuronidation or sulfation and then gets excreted in the urine the remaining 3% is metabolized by the p450
System to metabolite called nat key this is the metabolite that causes the powder toxicity seen in acetaminophen overdose he is rapidly metabolized by glutathione in the liver to non toxic metabolites which get excreted in the urine when acetaminophen is ingested in large doses the metabolism of nap ki depletes glutathione stores when glutathione levels reach 30%
Or less the pata toxic effects of napkin begin to take place patients with chronic liver disease malnutrition or alcoholism are much more sensitive to the effects of nap key and hepatotoxicity can be seen in lower dose ingestion of acetaminophen this is mainly because these patients are deficient in glutathione you the clinical presentation takes place in four
Stages stage one presents with very nonspecific constitutional and gi symptoms which can make the diagnosis especially challenging if the patient does not volunteer information on an acetaminophen ingestion this stage lasts for up to 24 hours post suggestion stage two the powder toxic effects of nap key b in clinical appetite is develops with rising liver enzymes
Right upper quadrant pain and right upper quadrant tenderness on exam typically blood levels of acetaminophen are low at this point because it has been completely metabolized serum drug tests test only for acetaminophen and not the metabolites of acetaminophen this stage is seen between 24 hours and 48 hours post ingestion stage three is the point of maximum
Toxicity liver enzymes peak at ten to twenty thousand other causes of acute hepatitis such as viruses and alcohol usually do not result in profound transam and itís like acetaminophen toxicity other signs of liver failure also begin to appear such as encephalopathy or coagulopathy this is typically seen days three and four post ingestion stage four is either a
Recovery phase with return of normal liver function and no long-term damage or a stage where patients go into fulminant hepatic failure and can require transplantation lasts up to two weeks post ingestion typically acetaminophen toxicity takes place in injections that are greater than 150 milligrams per kilogram and children and greater than seven and a half to
Ten grams and adults when deciding if treatment with an acetylcysteine which is the antidote is necessary we use the room act matthew nomogram this nomogram is based on me acetaminophen level at four hours or greater post ingestion as well as the half-life of acetaminophen luckily acetaminophen overdose does have an antidote which is the mainstay of treatment
This is an acetyl cysteine or knack for short this is metabolized to precursor glutathione which can then be used to metabolize the toxic nap key it is a hundred percent effective if given within eight hours of ingestion making this diagnosis especially time sensitive gastric lavage and the use of epik to induce vomiting are no longer recommended mainly because
Of the risk of aspiration and causing a pneumonitis gie decontamination with activated charcoal can be used in large ingestion x’ and if the patient presents within 2 hours this is the room act matthew nomogram it is based on any level of acetominophen at four hours or greater and the half-life of acetaminophen nomogram is divided into three areas the area above
Line one represents probable toxicity the patient falls above this line on their acetaminophen level they will likely go on to develop ahead of toxicity and all these patients should be started on nak therapy the area below line 2 represents no toxicity and patients that should not go on to develop hepatic toxicity from nap key so these patients do not need to
Be treated the area between line lines 1 & 2 is kind of a grey zone or on the case of this diagram a pink zone this is the area of possible toxicity it’s the standard of care in the united states to initiate nak therapy in patients that fall in this this area and then to trend their liver enzymes and their coagulation studies keep in mind that patients with
Alcoholism malnutrition and chronic liver disease can have toxic ingestions at lower doses so if those patients aren’t in the possible or probable toxicity levels you might want also still consider treating them with an acetylcysteine basically knack should be administered in three situations the first is a patient that falls in the possible or probable toxicity
Areas the second is when a patient in a large dose of acetaminophen the time of ingestion is unknown but your serum acetaminophen level is elevated and the third would be a patient that reports a large ingestion but not a toxic ingestion but also reports using acetaminophen over a long period of time these patients should have a level checked in it if it’s elevated
Or the liver enzymes are elevated then they should be treated with with and acetylcysteine as well there are currently two forms of of knack that are approved by the fda oral and iv just be aware that the oral version smells like rotten eggs and most patients don’t tolerate it very well in summary acetaminophen is not a benign medication it can have devastating
And sometimes fatal consequences nap ki is the head of toxic metabolites in acetaminophen overdose the clinical presentation can be very subtle initially and easily confused with alternate diagnosis but is one that needs to be made because of the time-sensitive nature of treatment and acetylcysteine is the antidote and is a hundred percent effective they’ve given
Within eight hours post ingestion therapy with and acetylcysteine is guided by the room act matthew nomogram so always reference this and once you have your for our see the benefit level you thank you very much
Transcribed from video
Acetaminophen Toxicity By Learning in 10
