We sit down with one of our toxicologists to discuss acetaminophen toxicity.
Hosts:
Marlis Gnirke, MD
Brian Gilberti, MD
https://media.blubrry.com/coreem/content.blubrry.com/coreem/Acetaminophen_Toxicity.mp3
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Toxicology
Show Notes
Table of Contents
0:35 – Hidden acetaminophen toxicity in OTC products
3:24 – Pharmacokinetics and toxicokinetics
6:06 – Clinical Course
9:22 – The antidote – NAC
11:02 – The Rumack-Matthew Nomogram
17:36 – Treatment protocols
22:34 – Monitoring and Lab Work
23:23 – Considerations when treating pediatric patients
23:57 – IV APAP overdose, fomepizole
25:42 – Take Home Points
Acetaminophen vs. Tylenol:
The importance of recognizing that acetaminophen is found in many products beyond Tylenol.
Common medications containing acetaminophen, such as Excedrin, Fioricet, Percocet, Dayquil/Nyquil, and others.
The risk of unintentional overdose due to combination products.
Prevalence of Acetaminophen Toxicity:
Widespread availability and under-recognition contribute to its prevalence.
The potential for unintentional overdose when taking multiple medications containing acetaminophen.
Pharmacokinetics and Metabolism:
Normal metabolism pathways of acetaminophen and the role of glutathione.
Formation of the toxic metabolite NAPQI during overdose situations.
Saturation of safe metabolic pathways leading to hepatotoxicity.
Pathophysiology of Liver Injury:
How excessive NAPQI leads to hepatocyte death, especially in zone III of the liver.
The difference between therapeutic dosing and overdose metabolism.
Clinical Stages of Acetaminophen Toxicity:
Stage 1: Asymptomatic or nonspecific symptoms (first 24 hours).
Stage 2: Onset of hepatic injury (24-72 hours), elevated AST/ALT.
Stage 3: Maximum hepatotoxicity (72-96 hours), signs of liver failure.
Stage 4: Recovery phase, complete hepatic regeneration if survived.
Antidote – N-Acetylcysteine (NAC):
Mechanisms of NAC in replenishing glutathione and detoxifying NAPQI.
The importance of early administration, ideally within 8 hours post-ingestion.
NAC’s role even in late presenters and in fulminant hepatic failure.
The Rumack-Matthew Nomogram:
How to use the nomogram for acute overdoses to determine the need for NAC.
Limitations in chronic overdoses and late presentations.
Emphasis on obtaining accurate time of ingestion and acetaminophen levels.
Treatment Protocols:
Standard 21-hour IV NAC protocol and dosing specifics.
Managing anaphylactoid reactions associated with IV NAC.
Criteria for extending NAC therapy beyond 21 hours.
Monitoring and Laboratory Work:
