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Tags: 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

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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:

• Importance of trending AST/ALT, INR, creatinine, lactate, and phosphate.


• Use of the King’s College Criteria for potential liver transplant evaluation.

Special Considerations:

• Adjustments in pediatric patients regarding NAC dosing volumes.


• Awareness of IV acetaminophen overdoses and their management.


• Emerging discussions on the use of fomepizole in massive overdoses.

Take-Home Points:

• Comprehensive Medication History: Always inquire about all medications taken to assess for potential acetaminophen exposure.


• Early Recognition and Treatment: Due to often silent initial stages, maintain a high index of suspicion and measure acetaminophen levels promptly.


• Understanding Metabolism and Toxicity: Recognize how overdose alters metabolism, leading to toxic NAPQI accumulation.


• N-Acetylcysteine Efficacy: NAC is most effective when administered early but remains beneficial even in advanced stages.


• Proper Use of the Nomogram: Utilize the Rumack-Matthew Nomogram appropriately for acute ingestions and consult toxicology when in doubt.


• Monitoring and Continuing Care: Be vigilant in monitoring laboratory values and prepared to extend NAC therapy as needed.


• Consultation and Resources: Engage with poison control centers and utilize available resources for complex cases.

 

Resources Mentioned

Rumack-Matthew Nomogram 

King’s College Criteria

• King’s College Criteria for Acetaminophen Toxicity


• Use this tool to assess the need for liver transplant evaluation in c