Tylenol Overdose and N-acetylcysteine Therapy

• Acetaminophen, a common ingredient in over-the-counter medications, poses significant risks of overdose and acute liver failure when misused or taken in excessive amounts. 
• Symptoms of Tylenol overdose include nausea, vomiting, abdominal pain, fatigue, and altered mental status, with potential progression to acute liver failure within two to five days of ingestion. 
• N-acetylcysteine therapy, when administered within eight hours of overdose, is a safe, effective, and cost-effective treatment for acetaminophen toxicity, emphasizing the importance of early intervention and medication literacy.
  

We reached a medical milestone in 2020.  

It was one of the deadliest years for opioid deaths in North America. The known dangers of prescription and illicit narcotic abuse are prevalent, but narcotic overdoses are not the only dangers consumers face.

Unintentional misuse of over the counter (OTC) medications, including those containing acetaminophen, can lead to acute liver failure and death. Medication literacy can protect consumers from the dangers of the active ingredient in acetaminophen (APAP) with proper instructions for over-the-counter use. 

An Introduction to Tylenol Overdose

Tylenol is one of the most ubiquitous pain relievers in the world and toxicity is the second most common cause of liver transplantation in the United States. As an antipyretic and fever reducer, and an ingredient in over the counter cold, cough and sinus medicines, acetaminophen is a common ingredient in over six hundred different over the counter medications. In fact, 23% of the adult American population reported using either OTC or prescription acetaminophen weekly. 

In the United States, 56,000 emergency department visits, 2,600 hospitalizations, and 500 deaths per year occur secondary to the use or misuse of acetaminophen. Overdose is more common in children.  

Despite an excellent safety profile with the recommended dose of four grams per day, acetaminophen toxicity develops at dosing of 7.5 g/day to 10 g/day or 140 mg/kg. The gastrointestinal (GI) tract absorbs acetaminophen, and the drug reaches therapeutic levels within 2 hours. Unless in the extended-release form, levels peak at 4. Compromised emptying, or co-ingestion with a drug that slows gastric motility can delay peak. If the patient presents within 1 hour of ingestion, alert patients can receive activated charcoal for GI decontamination.

Symptoms of Tylenol Overdose

The symptoms of a Tylenol overdose can occur as early as 12 hours after acetaminophen ingestion, including nausea, vomiting, abdominal pain, extreme fatigue, delirium, dark urine, altered mental status, early onset lactic acidosis, encephalopathy, coagulopathy, and renal failure. Jaundice may occur. The onset of acute liver failure can appear within two to five days after an individual consumes a large significant of acetaminophen.  

The most common antidote for acetaminophen is N-acetylcysteine and is most effective in treating an overdose if administered within eight hours. Initial lab work may show elevated levels of liver enzymes and bilirubin.  

There are four stages of acetaminophen toxicity. During the first stage the patient may be asymptomatic or may experience mild emesis. After 18 hours and within three days, the patient can experience right upper quadrant pain and hypotension. At four days, liver dysfunction, renal failure, , metabolic acidosis, and encephalopathy can occur. Death is most common at this stage.

The final stage is recovery, taking four days to three weeks. Patients with liver failure require blood pressure monitoring, oxygen saturation, and creatinine monitoring along with alanine aminotransferase, AST, and ALT levels at a minimum of 8 hours after the ingestion. 

Tylenol Overdose Treatment

Acetylcysteine therapy (NAC) for Tylenol overdose can be a safe and effective treatment. The benefit of acetylcysteine diminishes as the delay in treatment increases. It can prevent the onset of hepatotoxicity and may improve survival. It is a non-toxic agent, safe to use, and cost-effective.

The N-acetyl-p-benzoquinone imine (NAPQI) metabolite of acetaminophen is toxic to the liver. It interacts with various macromolecules, including cysteine, glutathione, and cytochrome P450 2E1. In a large clinical study, 2540 patients with acetaminophen ingestions received oral or IV N-acetylcysteine. No deaths occurred in the patients who received N-acetylcysteine therapy within 16 hours.  

There are three primary types of acetylcysteine: intravenous (IV), oral, and N-acetylcysteine. If a patient experiences severe vomiting, providers should avoid oral acetylcysteine. If there are no contraindications, provider should consider the IV form of acetylcysteine.

The loading dose is 140 mg per kilogram of body weight. Then, 70 mg per kilogram every four hours for seventeen doses. The duration of the course is 72 hours. In the United States, oral therapy is the standard and effective, but requires that the patient has no contraindications.  

The Rumack-Matthew nomogram is a semilogarithmic graph that calculates the relationship of acetaminophen plasma concentration (in µg/mL or µmol/L), the time after drug ingestion, and the risk of hepatic toxicity, though the nomogram has limitations. For example, it cannot estimate hepatotoxicity in patients for whom the time of ingestion is unknown.

During an acute acetaminophen overdose, the nomogram is a clinical tool that helps clinicians predict the potential for hepatotoxicity. The tool allows physicians to decide whether the patients warranted N-acetylcysteine therapy. Providers should consult with the local poison control center for up-to-date treatment protocols.  

The Bottom Line

In conclusion, the dangers of acetaminophen overdose cannot be understated, especially considering its prevalence in over-the-counter medications and the general population’s frequent use. The widespread nature of this issue emphasizes the importance of medication literacy and following proper instructions for use.

By understanding the symptoms of Tylenol overdose, the stages of acetaminophen toxicity, and the available treatments such as N-acetylcysteine therapy, both consumers and healthcare providers can work together to mitigate the risk of severe consequences, including acute liver failure and death.

It is crucial that individuals educate themselves on the safe usage of OTC medications and that healthcare professionals remain up-to-date on current treatment protocols. Ultimately, vigilance and awareness are essential in preventing the devastating impact of acetaminophen overdose on individuals. 

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