Acetaminophen (Paracetamol) Toxicity - A Review

What Is Acetaminophen Toxicity?

Acetaminophen (Paracetamol) is a very common drug used to relieve pain and fever. It is available over the counter in most countries. This medication is listed in the Essential Drug List (EDL) by the WHO (World Health Organization).

This medication is considered safe to use in children and even in pregnant women. Acetaminophen is available in various forms and strengths. These include oral tablets, capsules, liquid formulations, and suppositories.

Acetaminophen is safe at therapeutic doses, but its overdose can cause toxicity. Acetaminophen toxicity (AT) may occur due to a dosing error, accidental ingestion by children, or intentional self-harm. AT may occur purposely, such as when a person knowingly takes more than the recommended dose, or accidentally, when a person is unaware of the Acetaminophen present in different products they are taking. This may exceed the recommended maximum daily dose.

For the Acetaminophen toxicity to occur, a person must take several times the recommended dose of Acetaminophen. The recommended dose for a person weighing 70 kg (155 pounds) is two to three 325-milligram tablets every six hours. Toxicity is possible when taking around 30 tablets together, and death may occur if he takes 40 tablets or more together.

AT can occur when it is taken multiple times in smaller doses over time. This may cause liver damage. After liver damage, liver failure may occur. AT accounts for 50 percent of all liver failure cases in the United States and 20 percent of all liver transplant cases. Factors responsible for hepatotoxicity include underlying liver disease, alcohol use disorder, and unintentional overdose.

What Are the Symptoms of Acetaminophen Toxicity?

Symptoms may not be observed immediately. If an overdose has occurred, it may show in different stages. These include:

• Stage 1:

This stage may be observed after several hours. The affected person may vomit, but they do not appear to be seriously ill. Usually, symptoms are not seen in this stage.

• Stage 2:

It typically appears between 24 and 72 hours. At this stage, symptoms include vomiting, nausea, and abdominal pain. Blood tests show liver enzyme abnormalities.

• Stage 3:

This stage typically occurs 3 to 4 days after the initial infection. At this stage, vomiting worsens. Tests show the liver is not functioning properly; jaundice and bleeding may develop. In some cases, the kidneys may not function properly, and the pancreas may become inflamed, leading to pancreatitis.

• Stage 4:

This stage may appear after five days. The person may either recover or may experience fatal liver failure, and even other organs may fail.

If toxicity has occurred due to multiple smaller doses over a period, the first symptom is abnormal liver function, but sometimes jaundice or bleeding may occur first.

Other symptoms of AT include:

• Pain in the right side of the abdomen (below the ribs).

• Their appetite may be lost.

• They experience weakness.

• Urine may become dark or bloody.

• The affected person may get confused, feel sleepy, or lose consciousness.

• Breathing problems may occur.

• Vision may become blurred.

How to Diagnose Acetaminophen Toxicity?

The diagnosis of AT can be done in the following ways.

• The healthcare provider asks about your medical history, which includes recent medications you are taking. He will also ask details about how much was ingested, how much time has passed after the ingestion, and in what form it was ingested. Blood tests are done to determine the levels of Acetaminophen. A liver function test is performed to assess whether the liver is functioning.

Other tests include:

• Tests for electrolytes, amylase, kidney function tests, lipase, and coagulation factors.

• Imaging tests, such as ultrasound, are used to assess liver enlargement.

• The Rumack-Matthew Nomogram is used to check hepatotoxicity. This test can be used only if the time of acute ingestion is known.

• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels are measured.

What Is the Treatment for Acetaminophen Toxicity?

The treatment option is determined based on the timing of Acetaminophen ingestion.

• Gastric lavage:

If the overdose occurred within 30 minutes of treatment, gastric lavage may be considered. A healthcare provider may try to empty the stomach content. A tube may be used and inserted through the mouth to empty the stomach. This procedure is gastric lavage.

• Activated charcoal:

If the overdose occurred just four hours before the treatment, activated charcoal may be used. Activated charcoal is a powder mixed with a liquid. This activated charcoal binds with toxic chemicals. These chemicals pass through the intestines and exit the body without getting absorbed.

• N-acetylcysteine (NAC):

NAC acts as an antidote for AT. This medication can be given after eight hours of overdosing. It can help prevent liver damage. NAC is a precursor of glutathione. This helps in decreasing AT by increasing glutathione stores in the liver and through other mechanisms. It cannot reverse the damage already caused in the liver. Many doses of NAC may have to be given, and it depends on AT.

• Liver transplant:

If the liver damage is severe, your healthcare provider may suggest a liver transplant.

What Are the Acetaminophen Toxicity Complications?

The complications of AT are life-threatening conditions if not addressed soon. These include:

• Liver damage may further lead to liver failure.

• Kidney failure may occur.

• Inflammation of the pancreas (pancreatitis).

• Sometimes death may result.

• Acute tubular necrosis (acute kidney injury to the filtering tubules due to toxic substances or lack of blood flow).

• Hepatorenal syndrome (advanced liver disease, like cirrhosis, in which the kidneys fail without any intrinsic damage).

• Encephalopathy (a brain disorder that affects brain function).

• Bleeding diathesis (abnormal tendency to bleed).

• Non-IgE-mediated anaphylaxis reaction to N-acetylcysteine (pseudoallergic reaction).

• Stevens-Johnson syndrome (fatal skin reaction, triggered by medications).

• Toxic epidermal necrolysis (a life-threatening condition with widespread, painful rash causing blister-like severe burn).

• Acute generalized exanthematous pustulosis (Severe skin reaction causing sudden pustules on skin with fever and increased white blood cells).

How to Prevent Acetaminophen Toxicity?

Following the dosage instructions is the best option to prevent AT. Though Acetaminophen is an over-the-counter medication, it should be taken with a healthcare provider’s prescription, and it should not be combined with other drugs that contain Acetaminophen.

Preventive measures to avoid AT include:

• Medications should be kept out of reach of children and those who tend to take them frequently.

• The label should be read and understood before consuming or giving it to others. If you have doubts regarding the dosages, please talk to your doctor.

• Avoid giving double doses. Be careful while giving combined medications, as both may contain Acetaminophen. Read the label carefully, and then give or take for yourself.

• Always follow your healthcare provider’s instructions. Do not give or take medicines more than the recommended doses. There should be a gap between the doses as instructed by your doctor. When giving liquid medicine, always use a measuring device to administer or adjust the dose.

• Write and keep a track of dosages taken or given.

• While giving or taking medicine, please do not be in a dark room; instead, take medicines in a well-lit area.

When to See a Doctor for Acetaminophen Toxicity?

AT can be life-threatening, and death may occur if not addressed immediately. Hence, if you believe the dose consumed is unsafe, please immediately contact the emergency room for assistance. You can also seek help from the poison control center.

Conclusion

Acetaminophen, also known as Paracetamol, is a common over-the-counter medication used for pain relief and fever reduction. It is a safe drug that can be used even without a prescription. Sometimes, it's overdosing that can occur due to intentional or unintentional use of an overdose. In such cases, immediate help should be sought from your doctor to avoid a life-threatening emergency. Hence, it is important to know in detail about AT.

Key Takeaway From iCliniq

Acetaminophen is a common drug used in day-to-day life. Acetaminophen toxicity cannot be taken lightly as it may cause emergency and even death if not addressed. For more information, you can consult a general medicine physician at iCliniq.