What Are the Different Antidotes for Acetaminophen?

There are two drug antidotes for acetaminophen, N-acetylcysteine (NAC) and methionine. NAC is the customary antidote for acetaminophen, but methionine may be administered when NAC is not a viable option. Activated charcoal, a highly porous form of carbon, can also be viewed as a universal antidote appropriate for treating an acetaminophen overdose in select cases.

Also known as paracetamol, acetaminophen is a medication taken for pain management and fever reduction. With various dosage strengths and brand names available, the drug is found in numerous over-the-counter and prescription painkillers, where it is usually combined with other drugs. Wide availability has made the drug a primary cause of liver damage and liver failure, sometimes leading to death. When an antidote is warranted, physicians will usually take into account the length of time before the victim presents for treatment to determine which antidotes for acetaminophen to use.

Once taken, oral acetaminophen is rapidly absorbed into the gastrointestinal (GI) tract and then into the bloodstream. As the blood filters the drug through the liver, it is broken down. A small amount of the compound breaks down into N-acetyl-p-benzoquinone imine (NAPQI), a toxic byproduct. This byproduct is not an issue when consuming the drug at regular doses because the liver naturally produces glutathione, a chemical that neutralizes NAPQI. Overdosing or regular consumption at higher than recommended levels, however, causes more NAPQI to be made and depletes glutathione. As a result, liver damage or liver failure leading to death can occur unless antidotes for acetaminophen are given.

Activated charcoal is usually given only when an overdose is treated immediately after taking acetaminophen, generally within the first two hours. The odorless tasteless powder is normally mixed with water and given orally, either by drinking or through a tube. Similar to using a dry sponge to soak up water, the charcoal attracts and binds up much of the substance while it is still in the GI tract. This may prevent dangerous levels of NAPQI from occurring because less of the drug makes it to the bloodstream and into the liver. The charcoal cannot be digested and will carry the trapped drugs through the GI tract before being eliminated as waste.

Of the possible antidotes for acetaminophen, NAC is the universal standard. The compound is a derivative of cysteine, an amino acid found in foods and naturally produced by the body. It works to boost the body’s production of glutathione to render NAPQI inert. Although NAC is thought to be equally effective in oral or intravenous (IV) forms, an IV is more likely to be given to overdose victims who are unconscious, persistently vomiting, or asphyxiating to ensure the drug is absorbed. Studies indicate that NAC provides maximum protection against toxicity when given within 10 hours after overdosing but can be somewhat effective if received within 24 hours.

Antidotes for acetaminophen also include methionine, an oral drug. This essential amino acid is not created by the body but must be ingested from food sources or supplements. In the body, methionine is used to create cysteine, so it can also be beneficial to improving glutathione production. The drug has less clinical data studying its effectiveness, however, and seems to have a drastic reduction in protecting the liver if taken 10 hours after overdosing. Therefore, its usage is generally limited to emergency treatment occurring outside of health care facilities when NAC is unavailable.

With unintentional overdoses, it is more likely that the victim will not be treated with antidotes for acetaminophen, as symptoms may not immediately present. When treatment is delayed, liver failure may be more likely to occur and the victim may require a liver transplant in order to survive. If an acetaminophen overdose is suspected, it is vital that emergency medical assistance begin immediately to reduce liver damage.