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Acetaminophen, Tylenol Liver Damage

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  • claudine intexas
    Acetaminophen, Tylenol Liver Damage Is it safe for me to take Tylenol? Tylenol is currently the most popular painkiller in the United States. Americans take
    Message 1 of 2 , Jan 30, 2003
      Acetaminophen, Tylenol Liver Damage
      "Is it safe for me to take Tylenol?"

      Tylenol is currently the most popular painkiller in the United
      States.
      Americans take over 8 billion pills (tablets or capsules) of Tylenol
      each year. Acetaminophen is the general (generic) name for Tylenol,
      which
      is a brand name. Although acetaminophen is contained in over 200
      medications, most of them do not have the name 'Tylenol' on their
      labels.
      Moreover, just about every patient with liver disease in my practice
      invariably asks: Is it safe for me to take Tylenol? or How much
      Tylenol
      can I take? These questions highlight the public's awareness of the
      potential for acetaminophen to cause liver damage or injury.

      Tylenol is a very effective pain-killing (analgesic) and
      fever-reducing
      (anti-pyretic) agent. It is also a very safe drug as long as the
      recommended dosage is not exceeded. In fact, the use of Tylenol
      instead of
      aspirin to treat fevers in infants has greatly reduced the occurrence
      of
      Reyes syndrome, an often fatal form of liver failure. Ironically,
      however, taking too much Tylenol (an overdose) can also cause liver
      failure,
      although by a different process (mechanism), as discussed below.

      Do the recommended doses of Tylenol cause any liver damage?

      Some early reports did describe the occurrence of chronic liver
      disease
      that was associated with the long-term use of Tylenol in the
      recommended doses. These studies were published in the 1970s,
      however, and I
      suspect that many of these patients may have had unrecognized chronic

      hepatitis C infection. Anyway, today, the consensus is that the usual
      doses
      of Tylenol cause significant liver damage only rarely or not at all
      in
      people with normal livers.

      Likewise, a person with liver disease does not appear to be at an
      increased risk of developing additional liver injury from taking
      Tylenol.
      This is so regardless of the cause of the liver disease and provided
      the
      patient does not drink alcohol regularly. Thus, Tylenol is quite safe

      to use in the usual dose in patients with acute (brief duration) or
      chronic (long duration) hepatitis. For example, Tylenol is routinely
      prescribed to treat the flu-like symptoms that can be caused by
      interferon
      treatments for patients with chronic hepatitis. Keep in mind,
      however,
      that all drugs, including Tylenol, should be used with caution, if at

      all, in patients with severe liver disease, such as advanced
      cirrhosis
      (scarring of the liver) or liver failure.

      Why should we know that the generic name of Tylenol is acetaminophen?


      For the remainder of this discussion, the generic name acetaminophen,

      rather than to the brand name Tylenol will be used. I decided to do
      this
      to emphasize the need for people to read the labels of medicine
      bottles
      carefully. As mentioned above, the labels usually will say
      acetaminophen rather than Tylenol. For example, each tablespoon of
      the common
      nighttime cold remedy, Nyquil, contains 500 milligrams (mg) of
      acetaminophen. Similarly, each tablet of Vicodin, a popular, potent
      painkiller that
      contains a narcotic, has also either 500, 650, or 750 mg of
      acetaminophen, depending on the formulation.

      As already mentioned, an overdose of acetaminophen can cause liver
      damage. This damage occurs in a dose-related manner. (Some other
      medications can cause liver injury in an unpredictable fashion that
      is unrelated
      to the dose.) In other words, liver injury from acetaminophen occurs
      only when someone takes more than a certain amount of the drug.
      Likewise,
      the higher the dose, the greater is the likelihood of the damage.
      What
      is more, this liver injury from an overdose of acetaminophen is a
      serious matter because the damage can be severe and result in liver
      failure
      and death. In fact, acetaminophen overdose is the leading cause of
      acute (rapid onset) liver failure in the U.S. and the United Kingdom.


      Just how much acetaminophen is safe to take?

      For the average healthy adult, the recommended maximum dose of
      acetaminophen over a 24 hour period is four grams (4000 mg) or eight
      extra-strength pills. (Each extra-strength pill contains 500 mg and
      each regular
      strength pill contains 325 mg.) A person who drinks more than two
      alcoholic beverages per day, however, should not take more than two
      grams of
      acetaminophen over 24 hours, as discussed below. For children, the
      dose
      is based on their weight and age, and explicit instructions are given

      in the package insert. If these guidelines for adults and children
      are
      followed, acetaminophen is safe and carries essentially no risk of
      liver
      injury.

      On the other hand, a single dose of 7 to 10 grams of acetaminophen
      (14
      to 20 extra-strength tablets) can cause liver injury in the average
      healthy adult. Note that this amount is about twice the recommended
      maximum dose for a 24 hour period. In children, a single dose of 140
      mg/kg
      (body weight) of acetaminophen can result in liver injury. Amounts of

      acetaminophen, however, as low as 3 to 4 grams in a single dose or 4
      to 6
      grams over 24 hours have been reported to cause severe liver injury
      in
      some people, sometimes even resulting in death. It seems that certain

      individuals, for example, those who regularly drink alcohol, are more

      prone than others to developing acetaminophen-induced liver damage.
      To
      understand this increased susceptibility in some people, it is useful
      to
      know how acetaminophen is processed (metabolized) in the liver and
      how
      the drug causes liver injury.

      How is acetaminophen processed (metabolized) in the body?

      The liver is the primary site in the body where acetaminophen is
      metabolized. In the liver, acetaminophen first undergoes sulphation
      (binding
      to a sulphate molecule) and glucuronidation (binding to a glucuronide

      molecule) before being eliminated from the body by the liver. The
      parent
      compound, acetaminophen, and its sulphate and glucuronide compounds
      (metabolites) are themselves actually not harmful. An excessive
      amount of
      acetaminophen in the liver, however, can overwhelm (saturate) the
      sulphation and glucuronidation pathways. When this happens, the
      acetaminophen is processed through another pathway, the cytochrome
      P-450 system.
      From acetaminophen, the P-450 system forms an intermediate metabolite

      referred to as NAPQI, which turns out to be a toxic compound.
      Ordinarily,
      however, this toxic metabolite is rendered harmless (detoxified) by
      another pathway, the glutathione system.

      How does an overdose of acetaminophen cause liver injury?

      The answer is that liver damage from acetaminophen occurs when the
      glutathione pathway is overwhelmed by too much of acetaminophen's
      metabolite, NAPQI. Then, this toxic compound accumulates in the liver
      and causes
      the damage. Furthermore, alcohol and certain medications such as
      phenobarbital, phenytoin, or carbamezepine (anti-seizure medications)
      or
      isoniazid (anti-TB drug) can significantly increase the damage. They
      do
      this by making the cytochrome P-450 system in the liver more active.
      This
      increased P-450 activity, as you might expect, results in an
      increased
      formation of NAPQI from the acetaminophen. Additionally, chronic
      alcohol use, as well as the fasting state or poor nutrition, can each
      deplete
      the liver's glutathione. So, alcohol both increases the toxic
      compound
      and decreases the detoxifying material. Accordingly, the bottom line
      in
      an acetaminophen overdose is that when the amount of NAPQI is too
      much
      for the available glutathione to detoxify, liver damage occurs.

      Is overdose with acetaminophen usually accidental or intentional?

      In the U.S., suicide attempts account for over two thirds of
      acetaminophen-related liver injury, whereas accidental overdose
      accounts for only
      one third of the cases. In young children, accidental overdose
      accounts, surprisingly, for an even lower percent of the cases. That
      is, among
      these often-curious toddlers, accidental overdose is responsible for
      less than 10% of the instances of acetaminophen toxicity. Moreover,
      the
      vast majority of these accidental overdoses were due to unintentional

      overdoses given by the caregivers of the children.

      How can accidental overdose be avoided in adults?

      To avoid unintentional overdoses among adults, I offer the following
      suggestions.


      Read the labels of the medication bottles carefully and determine the

      amount or strength of acetaminophen in each pill or spoonful.
      Become familiar with all of the other medications that you are
      taking.
      Remember that over 200 drugs contain acetaminophen as one of the
      ingredients and that certain drugs, such as phenobarbital, can
      significantly
      increase liver damage.
      Before you take the medication, write down (record) the maximum safe
      number of pills or spoonfuls that you can ingest over 24 hours. Stick
      to
      that quantity and do not deviate. If, however, you are unsure of the
      safe number of doses or think that you need to take more than you
      should,
      call your doctor or pharmacist.
      When you receive a prescription for a new medication, ask your doctor

      or pharmacist whether it affects the body's metabolism (processing)
      of
      the other medications that you are taking, including acetaminophen.
      If you have been drinking alcohol regularly, do not exceed taking 2
      grams of acetaminophen over 24 hours. Be honest with yourself about
      the
      ingestion of alcohol.
      Record the number of pills or spoonfuls of acetaminophen and the time

      that you take them.

      How can overdose be avoided in children?

      The dosing of acetaminophen for children, as previously mentioned,
      depends on their weight and age. To avoid overdose in children,
      follow the
      same procedures for them as suggested above for adults. Beyond that,
      two adults should independently determine the dose of acetaminophen
      for a
      child. If there is disagreement about the recommended dose, consult a

      pharmacist or physician. These precautions are not excessive when you

      consider that in one experimental mock situation, only 30% of adults
      correctly calculated the dose of acetaminophen for their child. If a
      baby-sitter is caring for a sick child, parents should carefully
      write out
      the dose and schedule for the administration of the drug. The fact is

      that each year, in children with high fevers who were given
      repetitive
      doses of acetaminophen, deaths have occurred due to accidental
      overdose
      and the resulting liver damage.

      What happens to a person with acetaminophen-induced liver damage?

      Three clinical stages (phases) of acetaminophen-induced liver injury
      have been described. During the first phase, that is, the initial 12
      to
      24 hours or so after ingestion, the patient experiences nausea and
      vomiting. For the next perhaps 12 to 24 hours, which is the second
      phase or
      the so-called inactive (latent) phase, the patient feels well. In the

      third phase, which begins about 48 to as late as 72 hours after the
      ingestion of acetaminophen, liver blood test abnormalities begin to
      appear.
      Most notably, extremely high (abnormal) levels of the liver blood
      tests, AST and ALT, are common with this type of liver injury. The
      outcome
      (prognosis) of the liver injury can be predicted fairly accurately on

      the basis of the patient's clinical exam and blood tests. For
      example, at
      one extreme, if the patient develops severe acid buildup in the
      blood,
      kidney failure, bleeding disorders, or coma, then death is almost
      certain. Only a liver transplant can possibly save such a patient.

      What should be done if acetaminophen toxicity is suspected?

      A physician should evaluate the individual immediately. Remember that

      bringing the bottles of acetaminophen and all of the person's other
      medications to the emergency room is always useful. The risk that an
      acetaminophen overdose will cause liver injury correlates with the
      blood
      level of acetaminophen relative to the time the drug was taken.
      Physicians,
      therefore, are able to estimate the patient's probability of
      developing
      liver injury after an overdose. To make this determination, they
      obtain
      the patient's history of acetaminophen ingestion and measure the
      blood
      level of the drug. With this information, the doctor then can refer
      to
      a table (nomogram) that provides an estimate of the risk of
      developing
      liver injury. The accuracy of this estimate, however, depends on the
      reliability of the time of ingestion and whether the acetaminophen
      was
      taken over a period of time or all at once.

      With suspected acetaminophen overdose, the doctors usually will pump
      (gavage) the patient's stomach to remove pill fragments. In reality,
      many
      individuals who overdose with acetaminophen in a suicide attempt will

      have taken other pills in addition. Some doctors, therefore, will
      consider treating the patient with activated charcoal, which binds
      (and
      thereby inactivates) many medications. However, this treatment is
      controversial because of a concern that the activated charcoal may
      also bind the
      antidote for acetaminophen overdose.

      Patients who are thought to be at a high-risk or even only at a
      possible risk of developing acetaminophen liver injury should be
      given the
      antidote, N-acetyl cystiene (Mucomyst) orally (or intravenously in
      Europe). This drug works by indirectly replenishing glutathione. The
      glutathione, as you recall, detoxifies the toxic metabolite of the
      acetaminophen. The N-acetyl cystiene is most effective when
      administered within 12
      to 16 hours after the acetaminophen was taken. Most physicians
      however,
      will administer N-acetyl cystiene even if the patient is first seen
      beyond this 16 hour period. Thus, a British study showed that
      patients
      already with liver failure who then received the N-acetyl cystiene
      were
      more likely to survive than patients who did not receive the
      antidote.
      Moreover, the survival occurred in these patients regardless of the
      time
      of initial administration of N-acetyl cystiene. Finally, people who
      recover from acetaminophen-induced liver damage are left,
      fortunately,
      with no residual or ongoing (chronic) liver disease.

      Acetaminophen (Tylenol) Liver Damage:

      Acetaminophen is a very safe drug when taken as directed, even for
      people with liver disease. Nevertheless, every drug carries risks.
      Liver damage from acetaminophen, which can be severe, can result
      either
      from an overdose or from regular doses that are taken while drinking
      alcohol.
      Most cases of acetaminophen-induced liver injury are caused by an
      intentional or suicidal overdose.
      Unintentional or accidental overdose of acetaminophen can usually be
      avoided with care and attention to the dosing.
      Physicians can estimate a patient's probability of developing liver
      injury based on the timing of the overdose and the blood level of the

      drug.
      In patients with acetaminophen liver damage, the usual clinical
      sequence is nausea and vomiting for the first 12-24 hours, then the
      patient
      seems well for the next 12-24 hours, after which abnormal liver blood

      tests develop.
      An antidote, N-acetyl cystiene, is available and should be given to
      the
      patient as soon as possible, preferably within 16 hours after the
      acetaminophen was taken.
      Medical Author: Tse-Ling Fong, M.D.
      Source: http://hepcvets.com/drugs/tylenol.html



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