The Effects
of Acetaminophen on the Liver
The effects of acetaminophen, also referred to as paracetamol (par-a-cet-a-mol), on the
liver
can lead to rapidly progressing liver failure in the event of an overdose or when it is combined with other drugs such as isoniazid (i-so-ni-a-zid) - a colorless crystalline compound used to treat tuberculosis; carbamazepine (car-ba-maz-e-pine) - an analgesic anticonvulsant drug used to treat epilepsy, pain, and bipolar disorder; or phenytoin (phen-y-to-in) – a drug that controls epileptic convulsions.
The reason paracetamol can cause liver damage is because it ordinarily breaks down into harmless metabolites in the liver when the amount ingested is low and the liver is healthy. When the liver isn't healthy, it is metabolized through a different system, which leads to its conversion into harmful metabolites that have toxic effects on the liver.
Even in a healthy liver, when the proper risk factors are present, acetaminophen can cause liver damage.
In order to understand how acetaminophen can cause liver damage, first you must have a basic working knowledge of the interaction between the liver and this drug.
Normally, in a healthy liver, paracetamol is broken down before being eliminated from the body by the liver. During this metabolic pathway, no harmful or toxic intermediate compounds are formed, so the liver does not suffer from and toxic or harmful side effects.
Problems with liver toxicity occur when there is too much drug challenging the liver at one time. In this situation, another metabolic process is activated, known as the CYP-450 system. During CYP-450 metabolism, a toxic intermediate metabolite known as NAPQI is formed.
NAPQI is an acronym for the chemical N-acetyl-p-benzo-quinone imine, which is a toxic byproduct produced during the xenobiotic (xen-o-bi-ot-ic) metabolism of the analgesic paracetamol.
Xenobiotic describes a chemical compound such as a drug or pesticide that is foreign to the body of a living organism.
In most cases when prescribed amounts of paracetamol are adhered to, NAPQI is normally produced only in small amounts which is then almost immediately detoxified in the liver by the glutathione (glu-ta-thi-one) system.
Glutathione is an important antioxidant that protects our cells from toxins such as free radicals.
When an overdose of paracetamol takes place, larger amounts of NAPQI are produced causing the glutathione system to get overwhelmed resulting in the NAPQI not being effectively detoxified, resulting in severe damage to the liver.
This situation may result in death from sudden and severe liver failure several days after the overdose.
Filtering
alcohol
, one of many poisonous substances the liver filters from our blood, depletes the liver of glutathione.
In a healthy liver, acetaminophen is unlikely to build up fast enough to cause liver damage. However, in some healthy people, it can cause liver damage simply because they have an overactive CYP-450 system.
An overactive CYP-450 system is caused by chronic alcohol use as well as CYP-450 inducing drugs like carbamazepine, isoniazid, and phenytoin.
These drugs cause the CYP-450 system to become overactive, and therefore overwhelm the ability of the liver to clear NAPQI, leading to liver damage.
In a diseased liver, the probability of toxic buildup of NAPQI is much higher simply because the liver is forced to deal with acetaminophen while having a decreased ability to detoxify the metabolites. This leads to damage which will occur at a much more rapid pace than in a healthy liver.
Anyone who is on CYP-450 inducing drugs or has liver damage should consult a doctor before considering the use of acetaminophen for pain.
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