Figure 1: Structure of paracetamol
Paracetamol (acetaminophen) an analgesic and
antipyretic agent (styrt et al, 1990) is a useful drug in the treatment of mild
to moderate pain such as headache, myalgia, postpartum pain and other
circumstances.
PARACETAMOL METABOLISM
Paracetamol is metabolized primarily in the
liver, where its major metabolites inactive sulfate and glucuronide conjugates,
which are excreted by the kidneys (styrt et al, 1990). Only a small yet significant amount
is metabolized via the hepatic cytochrome p450 enzyme system, which is
responsible for the toxic effects of
paracetamol due to a minor alkylating
metabolite (N-acetyl –p- benzo- quinone imine, abbreviated as NAPQI).
Figure 2 Reactions involved in paracetamol
metabolism (Katzung B, 1999).
The
metabolism of paracetamol is an excellent example of toxication, because the
metabolite NAPQI is primarily responsible for toxicity rather than paracetamol
itself (styrt et al, 1990).
At usual doses, the toxic metabolite
NAPQI is quickly detoxified by combining irreversibly with the sulfhydryl
groups of glutathione or administration of a sulfhydryl compound such as N-
acetylcysteine, to produce a non-toxic conjugate that is eventually excreted by
the kidneys (katzung B, 1990).
PARACETAMOL AS AN AGENT OF OXIDATIVE STRESS
The Liver is the center of drug metabolism,
in the case of an overdose, the liver is overwhelmed by the drug and this can
lead to oxidative stress. Thus oxidative stress is any condition that
consistently interferes with normal body function (Katzung B, 1998)
Paracetamol is contained in many preparations
(both over- the – counter and prescription only medications). In some animals
for example cats – small doses are toxicity. Without timely treatment, overdose
can lead liver failure and death within days; paracetamol toxicity is by far,
the most common cause of acute liver failure in both the United States and the
United Kingdom (styrt et al, 1990).
It is sometimes used in suicide attempts by those unaware of
the prolonged time course and high morbidity associated with paracetamol –
induced toxicity in survivors. Thus in
this research works, paracetamol will be overdose will be administrated to rats
and analysis done to measure the extent of per oxidation