02.03.7 Pharmacological Toxic Metabolites

In addition to the metabolites of drug being therapeutic, metabolites may be toxic. Paracetamol is considered by many to be a relatively safe drug. It is considered safe enough to be sold without a prescription. Normally most of the paracetamol is conjugated and excreted in urine (Figure 2.6).

Figure 2.6 Metabolism of paracetamol (Copyright QUT, Sheila Doggrell)

However, a small amount of paracetamol is metabolised by the CYP enzyme system to NAPQI. NAPQI is potentially very toxic to the liver. Fortunately small amounts of NAPQI, in the presence of glutathione, are readily excreted in the urine. Thus, normally, we do not observe toxicity with paracetamol. However, when high doses of paracetamol are administered, the glutathione gets used up, NAPQI levels build up, and become toxic. The main feature of paracetamol poisoning is liver failure. Paracetamol poisoning will be discussed further under treatment of poisoning.