The liver plays an important role in the metabolism of drugs. In elderly, the liver mass is decreased as well as the blood flow through the liver. The latter is mainly due to a decreased cardiac output. There is also a decline in viable liver cells and thus of the rate of metabolism. The activity of the phase II metabolic enzymes (conjugations: glucuronidation and sulphation) is quite well preserved during ageing. However, the intrinsic activities of Phase I reactions (oxidation, reduction and hydrolysis)
are diminished. Specifically, the cP450 enzymes have been well characterised and age-induced alterations in their metabolic activity for various drugs are usually studied. The clinical importance of altered biotransformation is the possibility of drugs being active for a longer period of time than expected. E.g. if a drug is given in daily dosages, it can accumulate to the point of toxicity. Alternatively, drugs may not become active or much later; e.g. when a prodrug needs enzymatic conversion.
Lorazepam and diazepam are two drugs used for anxiety. The first drug will be conjugated; the second oxidised. Which would you use for an elderly anxious patient?
Extra info: Since phase II reactions such as conjugation are preserved in the elderly (whereas phase I reactions such as oxidation are not), lorazepam is the drug of choice.