Liver and Polypharmacy

Polypharmacy

Basic medication research does not always take into account the reality that elderly people with only one chronic condition are a rarity and will become even rarer as life expectancy, and thus the accumulation of chronic diseases, continues to increase.

For example, in diabetes 2, a large proportion of patients are elderly and often suffer from a series of ailments, each of which requires a treatment guideline. Cross-fertilization of diseases and treatments has hardly been studied to date. For many medicines, the effect on elderly patients has not been specifically studied, while such research is needed to substantiate treatment prescriptions. Standardization has shortcomings.

Some medicines are already metabolised (activated or inactive) in the intestine by the cytochrome P450 enzyme system (CYP450) and in particular the subfamily 3A4. The substance is then transported to the liver via the portal vein system. Many medicines undergo (further) processing in the liver. This processing usually involves converting the medicine into an inactive substance. This step is also carried out by the CYP450. The activity of this system decreases slightly with age, partly due to reduced liver blood flow and a decrease in liver volume.

This can therefore mean that a medicine remains in the body for longer in higher doses in the elderly and therefore accumulates more quickly with a standard dose.

Another important problem with the CYP450 system is that many medicines can influence the functioning of these enzymes. The distribution of medicines is slightly influenced when total body water and lean body mass decrease with age, resulting in a relative increase in body fat. This may lead to a prolonged half-life of lipophilic drugs (e.g. diazepam) due to the relative increase in adipose tissue, especially in the case of polar (hydrophilic) agents (digitoxin, theophylline, gentamicin, alcohol).