Each week we will aim to bring out a concise email that provides 4-5 key pieces of information addressing a specific issue in clinical therapeutics.
This week: Pharmacogenomics (part 2)
It is clear that pharmacogenomic differences between people can be used to predict some aspects of the response to treatment with some medications. This may arise from the way a medication interacts with specific receptors, or by virtue of variability in the disposition (pharmacokinetics) or the drugs.
- One practical aspect of pharmacogenomics that has already established clinical utility relates to the activity of certain enzymes acting in the liver. The Cytochrome P450 (CYP) isoenzymes are critical in the metabolism of various drugs. The relative activity of these enzymes is subject to genetically determine variability and can impact directly upon the pharmacologial activity of the medicines.
- Many drugs are metabolised by one of a small number of the CYP isoenzymes – the most important of these are CYP1A2, CYP2D6, CYP2C9 and CYP3A4. Genotypes encountered in each person can mean that an individual may have reduced, normal or increased activity of each of the CYP enzymes. This can have a profound effect on the activity of various medications.
- It is usually the case that when the activity of an enzyme is reduced (compared to the activity observed in other people), the pharmacological activity of that drug tends to be increased. The individual is sometimes referred to as a ” slow metaboliser.”
- However, some medications are actually administered in an inactive form, and require metabolic activation to achieve pharmacological effect. In these cases, a slow metaboliser will actually tend to experience reduced pharmacological effects of the drug.
Please consider these issues when preparing or interpreting RMMR reports or education sessions. Contributions of content or suggested topics are welcome and should be sent directly to firstname.lastname@example.org.