Precision medicine for Defence?

Abstract

Proteins control individual patient's response to pharmaceutical medication, be they receptors, transporters or enzymes. These proteins are under the control of genes. The study of these genes and the interplay between multiple genes is pharmacogenomics, with individual genes being termed pharmacogenes. The greatest understanding of pharmacogenetics is of the drug metabolising enzymes, the cytochrome P450s. Almost the entire UK population is likely to have at least one genetic variant that controls these P450s and thus the phenotype for metabolic competence. This means two patients receiving the same medication and dose may have very different responses, from adverse reaction to being ineffective. An individual military person's response to medications can be predicted from their pharmacogenetics, as an example; the response to the commonly prescribed 'pain killers', codeine, tramadol, hydrocodone or oxycodone. These opioids are metabolised into their active forms by the cytochrome 2D6. Four phenotypes classify an individual's metabolic competency: ultra-rapid, extensive, intermediate or poor. A poor metaboliser is at risk of ineffective pain relief from one of the opioids listed, whereas an ultra-rapid metaboliser is at risk of overexposure and subsequent dependency or abuse. In white European populations, the prevalence of the phenotypes is well known and may be used to guide prescribing; however, in other populations such as Nepalese or Pacific Islander the distribution of these phenotypes is unknown. Genotyping provides a framework for the precise treatment of patients and cost-effective use of medication for the UK Armed Forces, as well as potentially providing equity for minority groups.