CPS1: Responding to individual metabolism by genomics and metabolomics

ACPE UAN: 0475-0000-19-020-L04-P. A knowledge based activity.

Linked to EAHP Statements

Section 1 – Introductory Statements and Governance: Statements 1.1, 1.2, 1.3, 1.5, 1.6
Section 4 – Clinical Pharmacy Services: Statements 4.1, 4.3, 4.6, 4.7, 4.8
Section 5 – Patient Safety and Quality Assurance: Statements 5.1, 5.2, 5.4, 5.8, 5.9
Section 6 – Education and Research: Statements 6.2, 6.3, 6.5

Abstract

It is widely accepted that times of the one-fits-all strategy in pharmacotherapy is coming to its end. Public health focuses more and more on personalised and precision medicine. Several challenges have to be considered in terms of policies, human and technical resources, financial balances.
Single nucleotide polymorphisms (SNPs) and their inherited interrelation with non-communicable diseases have detected in the past years by genome-wide association studies (GWAS). Therapeutic Drug Monitoring (TDM) is expanded by omics technology in a way that not only snapshots will result, but a progress in almost real-time. Furthermore, drug selection and dose adaption can be justified on a scientific basis of genes expressed as enzyme activities and metabolites.
A response to medicines as expected for an average patient group depends on normal functions of enzymes on the pharmacokinetic pathway and on normal structures of the receptors on a pharmacodynamic level. Genomics gives the answers on whether inherited inborn errors afford a specific kind of treatment.
This seminar focuses on the analytical techniques followed up by interpretational challenges encountered in today’s pharmacotherapy, sports and black-market scenes. An outlook is presented on the role of the hospital pharmacist as member of the inter- and multi-professional medical care team.

Learning objectives

After the seminar, participants should be able to:
• take into consideration typical analytical challenges of the omics technologies;
• recognise limits of methodologies used in genetic analyses, sports and doping analytics;
• assume best practices and safety criteria as related to omics-based pharmacotherapy;
• assess the challenges of omics data interpretation:
       – for tailoring individual pharmacotherapy in cases of inherited and non-communicable diseases such as cardio-vascular diseases, diabetes mellitus type 2, obesity;
       – for identification of drug-drug and food-drug interactions;
       – for prediction of responders, partial responders, and non-responders in special patient groups and in several ethnicities/migrants.
• explain commonalities in clinical and sports laboratory methodologies for applied activity as hospital pharmacists.

Educational need addressed

Since 2000, omics technologies have become an emerging technology to analyse – among others – the genome, proteome, and metabolome, facilitated by sequencing engines such as the Illumina®. In this way, not only orphan genetic diseases can be diagnosed and treated in time to prevent outbreak of metabolic deterioration, but also life-style behaviour bound to non-communicable diseases with relevance for public health.
Hospital pharmacists are widely concerned by the new technologies as related to whether pharmacotherapy will remain a trial-and-error approach or turn to become rather a tool for fine-tuning precision medicine.

Keywords: Genome-wide association studies, responders and non-responders, one-dose-does-not-fit-all, tailored doses based on omics testing, impact of genomics on clinical pharmacokinetics and dynamics, functionality of hepatic and intestinal CYP450-isoenzymes and receptors as drug and metabolite targets, metabolomics for therapeutic drug monitoring.