Pharmacogenomics is the study of how a person’s genetic make-up can affect response to medication. Depending on the genetic variations a person carries, the function of medications can be increased or made ineffective. Pharmacogenomics can also be used to predict which patients will suffer from side-effects. This is a vital tool in clinical decision making, particularly as adverse drug reactions (ADRs) are responsible for a significant number of hospitalizations and deaths each year. In the UK, for example, ADRs are estimated to cost the NHS £600 million annually.
Optimization of drug therapy according to a person’s genotype allows maximum efficiency of a drug with a minimum of side-effects. As drug treatment moves away from a ‘one-dose-fits-all’ approach, the study of genetic variation and its effect on drug treatment response has a vital role to play in the development of personalized medicine.
The two main ways that drugs interact with the body are known as pharmacokinetics and pharmacodynamics. Both of these processes can be impacted by genomics.
Pharmacokinetics
Pharmacokinetic processes are those that affect how the body processes a drug and can be broken down into absorption, distribution, metabolism and excretion. After a drug is given, it must be absorbed and distributed throughout the body. Genomic variation, for example in CYP2D6, can affect this process. Variations in genes make individuals fast or slow metabolisers of drugs. Fast metabolisers are subject to less effect of a drug as it is eliminated quickly from the body. Slow metabolisers are more likely to experience side-effects as levels of drug build up in the body.
Pharmacodynamics
Pharmacodynamics is the effect of the drug on its targets in the body with effects being ‘on-target’ (producing therapeutic effect) and ‘off-target’ (producing undesired effects). Some genetic variants in pharmacodynamic pathways are associated with serious side-effects, such as carbamazepine which can lead to severe hypersensitivity reactions in genetically susceptible people.
As well as its role in streamlining treatment for patients and reducing healthcare costs, the use of genomic information throughout drug development and the clinical trial process will allow for the identification of clinically important genes, allowing better prediction of a drug’s safety and efficacy.
As pharmacogenomics implementation becomes more widespread medical education of healthcare professionals will become fundamental to providing optimum patient care.