Pharmacogenomics: How Genetics Can Optimize Your Treatment

Pharmacogenomics or pharmacogenetics is the discipline that studies the influence of genes on individual response to drug treatment. This information makes it possible to understand why some drugs work more effectively in some people, while in others they may cause serious side effects or simply not be effective.

The goal of pharmacogenomics is to identify genetic variants that alter the pharmacokinetics or pharmacodynamics of the drug. Pharmacokinetics is related to the absorption, distribution, metabolism and elimination of drugs, while pharmacodynamics is related to the effect of the drug in the body, so any variant that modifies the biological pathways can alter this effect.

Metabolism of drugs

Drugs are chemical substances that are administered to prevent, diagnose or treat disease. Prodrugs, on the other hand, are inactive forms of a drug that are activated in the body by metabolic processes.

Drug metabolism is mediated by enzymes, proteins that carry out chemical reactions that modify the structure of the drug in order to eliminate it from the body. These enzymes are encoded by genes and therefore the presence of genetic variants can affect enzyme activity and consequently the way in which we metabolize drugs.

The effect of genetics on metabolic enzymes can cause one person to metabolize a drug faster or slower than another. This can have a significant impact on the efficacy and safety of drug treatment.

Based on enzyme activity in drug metabolism, individuals can be classified into the following categories or phenotypes:

• Ultrarapid metabolizers
• Fast metabolizers
• Normal metabolizers
• Intermediate metabolizers
• Slow metabolizers

If a person is a slow metabolizer for a certain gene, the implications will be different for different drugs that are metabolized by that pathway. Factors such as therapeutic range or whether the drug is a prodrug or a prodrug will influence the recommendations described in clinical guidelines.

Why is pharmacogenomics important?

Pharmacogenomics is a highly valuable tool that allows us to drastically improve the way we treat diseases. By knowing a patient's genetics, physicians can:

• Selecting the most appropriate drug: based on the genetic profile, the most effective and safest drug can be chosen for each patient.
• Determine the optimal dose: the dose of a drug can be adjusted according to the patient's genetic profile, avoiding side effects and maximizing the efficacy of the treatment.
• Prevent adverse reactions: some people may have immune reactions, toxicity or severe side effects to certain drugs due to genetic variations; by adapting the prescription based on pharmacogenomics we can reduce these types of events.
• Reduce costs: about 3.5% of hospital admissions are due to adverse drug reactions. Pharmacogenomics can help to reduce the associated healthcare costs, in addition to improving the efficacy of pharmacological treatments by avoiding attempts with different drugs and doses, as well as the clinical consequences of ineffective treatments.

How to perform a pharmacogenomic test?

A pharmacogenomic test is usually performed on a saliva or blood sample. DNA is extracted from the sample and genetic variants associated with response to drugs are analyzed with clinical guidelines to guide medical management based on the results. The results are interpreted by a health professional and used to personalize the patient's treatment. It is important to keep in mind that the medication regimen should never be changed except on the advice of a physician.

How is pharmacogenomics applied to clinical practice?

The clinical implementation of pharmacogenomics is becoming increasingly widespread. This is due to the benefits it brings in terms of being able to select the right drug at the optimal dose for each patient. Let us look at several clinical examples:

Clopidogrel

A platelet antiplatelet commonly used in cases of acute myocardial infarction, cerebral infarction, acute coronary syndrome, among others. This drug is administered in its inactive form (prodrug) and is metabolized by CYP2C19 to form the active ingredient. Some variants in the gene are associated with slower than usual metabolism and therefore low levels of the active metabolite, which implies a significant risk of therapeutic failure that justifies a change in medication.

Fluoropyrimidines

Chemotherapeutic agents such as capecitabine and fluorouracil, frequently used for the treatment of solid tumors (gastrointestinal, pancreatic, breast, head and neck). One of the most important enzymes in the metabolism of these drugs is encoded by the DPYD gene. Variants in this gene could reduce the activity of the enzyme, affecting drug metabolism and therefore increasing the risk of adverse reactions that justify a change of medication.

Although pharmacogenomics influences drug response, there are other factors that must also be taken into account as they can intervene in the effectiveness or toxicity of the treatment. Age, gender, weight or even diet or lifestyle habits can influence how a person metabolizes a drug. For this reason, a patient who is prescribed several drugs or nutritional supplements runs the risk that some of them will not exert the necessary therapeutic effect, if they are metabolized by the same enzyme.

Pharmacogenomics represents a breakthrough in personalized medicine. By understanding how our genetic variations are associated with drug response, we can offer safer and more effective treatments for each patient.

From Veritas we offer myPharma, the advanced pharmacogenomic test based on international clinical guidelines that provides simple recommendations for the adaptation of the patient's medication, according to their genetic profile. If you want more information, do not hesitate to contact us.