Pharmacogenetics: adapting drugs to genes

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Pharmacogenetics is an area of clinical pharmacology that studies how the variations present in the genome of individuals they can influence the response to medications, aiming to customize the treatment according to the genetic characteristics of each person. In particular, they seek to identify genes that: predispose to disease; modulate drug responses; affect the pharmacokinetics and/or pharmacodynamics of drugs; are associated with adverse reactions.

Also read: Dystrophies retinal: First gene therapy drug is approved in Brazil

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Variations and consequences

The great variability in the response of patients to the same drug is due to several factors, such as: therapeutic adherence, stage of the disease , associated systemic diseases, diet, lifestyle and genetic variations, among others. Differences in therapeutic responses between individuals are generally associated with genetic polymorphisms present in genes that affect pharmacokinetics or pharmacodynamics.

Genes are basically constituted of DNA, which is a large molecule, composed of complex nucleotide sequences (Adenine, Thymine, Guanine, Cytosine). Variations in these sequences are called genetic polymorphisms and are found in the general population in a stable way. The most common forms of genetic polymorphisms are: deletions; mutations; single base substitutions (SBU) or variations in the number of repeated sequences.

Polymorphisms in genes encoding enzymes that participate in metabolism hepatic may affect phase I (oxidation, reduction and hydrolysis) and phase II (conjugation, acetylation, glucuronidation, sulfation and methylation) reactions, particularly the various cytochrome P450 isoforms.

These changes can generate 3 phenotypes:

Slow Metabolizers : individuals usually with decreased or absent metabolizing enzyme. More susceptible to toxicity and adverse reactions.

Intermediate Metabolizers: individuals with “normal” metabolism, considered as the majority of the population.

Fast metabolizers: individuals with increased production of the metabolizing enzyme, which may not reach the expected effect for same dose administered for the majority of the population.
Currently, there are several tests of pharmacogenetic profiles that can assist the physician in prescribing a drug, helping him to recommend the dosage, increasing the effectiveness of the treatment and reducing the risk of adverse reactions. The pharmacogenetic panels used for tests evaluate drugs used in different types of treatment, such as high blood pressure, allergies, respiratory diseases, psychiatric disorders (anxiety, depression, insomnia, psychosis, epilepsy, Alzheimer’s, Parkinson’s, ADHD), chemotherapy, antibiotics, analgesics, anticoagulants, antiarrhythmics, hormones etc.

Learn more: Medical genetics: what do you know about this specialty?

Pharmacogenetics is a research field still in development, which can bring many benefits to public health, avoiding adverse drug reactions in genetically distinct patient subgroups, facilitating the development of new drugs, reducing costs and risks, assisting physicians in prescribing drugs that and will have greater efficacy and greater safety profile.

Author:

Graduation in Medicine from the Federal University of Rio de Janeiro – UFRJ ⦁ Medical Residency in Anesthesiology by the Ministry of Education and Culture ⦁ Title of Specialist in Anesthesiology by Brazilian Society of Anesthesiology at Hospital Federal Andaraí, RJ ⦁ Preceptor of Medical Residency in Anesthesiology at Hospital Federal Andaraí, RJ ⦁ Preceptor of residents in Anesthesiology at the State Institute of Cardiology Aloysio de Castro, RJ ⦁ Post-Graduate Lato sensu in Pain by the Albert Einstein Israeli Faculty of Health Sciences ⦁ Equivalence in Medicine at the University of Lisbon.

References:

Suarez-Kurtz G. Pharmacogenetic testing in oncology: a Brazilian perspective. Clinics (Sao Paulo). 2018 Oct 11;73(suppl 1):e565s. doi: 10.6061 /clinics/2018/e565s.

Metzger IF, Souza-Costa DC, Tanus-Santos JE. Pharmacogenetics: principles, applications and perspectives. Medicine (Ribeirão Preto). December 30, 2006 ;39(4):515-21. It hurts: 10.11606/issn.2176-7262.v39i4p515-521

Roden DM, Van Driest SL, Mosley JD, Wells QS, Robinson JR, Denny JC, Peterson JF. Benefit of Preemptive Pharmacogenetic Information on Clinical Outcome. Clin Pharmacol Ther. 2018 May;103(5):787-794. It hurts: 10.1002/cpt.1035. See more benefits of being a user of Portal PEBMED:

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The PEBMED Portal is intended for doctors and health professionals . Our contents inform recent panoramas of medicine.

If you are interested in publishing your curriculum on the internet, connecting with patients and increasing your differentials, create a free profile on AgendarConsulta, the partner site of PEBMED.

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