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Abstract(s)
Introdução
A Hipertensão Arterial (HTA) ocorre quando a pressão arterial, isto é, a força que o sangue
exerce contra as paredes arteriais, é persistentemente elevada. A HTA é multifatorial,
estando dependente de fatores ambientais, vasculares, hormonais e genéticos, entre
outros A sua prevalência crescente constitui um problema de saúde pública, dados os
conhecidos efeitos da HTA no organismo a nível de vários sistemas: cardiovascular,
neurológico, músculo-esquelético e renal, para nomear alguns.
A sua terapêutica inclui intervenções não farmacológicos, como a adoção de um estilo de
vida mais saudável, e farmacológicas. As classes farmacológicas mais usadas são os
Inibidores da Enzima Conversora de Angiotensina, os Antagonistas dos Recetores de
Aldosterona, os Bloqueadores dos Canais de Cálcio, os Diuréticos Tiazídicos e os Betabloqueantes.
Vários estudos têm tido como objetivo identificar possíveis fatores que influenciam a
resposta à terapêutica anti-hipertensora. Muitos deles estabeleceram uma interação entre
o genoma humano (e as suas variações) e a resposta à farmacoterapia instituída. Este facto
justifica a importância da farmacogenómica, que estuda a influência da variabilidade
genética na resposta à terapêutica de diversas patologias, entre as quais, a HTA. A
importância da individualização terapêutica tem vindo a ganhar espaço na otimização da
terapêutica. Na HTA, um dos fármacos clássicos utilizados tem sido a Hidroclorotiazida,
um diurético tiazídico, cuja variabilidade interindividual à resposta à terapêutica tem
vindo a ser associada a diversos polimorfismos genéticos. O estudo destes polimorfismos
numa população poderá levar a uma melhor aplicação deste fármaco.
Objetivos
O objetivo principal desta dissertação é o desenvolvimento de um projeto para avaliar a
variabilidade genética interindividual da resposta à hidroclorotiazida em doentes
portugueses com HTA. Metodologia
Para a atualização do tema e estudo de outros projetos neste âmbito, foram consultadas
guidelines atuais da terapêutica da HTA e foi realizada uma pesquisa bibliográfica, com
recurso à plataforma PubMed, durante o período de outubro de 2022 a março de 2023. As
palavras-chave utilizadas foram as seguintes: hipertensão arterial, farmacogenómica,
farmacogenética, variabilidade genética, polimorfismos genéticos, hidroclorotiazida,
diuréticos tiazídicos, beta-bloqueantes, bloqueadores dos canais de cálcio, inibidores da
enzima conversa de angiotensina e antagonistas dos recetores de aldosterona.
Para o desenho dos primers, foi utilizada a base de dados GenBank.
Após a análise do material encontrado, foi realizada esta dissertação.
Resultados e Discussão
Após uma breve revisão e atualização do tema, concluiu-se que existem inúmeros genes
que influenciam a resposta terapêutica aos fármacos anti-hipertensores. A presença de
polimorfismos nestes genes é responsável por uma variação do controlo tensional, que
pode, ou não, ser favorável. Assim, é importante perceber se os indivíduos com o
diagnóstico de HTA apresentam polimorfismos genéticos que possam modificar a resposta
à terapêutica farmacológica anti-hipertensora que efetuam. Ao identificar a presença
destas variações interindividuais, torna-se possível o ajuste terapêutico de forma a que a
medicação seja personalizada e o mais eficaz possível para o doente em questão.
Neste sentido, foi desenvolvido um projeto para a avaliação da variabilidade genética
interindividual da resposta à hidroclorotiazida em doentes portugueses com HTA. Após a
referida atualização do tema, foi possível identificar o gene candidato, o polimorfismo
genético candidato e proceder à descrição do projeto que se encontra pronto a ter início. Conclusões
De facto, continua a ser pertinente o estudo da influência dos polimorfismos genéticos na
resposta à hidroclorotiazida e outros fármacos anti-hipertensores, estudo esse que deve
ser desenvolvido a nível nacional. É de extrema importância perceber a prevalência destes
polimorfismos e adaptar a medicação consoante a presença dos mesmos, de forma a obter
uma resposta terapêutica o mais eficaz possível.
Introduction Arterial Hypertension (HT) occurs when blood pressure, that is, the force that blood exerts against arterial walls, is persistently high. Hypertension is multifactorial, depending on environmental, vascular, hormonal and genetic factors, among others. Its growing prevalence constitutes a public health problem, given the known effects of hypertension in various systems of the body: cardiovascular, neurological, musculoskeletal and renal, to name a few. Its therapy includes non-pharmacological interventions, such as adopting a healthier lifestyle, and pharmacological ones. The most used pharmacological classes are Angiotensin-Converting Enzyme Inhibitors, Aldosterone Receptor Antagonists, Calcium Channel Blockers, Thiazide Diuretics and Beta-blockers. Several studies have aimed to identify possible factors that influence the response to antihypertensive therapy. Many of them established an interaction between the human genome (and its variations) and the response to the instituted pharmacotherapy. This fact justifies the importance of pharmacogenomics, which studies the influence of genetic variability on the response to therapy for various pathologies, including hypertension. The importance of therapeutic individualization has been gaining ground in the optimization of therapy. In HT, one of the classic drugs that has been used is Hydrochlorothiazide, a thiazide diuretic, whose interindividual variability in response to therapy has been associated with several genetic polymorphisms. The study of these polymorphisms in a population could lead to a better application of this drug. Goals The main goal of this dissertation is the development of a project to evaluate the interindividual genetic variability of the response to hydrochlorothiazide in Portuguese patients with hypertension. Methodology In order to update the theme and study other projects in this field, current guidelines for the treatment of hypertension were consulted and bibliographical research was carried out, using the PubMed platform, from October 2022 to March 2023. The following keywords were used: arterial hypertension, pharmacogenomics, pharmacogenetics, genetic variability, genetic polymorphisms, hydrochlorothiazide, thiazide diuretics, betablockers, calcium channel blockers, angiotensin converting enzyme inhibitors and aldosterone receptor antagonists. For the design of the primers, the GenBank database was used. After analyzing all the material, this dissertation was made. Results and discussion After a brief review and update of the topic, it was concluded that there are numerous genes that influence the therapeutic response to antihypertensive drugs. The presence of polymorphisms in these genes is responsible for a variation in blood pressure control, which may or may not be favorable. Thus, it is important to understand whether individuals diagnosed with HT have genetic polymorphisms that may modify their response to the antihypertensive pharmacological therapy they undergo. By identifying the presence of these inter-individual variations, it becomes possible to adjust the therapy so that the medication is personalized and as effective as possible for the patient in question. In this light, a project was developed to evaluate the interindividual genetic variability of the response to hydrochlorothiazide in Portuguese patients with hypertension. After the referred update of the topic, it was possible to identify the candidate gene, the candidate genetic polymorphism and proceed to the description of the project, which is ready to be started.Conclusions It is relevant to study the influence of genetic polymorphisms on the response to hydrochlorothiazide and other antihypertensive drugs, a study that should be carried out at national level. It is extremely important to understand the prevalence of these polymorphisms and adapt the medication according to their presence, in order to obtain the most effective therapeutic response possible.
Introduction Arterial Hypertension (HT) occurs when blood pressure, that is, the force that blood exerts against arterial walls, is persistently high. Hypertension is multifactorial, depending on environmental, vascular, hormonal and genetic factors, among others. Its growing prevalence constitutes a public health problem, given the known effects of hypertension in various systems of the body: cardiovascular, neurological, musculoskeletal and renal, to name a few. Its therapy includes non-pharmacological interventions, such as adopting a healthier lifestyle, and pharmacological ones. The most used pharmacological classes are Angiotensin-Converting Enzyme Inhibitors, Aldosterone Receptor Antagonists, Calcium Channel Blockers, Thiazide Diuretics and Beta-blockers. Several studies have aimed to identify possible factors that influence the response to antihypertensive therapy. Many of them established an interaction between the human genome (and its variations) and the response to the instituted pharmacotherapy. This fact justifies the importance of pharmacogenomics, which studies the influence of genetic variability on the response to therapy for various pathologies, including hypertension. The importance of therapeutic individualization has been gaining ground in the optimization of therapy. In HT, one of the classic drugs that has been used is Hydrochlorothiazide, a thiazide diuretic, whose interindividual variability in response to therapy has been associated with several genetic polymorphisms. The study of these polymorphisms in a population could lead to a better application of this drug. Goals The main goal of this dissertation is the development of a project to evaluate the interindividual genetic variability of the response to hydrochlorothiazide in Portuguese patients with hypertension. Methodology In order to update the theme and study other projects in this field, current guidelines for the treatment of hypertension were consulted and bibliographical research was carried out, using the PubMed platform, from October 2022 to March 2023. The following keywords were used: arterial hypertension, pharmacogenomics, pharmacogenetics, genetic variability, genetic polymorphisms, hydrochlorothiazide, thiazide diuretics, betablockers, calcium channel blockers, angiotensin converting enzyme inhibitors and aldosterone receptor antagonists. For the design of the primers, the GenBank database was used. After analyzing all the material, this dissertation was made. Results and discussion After a brief review and update of the topic, it was concluded that there are numerous genes that influence the therapeutic response to antihypertensive drugs. The presence of polymorphisms in these genes is responsible for a variation in blood pressure control, which may or may not be favorable. Thus, it is important to understand whether individuals diagnosed with HT have genetic polymorphisms that may modify their response to the antihypertensive pharmacological therapy they undergo. By identifying the presence of these inter-individual variations, it becomes possible to adjust the therapy so that the medication is personalized and as effective as possible for the patient in question. In this light, a project was developed to evaluate the interindividual genetic variability of the response to hydrochlorothiazide in Portuguese patients with hypertension. After the referred update of the topic, it was possible to identify the candidate gene, the candidate genetic polymorphism and proceed to the description of the project, which is ready to be started.Conclusions It is relevant to study the influence of genetic polymorphisms on the response to hydrochlorothiazide and other antihypertensive drugs, a study that should be carried out at national level. It is extremely important to understand the prevalence of these polymorphisms and adapt the medication according to their presence, in order to obtain the most effective therapeutic response possible.
Description
Keywords
Gnb3 Hidroclorotiazida Hipertensão Arterial Polimorfismos Genéticos Variabilidade Genética