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Authors
Abstract(s)
No âmbito da unidade curricular “Estágio”, o presente relatório para a obtenção do grau
de Mestre em Ciências Farmacêuticas encontra-se dividido em três capítulos – I, II e III
– referentes ao trabalho realizado na vertente de investigação e às experiências
profissionalizantes em farmácia hospitalar e comunitária, respetivamente.
O capítulo I intitula-se «Revisão sistemática sobre as aplicações terapêuticas da
associação senolítica “Dasatinib e Quercetina” em patologias características do
envelhecimento».
Numa sociedade mundialmente envelhecida, a longevidade é tanto um reflexo positivo
dos avanços tecnológicos e da saúde, como um desafio. Acrescentar anos à vida não
significa necessariamente o inverso e, sendo o envelhecimento particularmente pautado
por múltiplas e, por vezes, complexas doenças associadas à idade, torna-se urgente
melhorar a qualidade de vida geriátrica.
A senescência celular trata-se de um processo biológico transversal às diferentes fases da
vida humana, demonstrando-se fisiologicamente imprescindível ao desenvolvimento,
mas também nefasta e intimamente relacionada com várias doenças, nomeadamente as
de cariz associado à idade. É, por isso, um dos principais mecanismos biológicos
responsáveis pelo envelhecimento. Desta forma, as diversificadas, mas típicas
características das células senescentes, têm sido pertinentes de considerar na
investigação de estratégias terapêuticas. Ao identificar a tríade «envelhecimento
biológico – senescência celular – patologias geriátricas», a comunidade científica
debruçou-se no estudo das implicações que a eliminação seletiva de células senescentes
teria na saúde dos idosos.
Atualmente, as abordagens senoterapêuticas podem ser divididas em dois tipos de
estratégias farmacológicas: os senolíticos e os senomórficos ou senostáticos. Em 2015,
foram descobertos os primeiros agentes senolíticos. Tendo por base a associação de dois
desses compostos potencialmente senolíticos, dasatinib e quercetina (DQ), este trabalho
de investigação teve como intuito rever a literatura científica, sistematizando as suas
aplicações terapêuticas, em patologias associadas ao envelhecimento.
Partindo de ensaios pré-clínicos executados em roedores, comprovou-se que in vitro e in
vivo a combinação DQ é uma terapia com especificidade para a idade, demonstrando-se
que a sua aplicação é uma estratégia promissora em algumas doenças do
envelhecimento. Destas, podem destacar-se condições metabólicas, doenças
neurodegenerativas, perturbações oculares, alterações vasculares, doenças pulmonares, patologias ósseas e disfunções genitourinárias. A DQ torna-se uma ferramenta
farmacológica útil ao atenuar alguns efeitos secundários decorrentes de transplantes ou
da radioterapia, como acontece no cancro da cabeça e pescoço e cancro da mama. Esta
associação ainda mostra ser passível de se aplicar em concomitância com outras
estratégias farmacológicas, como o inibidor da ceramidase ácida. Contudo DQ é ineficaz
na regressão do carcinoma hepatocelular.
Segundo os ensaios clínicos analisados, DQ é uma terapia promissora para a fibrose
pulmonar idiopática e nefropatia diabética. Todavia, os ensaios clínicos em decurso
ainda se encontram em fase I, pelo que são necessários mais estudos abrangentes e
randomizados que corroborem as evidências obtidas até ao momento. É ainda
particularmente importante compreender a influência das diferenças de género,
genéticas e metabólicas em roedores e seres humanos.
Em suma, depreende-se que DQ é uma estratégia farmacológica terapeuticamente
versátil e de caráter promissor para a gerociência. Aliando-se a um estilo de vida
saudável, conclui-se que DQ se trata de uma associação de compostos senolíticos com
capacidade de promover o envelhecimento biológico saudável, aumentando a qualidade
de vida.
O capítulo II diz respeito ao relatório de estágio em Farmácia Hospitalar que decorreu
nos Serviços Farmacêuticos do Centro Hospitalar Universitário Cova da Beira. Este
capítulo aborda o circuito do medicamento em meio hospitalar, refletindo sobretudo a
dinâmica dos setores relativos à logística farmacêutica, farmacotecnia, distribuição
individual diária de dose unitária e distribuição em ambulatório. Ao longo do relatório,
é apresentado o funcionamento destes setores, expondo a legislação que os regulamenta
e as diferentes responsabilidades do farmacêutico hospitalar.
O capítulo III trata-se do relatório de estágio relativo à experiência profissionalizante no
contexto da Farmácia Comunitária, decorrido na Farmácia Lusitana. À semelhança do
capítulo II, descreve o circuito do medicamento e diferentes produtos da saúde. Através
da experiência vivida e relatada, corrobora-se o papel ativo e diversificado do
farmacêutico comunitário.
Within the scope of the curricular unit "Practical Training”, this report for obtaining the master’s degree in Pharmaceutical Sciences is divided into three chapters - I, II and III - referring to the work carried out in the research area and professional experiences in Hospital and Community Pharmacy, respectively. Chapter I is entitled «Systematic review of therapeutic applications of the senolytic association “Dasatinib and Quercetin” in typical pathologies of ageing». In an ageing society worldwide, longevity is both a positive reflection of technological and health advances and a challenge. Adding years to life doesn’t necessarily mean the opposite and, since ageing is particularly characterized by multiple and, sometimes, complex diseases associated with age, it is urgent to improve the geriatric quality of life. Cellular senescence is a biological process that occurs at different stages of human life, proving to be physiologically essential for development, but also harmful and closely related to various diseases, namely those associated with age. Therefore, it is one of the main biological mechanisms responsible for ageing. This way, the diversified but typical characteristics of senescent cells have been relevant to consider in the investigation of therapeutic strategies. By identifying the triad «biological ageing – cellular senescence – geriatric pathologies», the scientific community focused on the study of the implications that the selective elimination of senescent cells would have on the health of the elderly. Currently, senotherapeutic approaches can be divided into two types of pharmacological strategies: senolytic and senomorphic or senostatic. In 2015, the first senolytic agents were discovered. Based on the association of two of these potentially senolytic compounds, dasatinib and quercetin (DQ), this research work aimed to review the scientific literature, systematizing their therapeutic applications in pathologies associated with ageing. Based on pre-clinical trials performed on rodents, it was proved that in vitro and in vivo DQ is an age-specific therapy, showing that its application is a promising strategy in some ageing diseases. Of these, metabolic conditions, neurodegenerative diseases, eye disorders, vascular alterations, lung diseases, bone pathologies and genitourinary disorders can be highlighted. DQ becomes a useful pharmacological tool in mitigating some side effects resulting from transplants or radiotherapy, as in head and neck cancer and breast cancer. This association also shows that it can be applied concomitantly with other pharmacological strategies, such as the acid ceramidase inhibitor. However, DQ is ineffective in the regression of hepatocellular carcinoma. According to the clinical trials analyzed, DQ is a promising therapy for patients suffering from idiopathic pulmonary fibrosis and diabetic nephropathy. However, the ongoing clinical trials are still in phase I, so more comprehensive and randomized studies are needed to corroborate the evidence obtained so far. It is also particularly important to understand the influence of gender, genetic and metabolic differences in rodents and humans. In conclusion, DQ appears to be a therapeutically versatile and promising pharmacological strategy for geroscience. Allied to a healthy lifestyle, it is concluded that DQ is an association of senolytic compounds with the ability to promote healthy biological ageing, increasing the quality of life. Chapter II concerns the internship report in Hospital Pharmacy that took place in the Pharmaceutical Services of Centro Hospitalar Universitário Cova da Beira. This chapter addresses the medicine circuit in hospitals, reflecting above all the dynamics of the sectors related to pharmaceutical logistics, pharmacotechnics, individual daily unit dose distribution and outpatient distribution. Throughout the report, the functioning of these sectors is presented, exposing the legislation that regulates them and the different responsibilities of the hospital pharmacist. Chapter III is dedicated the internship report on the professional experience in the context of Community Pharmacy that took place at Farmácia Lusitana. As in chapter II, it describes the drug and different health products circuit. Through the lived and reported experience, the active and diversified role of the community pharmacist is confirmed.
Within the scope of the curricular unit "Practical Training”, this report for obtaining the master’s degree in Pharmaceutical Sciences is divided into three chapters - I, II and III - referring to the work carried out in the research area and professional experiences in Hospital and Community Pharmacy, respectively. Chapter I is entitled «Systematic review of therapeutic applications of the senolytic association “Dasatinib and Quercetin” in typical pathologies of ageing». In an ageing society worldwide, longevity is both a positive reflection of technological and health advances and a challenge. Adding years to life doesn’t necessarily mean the opposite and, since ageing is particularly characterized by multiple and, sometimes, complex diseases associated with age, it is urgent to improve the geriatric quality of life. Cellular senescence is a biological process that occurs at different stages of human life, proving to be physiologically essential for development, but also harmful and closely related to various diseases, namely those associated with age. Therefore, it is one of the main biological mechanisms responsible for ageing. This way, the diversified but typical characteristics of senescent cells have been relevant to consider in the investigation of therapeutic strategies. By identifying the triad «biological ageing – cellular senescence – geriatric pathologies», the scientific community focused on the study of the implications that the selective elimination of senescent cells would have on the health of the elderly. Currently, senotherapeutic approaches can be divided into two types of pharmacological strategies: senolytic and senomorphic or senostatic. In 2015, the first senolytic agents were discovered. Based on the association of two of these potentially senolytic compounds, dasatinib and quercetin (DQ), this research work aimed to review the scientific literature, systematizing their therapeutic applications in pathologies associated with ageing. Based on pre-clinical trials performed on rodents, it was proved that in vitro and in vivo DQ is an age-specific therapy, showing that its application is a promising strategy in some ageing diseases. Of these, metabolic conditions, neurodegenerative diseases, eye disorders, vascular alterations, lung diseases, bone pathologies and genitourinary disorders can be highlighted. DQ becomes a useful pharmacological tool in mitigating some side effects resulting from transplants or radiotherapy, as in head and neck cancer and breast cancer. This association also shows that it can be applied concomitantly with other pharmacological strategies, such as the acid ceramidase inhibitor. However, DQ is ineffective in the regression of hepatocellular carcinoma. According to the clinical trials analyzed, DQ is a promising therapy for patients suffering from idiopathic pulmonary fibrosis and diabetic nephropathy. However, the ongoing clinical trials are still in phase I, so more comprehensive and randomized studies are needed to corroborate the evidence obtained so far. It is also particularly important to understand the influence of gender, genetic and metabolic differences in rodents and humans. In conclusion, DQ appears to be a therapeutically versatile and promising pharmacological strategy for geroscience. Allied to a healthy lifestyle, it is concluded that DQ is an association of senolytic compounds with the ability to promote healthy biological ageing, increasing the quality of life. Chapter II concerns the internship report in Hospital Pharmacy that took place in the Pharmaceutical Services of Centro Hospitalar Universitário Cova da Beira. This chapter addresses the medicine circuit in hospitals, reflecting above all the dynamics of the sectors related to pharmaceutical logistics, pharmacotechnics, individual daily unit dose distribution and outpatient distribution. Throughout the report, the functioning of these sectors is presented, exposing the legislation that regulates them and the different responsibilities of the hospital pharmacist. Chapter III is dedicated the internship report on the professional experience in the context of Community Pharmacy that took place at Farmácia Lusitana. As in chapter II, it describes the drug and different health products circuit. Through the lived and reported experience, the active and diversified role of the community pharmacist is confirmed.
Description
Keywords
Dasatinib Doenças Associadas ao Envelhecimento Envelhecimento Gerociência Qualidade de Vida Quercetina Senescência Celular Senolítico