Telmisartán y losartán: las marcadas diferencias entre sus propiedades químicas y farmacológicas pueden explicar la diferencia en la eficacia terapéutica en pacientes hospitalizados con covid-19 / Telmisartan and losartan: marked differences in chemical and pharmacological properties may explain differences in therapeutic efficacy in hospitalized patients with COVID-19

El objetivo de este artículo es comparar las propiedades químicas y farmacológicas del telmisartán y el losartán, y su metabolito activo EXP3174, con el fin de entender por qué el telmisartán es efectivo en pacientes hospitalizados con Covid-19 mientras que el losartán no lo es. Se llevó a cabo una revisión bibliográfica exhaustiva de las propiedades químicas, farmacocinéticas y farmacodinámicas de ambos fármacos y se destacaron las diferencias más importantes que podrían estar relacionadas con su efectividad en pacientes con Covid-19. Se concluyó que las propiedades farmacológicas del telmisartán, como su mayor afinidad por el receptor AT1, su duración de acción prolongada y su capacidad para modular la inflamación podrían explicar su efectividad en pacientes con Covid-19. Por otro lado, las propiedades farmacológicas del losartán, como su menor afinidad por el receptor AT1 y su rápido metabolismo, pueden limitar su efectividad en pacientes con Covid-19. Estos resultados resaltan la importancia de comprender las propiedades químicas y farmacológicas de los medicamentos para identificar posibles candidatos terapéuticos efectivos en el tratamiento de Covid-19. (AU)

The objective of this article is to compare the chemical and pharmacological properties of telmisartan and losartan and their active metabolite EXP3174 to understand why telmisartan is effective in hospitalized patients with COVID-19 while losartan is not. A comprehensive literature review of the chemical, pharmacokinetic and pharmacodynamic properties of both drugs was done to highlight the most important differences that may be related to their efficacy in patients with COVID-19. It was concluded that the pharmacological properties of telmisartan, such as its higher affinity for the AT1 receptor, its long duration of action and its ability to modulate inflammation, could explain its efficacy in patients with COVID-19. On the other hand, the pharmacological properties of losartan, such as its lower affinity for the AT1 receptor and its rapid metabolism, may limit its efficacy in patients with COVID-19. These results highlight the importance of understanding the chemical and pharmacological properties of drugs to identify potential effective therapeutic candidates for the treatment of COVID-19. (AU)

Informe diário de evidências COVID-19: busca realizada em 12 de agosto de 2020 / COVID-19 daily evidence report: search conducted on August 12, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 13 artigos e 10 protocolos.

Informe diário de evidências COVID-19: busca realizada em 14 de maio de 2020 / COVID-19 daily evidence report: search conducted on May 14, 2020

Essa é uma produção do Departamento de Ciência e Tecnologia (Decit) da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde (SCTIE) do Ministério da Saúde (Decit/SCTIE/MS), que tem como missão promover a ciência e tecnologia e o uso de evidências científicas para a tomada de decisão do SUS, tendo como principal atribuição o incentivo ao desenvolvimento de pesquisas em saúde no Brasil, de modo a direcionar os investimentos realizados em pesquisa pelo Governo Federal às necessidades de saúde pública. Informar sobre as principais evidências científicas descritas na literatura internacional sobre tratamento farmacológico para a COVID-19. Além de resumir cada estudo identificado, o informe apresenta também uma avaliação da qualidade metodológica e a quantidade de artigos publicados, de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, entre outros). Foram encontrados 15 artigos.

Effect of telmisartan on expression of metadherin in the kidney of mice with unilateral ureter obstruction / 南方医科大学学报

OBJECTIVE@#To explore the effect of telmisartan on the expression of metadherin in the kidney of mice with unilateral ureter obstruction.@*METHODS@#Eighteen male C57 mice were randomized into sham-operated group, model group and telmisartan treatment group. In the latter two groups, renal interstitial fibrosis as the result of unilateral ureter obstruction (UUO) was induced by unilateral ureteral ligation with or without telmisartan intervention. Renal pathological changes of the mice were assessed using Masson staining, and immunohistochemistry and Western blotting were used to detect the expression of extracellular matrix proteins and metadherin in the kidney of the mice. In the experiment, cultured mouse renal tubular epithelial cells (mTECs) were stimulated with transforming growth factor-β1 (TGF-β1) and transfected with a siRNA targeting metadherin, and the changes in the expressions of extracellular matrix proteins and metadherin were detected using Western blotting.@*RESULTS@#The expressions of extracellular matrix proteins and metadherin increased significantly in the kidney of mice with UUO ( < 0.05). Intervention with telmisartan significantly lowered the expressions of extracellular matrix proteins and metadherin and alleviated the pathology of renal fibrosis in mice with UUO ( < 0.05). In cultured mTECs, siRNA-mediated knockdown of metadherin obviously reversed TGF-β1-induced increase in the expressions of extracellular matrix proteins and metadherin.@*CONCLUSIONS@#Telmisartan can suppress the production of extracellular matrix proteins and the expression of metadhein to attenuate UUO-induced renal fibrosis in mice.

J-curve Phenomenon Might Be Inherent: How to Know If It Is Treatment Induced?

No abstract available.

Effect of government-mediated access pricing on availability of directly affected drugs in retail drug stores in the Philippines from 2009 to 2011

BACKGROUND: There is a scarcity of studies on the effects of government-mediated access pricing (GMAP) as another price regulation approach on drug availability. OBJECTIVES: This study was done to compare changes in percent availability in drug stores from 2009 to 2011 of innovator drugs, competitor drugs and cheap generic drugs containing drug molecules affected by GMAP policies in the Philippines. METHODS: Data from a random survey of 600 drug stores stratified by location and retail type, undertaken separately in 2009 and 2011 by IMS Health Philippines, were analyzed. Percent availability of the innovator brand, a competitor, and cheapest generic version for 11 selected drug molecules in said drug stores were compared for 2009 and 2011. RESULTS: Of the 11 innovator drugs, 3 had significant reductions in percent availability in drugstores ranging from 9.7% to 39.0%. Among competitor drugs, 3 had reductions ranging from 37.4% to 81.7%. The availability of cheap generic versions of drug molecules in drug stores immensely increased in 2011 except for telmisartan. CONCLUSION: GMAP could have adversely affected availability in drug stores of both innovator and competitor drugs. Cheaper generic drugs have become more available in the Philippines.

Nephrotoxicity of high- and low-osmolar contrast media: Protective role of fosinopril or telmisartan in a rat model / 中南大学学报(医学版)

OBJECTIVE@#To compare the nephrotoxicity of high- and low-osmolar contrast media (HOCM and LOCM), and to determine the protective role of fosinopril or telmisartan and its possible mechanism.@*METHODS@#Forty eight healthy SD rats were randomly divided into 6 groups: a normal control group, a glycerol control group, a low-osmolar contrast media (LOCM) group, a high-osmolar contrast media (HOCM) group, a fosinopril group, and a telmisartan group. Glycerine for inducing kidney damage was given to all rats except the normal control group. Twenty-four hours after the injection of glycerine, the mixed fosinopril suspension (10mg/kg) or telmisartan (5mg/kg) was poured into the stomach in the preventive group. Serum creatinine (SCr) and plasma angiotensin II (AngII) levels were detected by an automatical biochemical analyzer and radioimmunoassay; caspase-3 activity and claudin-1 expression of the renal tissue were detected by fluorometric method and immunohistochemical method. The renal injury was assessed by hematoxylin and eosin (HE) staining and terminal deoxynucleotide mediated nick and labeling (TUNEL) staining, respectively.@*RESULTS@#In diatrizoate-injected rats, SCr and AngII levels were increased (P<0.05). Expression of claudin-1 protein and caspase-3 activity in the renal tissue was upregulated. The histologic changes and percentage of apoptotic cells were milder in the LOCM rats than those in the HOCM rats. In the group pretreated with fosinopril or telmisartan, no increase in the levels of SCr and AngII was discovered. The expression of claudin-1 protein and caspase-3 activity was significantly lower than that in the HOCM group. The renal injuries induced by diatrizoate were alleviated.@*CONCLUSION@#Both HOCM and LOCM could cause cellular apoptosis in the kidney.LOCM was less toxic to rat kidney than HOCM. Nephrotoxicity induced by HOCM might be related to caspase-3, claudin-1 and AngII. Fosinopril or telmisartan may protect the renal tissue from nephrotoxicity induced by diatrizoate.