Artículos (Farmacología)

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Synthesis and Bioevaluation of New Stable Derivatives of Chrysin-8-C-Glucoside That Modulate the Antioxidant Keap1/Nrf2/HO-1 Pathway in Human Macrophages
(MDPI, 2024-10-17) Ávila Román, Francisco Javier; Quevedo-Tinoco, Lirenny; Oliveros-Ortiz, Antonio J.; García Gil, Sara; Rodríguez-García, Gabriela; Motilva Sánchez, Virginia; Gómez Hurtado, Mario A.; Talero Barrientos, Elena Mª; Universidad de Sevilla. Departamento de Farmacología; Junta de Andalucía
Background/Objectives: The beneficial effects of the flavonoid chrysin can be reduced by its poor oral bioavailability. It has been shown that chrysin-8-C-glucoside (1) has a better absorption capability. The aim of this study was to evaluate the antioxidant and anti-inflammatory activity of this glucoside, as well as the respective hexa-acetate derivative 1a and the hexa-ethyl carbonate derivative 1b since the inclusion of moieties in bioactive molecules may increase or modify their biological effects. Methods: THP-1 macrophages were used to determine the viability in the presence of chrysin derivatives, and non-cytotoxic concentrations were selected. Subsequently, lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) production and inflammatory mediators were examined. The involvement of chrysin derivatives with the Keap1 and Nrf2 antioxidant system was determined by docking and Western blotting studies. Results: Our data demonstrated, for the first time, that pretreatment with the three compounds caused a significant reduction in LPS-induced reactive oxygen species (ROS) production and pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β) levels, as well as in cyclooxygenase 2 (COX-2) expression. The mechanisms underlying these protective effects were related, at least in part, to the competitive molecular interactions of these phenolic compounds with Kelch-like ECH-associated protein 1 (Keap1)–nuclear factor erythroid 2-related factor 2 (Nrf2), which would allow the dissociation of Nrf2 and its translocation into the nucleus and the subsequent up-regulation of hemo-oxygenase 1 (HO-1) expression. Conclusions: Compared to the 8-C-glucoside parent chrysin, compound 1a exhibited the strongest antioxidant and anti-inflammatory activity. We hypothesized that the incorporation of an acetate group (1a) may reduce its polarity and, thus, increase membrane permeability, leading to better pharmacological activity. These findings support the potential use of these phenolic compounds as Nrf2 activators against oxidative-stress-related inflammatory diseases.
Prevalence of Polypharmacy and Association to Pharmacotherapy Complexity in Older HIV-Positive Patients. The Sevihlla Study
(eSciPub LLC, 2019) Morillo Verdugo, Ramón Alejandro; Robustillo Cortés, María de las Aguas; Abdel-Kader Martín, Laila; Álvarez de Sotomayor Paz, María; Lozano de León Naranjo, Fernando; Almeida González, Carmen V.; Universidad de Sevilla. Departamento de Farmacología
Background: Increased life expectancy of older HIV-positive patients has been associated to a parallel increase in age-related comorbidities. Objectives: To ascertain the prevalence of polypharmacy and its association to pharmacotherapy complexity, as measured by the Medication Regimen Complexity Index, in older HIV-positive patients; to calculate the median value of pharmacotherapy complexity; to identify polypharmacy and multimorbidity patterns; and to address adherence to antiretroviral and concomitant drugs. Methods: A cross-sectional, observational study was conducted in patients over 50 years of age receiving active antiretroviral drugs during 2014 at outpatient pharmacy services of a tertiary hospital in Spain. Data collected from the electronic medical record included demographic, clinical and comorbidity related endpoints. The primary endpoint was the proportion of patients with polypharmacy and major polypharmacy. Polypharmacy was defined as treatment with six or more drugs (including antiretroviral). Major polypharmacy (more than 11 drugs) was also considered. Patients was categorized according to their polypharmacy pattern. Three patterns were applied based on age of participants: cardiovascular, depression-anxiety, and chronic obstructive pulmonary (COPD) disease patterns. A patient was classified into a pattern when at least three drugs of the treatment were in the same pattern. Antiretroviral treatment adherence was measured using the SMAQ questionnaire and hospital dispensing records. Adherence to concomitant medication was measured using the Morisky-Green questionnaire and electronic pharmacy dispensing records. Pharmacotherapy complexity index, as assessed by MRCI, was also considered. Patients were classified as low MRCI (less than 14 points) or high MRCI (more than 14 points). Results: The study sample consisted of 223 patients (86.5% men), with a median age of 53.0 years. More than 80.0% of the patients were viro-inmunological controlled. Prevalence of polypharmacy was 56.1%. The median value of pharmacotherapy complexity was 11.0. The main contribution to this value was from the concomitant medication. The polypharmacy pattern mainly calculated was cardiovascular (60.0%) and the multimorbidity pattern was cardiometabolic (73.8%). Presence of polypharmacy was associated to greater pharmacotherapy complexity (p<0,001). Adequate adherence to the antiretroviral and to concomitant medication was found in 83.6% and 37.9% of patients respectively. Conclusions: More than a half of the older HIV-positive patients received six or more different drugs with a significant pharmacotherapy complexity showing adequate adherence to antiretroviral but not to concomitant drugs. Cardiovascular conditions were most common in terms of prescriptions and comorbidities.
Adherence to disease-modifying treatments in patients with multiple sclerosis in spain
(Dove Press, 2019) Morillo Verdugo, Ramón Alejandro; Ramírez Herráiz, Esther; Fernández Del Olmo, Raquel; Roig Bonet, Montserrat; Valdivia García, María; Universidad de Sevilla. Departamento de Farmacología
Purpose: Adherence to disease-modifying treatments is essential in order to maximize the beneficial effects of treatment for multiple sclerosis (MS). There are numerous treatments that have been approved. Treatment selection is essential in patient adherence. In addition, patient preference plays an increasingly significant role in treatment decision-making. This study aims to evaluate the degree of adherence, along with other variables that may influence this adherence, in Spain. Methods: A cross-sectional study was conducted with 157 MS patients with disease-modifying treatments. Adherence was assessed using the Morisky Green scale, and other related factors were measured using a questionnaire that addressed demographics, disease characteristics, global perception of pathology, impact of medication on patient’s life, and treatment decision-making. Results: The adherence rate was 71% and was associated with the following variables: older age, more treatments received, time to diagnosis 5–10 years, absence of exacerbations, better cognitive status, being married/in a union, clear information about the disease, and higher treatment satisfaction. The main cause for non-compliance was forgetfulness (27%). Conclusion: The adherence rate is acceptable. It is widely known that treatment satisfaction is related to adherence. In our study, patients’ level of satisfaction was higher with oral treatments. However, oral administration showed a greater lack of adherence. The main cause of lack of adherence was forgetfulness. In relation to other variables, cognitive status and family support showed a correlation with treatment adherence.
Diseño de un protocolo de intervención para aplicar a pacientes de riesgo cardiovascular atendidos en la farmacia comunitaria
(Real e Ilustre Colegio Oficial de Farmacéuticos, 2020) Buenavida Jurado, Pilar; Matta Martín, María José de la; Puerta Vázquez, Rocío de la; Martín Calero, María José; Universidad de Sevilla. Departamento de Farmacología
Objetivo: implementar una intervención compleja en pacientes de riesgo cardiovascular (RCV) en farmacia comunitaria (FC) para ayudarles a mejorar la gestión de su enfermedad. Metodología. La experiencia se realizará en cuatro FC. Tras ser caracterizados, los pacientes se distribuirán, aleatoriamente, en dos grupos, control (GC) e intervención (GI). El GC solo recibirá los cuidados farmacéuticos habituales. Al GI se le aplicarán protocolos específicos de seguimiento farmacoterapéutico (SFT) y educación terapéutica (ET) bimensualmente durante 6 meses. Al finalizar, se compararán en ambos grupos: Cifras de presión arterial (PA), hemoglobina glicada, perfil lipídico, peso, actividad física, tabaquismo, conocimiento del RCV, adherencia al tratamiento y capacidad de autogestión terapéutica. Conclusiones. Experiencias similares con pacientes hospitalarios nos animaron a ensayar estos protocolos en FC. Pero los resultados tendrán que evaluarse antes de concluir su bondad en nuestro ámbito.
Pretreatment with Oleuropein Protects the Neonatal Brain from Hypoxia-ischemia by Inhibiting Apoptosis and Neuroinflammation
(Sage, 2024) Reyes Corral, Marta; Gil González, Laura; González Díaz, Ángela; Tovar Luzón, Javier; Ayuso, María Irene; Lao Pérez, Miguel; Montaner, Joan; Puerta Vázquez, Rocío de la; Fernández Torres, Rut; Ybot González, Patricia; Universidad de Sevilla. Departamento de Química Analítica; Universidad de Sevilla. Departamento de Farmacología; Junta de Andalucía; European Union (UE)
Hypoxic-ischemic (HI) encephalopathy is a cerebrovascular injury caused by oxygen deprivation to the brain and remains a major cause of neonatal mortality and morbidity worldwide. Therapeutic hypothermia is the current standard of care but it does not provide complete neuroprotection. Our aim was to investigate the neuroprotective effect of oleuropein (Ole) in a neonatal (seven-day-old) mouse model of HI. Ole, a secoiridoid found in olive leaves, has previously shown to reduce damage against cerebral and other ischemia/reperfusion injuries. Here, we administered Ole as a pretreatment prior to HI induction at 20 or 100 mg/kg. A week after HI, Ole significantly reduced the infarct area and the histological damage as well as white matter injury, by preserving myelination, microglial activation and the astroglial reactive response. Twenty-four hours after HI, Ole reduced the overexpression of caspase-3 and the proinflammatory cytokines IL-6 and TNF-α. Moreover, using UPLC-MS/MS we found that maternal supplementation with Ole during pregnancy and/or lactation led to the accumulation of its metabolite hydroxytyrosol in the brains of the offspring. Overall, our results indicate that pretreatment with Ole confers neuroprotection and can prevent HI-induced brain damage by modulating apoptosis and neuroinflammation.
Alfabetización en salud y COVID-19 en mayores: aproximación desde la Farmacia Comunitaria
(Pharmaceutical Care España, 2022) Álvarez de Sotomayor Paz, María; Fernández Cuesta, Paula María; Universidad de Sevilla. Departamento de Farmacología
Introducción: La alfabetización en salud son las habilidades cognitivas y sociales que determinan que los individuos puedan acceder, entender y usar la información para promover y mantener su salud. La necesidad de estas habilidades ha sido notable en la pandemia. Método: Se realiza un cuestionario específico a los pacientes mayores de 60 años. Este consta de tres partes: el instrumento HLS-EU-Q16 adaptado a COVID-19, preguntas sobre la actuación del farmacéutico y la herramienta SAHLSA. Resultados: La población era mayoritariamente femenina (75,4%) y su edad era de 79,2±9,4 años. El nivel educativo mayoritario fue de educación primaria (34,4%), predominando éste y el sin estudios en mayores de 80 años. El cuestionario HLS-EU-Q16 reveló que la alfabetización en salud sobre COVID-19 era deficiente (23%), insuficiente (70,5%) y suficiente (6,6%). El cuestionario SAHLSA mostró alfabetización suficiente en el 80%. Mientras que el primer cuestionario no mostró relación con el nivel educativo, ningún bachiller o universitario presentó valores insuficientes en el cuestionario SAHLSA. Por último, los entrevistados consideraron como primer sanitario al que acudir para obtener información fiable al médico (77%), seguido por el farmacéutico (13%). El 75% consideró que el farmacéutico le había ayudado a comprender las precauciones frente a la COVID-19. Conclusiones: Los pacientes presentan dificultades para identificar la información fiable y para encontrar información de tratamientos frente a la COVID. Esta necesidad no está relacionada con el nivel educativo ni con la alfabetización en salud en otras áreas. El farmacéutico puede ser un agente clave en resolver esta necesidad.
Value Contribution of Cenobamate for the Treatment of Focal-Onset Seizures (FOS) in Patients with Drug-resistant Epilepsy (DRE) in Spain through Reflective Multi-Criteria Decision Analysis (MCDA)
(Elsevier, 2023) Falip, Mercè; López González, Francisco Javier; Martín Herranz, Isabel; Merino Bohórquez, Vicente; Montoya, Javier; Rey Gómez-Serranillos, Isabel; Rodriguez Uranga, Juan Jesús; Ruiz, Elías; Sancho López, Aranzazu; Trillo Mata, Jose Luis; Gil, Alicia; Universidad de Sevilla. Departamento de Farmacología
Introduction: Epilepsy is one of the most common neurological conditions worldwide. The main goal of its treatment is to achieve seizure freedom without intolerable adverse effects. However, despite the availability of many anti-seizure medications, including the latest options, called third-generation anti- seizure medications (ASMs), approximately 40% of people with epilepsy present drug-resistant epilepsy (DRE). Cenobamate is the first ASM approved in Spain for the adjunctive treatment of Focal-Onset Seizures (FOS) in adult patients with DRE. In a chronic disease with a portfolio of available ASMs, the deci- sion to introduce a new therapeutic alternative must follow a holistic evaluation of value provided. Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine the value contribu- tion of a treatment in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders. Purpose: The aim of this study was to determine the relative value contribution of cenobamate in the treatment of FOS in patients with DRE compared with third-generation ASMs using reflective MCDA- based methodology. Methods: A systematic literature review (combining biomedical databases and grey literature sources) was performed to populate the Evidence and Value: Impact on DEcisionMaking (EVIDEM) MCDA frame- work adapted to determine what represents value in the management of FOS in patients with DRE in Spain. The study was conducted in two phases. The first took place in 2021 with a multi-stakeholder group of eight participants. The second phase was conducted in 2022 with a multi-stakeholder group of 32 participants. Participants were trained in MCDA methodology and scored four evidence matrices (cenobamate vs. brivaracetam, vs. perampanel, vs. lacosamide and vs. eslicarbazepine acetate). Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology. Results: DRE is considered a very severe condition associated with many important unmet needs, mainly with regard to the lack of more effective treatments to achieve the ultimate goal of treatment. Compared to third-generation ASMs, cenobamate is perceived to have a better efficacy profile based on improve- ments in responder rate and seizure freedom. Regarding safety, it is considered to have a similar profile to alternatives and a positive quality-of-life profile. Cenobamate results in lower direct medical costs (ex- cluding pharmacological) and indirect costs. Overall, cenobamate is regarded as providing a high thera- peutic impact and supported by high-quality evidence. Conclusions: Based on reflective MCDA methodology and stakeholders’ experience in clinical manage- ment of epilepsy in Spain, cenobamate is perceived as a value-added option for the treatment of patients with DRE when compared with third-generation ASMs.
Evaluation of Anticancer Activity of 76 Plant Species Collected in Andalusia (Spain) against Lung Cancer Cells
(MDPI, 2023) Jiménez González, Víctor; Benítez, Guillermo; Pastor Díaz, Julio Enrique; López Lázaro, Miguel; Calderón Montaño, José Manuel; Universidad de Sevilla. Departamento de Biología Vegetal y Ecología; Universidad de Sevilla. Departamento de Farmacología; Junta de Andalucía; Universidad de Sevilla
Every year, cancer kills millions of people around the world. Finding more selective anticancer agents is essential to improve the low survival rates of patients with metastatic cancers. Since the research of natural products is a valuable approach to the discovery of new compounds and the Iberian flora offers a rich source of unstudied plants, we have carried out a random screening of 76 plant species from 43 families collected in Andalusia (South of Spain). Using non-malignant cells (HaCaT) and lung cancer cells (A549), we found that the extract from Arum italicum Mill. subsp. italicum (Araceae), Mandragora autumnalis Bertol. (Solanaceae), Rhamnus alaternus L. (Rhamnaceae), and Lomelosia simplex (Desf.) Raf. subsp. dentata (Jord. & Fourr.) Greuter & Burdet (Dipsacaceae) showed selective cytotoxicity against lung cancer cells. Extracts of plant species belonging to the Iridaceae family showed high selective activity against cancer cells, highlighting that the Xiphion xiphium (L.) M.B. Crespo, Mart.-Azorín & Mavrodiev flower extract was more selective against lung cancer cells than the standard anticancer drugs, cisplatin and 5-fluorouracil. This extract also showed modest selective cytotoxicity against bladder carcinoma cells (T24). The number of cells in the G1 phase increased after treatment with the extract from Xiphion xiphium. Our research indicates that various plants are potential sources for the isolation and development of new anticancer drugs.
Daidzein and Equol: Ex Vivo and In Silico Approaches Targeting COX-2, iNOS, and the Canonical Inflammasome Signaling Pathway
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-05-16) Márquez Flores, Yazmín K.; Martínez Galero, Elizdath; Correa Basurto, José; Sixto López, Yudibeth; Villegas Lama, Isabel; Rosillo Ramírez, María de los Ángeles; Cárdeno Galván, Ana; Alarcón de la Lastra Romero, Catalina; Universidad de Sevilla. Departamento de Farmacología; Ministerio de Economía y Competitividad (MINECO). España; Junta de Andalucía; Instituto Politécnico Nacional, Mexico; Consejo Nacional de Ciencia y Tecnología (CONACYT). México
Background: The inflammasome is a cytosolic multiprotein complex associated with multiple autoimmune diseases. Phytochemical compounds in soy (Glycine max) foods, such as isoflavones, have been reported for their anti-inflammatory properties. Aim: the anti-inflammatory activity of DZ (daidzein) and EQ (equol) were investigated in an ex vivo model of LPS-stimulated murine peritoneal macrophages and by molecular docking correlation. Methods: Cells were pre-treated with DZ (25, 50, and 100 µM) or EQ (5, 10, and 25 µM), followed by LPS stimulation. The levels of PGE2, NO, TNF-α, IL-6, and IL-1β were analyzed by ELISA, whereas the expressions of COX-2, iNOS, NLRP3, ASC, caspase 1, and IL-18 were measured by Western blotting. Also, the potential for transcriptional modulation by targeting NF-κB, COX-2, iNOS, NLRP3, ASC, and caspase 1 was investigated by molecular docking. Results: The anti-inflammatory responses observed may be due to the modulation of NF-κB due to the binding of DZ or EQ, which is translated into decreased TNF-α, COX-2, iNOS, NLRP3, and ASC levels. Conclusion: This study establishes that DZ and EQ inhibit LPS-induced inflammatory responses in peritoneal murine macrophages via down-regulation of NO and PGE2 generation, as well as the inhibition of the canonical inflammasome pathway, regulating NLRP3, and consequently decreasing IL-1β and IL-18 activation.
Protective effect of sucrose esters from cape gooseberry (Physalis peruviana L.) in TNBS-induced colitis
(PUBLIC LIBRARY SCIENCE, 2024) Ocampo, Yanet C.; Castro, Jenny P.; Pájaro, Indira B.; Caro, Daneiva; Talero Barrientos, Elena Mª; Motilva Sánchez, Virginia; Franco, Luis A.; Universidad de Sevilla. Departamento de Farmacología
Phytotherapy is an attractive strategy to treat inflammatory bowel disease (IBD) that could be especially useful in developing countries. We previously demonstrated the intestinal antiinflammatory effect of the total ethereal extract from the Physalis peruviana (Cape gooseberry) calyces in TNBS-induced colitis. This work investigates the therapeutic potential of Peruviose A and B, two sucrose esters that constitute the major metabolites of its calyces. The effect of the Peruvioses A and B mixture on TNBS-induced colitis was studied after 3 (preventive) and 15-days (therapy set-up) of colitis induction in rats. Colonic inflammation was assessed by measuring macroscopic/histologic damage, MPO activity, and biochemical changes. Additionally, LPS-stimulated RAW 264.7 macrophages were treated with test compounds to determine the effect on cytokine imbalance in these cells. Peruvioses mixture ameliorated TNBS-induced colitis in acute (preventive) or established (therapeutic) settings. Although 3-day treatment with compounds did not produce a potent effect, it was sufficient to significantly reduce the extent/severity of tissue damage and the microscopic disturbances. Beneficial effects in the therapy set-up were substantially higher and involved the inhibition of pro-inflammatory enzymes (iNOS, COX-2), cytokines (TNF-α, IL-1β, and IL-6), as well as epithelial regeneration with restoration of goblet cells numbers and expression of MUC-2 and TFF-3. Consistently, LPS-induced RAW 264.7 cells produced less NO, PGE2, TNF-α, IL-6, and MCP-1. These effects might be related to the inhibition of the NF-κB signaling pathway. Our results suggest that sucrose esters from P. peruviana calyces, non-edible waste from fruit production, might be useful as an alternative IBD treatment.
Dietary oleacein, a secoiridoid from extra virgin olive oil, prevents collagen-induced arthritis in mice
(ROYAL SOC CHEMISTRY, 2024) Rosillo Ramírez, María de los Ángeles; Villegas Lama, Isabel; Vázquez Román, María Victoria; Fernández-Santos, José María; Ortega Vidal, Juan; Salido, Sofía; González Rodríguez, María Luisa; Alarcón de la Lastra Romero, Catalina; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Universidad de Sevilla. Departamento de Farmacología; Junta de Andalucía
Olacein (OLA), one of the main secoiridoids derived from extra virgin olive oil (EVOO), has been shown to modulate oxidative and inflammatory responses in various pathological conditions; however, its potential benefit in joint disorders such as rheumatoid arthritis (RA) is unknown. Therefore, this study was designed to evaluate the preventive role of the effects of an OLA-supplemented diet in the murine model of collagen-induced arthritis (CIA), delving into the possible mechanisms and signaling pathways involved. Animals were fed an OLA-enriched preventive diet for 6 weeks prior to CIA induction and until the end of the experimental time course. On day 43 after the first immunization, mice were sacrificed: blood was collected, and paws were histologically and biochemically processed. Dietary OLA prevented collageninduced rheumatic bone, joint and cartilage conditions. Circulating matrix metalloproteinase (MMP)-3 and proinflammatory cytokine (IL-6, IL-1β, TNF-α, IL-17) levels were significantly decreased in the joint, as well as MMP-9 and cathepsin-K (CatK) expression in secoiridoid-fed animals. In addition, dietary OLA was able to decrease COX-2, mPGES-1 and iNOS protein expressions and, also, PGE2 levels. The mechanisms possibly involved in these protective effects could be related to the activation of the Nrf-2/HO-1 axis and the inhibition of proinflammatory signaling pathways, including JAK-STAT, MAPKs and NF-κB, involved in the production of inflammatory and oxidative mediators. These results support the interest of OLA, as a nutraceutical intervention, in the management of RA.
Comparación de la calidad de vida en personas que viven con infección por VIH en seguimiento mediante atención farmacéutica según metodología capacidadmotivación- oportunidad vs. seguimiento convencional. Proyecto MAS-VIH
(Sociedad Española de Quimioterapia, 2024) Martínez Sesmero, José Manuel; Margusino Framiñán, Luis; Áreas del Águila, Vera; Navarro Aznares, Herminia; Huertas Fernández, María José; Molina Cuadrado, Emilio; Díaz Ruiz, Pilar; Martín Conde, María Teresa; Alonso Grandes, Elena; Morillo Verdugo, Ramón Alejandro; Universidad de Sevilla. Departamento de Farmacología
Objetivo. Comparar la calidad de vida en personas que viven con infección por el Virus de la Inmunodeficiencia Humana según el modelo de Atención Farmacéutica que reciben en los Servicios de Farmacia Hospitalaria: CMO (capacidad, motivación y oportunidad), versus seguimiento convencional. Método. Estudio longitudinal, prospectivo, multicéntrico, realizado entre octubre-2019 y noviembre-2021 en 14 Servicios de Farmacia Hospitalaria de España. Se incluyeron pacientes mayores de 18 años, que recibían tratamiento antirretroviral y acudían a las consultas de Atención Farmacéutica durante ≥1 año. Se excluyeron aquellos pacientes sin autonomía para completar los cuestionarios previstos. Los centros fueron aleatorizados a seguir utilizando la misma sistemática de trabajo (seguimiento tradicional) o implementar el modelo CMO, utilizando la estratificación, establecimiento de objetivos farmacoterapéuticos, uso de entrevista motivacional, así como el seguimiento longitudinal con nuevas tecnologías. La variable principal fue la diferencia en el número de dimensiones afectadas negativamente, en cada rama, a las 24 semanas, según cuestionario MOS-HIV. En el brazo CMO se registraron las intervenciones más frecuentemente realizadas. Resultados. Se incluyeron 151 pacientes. La mediana de edad fue de 51,3 años. Se encontró mejora significativa de la calidad de vida al final del seguimiento en el grupo CMO, reduciéndose el número de pacientes con dimensiones afectadas negativamente (2/11 vs 8/11). Las intervenciones más frecuentes llevadas a cabo, según la taxonomía, fueron: Motivación (51,7%) y Revisión y validación del TAR (49,4%). Conclusiones. La calidad de vida de los pacientes es superior en aquellos centros que desarrollan Atención Farmacéutica basada en metodología CMO en comparación con el seguimiento tradicional.
Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment
(ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2024) Salvador-Martín, Sara; Rubbini, Gianluca; Vellosillo, Perceval; Zapata Cobo, Paula; Velasco, Marta; Palomino, Laura M.; Clemente, Susana; Segarra, Oscar; Merino Bohórquez, Vicente; López Fernández, Luis Andrés; Universidad de Sevilla. Departamento de Farmacología; Instituto de Salud Carlos III; Comunidad Autónoma de Madrid
Background/aims: Changes in gene expression profiles among individuals with inflammatory bowel diseases (IBDs) could potentially influence the responsiveness to anti-TNF treatment. The aim of this study was to identify genes that could serve as predictors of early response to anti-TNF therapies in pediatric IBD patients prior to the initiation of treatment.Methods: We conducted a prospective, longitudinal, and multicenter study, enrolling 24 pediatric IBD patients aged less than 18 years who were initiating treatment with either infliximab or adalimumab. RNA-seq from blood samples was analyzed using the DESeq2 library by comparing responders and non-responders to anti-TNF drugs. Results: Bioinformatic analyses unveiled 102 differentially expressed genes, with 99 genes exhibiting higher expression in responders compared to non-responders prior to the initiation of anti-TNF therapy. Functional enrichment analyses highlighted defense response to Gram-negative bacteria (FDR = 2.3 ×10–7) as the most significant biological processes, and hemoglobin binding (FDR = 0.002), as the most significant molecular function. Gene Set Enrichment Analysis (GSEA) revealed notable enrichment in transcriptional misregulation in cancer (FDR = 0.016). Notably, 13 genes (CEACAM8, CEACAM6, CILP2, COL17A1, OLFM4, INHBA, LCN2, LTF, MMP8, DEFA4, PRTN3, AZU1, and ELANE) were selected for validation, and a consistent trend of increased expression in responders prior to drug administration was observed for most of these genes, with findings for 4 of them being statistically significant (CEACAM8, LCN2, LTF2, and PRTN3). Conclusions: We identified 102 differentially expressed genes involved in the response to anti-TNF drugs in children with IBDs and validated CEACAM8, LCN2, LTF2, and PRTN3. Genes participating in defense response to Gram-negative bacterium, serine-type endopeptidase activity, and transcriptional misregulation in cancer are good candidates for anticipating the response to anti-TNF drugs in children with IBDs.
Switching from reference infliximab to CT-P13 in patients with inflammatory bowel disease: results of a multicenter study after 12 months
(Aran Ediciones S.A., 2018) Guerra Veloz, María Fernanda; Vázquez Morón, Juan María; Belvis Jiménez, María Inmaculada; Pallares Manrique, Héctor; Valdés Delgado, Teresa; Castro Laria, Luisa; Merino Bohórquez, Vicente; Vilches Arenas, Ángel; Argüelles Arias, Federico; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública
Background and aims: infliximab has changed the natural history of inflammatory bowel disease (IBD). The advent of biosimilar treatments such as CT-P13 will hopefully improve the availability of biological therapies. Data with regard to drug switching are currently limited. The objective of the study was to assess the effectiveness and safety of switch ing from the reference product (RP), infliximab, to CT-P13 in patients with IBD. Methods: this was a multicenter prospective observational study in patients with Crohn’s disease (CD) and ulcerative colitis (UC). All patients had switched from infliximab RP (Remicade®) to CT-P13 treatment and were followed up for 12 months. The efficacy endpoint was the change in clinical remission assessed at 0 and 12 months, according to the Harvey-Bradshaw score and partial Mayo score for patients with CD and UC, respectively. Adverse events were moni tored and recorded throughout the study. Results: a total of 167 patients (116 CD/51 UC) were includ ed; 88.8% (103/116) of patients with CD were in remission at the time of the drug switch and 69.7% were in remis sion at 12 months. The Harvey-Bradshaw (HB) score sig nificantly changed at 12 months (p = 0.001); 84.3% (43/51) of patients with UC were in remission at the time of the drug switch and 76.7% were in remission at 12 months. No significant changes in the median partial Mayo score (p = 0.87) were observed at 12 months. Serious adverse events related to medication were reported in 12/167 (7.2%) cases. Conclusion: switching from infliximab RP to CT-P13 is safe and effective at 12 months. The loss of efficacy at 12 months was 15.7%.
Cut-off ranges of infliximab serum levels in Crohn’s disease in the clinical practice
(Aran Ediciones S.A., 2020) Valdés Delgado, Teresa; Guerra Veloz, María Fernanda; Castro Laria, Luisa; Maldonado Pérez, Belén; Perea Amarillo, Raúl; Merino Bohórquez, Vicente; Sáez, Antonia; Caunedo Álvarez, Ángel; Argüelles Arias, Federico; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Departamento de Medicina
Introduction: between 30 % and 40 % of patients treated with infliximab lose response during maintenance. Ther apeutic drug monitoring could be used to optimize man agement in these situations. However, infliximab serum levels are not well defined. The aim of this study was to determine the cut-off range of infliximab serum levels in Crohn’s disease patients in remission in the clinical practice. Methods: an observational retrospective study was per formed from 2016 to 2017. Patients were included with established Crohn’s disease, who had been on a mainte nance dose schedule of infliximab. Infliximab levels and antibodies to infliximab were measured at least twice in all patients, after induction and after six months of treat ment. Clinical remission was defined as ≤ 4 using the Har vey-Bradshaw index. Cluster analysis was used to analyze the results. Results: one hundred and five Crohn’s disease patients were included in the study; 57.1 % were male with a mean age of 39 years (SD ± 12.9). The median (range) time of the disease was eleven years (7-15) and the median (range) time of follow-up was 32 months (22-38). Patients who achieved remission had infliximab serum levels between 4.26-8.26 ug/ml versus 0.06-1.43 ug/ml in patients who did not achieve remission after induction. Infliximab serum levels were 2.84-7.75 ug/ml and 0.05-2.69 ug/ml in patients who achieved remission versus those who did not achieve remission after six months of treatment. Overall, 4.26-8.26 ug/ml was found to be the best cut-off range for remission. Conclusions: in our clinical practice, serum levels of inflix imab in Crohn’s disease patients should be higher than 4 ug/ml to achieve clinical remission.
Prevalence of Potentially Inappropriate Medication Use in Older Adults with Chronic Diseases
(MDPI, 2024-04-11) Nascimento, Tania; Andrade, Amanda; Cabrita, Catarina; Pais, Sandra; Puerta Vázquez, Rocío de la; Universidad de Sevilla. Departamento de Farmacología
Older adults often consume high amounts of medicines, some of which may not be suitable for their age. A cross-sectional descriptive study was carried out on elderly people (>60 years) diagnosed with chronic diseases and taking at least one medication. The consumption of potentially inappropriate medication (PIM) was analyzed using the EU(7)-PIM List. Of the 65 elderly included, the majority were women (83.1%), diagnosed with hypertension (60.0%), and took 4.09 ± 2.104 medicines. More than 58% consumed at least one PIM. Nervous system PIMs were the most prevalent (29.2%, n = 19). There is a high prevalence of PIM use among the elderly, necessitating regular evaluation for safer medication use.
Impact of pharmaceutical care for asthma patients on health‐related outcomes: An umbrella review
(Wiley Open Access, 2024-04-21) Montero Pérez, Olalla; Salazar González, Fernando; Sánchez Gómez, Ernesto; Pérez Guerrero, María Concepción; Universidad de Sevilla. Departamento de Farmacología
Recent systematic reviews suggest that pharmacists' interventions in asthma patients have a positive impact on health-related outcomes. Nevertheless, the association is not well established, and the role of clinical pharmacists is poorly represented. The aim of this overview of systematic reviews is to identify published systematic reviews assessing the impact of pharmacists' interventions on healthrelated outcomes measured in asthma patients. PubMed, Embase, Scopus, and Cochrane Library were searched from inception to December 2022. Systematic reviews of all study designs and settings were included. Methodological quality was assessed using AMSTAR 2. Two investigators performed study selection, quality assessment and data collection independently. Nine systematic reviews met the inclusion criteria. Methodological quality was rated as high in one, low in two, and critically low in six. Reviews included 51 primary studies reporting mainly quality of life, asthma control, lung capacity, and therapeutic adherence. Only four studies were carried out in a hospital setting and only two reviews stated the inclusion of severe asthma patients. The quality of the systematic reviews was generally low, and this was the major limitation of this overview of systematic reviews. However, solid evidence supports that pharmaceutical care improves health-related outcomes in asthma patients.
Programa de Formación en Innovación educativa para el profesorado novel de la Facultad de Farmacia (RADIF)
(Real e Ilustre Colegio Oficial de Farmacéuticos, 2023) Álvarez de Sotomayor Paz, María; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla
En la Facultad de Farmacia de la Universidad de Sevilla un 15% del personal docente son profesores noveles con menos de 5 años de experiencia. El programa RADIF (Red de Apoyo a la Docencia e Innovación educativa en la Facultad de Farmacia), se dirige a profesores noveles con menos de 3 años de experiencia y está avalado por el Secretariado de Innovación Educativa de la Universidad de Sevilla. El objetivo de RADIF es ofrecer una formación específica en la docencia en Farmacia, incluyendo planificación de la enseñanza, metodología para la docencia innovadora y métodos de evaluación basados en competencias. El programa comenzó en septiembre de 2022 ofertando 20 plazas e incluía cursos sobre planificación, programación y gestión de la docencia, motivación del estudiante, recursos TIC para un laboratorio instrumental, métodos de aprendizaje activo, presentaciones interactivas, evaluación por competencias y difusión de resultados en docencia. A cada docente inscrito se le asignó un profesor mentor para el desarrollo de un proyecto de innovación docente. En el programa se preinscribieron 32 profesores noveles de los que se seleccionaron 20. Además, participaron 16 profesores en los cursos de formación y 21 como mentores. Los participantes pertenecen a 12 departamentos diferentes. En la I Jornada de Innovación Docente, se presentaron 17 proyectos de innovación docente que incluyeron propuestas de gamificación (4 proyectos), recursos TIC (6 proyectos), clase invertida (7 proyectos), aprendizaje basado en problemas (5 proyectos) y aprendizaje-servicio (2 proyectos). Los profesores participantes en el programa otorgaron valoraciones de satisfacción muy altas a la organización y contenido de los cursos y expresaron su interés en poder llevar a cabo los proyectos innovadores propuestos. El programa RADIF cumplió sus objetivos y constituyó el germen de la creación de una red de profesorado implicada en la innovación educativa.
Potentially inappropriate medications according to Marc, STOPP and PRISCUS criteria in a cohort of elderly HIV+ patients. The COMMPI project
(Sociedad Española de Quimioterapia, 2022-11-23) García Lloret, Patricia; Borrego Izquierdo, Yolanda; Manzano García, Mercedes; Cantillana Suárez, María G.; Gutiérrez Pizarraya, Antonio; Morillo Verdugo, Ramón Alejandro; Universidad de Sevilla. Departamento de Farmacología
Introduction. The objective is to determine the prevalence of potentially inappropriate drugs according to the Marc, STOPP, and PRISCUS lists in elderly HIV patients. Patients and methods. It was an observational, retrospective, and multicenter study. People living with HIV 65 years or older who underwent chronic concomitant treatment were included. Descriptive and multivariate analyzes were performed to study the association between polypharmacy and potentially inappropriate medication compliance. Results. A total of 55 patients were included, 81.8% men and a median age of 69 years (IQR: 67-73). The median number of comorbidities was 3 (IQR: 2-5) and the most frequent pattern of multimorbidity was cardiometabolic (62.9%). The predominant antiretroviral treatment was triple therapy (65.5%). Polypharmacy was present in 70.9% of the patients and 25.5% had major polypharmacy. The most frequent polypharmacy pattern was cardiovascular (69.2%). The percentage of potentially inappropriate medications according to the Marc, STOPP and PRISCUS lists was 65.5%, 30.9% and 14.5%, respectively (p<0.001). Adjusted for age and sex, polypharmacy was not independently associated with potentially inappropriate medication compliance in any of the lists. Conclusion. Polypharmacy and potentially inappropriate medications have a high prevalence. There is great variability in the percentage according to the list applied. Age, sex, and presence of polypharmacy are not predisposing factors to the presence of potentially inappropriate medications.
Patient-reported outcome measures in severe asthma: an expert consensus
(Taylor and Francis Group, 2023-12-16) Martínez Moragón, Eva; Antepara Ercoreca, Ignacio; Muñoz García, María; Casas Maldonado, Francisco; Calvín Lamas, Marta; Chiner Vives, Eusebi; Merino Bohórquez, Vicente; Sánchez Cuellar, Silvia; Universidad de Sevilla. Departamento de Farmacología; GlaxoSmithKline GSK
Objective The study aimed to reach a consensus on the most relevant patient-reported outcomes (PROs), the corresponding measures (PROMs), and measurement frequency during severe asthma patient follow-up. Methods Two Delphi rounds were conducted. The questionnaire was developed based on a systematic literature review, a focus group with patients, and a nominal group with experts. It assessed PROs’ relevance and the appropriateness (A) and feasibility (F) of PROMs using a Likert scale (1=totally agree; 9=totally disagree). The consensus was established when ≥75% of participants agreed (1-3) or disagreed (7-9). Results Sixty-three professionals (25 hospital pharmacists, 14 allergists, 13 pulmonologists, and 11 nurses) and 5 patients answered the Delphi questionnaire. A consensus was reached on all PROs regarding their relevance. Experts agreed on the use of ACT (A:95.24%; F:95.24%), mini AQLQ (A:93.65; F:79.37%), mMRC dyspnea scale (A:85.71%; F:85.71%), TAI (A:92.06%; F:85.71%), MMAS (A:75.40%; F:82%), and the dispensing register (A:96.83%; F:92.06%). Also considered suitable were: SNOT-22 (A:90.48%; F:73.80%), PSQI (A:82.54; F:63.90%), HADS (A:82.54; F:64%), WPAI (A:77.78%; F:49.20%), TSQM-9 (A:79.37; F:70.50%) and knowledge of asthma questionnaire (A:77%; F:68.80%); however, their use in clinical practice was considered unfeasible. Panelists also agreed on the appropriateness of EQ-5D, which was finally included despite being considered unfeasible (A: 84.13%; F:67.20%) in clinical practice. Agreement was reached on using ACT, TAI, mMRC, and a dispensing register every three months; mini-AQLQ and MMAS every six months; and EQ-5D every twelve months. Conclusion This consensus paves the way toward patient-centered care, promoting the development of strategies supporting routine assessment of PROs in severe asthma management.

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