Override rate of drug-drug interaction alerts in clinical decision support systems: A brief systematic review and meta-analysis.

Primary studies have demonstrated that despite being useful, most of the drug-drug interaction (DDI) alerts generated by clinical decision support systems are overridden by prescribers. To provide more information about this issue, we conducted a systematic review and meta-analysis on the prevalence of DDI alerts generated by CDSS and alert overrides by physicians. The search strategy was implemented by applying the terms and MeSH headings and conducted in the MEDLINE/PubMed, EMBASE, Web of Science, Scopus, LILACS, and Google Scholar databases. Blinded reviewers screened 1873 records and 86 full studies, and 16 articles were included for analysis. The overall prevalence of alert generated by CDSS was 13% (CI95% 5-24%, p-value <0.0001, I^2 = 100%), and the overall prevalence of alert override by physicians was 90% (CI95% 85-95%, p-value <0.0001, I^2 = 100%). This systematic review and meta-analysis presents a high rate of alert overrides, even after CDSS adjustments that significantly reduced the number of alerts. After analyzing the articles included in this review, it was clear that the CDSS alerts physicians about potential DDI should be developed with a focus on the user experience, thus increasing their confidence and satisfaction, which may increase patient clinical safety.

Prevalence of polypharmacy and drug interaction in older adults with rheumatic disease.

INTRODUCTION/AIM: Older people with rheumatic diseases tend to have a greater number of associated comorbidities, which will require the use of more drugs, increasing the risk of hospitalizations, complications, and drug interactions. In Mexico, there has been an estimated prevalence of polypharmacy of up to 55%, however there are scarce reports on the topic in our elderly population with rheumatic diseases. We aimed to determine the prevalence of polypharmacy and the association of drug interactions in patients treated for rheumatic disease. METHODS: A retrospective observational study was conducted on patients undergoing treatment for rheumatic diseases who were treated in geriatrics and rheumatology clinics from January to December 2021. The presence of polypharmacy and drug interactions was evaluated using the BOT Plus Pharmacological Surveillance System. The prevalence of polypharmacy and the association of drug interactions were estimated. RESULTS: We evaluated 320 patients, with a mean age of 67.05±5.8 years, predominantly female (85%). The prevalence of polypharmacy was 68.1% (n=218), of which 214 (98.1%) patients had related drug interactions; 27.1% were severe and 53.2% as moderate interactions. Factors related with increased risk of drug interactions were being exposed to hypertension increased the risk of drug interactions (POR 1.75, 95% CI 1.44-2.14; P<0.001), having osteoarthritis (POR 1.21, 95% CI 1.04-1.42; P=0.032) and thyroid disease (POR 1.45, 95% CI 1.28-1.65; P=0.001). The most prevalent serious interactions were leflunomide-methotrexate in 27 (46.5%) patients and buprenorphine-tramadol in 8 (13.7%). CONCLUSIONS: A high prevalence of polypharmacy and drug interactions was observed in elderly patients with rheumatic diseases. The main associated factors were comorbidities, particularly high blood pressure, osteoarthritis and thyroid diseases.

Aplicación de un modelo farmacocinético poblacional para el seguimiento de pacientes en tratamiento con dolutegravir: estudio piloto / Application of a Population Pharmacokinetic Model for the Monitoring of Patients Undergoing Treatment with Dolutegravir: pilot study / Aplicação de modelo farmacocinético populacional para acompanhamento de pacientes tratados com dolutegravir: estudo piloto

Introducción: a pesar de los avances en tratamiento antirretroviral, existe la posibilidad de que personas que viven con el virus de la inmunodeficiencia humana (VIH) experimenten falla terapéutica vinculada a múltiples factores que impactan en la respuesta al fármaco. Objetivos: evaluar la utilidad de aplicar un modelo farmacocinético en pacientes con diagnóstico de VIH en tratamiento con dolutegravir para el análisis de las concentraciones plasmáticas experimentales. Adicionalmente, se pretende identificar potenciales interacciones farmacológicas, evaluar adherencia y fallo terapéutico. Material y método: se realizó un estudio piloto transversal y observacional en pacientes VIH tratados con dolutegravir que incluyó la dosificación de la concentración plasmática, evaluación de adherencia mediante el cuestionario simplificado de adherencia a la medicación (SMAQ) y retiro de medicación. Se utilizó un modelo poblacional referenciado en la bibliografía para la predicción de concentraciones de dolutegravir en cada paciente y se compararon con las concentraciones experimentales. Resultados: fueron incluidos en el estudio 21 pacientes. Al cotejar las concentraciones plasmáticas experimentales con la simulación farmacocinética se encontraron diferencias para 12 pacientes, las cuales se explican por posibles interacciones farmacológicas, mala adherencia u otros factores que afectan la farmacocinética. Se detectó 38% de no adherencia de acuerdo con SMAQ y 23% de acuerdo con el retiro de medicación. Conclusiones: se expone el rol potencial de los modelos farmacocinéticos para la interpretación de concentraciones plasmáticas y se genera la necesidad de avanzar en este tipo de estudios para el establecimiento de rango terapéutico y aplicabilidad clínica.

Introduction: Despite advances in antiretroviral treatment, there is a possibility that people living with HIV may experience treatment failure linked to multiple factors that impact drug response. Objective: To evaluate the usefulness of applying a pharmacokinetic model in patients diagnosed with HIV undergoing treatment with dolutegravir for the analysis of experimental plasma concentrations. Additionally, the aim is to identify potential drug interactions, assess adherence, and therapeutic failure. Method: A cross-sectional, observational pilot study was conducted in HIV patients treated with dolutegravir, which included plasma concentration dosing, assessment of adherence using the Simplified Medication Adherence Questionnaire (SMAQ), and medication withdrawal. A population-based model referenced in the literature was used to predict dolutegravir concentrations in each patient and these were compared with experimental concentrations. Results: Twenty-one patients were included in the study. When comparing experimental plasma concentrations with pharmacokinetic simulation, differences were found for 12 patients, which can be explained by possible drug interactions, poor adherence, or other factors affecting pharmacokinetics. Non-adherence was detected in 38% according to the SMAQ and 23% according to medication withdrawal. Conclusions: The potential role of pharmacokinetic models in the interpretation of plasma concentrations is highlighted, emphasizing the need to advance in this type of studies to establish therapeutic ranges and clinical applicability.

Introdução: Apesar dos avanços no tratamento antirretroviral, existe a possibilidade de que pessoas que vivem com HIV experimentem falha terapêutica ligada a múltiplos fatores que impactam na resposta ao medicamento. Objetivos: Avaliar a utilidade da aplicação de um modelo farmacocinético em pacientes com diagnóstico de HIV em tratamento com dolutegravir para análise de concentrações plasmáticas experimentais. Além disso, pretende-se identificar potenciais interações medicamentosas, avaliar a adesão e a falha terapêutica. Método: Um estudo piloto observacional transversal foi conduzido em pacientes HIV tratados com dolutegravir que incluiu dosagem de concentração plasmática, avaliação de adesão usando o questionário simplificado de adesão à medicação (SMAQ) e retirada da medicação. Um modelo populacional referenciado na literatura foi utilizado para prever as concentrações de dolutegravir em cada paciente e compará-las com as concentrações experimentais. Resultados: 21 pacientes foram incluídos no estudo. Ao comparar as concentrações plasmáticas experimentais com a simulação farmacocinética, foram encontradas diferenças em 12 pacientes, que são explicadas por possíveis interações medicamentosas, má adesão ou outros fatores que afetam a farmacocinética. Foram detectadas 38% de não adesão segundo o SMAQ e 23% segundo retirada da medicação. Conclusões: Fica exposto o papel potencial dos modelos farmacocinéticos para a interpretação das concentrações plasmáticas e gera-se a necessidade de avançar neste tipo de estudos para estabelecer a faixa terapêutica e a aplicabilidade clínica.

STOPP-START Criteria Used to Identify the Elderly Population Prone to Potentially Inadequate Prescribing in a Colombian Cohort.

BACKGROUND: Elderly people have multiple comorbidities that often require treatment with multiple medications. Having strategies to lessen the risks associated with pharmacological interactions and potentially inadequate prescribing (PIP) is of major importance. The STOPP- START criteria are useful in identifying PIP along with other tools, such as LASA (look alike/sound alike) drugs and high-risk medications (HRM). OBJECTIVE: We aimed to clinically and sociodemographically characterize the population with PIP according to the STOPP-START criteria in hospitalized elderly patients over 6 months in a third-level hospital in Colombia, South America. We also aimed to calculate the prevalence of PIP, LASA drugs and HRM and to identify other problems related with medication. Finally, we proposed an algorithm for the identification of PIP in this population. METHODS AND MATERIALS: This was a descriptive, cross-sectional study in hospitalized patients older than 60 years during the first semester of 2021 to identify PIP according to STOPP- START criteria. An analysis of clinical and sociodemographic variables was conducted, as well as the construction of an algorithm to identify PIP in the elderly in a semiautomated way. Data were collected and analyzed using the software SPSS 2021, using descriptive statistics and measures of central tendency. RESULTS: The prevalence of PIP in the study population was 25%. Furthermore, 60% of patients had one problem related to medication, and 27% used at least one LASA drug or HRM. CONCLUSION: This study allows one to characterize, for the first time, the Colombian population prone to PIP, as well as the construction of an algorithm that identifies PIP in a semiautomated way.

Drug-Drug Interaction Between Cannabidiol, Cyclosporine, and Mycophenolate Mofetil: A Case Report.

Kidney transplantation remains the optimal therapy for many patients with end-stage kidney disease (ESKD). Chronic pain is one of the most common and distressing symptoms among patients with ESKD, and its treatment is a complex and challenging task to accomplish. The benefits of cannabidiol (CBD) in chronic pain treatment have been reported recently. Cannabidiol is metabolized by cytochrome P450, mainly CYP3A4 and CYP2C19, and can also undergo direct conjugation via UDP-glucuronosyltransferase enzymes, with a growing body of evidence suggesting it is also a potent inhibitor or inducer of these pathways. Cannabidiol was also found to be a potent inhibitor of carboxylesterases in vitro. Because cytochrome P450 enzymes and carboxylesterases are also responsible for the clearance and activation of immunosuppressants, respectively, drug-drug interactions are likely to occur. Here, we report a pharmacokinetic drug interaction between CBD and cyclosporine and mycophenolate mofetil in a patient with ESKD with a kidney transplantation. It is thus crucial to take into account these interactions and monitor drug levels to avoid drug toxicity or a lack of efficacy. This study is in accordance with the guidelines of the Declaration of Helsinki and the Declaration of Istanbul.

Human Data on Pharmacokinetic Interactions of Cannabinoids: A Narrative Review.

Concomitant use of cannabinoids with other drugs may result in pharmacokinetic drug-drug interactions, mainly due to the mechanism involving Phase I and Phase II enzymes and/or efflux transporters. Cannabinoids are not only substrates but also inhibitors or inducers of some of these enzymes and/or transporters. This narrative review aims to provide the available information reported in the literature regarding human data on the pharmacokinetic interactions of cannabinoids with other medications. A search on Pubmed/Medline, Google Scholar, and Cochrane Library was performed. Some studies were identified with Google search. Additional articles of interest were obtained through cross-referencing of published literature. All original research papers discussing interactions between cannabinoids, used for medical or recreational/adult-use purposes, and other medications in humans were included. Thirty-two studies with medicinal or recreational/adult-use cannabis were identified (seventeen case reports/series, thirteen clinical trials, and two retrospective analyses). In three of these studies, a bidirectional pharmacokinetic drug-drug interaction was reported. In the rest of the studies, cannabinoids were the perpetrators, as in most of them, concentrations of cannabinoids were not measured. In light of the widespread use of prescribed and non-prescribed cannabinoids with other medications, pharmacokinetic interactions are likely to occur. Physicians should be aware of these potential interactions and closely monitor drug levels and/or responses. The existing literature regarding pharmacokinetic interactions is limited, and for some drugs, studies have relatively small cohorts or are only case reports. Therefore, there is a need for high-quality pharmacological studies on cannabinoid-drug interactions.

Unravelling drug-drug interactions in pigs: Induction of hepatic cytochrome P450 1A (CYP1A) metabolism after the in-feed medication with the anthelmintic fenbendazole.

The anthelmintic fenbendazole (FBZ) undergoes hepatic S­oxygenation by monooxygenases belonging to the cytochrome P450 (CYP) and flavin-monooxygenase (FMO) families. The in-feed medication with FBZ induced CYP1A-dependent metabolism in pig liver. This fact may alter the metabolism of the anthelmintic itself, and of CYP1A substrates like aflatoxin B1 (AFB1). This work evaluated the effect of the in-feed administration of FBZ on CYP1A-dependent metabolism, on its own pattern of hepatic S­oxygenation, and on the metabolism of AFB1. Landrace piglets remained untreated (n = 5) or received a pre-mix of FBZ (n = 6) in feed for 9 days. Pigs were slaughtered for preparation of liver microsomes used for: CYP content determination; monitoring the CYP1A-dependent enzyme activities, 7-ethoxyresorufin O-deethylase (EROD) and 7-methoxyresorufin O-demethylase (MROD); measurement of FBZ (50 µM) S­oxygenation, and AFB1 (16 nM) disappearance from the incubation medium. In microsomes of FBZ-treated animals, EROD and MROD increased 19-fold (p = 0.002) and 14-fold (p = 0.003), respectively. An enhanced (3-fold, p = 0.004) participation of the CYP pathway in FBZ S­oxygenation was observed in the liver of piglets treated with the anthelmintic (210 ± 69 pmol/min.nmol CYP) compared to untreated animals (68 ± 34 pmol/min.nmol CYP). AFB1 metabolism was 93% higher (p = 0.009) in the liver of FBZ-treated compared to untreated pigs. Positive and significant (p < 0.05) correlations were observed between CYP1A-dependent enzyme activities and FBZ or AFB1 metabolism. The sustained administration of FBZ caused an auto-induction of the CYP1A-dependent S­oxygenation of this anthelmintic. The CYP1A induction triggered by the anthelmintic could amplify the production of AFB1 metabolites in pig liver, including the hepatotoxic AFB1-derived epoxide.+.

Relação entre benefício e risco em interações medicamentosas nas prescrições médicas de um hospital universitário no estado de São Paulo / Benefit-risk relationship in drug interactions in prescriptions from a university hospital in the state of São Paulo / Relación beneficio-riesgo en interacciones medicamentosas en prescripciones de un hospital universitario del estado de São Paulo

Objetivo: Avaliar interações medicamentosas (IM), em que os riscos se so- brepõem aos benefícios (nível I) ou os benefícios se sobrepõem aos riscos (nível II); a partir da análise retrospectiva de prescrições médicas em um Hospital Universitário no estado de São Paulo, Brasil. Métodos: Foram analisadas 19762 prescrições médicas des- tinadas à farmácia do hospital, de janeiro a setembro de 2009; com o auxílio de programas sobre IM, para categorizar IM de nível I e II. Resultados: Na análise 26,53% apresentaram IM, em que 23,64% foram classificadas em nível I e 76,35% em nível II. Dentre as IM com maior frequência no nível I, estavam: ácido acetilsalicílico (AAS) e clopidogrel, AAS e heparina, captopril e espironolactona, digoxina e hidroclorotiazida. Houve uma redução em percentual de IM de nível I, comparando janeiro representado por 26,5% e setembro representado por 18,4%. Já nas IM de nível II, tem-se as seguintes associações com maior frequência: AAS e propranolol, AAS e insulina regular humana, AAS e ate- nolol, AAS e enalapril, AAS e carvedilol. Conclusão: A atuação dos farmacêuticos cola- borou à redução de IM de nível I, devido à intervenção por meio de comunicação estabe- lecida com os prescritores; sinalizando a importância da equipe interprofissional em saúde.

Objective: To evaluate drug interactions (MI), in which risks outweigh the benefits (level I) or benefits outweigh the risks (level II); from the retrospective analysis of medical prescriptions in a University Hospital in the state of São Paulo, Brazil. Methods: 19,762 prescriptions destined to the hospital pharmacy were analyzed, from January to September 2009; with the help of programs on MI, to categorize level I and II MI. Results: In the analysis 26.53% presented MI, in which 23.64% were classified in level I and 76.35% in level II. Among the most frequent level I MI were: acetylsalicylic acid (ASA) and clopidogrel, ASA and heparin, captopril and spironolactone, digoxin and hydrochlorothiazide. There was a reduction in the percentage of level I MI, comparing January, which accounted for 26.5%, and September, which accounted for 18.4%. As for level II MI, the following associations were more frequent: ASA and propranolol, ASA and regular human insulin, ASA and atenolol, ASA and enalapril, ASA and carvedilol. Conclusion: The role of pharmacists collaborated to the reduction of level I MI, due to the intervention by means of communication established with the prescribers; signaling the importance of the interprofessional health team.

Objetivo: Evaluar las interacciones medicamentosas (IM), en las que los riesgos superan a los beneficios (nivel I) o los beneficios superan a los riesgos (nivel II); a partir del análisis retrospectivo de las prescripciones médicas en un Hospital Universitario del estado de São Paulo, Brasil. Métodos: Se analizaron 19.762 prescripciones destinadas a la farmacia del hospital, de enero a septiembre de 2009; con la ayuda de programas sobre IM, para categorizar los IM de nivel I y II. Resultados: En el análisis el 26,53% presentaron IM, en el que el 23,64% se clasificaron en nivel I y el 76,35% en nivel II. Entre los IM de nivel I más frecuentes estaban: ácido acetilsalicílico (AAS) y clopidogrel, AAS y heparina, captopril y espironolactona, digoxina e hidroclorotiazida. Hubo una reducción del porcentaje de IM de nivel I, comparando enero, que supuso el 26,5%, y septiembre, que supuso el 18,4%. En cuanto a los IM de nivel II, fueron más frecuentes las siguientes asociaciones: AAS y propranolol, AAS e insulina humana regular, AAS y atenolol, AAS y enalapril, AAS y carvedilol. Conclusiones: El papel de los farmacéuticos colaboró a la reducción de las IM de nivel I, debido a la intervención mediante la comunicación establecida con los prescriptores; señalando la importancia del equipo sanitario interprofesional.

Polypharmacy and Drug Interactions in the COVID-19 Pandemic.

The COVID-19 pandemic generated a great impact on health systems. We compared evolution, polypharmacy, and potential drug-drug interactions (P-DDIs) in COVID-19 and non-COVID-19 hospitalizations during first wave of pandemic. Prescriptions for hospitalized patients ≥ 18 years (COVID-19 and non-COVID-19 rooms) between April and September 2020 were included. The computerized medical decision support system SIMDA and the physician order entry system Hdc.DrApp.la were used. Patients in COVID-19 rooms were divided into detectable and non-detectable, according to real-time reverse transcription polymerase chain reaction (RT-PCR). Number of drugs, prescribed on day 1, after day 1, and total; polypharmacy, excessive polypharmacy, and P-DDIs were compared. 1,623 admissions were evaluated: 881 COVID-19, 538 detectable and 343 non-detectable, and 742 non-COVID-19. Mortality was 15% in COVID-19 and 13% in non-COVID-19 (RR [non-COVID-19 vs. COVID-19]: 0.84 [95% CI] [0.66-1.07]). In COVID-19, mortality was 19% in detectable and 9% in non-detectable (RR: 2.07 [1.42-3.00]). Average number of drugs was 4.54/patient (SD ± 3.06) in COVID-19 and 5.92/patient (±3.24) in non-COVID-19 (p<0.001) on day 1 and 5.57/patient (±3.93) in COVID-19 and 9.17/patient (±5.27) in non-COVID-19 (p<0.001) throughout the hospitalization. 45% received polypharmacy in COVID-19 and 62% in non-COVID-19 (RR: 1.38 [1.25-1.51]) and excessive polypharmacy 7% in COVID-19 and 14% in non-COVID-19 (RR: 2.09 [1.54-2.83]). The frequency of total P-DDIs was 0.31/patient (±0.67) in COVID-19 and 0.40/patient (±0.94) in non-COVID-19 (p=0.022). Hospitalizations in the COVID-19 setting are associated with less use of drugs, less polypharmacy and less P-DDIs. Detectable patients had higher mortality.

Interactions between local medical systems and the biomedical system: a conceptual and methodological review in light of hybridization subprocesses.

Local medical systems (LMSs) are complex and dynamic, encompassing local perceptions of diseases, prevention and treatment strategies, and evaluations of therapeutic responses. These systems are not isolated and interact with other medical systems, such as the biomedical system. The interaction between these systems creates a "contact zone", which some authors refer to as intermedicality, involving both competitive and complementary interactions. However, there is limited discussion in the literature regarding the complexity of these interactions. Some studies seek to understand this interaction through the lens of hybridization, a concept introduced to ethnobiology by Ana Ladio and Ulysses Albuquerque. The authors conceptualize hybridization as "discrete structures and practices coming together to form a new practice not necessarily implying homogenization." They discuss hybridization in the context of medicinal plants used in urban settings and propose seven hybridization subprocesses to gain a deeper understanding of this phenomenon. In this study, we update these hybridization subprocesses, expanding the concepts to comprehend the specific interaction of resources from LMS and biomedical systems known and used by different human groups. In this context, we propose a new subprocess and have made adjustments to the existing subprocesses to encompass the diversity of possible interactions between medicinal plants and pharmaceuticals, providing evidence from the literature demonstrating interactions that can be classified within the proposed subprocesses. Furthermore, we discuss, from a theoretical standpoint, how these subprocesses may have implications for the resilience of medical systems. Moreover, we propose a flowchart that can be utilized to identify these hybridization subprocesses in intermedicality contexts in future studies. These classifications are crucial because they enable us to comprehend the complexity of interactions between medicinal plants and pharmaceuticals, as well as the impacts that these different interactions can have on the resilience of LMSs.

Análise das prescrições de pacientes com covid-19 em uso de hidroxicloroquina em uma unidade de terapia intensiva / Analysis of prescriptions of patients with COVID-19 using hydroxychloroquine in an Intensive Care Unit / Análisis de las prescripciones de pacientes con COVID-19 en uso hidroxicloroquina en una unidad de terapia intensiva

Mesmo em emergências sanitárias, quando terapias experimentais são empregadas, é importante prezar pela segurança e eficácia no uso de medicamentos, e a análise de prescrições médicas é uma das maneiras de monitorar aspectos de segurança. Objetivo: Quantificar e classificar as interações medicamentosas potenciais com hidroxicloroquina de acordo com o riscoem prescrições de pacientes com COVID-19 em pacientes com COVID-19 em uso de hidroxicloroquina admitidos em uma unidade de terapia intensiva de um Hospital de Ensino.Metodologia:Este estudo transversal baseou-se na análise de 162 prescrições de 38 pacientes admitidos em uma unidade de terapia intensiva de um Hospital de ensino entre abril e junho de 2020.O Micromedex® e o UpToDate® foram as bases de dados de apoio à conduta clínica utilizadas para estabelecer as interações medicamentosas potenciais. Resultados:A média de dias de internamento foi de 16,1 ± 14,0 e a média de dias em uso de hidroxicloroquina foi de 4,26 ± 1,74. 87,14% das prescrições apresentaram interações medicamentosas potenciais e a mais comum foi entre hidroxicloroquina e azitromicina. 76,4% das prescrições analisadas apresentaram interações medicamentosas potenciais com hidroxicloroquina. 73,5% das prescrições tiverampelo menos uma interação medicamentosa potencial entre medicamentos que prolongam o intervalo QT. Conclusões: Tendo em vista os riscos da exposição de pacientes críticos às interações medicamentosas, este estudo demonstra a necessidade de fortalecer nas instituições hospitalares a cultura de monitoramento de parâmetros de segurança e eficáciano uso de medicamentos, inclusive em terapias experimentais com a utilização de medicamentos off-labelpara minimizar riscos e ampliar possíveis benefícios (AU).

Even in health emergencies, when experimental therapies are employed, it is important to ensure the safety and efficacy of medicines, and the analysis of medical prescriptions is one of the ways to monitor safety aspects.Objective: Quantify and rank potential drug interactions with hydroxychloroquine according to risk in prescriptions of COVID-19 patients taking hydroxychloroquine admitted to an intensive care unit of a TeachingHospital.Methodology: This cross-sectional study was based on the analysis of 162 prescriptions of 38 patients admitted to an intensive care unit of a teaching hospital between April and June 2020. Micromedex® and UpToDate® were the clinical practice support databases used to establish potential drug interactions. Results: The mean number of days of hospitalization was 16.1 ± 14.0 and the mean number of days of days on hydroxychloroquine was 4.26 ± 1.74. 87.14% of the prescriptions presented potential drug interactions and the most common was between hydroxychloroquine and azithromycin. 76.4% of the analyzed prescriptions had potential drug interactions with hydroxychloroquine. 73.5% of prescriptions had at least one potential drug interaction between drugs that prolong the QT interval. Conclusions: In view of the risks of exposure of critically ill patients to drug interactions, this study interactions, this study demonstrates the need to strengthen in hospital institutions the culture of institutions the culture of monitoring safety and efficacy parameters in the use of medicines, including experimental therapies with the use of off-label drugs to minimize risks and increase possible benefits (AU).

Aunque en médio aemergencias sanitarias, cuando son empleadas terapias experimentales, es importante estimar la seguridad y eficacia en el uso de los medicamentos, y el análisis de prescripciones es una de las formas de acompanhar los aspectos de seguridad. Objetivo:Cuantificar y clasificar las interaciones farmacologicas potenciales con hidroxicloroquina de acuerdo com el riesgo em prescripciones de pacientes com Covid-19 em uso de hidroxicloroquina andmitidos em unidad de terapia intensiva de um Hospital Docente. Metodología: Este estudio transversal se asienta en el análisis de 162 prescripciones de 38 pacientes admitidos em uma unidad de terapia intensiva de um Hospital Docente entre abril y junio de 2020. El Micromedex®ï¸y el UpToDate®ï¸fueron las bases de datos de apoyo a la actuación clínica utilizadas para establecer las interacciones farmacológicas potenciales. Resultados:El promedio de días de internamiento fue de 16,1 ± 14,0 y el promedio de días en uso hidroxicloroquina fuede 4,26 ± 1,74. 87,14% de las prescripciones presentaron interacciones farmacológicas potenciales y la más común fue entre hidroxicloroquina y azitromicina. 76,4% de las prescripciones analizadas presentaron interaciones farmacológicas com hidroxicloroquina. 73,5% de las prescripciones tuvierion por lo menos uma interacción farmacológica potencial entre medicamentos que prolongam el intervalo QT. Conclusiones:Tenendo a la vista los riesgos de la exposición de pacientes críticos a las interaciones farmacológicas, este estudio demuestra la necesidad de reforzar em las instituiciones hospitalarias la cultura de monitoreo de parâmetros de seguridade y eficacio em el uso de medicamentos, incluso en terapias experimentales con utilización de medicamentos off-label, para minorar riesgos y ampliar los posibles beneficios (AU).

Control de la hipertensión arterial en el adulto mayor en Atención Primaria / Management of hypertension in the elderly in Primary Health Care

La hipertensión arterial sistémica es una enfermedad crónica de causa múltiple, que produce daño vascular sistémico e incrementa la morbilidad y mortalidad por diversas enfermedades cardiovasculares. El objetivo de esta investigación fue caracterizar la prescripción para el tratamiento de la hipertensión arterial y asociaciones de fármacos sugerentes de posibles interacciones medicamentosas potenciales en el adulto mayor, en un Consultorio Médico vinculado a la Farmacia Principal Municipal de Santa Clara. Los medicamentos más prescriptos fueron: hidroclorotiazida en tabletas de 25 mg, enalapril de 20 mg y amlodipino de 10 mg. El tratamiento más empleado fue la combinación de dos agentes antihipertensivos, preferentemente los inhibidores de la enzima convertidora de angiotensina con diuréticos tiazídicos. La combinación de medicamentos inhibidores de la enzima convertidora de angiotensina con espironolactona fue la interacción medicamentosa de mayor importancia clínica. Se concluyó que los pacientes de la tercera edad conforman el grupo etario más medicado de la sociedad.

Systemic arterial hypertension is a chronic disease of multiple etiologies, which produces systemic vascular damage and increases morbidity and mortality due to various cardiovascular diseases. The objective of this research was to characterize the prescription for the treatment of arterial hypertension and potential drug-drug interactions in the elderly from a doctor's office linked to the Main Municipal Pharmacy of Santa Clara. Hydrochlorothiazide 25 mg, enalapril 20 mg and amlodipine 10 mg were the most prescribed medications. The combination of two antihypertensive agents, preferably angiotensin-converting enzyme inhibitors with thiazide diuretics, was the most widely used treatment. The combination of angiotensin-converting enzyme inhibitor drugs with spironolactone was the most clinically important drug interaction. We concluded that elderly patients make up the most medicated age group in society.

Effect of Chronic Hepatitis C on the Activity of the Membrane Transporters P-gp and OATP1B1/BCRP on Patients With Different Stages of Hepatic Fibrosis.

The activity of the membrane transporters organic anion-transporting polypeptide 1B1 (OATP1B1) & breast cancer resistance protein (BCRP) (rosuvastatin) and P-glycoprotein (P-gp) (fexofenadine) was evaluated in patients with chronic hepatitis C virus (HCV) infection (n = 28), genotypes 1 and 3, investigated before the treatment with direct-acting antiviral agents (Phase 1) and up to 30 days after the assessment of the virologic response (Phase 2). Participants allocated in Groups 1 (n = 15; F0/F1 and F2, mild to moderate liver fibrosis) and 2 (n = 13; F3 and F4, advanced course of liver fibrosis/cirrhosis) received in both phases fexofenadine (10 mg) and rosuvastatin (2 mg). OATP1B1 & BCRP activity (rosuvastatin area under the plasma concentration-time curve of rosuvastatin from time zero to infinity (AUC0-∞ )) was reduced in Groups 1 and 2, respectively, by 25% (ratio 0.75 (0.53-0.82), P < 0.01) and 31% (ratio 0.69 (0.46-0.85), P < 0.05) in Phase 1 compared with Phase 2. OATP1B1 & BCRP activity was reduced in Phases 1 and 2, respectively, by 49% (median ratio 1.51 (1.17-2.20), P < 0.05) and 61% (ratio 1.39 (1.16-2.02), P < 0.01) in Group 2 compared with Group 1. P-gp activity (fexofenadine AUC0-∞ ) was also reduced in Phase 1 compared with Phase 2 (ratio Phase2/Phase1 0.79 (0.66-0.96) in Group 1 and 0.81 (0.69-0.96) in Group 2) as well as in Group 2 compared with Group 1 in both Phases (ratio Group2/Group1 1.47 (1.08-2.01) in Phase 1 and 1.51 (1.10-2.07) in Phase 2). Thus, clinicians administering OATP1B1 & BCRP and P-gp substrates with low therapeutic indexes should consider the evolution of the treatment and the stage of HCV infection.

Adaptogens on Depression-Related Outcomes: A Systematic Integrative Review and Rationale of Synergism with Physical Activity.

Depression is considered the most important disorder affecting mental health. The aim of this systematic integrative review was: (i) to describe the effects of supplementation with adaptogens on variables related to depression in adults; and (ii) to discuss the potential combination with physical exercise to aid planning and commissioning future clinical research. An integrative review was developed complementing the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement (PROSPERO registration: CRD42021249682). A total of 41 articles met the inclusion criteria. With a Price index of 46.4%, we found that: (i) Hypericum perforatum (St. John's Wort) is the most studied and supported adaptogen (17/41 [41.46%], three systematic reviews with meta-analysis) followed by Crocus sativus L. or saffron (6/41 [14.63%], three systematic reviews with meta-analysis and two systematic reviews); (ii) it is possible that the significantly better performance of adaptogens over placebo is due to the reduction of allostatic load via the action of secondary metabolites on BDNF regulation; and, (iii) the number of studies reporting physical activity levels is limited or null for those that combine an exercise program with the consumption of adaptogens. Aware of the need for a multidisciplinary approach for depression treatment, this systematic integrative review provides an up-to-date view for supporting the use of St. John's Wort and saffron as non-pharmacological strategies while also help commissioning future research on the efficacy of other adaptogens. It also contributes to the design of future clinical research studies that evaluate the consumption of herbal extracts plus physical exercise, mainly resistance training, as a potentially safe and powerful strategy to treat depression.

[Prescription errors and drug interactions in adults hospitalized in an intensive care unit in Barranquilla (Colombia).] / Errores de prescripción e interacciones farmacológicas en personas adultas hospitalizadas en una unidad de cuidados intensivos en Barranquilla (Colombia).

OBJECTIVE: Prescribing errors and drug-drug interactions constitute a relevant topic for health professionals in these hospital settings and for the strengthening of strategies to mitigate these errors. The aim of this article was to determine the prescribing errors and drug-drug interactions present in adult patients hospitalized in an intensive care unit in the city of Barranquilla (Colombia). METHODS: A quantitative study was conducted in which 158 medical records of adult patients who were hospitalized in an Intensive Care Unit (ICU) in the city of Barranquilla during 2019 were analyzed. Medication errors and drug-drug interactions were determined by means of the Medscape application. Statistical analysis was performed using the RStudio program, descriptive and inferential statistics were applied to the data. RESULTS: Sociodemographically, male sex prevailed, the most frequent pathological history was arterial hypertension, most patients were receiving between one±five drugs, the most common errors were related to omission of dosage, route and time of administration. Drug-drug interactions were reported in 64.5% (102) of the histories and, in terms of the level of severity of the interactions, moderate interactions predominated in 32.9% (52). CONCLUSIONS: It is evident that there is a high number of medication prescription errors in hospitalized adults, among which pharmacological interactions associated mainly with the number of medications received by individuals in the ICUs stand out.

OBJETIVO: Los errores de prescripción y las interacciones farmacológicas constituyen un tema relevante para los profesionales de salud que se encuentran en estos ámbitos hospitalarios y para el fortalecimiento de estrategias que permitan mitigar estos errores. El objetivo del artículo fue determinar los errores de prescripción e interacciones medicamentosas presentes en pacientes adultos hospitalizados en una unidad de cuidados intensivos en la ciudad de Barranquilla (Colombia). METODOS: Se realizó un estudio cuantitativo en el que se analizaron 158 historias clínicas de pacientes adultos que estuvieron hospitalizados en una Unidad de Cuidados Intensivos (UCI) de la ciudad de Barranquilla durante el año 2019. Se determinaron errores de medicación e interacciones medicamentosas por medio de la aplicación Medscape. El análisis estadístico se realizó mediante el programa RStudio, se aplicó estadística descriptiva e inferencial a los datos. RESULTADOS: Sociodemográficamente prevaleció el sexo masculino, el antecedente patológico con mayor frecuencia fue la hipertensión arterial, la mayoría de los pacientes estaban recibiendo entre uno±cinco medicamentos, los errores más comunes estaban relacionados con la omisión de la dosis, vía y horario de administración. Se reportaron interacciones medicamentosas en el 64,5% (102) de las historias y, en cuanto al nivel de gravedad de las interacciones, predominaron las moderadas en un 32,9% (52). CONCLUSIONES: Se evidencia que existe un alto número de errores de prescripción de medicamentos en los adultos hospitalizados, entre los que se destacan las interacciones farmacológicas asociadas principalmente con el número de medicamentos que reciben las personas en las UCI.

Interações potenciais entre os medicamentos comumente prescritos em cirurgia oral e os medicamentos em uso pelo paciente: estudo piloto / Potential interactions between drugs commonly prescribed in oral surgery and drugs used by the patient: a pilot study

Introdução: A alta prevalência do uso de medicamentos na população brasileira pode interferir na prescrição odontológica. Objetivos: Identificar os medicamentos em uso por pacientes atendidos em uma clínica de cirurgia oral menor e estimar os riscos de interações medicamentosas (IM) potenciais com fármacos comumente prescritos em procedimentos cirúrgicos. Materiais e Métodos: Realizou-se um estudo piloto analítico e transversal, sendo incluídos 24 pacientes atendidos na Clínica de Cirurgia Oral da Faculdade de Odontologia de uma universidade pública brasileira. Os dados foram coletados por meio de um questionário exploratório. Todos os medicamentos foram classificados no sistema Anatomical Therapeutic Chemical (ATC). As IM potenciais foram analisadas no banco de dados do Drugs® após correlação entre os medicamentos em uso pelo paciente e os medicamentos comumente prescritos em cirurgia oral.Resultados: Observou-se prevalência de 66,7% (n= 16) no uso de pelo menos 1 medicamento dentre os pacientes atendidos na clínica de cirurgia oral, com média de 3,5 (±2,2) medicamentos, sendo a polifarmácia identificada em 16,6% pacientes (n= 4). A média de idade dos usuários de medicamentos foi de 52 (±16) anos e totalizou-se 56 medicamentos. Os fármacos mais prevalentes foram aqueles atuantes nos sistemas nervoso e cardiovascular. Quando simuladas as adições dos fármacos comumente prescritos em cirurgia oral (anti-inflamatórios, analgésicos e antimicrobianos) aos medicamentos em uso pelos 16 pacientes, identificou-se 75 IM potenciais diferentes, sendo 61 (81%) de gravidade moderada e 14 (19%) de gravidade alta. As IM potenciais mais frequentes foram de anti-hipertensivos com anti-inflamatórios, enquanto as de importância clínica grave envolveram fármacos de ação central e analgésicos opioides. Conclusão: Observou-se alta prevalência na utilização de medicamentos pelos pacientes atendidos na clínica de cirurgia oral, com importante risco de interações com medicamentos prescritos em procedimentos cirúrgicos.

Introduction: The high prevalence of drug use in the Brazilian population can interfere with dental prescriptions.Objective: To identify drugs being used by patients seen at a minor oral surgery clinic and to estimate the risks of potential drug interactions (DI) with drugs commonly prescribed in surgical procedures. Materials and Methods: An analytical and cross-sectional pilot study was carried out, including 24 patients treated at the Oral Surgery Clinic of the Dental School of a Brazilian Federal University. Data were collected through an exploratory questionnaire. All drugs were classified in the Anatomical Therapeutic Chemical (ATC) system. Potential DI were analyzed in the Drugs® database after correlation between the drugs used by the patient and the drugs commonly prescribed in oral surgery.Results: There was a prevalence of 66.7% (n= 16) in the use of at least 1 medication among patients seen at the oral surgery clinic, with a mean of 3.5 (±2.2) medications, with polypharmacy identified in 16.6% patients (n= 4). Mean age of medication users was 52 (±16) years, totaling 56 medications. The most prevalent drugs were those acting on the nervous and cardiovascular systems. When the additions of drugs commonly prescribed in oral surgery (anti-inflammatory drugs, analgesics and antimicrobials) to the drugs used by the 16 patients were simulated, 75 different potential DI were identified, 61 (81%) of moderate severity and 14 (19%) of high gravity. The most frequent potential DIs were antihypertensives with anti-inflammatory drugs, while those of serious clinical importance involved centrally acting drugs and opioid analgesics. Conclusion: There was a high prevalence of medication use by patients seen at the oral surgery clinic, with a significant risk of interactions with prescribed medications in surgical procedures.

Concomitant use of allopathic medicine and herbal products for weight-loss among people with overweight or obesity from Central Mexico / Uso concomitante de medicina alopática y productos herbales para bajar de peso en personas con sobrepeso u obesidad del centro de México

This study evaluated the prevalence of concomitant use of herbal products for weight loss (HPWL) and allopathic medicine. Factors associated with the prevalence, adverse reactions, and the alteration of medication adherence with the concomitant use of HPWL alone and in combination with allopathic medicine, were assessed. The study was descriptive and cross-sectional using a questionnaire conducted among people with overweight or obesity (n=662) from five cities of Central Mexico. Adherence to medications was measured using the Morisky Medication Adherence Scale. The prevalence of adverse reactions induced by the concomitant use of HPWL, and allopathic medicine was 25.3%. The use of HPWL affected medication adherence by 68%. There is a high prevalence (45.2%) of concomitant use of HPWL and allopathic medicine in people with overweight or obesity in Central Mexico. The concomitant use of HPWL and allopathic medicine induces adverse reactions, mainly gastrointestinal, and thus, medication adherence is affected.

Este estudio evaluó la prevalencia del uso concomitante de productos a base de hierbas para bajar de peso (HPWL) y medicina alopática. Se evaluaron los factores asociados con la prevalencia, las reacciones adversas y la alteración de la adherencia a la medicación con el uso concomitante de HPWL solo y en combinación con medicina alopática. El estudio fue descriptivo y transversal mediante un cuestionario realizado entre personas con sobrepeso u obesidad (n = 662) de cinco ciudades del centro de México. La adherencia a los medicamentos se midió mediante la Escala de adherencia a la medicación de Morisky. La prevalencia de reacciones adversas inducidas por el uso concomitante de HPWL y medicina alopática fue del 25,3%. El uso de HPWL afectó la adherencia a la medicación en un 68%. Existe una alta prevalencia (45.2%) de uso concomitante de HPWL y medicina alopática en personas con sobrepeso u obesidad en el centro de México. El uso concomitante de HPWL y medicina alopática induce reacciones adversas, principalmente gastrointestinales, y por tanto, afecta la adherencia a la medicación.

Polifarmacia en pacientes mayores de 60 años en la Atención Primaria / Polypharmacy in patients over 60 years of age in primary health care

Los pacientes de la tercera edad conforman el grupo etario más medicado de la sociedad, principalmente por el incremento de la prevalencia de enfermedades crónicas, y por presentar tres características principales que lo diferencian de otros grupos de edad: polienfermedad, polifarmacia y cambios fisiológicos relacionados con el envejecimiento. El objetivo de esta investigación fue caracterizar la presencia de polifarmacia y las asociaciones de fármacos sugerentes de posibles interacciones medicamentosas potenciales, en el adulto mayor en un Consultorio Médico vinculado a la Farmacia Principal Municipal de Santa Clara.

Elderly patients make up the most medicated age group in society, mainly due to the increase in the prevalence of chronic diseases and because they have three main characteristics that differentiate them from other age groups: polypathology, polypharmacy and physiological changes related to aging. The objective of this research was to characterize the presence of polypharmacy and the associations of drugs suggestive of possible potential drug interactions in the elderly from a doctor's office linked to the Main Municipal Pharmacy of Santa Clara.

Development and Implementation of the Hdc.DrApp.la and SIMDA Programs to Reduce Polypharmacy and Drug-drug Interactions in Patients Hospitalized in Internal Medicine.

OBJECTIVES: We evaluated polypharmacy and possible drug-drug interactions (p-DDIs) in hospitalized patients before and after using the SIMDA Computerized Medical Decision Support System (CMDSS). MATERIALS AND METHODS: We included the prescriptions of ≥ 18 years hospitalized patients in the internal medicine department. We developed and implemented the Hdc.DrApp Physician Order Entry System and the CMDSS SIMDA, which detects p-DDIs and signals dosage adjustment based on renal function. To evaluate the impact of the CMDSS, we made a comparison Before (Survey) / After (Intervention): Survey between Oct/22/2019, and Mar/21/2020, and Intervention between Apr/4/2020 and Sep/3/2020. We analyze prescriptions from the first day and after the first day. We compared the number of drugs, polypharmacy (≥ 5 drugs), excessive polypharmacy (≥ 10 drugs), and p-DDIs. We evaluated differences with the X2 test, Yates correction, Fisher's exact test, ANOVA, and post hoc tests according to their characteristics. RESULTS: We evaluated 2,834 admissions: Survey 1,211 and Intervention 1,623. The number of drugs per patient was 6.02 (± 3.20) in Survey and 5.17 (± 3.22) in Intervention (p < 0.001) on the first day and 9.68 (± 5.60) in Survey and 7.22 (± 4.93) in Intervention (p < 0.001) throughout the hospitalization. Polypharmacy was present in 64% of the Survey and 53% of Interventions (RR: 0.83 (0.78-0.88); and excessive polypharmacy in 14% of the Survey and 10% of Intervention (RR: 0.73, 0.60-0.90). The frequency of total p-DDIs was 1.91/patient (± 4.11) in Survey and 0.35 (± 0.81) in the Intervention (p < 0.001). CONCLUSIONS: We developed and implemented the Hdc.DrApp and SIMDA systems that were easy to use and allowed us to quantify and reduce polypharmacy and p-DDIs.

Synergism of macrocyclic lactones against Haemonchus contortus.

A possible synergistic effect of macrocyclic lactones' (MLs) combination has been previously described against resistant gastrointestinal nematodes of cattle. In addition to synergism, drug-drug interactions between MLs can also result in additive or antagonistic effect, considering the different MLs pharmacokinetics, pharmacodynamics, and interactions with molecular mechanisms of resistance. Therefore, the aim of the current work was evaluated the effect of different MLs combinations against Haemonchus contortus. Infecting larvae of two isolates (one susceptible and one resistant to ivermectin) were used in the larval migration inhibition test. After estimating the half maximal effective concentration of abamectin (ABA), eprinomectin, (EPR), ivermectin (IVM), and moxidectin (MOX) for both isolates, combinations were delineated by a simplex-centroid mixture experiment, and the mixture regression analysis was applied to the special cubic model. A synergistic effect was found for the EPR + MOX against the susceptible isolate as well as the EPR + MOX, IVM + MOX, and ABA + EPR + IVM against the resistant isolate. An antagonistic effect of ABA + IVM + MOX was found against the susceptible isolate. For the susceptible isolate, a higher inhibition was found with greater proportions of EPR and lower proportions of the other drugs compared to the reference mixture. For the resistant isolate, inhibition greater than that of the reference mixture was found with higher proportions of IVM as well as lower proportions of the other drugs. The synergistic and antagonistic effects were dependent on the following: (a) parasite drug resistance profile, (b) the composition of the combination, and (c) the proportions used, with EPR and IVM exerting a greater impact on these effects.