Fármaco-seguridad al uso de antihipertensivos por adultos mayores de un programa para la salud psicofísica / Drug-safety to the use of antihypertensive drugs by older adults in a program for psychophysical health / Fármaco-segurança uso de anti-hipertensivos por adultos maiores de um programa para a saúde psicofísica

Resumen Introducción: la promoción de la salud psicofísica y la seguridad del uso responsable de los antihipertensivos es una necesidad para mejorar la calidad y esperanza de vida del paciente. Objetivo: indagar la relación de factores de riesgo que influyen en la farmacoseguridad del uso de antihipertensivos en un grupo de adultos mayores con enfermedad cardiovascular. Metodología: estudio cuantitativo exploratorio transversal descriptivo. Se aplicó el instrumento Sistema de Dispensación para usuarios Crónicos en validación a 45 adultos mayores entre 50 y 88 años con diagnóstico clínico de enfermedad cardiovascular durante 2015. Resultados: el ANOVA multifactorial con el paquete estadístico IBM SPSS 2016, evidenció relación estadística alta F (1) = 27,43; p< 0,001 entre los factores de riesgo, la no adherencia e ineficacia del uso antihipertensivo. El análisis comparativo de la diferencia de media entre la no adherencia al tratamiento y la media de la farmacoterapia eficaz e ineficaz, reveló una diferencia muy alta t (1) = 421.59, p< 0,001. Conclusiones: Este estudio muestra la necesidad de fomentar la práctica cotidiana de la promoción de la salud al adulto mayor, a fin de lograr una presión arterial estable y la prevención de algún evento y/o problema relacionado al uso del antihipertensivo que pueda incidir en el efecto terapéutico y en el bienestar del paciente.

Abstract Introduction: The promotion of psychophysical health and the safety of the responsible use of antihypertensive drugs, is a necessity to improve the quality and life expectancy of the patient. Objective: To explore the relationship of risk factors that influence the pharma security for the use of antihypertensive drugs by a group of older adults with cardiovascular disease. Methodology: Descriptive cross-sectional exploratory quantitative study. The Dispensing System for Chronic Users instrument was applied during 2015 in validation to 45 older adults with a clinical diagnosis of cardiovascular disease aged between 50 and 88 years old. Results: The multifactorial ANOVA with the statistical package IBM SPSS 2016, showed a high statistical relationship F (1) = 27.43; p< 0.001 between risk factors, non-adherence and ineffectiveness of antihypertensive use. The comparative analysis of the mean difference between non-adherence to treatment and the mean of effective and ineffective pharmacotherapy, revealed a very high difference t (1) = 421.59, p< 0.001. Conclusions: This study shows the need to encourage the daily practice of health promotion in the elderly, in order to achieve a stable blood pressure and the prevention of any event and/or problem related to the use of anti-hypertensive drugs that may affect the therapeutic effect and on the well-being of the patient.

Resumo Introdução: a promoção da saúde psicofísica e a segurança do uso responsável dos anti-hipertensivos é uma necessidade para melhorar a qualidade e esperança de vida do paciente. Objetivo: achar a relação de fatores de risco que influem na confiança nos fármacos dos pacientes que usam anti-hipertensivos em um grupo de adultos maiores com doença cardiovascular. Metodologia: estudo quantitativo exploratório transversal descritivo. Aplicou-se o instrumento Sistema de Dispensação para usuários Crónicos em validação a 45 adultos maiores entre 50 e 88 anos com diagnóstico clínico de doença cardiovascular durante 2015. Resultados: o ANOVA multifatorial com o pacote estatístico IBM SPSS 2016, evidenciou relação estatística alta F (1) = 27,43; p< 0,001 entre os fatores de risco, a não aderência e ineficácia o uso anti-hipertensivo. A análise comparativa da diferença de média entre a não aderência ao tratamento e a média da farmacoterapia eficaz e ineficaz, revelou uma diferença muito alta t (1) = 421.59, p< 0,001. Conclusões: Este estudo amostra a necessidade de fomentar a prática cotidiana da promoção da saúde ao adulto maior, a fim de obter uma pressão arterial estável e a prevenção de algum evento e/ou problema relacionado ao uso do anti-hipertensivo que possa incidir no efeito terapêutico e no bem-estar do paciente.

Eventos adversos del nimotuzumab en pacientes con tumor cerebral primario / Adverse events to the nimotuzumab in patients with primary cerebral tumor

Introducción: El nimotuzumab es un anticuerpo monoclonal empleado en el tratamiento de pacientes con tumor cerebral. Dada su novedad se justifica la realización de estudios de farmacovigilancia que avalen su seguridad. Objetivo: Caracterizar los eventos adversos relacionados con este medicamento en la práctica médica habitual. Métodos: Se realizó un estudio descriptivo y transversal de 41 pacientes con tumor cerebral primario tratados con nimotuzumab en el Departamento de Ensayos Clínicos del Hospital Provincial Docente Saturnino Lora Torres de Santiago de Cuba, desde mayo de 2017 hasta abril de 2019. Resultados: En la serie se identificaron 31 eventos adversos, de los cuales 17 eran conocidos y 14 desconocidos. Predominaron la cefalea (80,5 %), la debilidad en miembros inferiores (48,8 %) y la fosfatasa alcalina elevada (41,5 %). Cabe destacar que el total de los efectos no deseados se consideraron ligeros, según su intensidad; reversibles, según sus resultados y sin cambios, según la actitud respecto al medicamento. Conclusiones: Las características de los eventos adversos encontrados se asemejan a las descritas en otros estudios que también avalan la seguridad del fármaco.

Introduction: The nimotuzumab is a monoclonal antibody used in the treatment of patients with cerebral tumor. The realization of pharmaco surveillance studies that guaranteed its security is justified given its new features. Objective: To characterize the adverse events related to this medicine in the habitual medical practice. Methods: A descriptive and cross-sectional study of 41 patients with primary cerebral tumor treated with nimotuzumab in the Clinical Trial Department of Saturnino Lora Torres Teaching Provincial Hospital was carried out in Santiago de Cuba, from May, 2017 to April, 2019. Results: In the series 31 adverse events were identified, of which 17 were known and 14 were unknown. There was a prevalence of the headache (80.5 %), weakness in lower members (48.8 %) and the high alcaline phosphatase (41.5 %). It is necessary to highlight that all the non wanted effects were considered light according to the intensity; reversible, according to the results and without changes, according to the attitude regarding the medicine. Conclusions: The characteristics of the adverse events that were found resemble to those described in other studies that also guarantee the security of the drug.

Cost-utility analysis of pembrolizumab combined with chemotherapy in the first-line treatment of advanced or metastatic esophageal carcinoma / 中国药房

OBJECTIVE To evaluate the cost-utility of pembrolizumab combined with chemotherapy versus chemotherapy alone in the first-line treatment of advanced or metastatic esophageal carcinoma. METHODS Cost-utility analysis of pembrolizumab combined with chemotherapy versus chemotherapy alone for advanced or metastatic esophageal carcinoma was conducted by using a three-state partitioned survival model from the perspective of health system in China. The model use d a lifetime simulation time frame with 3 weeks as a cycle. The survival data were extrapolated using KEYNOTE- 590 data；cost data were obtained from the median of 2022 public winning bid on Yaozhi network ，among which the price of pembrolizumab was obtained after discounting by a patient assistance program ；utility data were obtained from the literatures ，and a 5％ discount rate was used for both cost and utility. One-way sensitivity analysis and probabilistic sensitivity analysis were also conducted to examine model robustness. RESULTS Analysis of the base case results showed that compared to chemotherapy alone ，the incremental cost-effectiveness ratio （ICER）of pembrolizumab combined with chemotherapy regimens were 950 528.42 yuan/QALY，107 845.39 yuan/QALY and 315 754.56 yuan/QALY for esophageal squamous cell carcinoma （ESCC），programmed deathligand- 1 combined positive score （PD-L1 CPS）≥10 and intention-to-treat population （ITT），respectively. The results of sensitivity analysis verified the robustness of the basic analysis results. CONCLUSIONS Under our healthcare system ，using a threshold of willingness-to-pay of 1-3 times our GDP per capita in 2021，pembrolizumab combined with chemotherapy regimen isn ’t cost-utility compared with chemotherapy alone in the ESCC and ITT subgroups of patients ，while it is cost-utility in the PD-L 1 CPS≥10 subgroup of patients.

Variantes genéticas del SARS-CoV-2 y sus implicaciones clínicas / Genetic variants of SARS-CoV-2 and its clinical implications

El SARS-CoV-2, agente causal de la actual pandemia de la COVID-19, va sufriendo mutaciones como consecuencia de su ciclo evolutivo, lo que ha originado diferentes variantes genéticas, que han sido agrupadas en dos categorías: preocupante (alfa o británica, beta o sudafricana, gamma o brasileña y delta o india) y de interés (lamdba, mu, épsilon, eta, iota, kappa, zeta, theta); estas conllevan implicaciones clínicas en la transmisibilidad, virulencia y resistencia del SARS-CoV-2 a la inmunidad natural y adquirida, lo que representa un serio desafío para los servicios de salud en todo el mundo. En este artículo se describen dichas variantes genéticas, con énfasis en su probable impacto clínico, y además se plantea la posibilidad de que aparezcan otras, como fenómeno natural en la evolución de los virus.

The SARS-CoV-2, causal agent of the COVID-19 current pandemic, is suffering mutations as a consequence of its evolutive cycle, what has originated different genetic variants that have been grouped in two categories: worrying (alpha or British, beta or South African, gamma or Brazilian and delta or Indian) and of interest (lamdba, mu, epsilon, eta, iota, kappa, zed, theta); these categories bear clinical implications in the transmissibility, virulence and resistance from SARS-CoV-2 to the natural and acquired immunity, what represents a serious challenge in health services worldwide. These genetic variants are described in this work, with emphasis in its probable clinical impact, and the possibility that other variants could appear is also explained, as natural phenomenon in the evolution of viruses.

Estudio de utilización de fármacos antigotosos en población colombiana, 2016 / Patterns of anti-gout drug use in a Colombian population: 2016

RESUMEN Objetivo: Identificar las características clínicas de los pacientes con gota y la forma de utilización de los medicamentos antigotosos en Colombia. Métodos: Estudio de corte transversal en el que se analizaron 310 historias clínicas de pacientes atendidos en el último trimestre del 2016 y que recibieron un medicamento antigotoso. Se identificaron variables sociodemográficas, clínicas, farmacológicas, comorbilidades y paraclínicas. Para cada medicamento antigotoso se determinó si el uso fue según las recomendaciones aprobadas por la Federal Drug Administration (FDA). Se realizaron análisis descriptivos, bivariados y multivariados. Resultados: Se evaluaron pacientes de 14 diferentes ciudades de Colombia, con un predominio masculino del 70,3% (n = 218) y una mediana de edad de 64 arios (RIC: 26-94 arios). El antigotoso más frecuentemente utilizado fue alopurinol (n = 255; 82,3%), seguido de colchicina (n = 54; 17,4%). Los diagnósticos hallados como indicación fueron: hiperuricemia (n = 181; 58,4%), gota (n = 34; 11%), artritis gotosa (n = 28; 9%). El 74,5% (n = 231) de las prescripciones tenía un uso aprobado según la FDA, especialmente alopurinol en el manejo de gota e hiperuricemias, mientras que colchicina se encontró siendo utilizada en indicaciones no aprobadas (n = 44; 81,4%). Las comorbilidades más frecuentes fueron hipertensión (68,4%) y dislipidemia (55,8%). Conclusiones: Los pacientes con gota en tratamiento farmacológico tienen una elevada frecuencia de comorbilidades cardiovasculares, y están siendo tratados con alopurinol para la prevención a largo plazo, mientras que una menor proporción recibe colchicina que comúnmente es utilizada para indicaciones no aprobadas por las agencias reguladoras.

ABSTRACT Objective: To identify the clinical characteristics of patients with gout, and the prescription patterns of anti-gout medications in Colombia. Methods: Cross-sectional study, that analysed the data from 310 medical records of patients treated in the last quarter of 2016, and who received an anti-gout medication. Sociodemographic, clinical, pharmacological, comorbidities, and paraclinical variables were identified. For each anti-gout drug used, it was determined whether the use was in accordance with Federal Drug Administration (FDA) approved recommendations. Descriptive, bivariate and multivariate analyses were performed. Results: Patients from 14 different cities in Colombia were evaluated, with a male predominance of 70.3% (n = 218) and a median age of 64 years (RIC: 26-94 years). The most frequently used anti-gout medication was allopurinol (n = 255; 82.3%), followed by colchicine (n = 54; 17.4%). The main diagnoses found as an indication were: hyperuricaemia (n=181, 58.4%), gout (n = 34; 11.0%), and gouty arthritis (n = 28; 9.0%). Almost three-quarters (74.5%; n = 231) of the prescriptions had an approved use according to the FDA, especially allopurinol in the management of gout and hyperuricaemia, while colchicine was found to be used in unapproved indications (n = 44, 81.4%). The most frequent comorbidities were hypertension (68.4%) and dyslipidaemia (55.8%). Conclusions: Patients with gout who are under pharmacological treatment have a high frequency of cardiovascular comorbidities. They were being treated with allopurinol for long-term prevention, while a smaller proportion received colchicine, which is often used for indications not approved by regulatory agencies.

Criterios de medicación potencialmente inapropiada para el anciano: una propuesta cubana / Medication approaches potentially inappropriate for the elderly: a Cuban proposal

Introducción: El impacto de la prescripción inapropiada de fármacos en el anciano ha llevado al desarrollo de métodos para su reducción en varias partes del mundo. Objetivo: Diseñar y validar los criterios de medicación potencialmente inapropiada en el anciano, adaptados al entorno sociosanitario de Cuba. Métodos: Se realizó una investigación cualitativa, en la cual los criterios fueron validados por medio de la metodología Delphi, por un comité de expertos (especialistas en medicina geriátrica y clínica de diferentes zonas geográficas del país), y se les calculó la consistencia interna mediante el coeficiente alfa de Cronbach. Resultados: Los criterios quedaron estructurados en tres listas: 1) medicación potencialmente inapropiada, medicamento indicado no prescripto, cuando no existe contraindicación para su uso; 2) medicación potencialmente inapropiada independiente del diagnóstico o la condición clínica; 3) medicación potencialmente inapropiada dependiente del diagnóstico o la condición clínica. Conclusiones: Se demostró la validez del contenido y la adecuada consistencia interna de los criterios diseñados para la identificación de medicación potencialmente inapropiada en el anciano.

Introduction: The impact of inappropriate prescription of medication in the elderly has led to the development of methods for its reduction in several parts of the world. Objective: To design and validate the medication approaches potentially inappropriate in the elderly, adapted to the socio-sanitary environment of Cuba. Methods: A qualitative investigation was carried out, in which the approaches were validated by means of the Delphi methodology, by an experts committee (specialists in geriatrics medicine and clinic from different geographical areas of the country), and the internal consistency was calculated by means of the alpha coefficient of Cronbach. Results: The approaches were structured in three lists: 1) potentially inappropriate medication, advised medication non prescribed, when contraindication doesn't exist for its use; 2) medication potentially inappropriate, independent from the diagnosis or clinical condition; 3) potentially inappropriate medication, depending on the diagnosis or clinical condition. Conclusions: The validity of the content and the appropriate internal consistency of the designed approaches for the medication identification potentially inappropriate in the elderly were demonstrated.

Enfermedad celíaca, epilepsia y calcificaciones cerebrales / Celiac disease, epilepsy and cerebral calcifications

Resumen Varón de 33 años con antecedentes de convulsiones febriles y discapacidad intelectual moderada grave, inició a los 2 años convulsiones tanto focales como generalizadas atónicas diarias, que ocasionaron traumas faciales. Debido a la farmacorresistencia se implantó un estimulador del nervio vago, con respuesta parcial al mismo. Durante su seguimiento, se hizo diagnóstico de enfermedad celíaca. Al realizar una tomografía de encéfalo se evidenciaron calcificaciones piriformes occipitales bilaterales, estableciéndose el diagnostico de enfermedad celiaca, epilepsia y calcificaciones cerebrales. Se le indicó dieta libre de gluten y continuar el tratamiento farmacológico, logrando de esta manera una reducción de las crisis.

Abstract A 33-year-old man with a history of febrile seizures and moderate-severe intellectual disability began, at 2 years, both focal and generalized daily atonic seizures, which caused facial trauma. Due to drug resistance, a vagus nerve stimulator was implanted, with partial response to it. During his follow-up, he was diagnosed with celiac disease. When performing a brain tomography, bilateral occipital pyriform calcifications were evidenced, establishing the diagnosis of celiac disease, epilepsy and cerebral calcifications. A gluten-free diet was indicated and pharmacological treatment continued, thus achieving a reduction in seizures.

Comparison between Pharmaco-invasive Strategy and Primary Percutaneous Coronary Intervention According to Percutaneous Coronary Intervention Related Delay

Aim:This study aimed to compare between the effect ofpharmacoinvasive strategy (PI)& primary percutaneous coronary intervention (P-PCI) according to PCIrelated delay (door to ballon) on the mortality and morbidityduring in-hospital stay and after 30-day follow up. Moreover, leftventricular systolic function was assessed by two-dimensional echocardiography at cardiology department, Tanta University. Patients and Methods:The study was conducted on 300 patients that were dividedinto 2 main groups. Group A consisted of patients had primaryPCI as reperfusion therapy and further divided into threegroups according to PCI related delay (door toballon). Group A1, PCI-related delay is ≤60 minute(92patients). Group A2, PCI-related delay is >60 to ≤ 90 minute. (54patients). Group A3, PCI-related delay is >90minute (78 patients). The second group (group B), include patients who undergopharmaco-invasive strategy, PCI within 24 hour afterthrombolysis (76 patients). the second group, coronary angiography was done immediately in cases of failedthrombolysis and for successful thrombolysis; coronaryangiography was performed within 3 –24 hours. Results:During hospital stay, more patients in group A3 died than those of group B orgroup A1, A2 with no statistical significance.In addition, morepatients in group A3 showed heart failure symptoms withstatistical significance than those of group B, A1 and A2. Bleeding complications occurred significantly moreingroupB. Duringfollowupvisits more patients in group A3 complained ofheart failure symptoms with statistical significance than those of group B, A1, A2 patients. Conclusion:Primary PCIwithout door to balloon time delay (≤90 minutes)was encouraged and hadthebest results on morbidity and mortality. Also, pharmacoinvasive strategy was encouraged as being better than primary PCIwhen door to balloon time showed marked delay( <90 minutes)

Post-marketing pharmaco-economics evaluation of Jinye Baidu Granules / 中国中药杂志

To evaluate the economy and applicability of Jinye Baidu Granules in the treatment of acute upper respiratory tract infection, a randomized, double-blind, positive drug parallel control clinical trial was conducted in this study. Stratified block random, double-blind and double simulation test was used. The experimental group took Jinye Baidu Granules, 10 g/time, three times a day, and Compound Shuanghua Granules placebo, 6 g/time, four times a day. The control group took Compound Shuanghua Granules, 6 g/time, 4 times a day, and Jinye Baidu Granules placebo, 10 g/time, 3 times a day. The course of treatment was 5 days. The total cost of this study included direct medical cost and indirect medical cost. The incremental cost-effect analysis method was used for evaluation. Treeage Pro software was used to build a pharmaco-economics model and make statistical analysis. Patients from 10 hospitals were divided into experimental group(304 cases) and control group(302 cases). The baseline values of age, sex ratio, clinical symptoms and signs scores, and important physical examination indexes of the two groups were compared. After 5 days of treatment, the cost per capita of the experimental group was(388.06±94.17) Yuan, and that of the control group was(378.47±95.46) Yuan. The cost of direct medical treatment per capita was(271.24±54.11) Yuan for the experimental group and(264.88±112.71) Yuan for the control group. The average cost of indirect medical treatment was(116.82±82.75) Yuan in the experimental group and(113.59±87.77) Yuan in the control group, with no significant difference in the cost of medical treatment per capita, the cost of direct medical treatment per capita and the cost of indirect medical treatment per capita between both groups. The results of incremental cost-effect analysis based on the total score difference in symptoms and signs after 5 days of treatment showed that ICER=23.39 Yuan/score, which was less than the willingness to pay 100 Yuan/score determined through expert interviews. The experimental group had economic advantages over the experimental group, with the economic probability of 53%. Sensitivity analysis supported the robustness of the results. The results of incremental cost-effect analysis based on the total recovery rate of symptoms and signs showed that compared with the experimental group, the control group had lower cost, better effect and absolute economic advantage, with a corresponding probability of 55%. Based on the above results, it is concluded that there is no significant difference in economic outcome between Jinye Baidu Gra-nules and Compound Shuanghua Granules in the treatment of acute upper respiratory tract infection.

Cost comparisons of five leading brands of the Antiplatelet drug, Clopidogrel, available in an Indian town

Background: Antiplatelet drugs need to be prescribed lifelong, for most of the selected patients, once started. Price disparity can lead to large financial stress on the patients, especially when cost related aspects are not paid heed to by the prescribing physician. This study was conducted to compare the cost, to the patient, of five most commonly prescribed preparations of different brands of Clopidogrel seventy five milligram, in Kolhapur city.Methods: The present study was undertaken during February 2019 to June 2019. Authors purchased a strip of 10 tablets each of the five leading brands of Clopidogrel seventy five milligram. The prices of the strip of 10 tablets of each of the five chosen brands were compared. Finally, the yearly cost of each of these five different preparations, was compared directly as well as using percentages. The data was collected, analyzed and presented in tabular forms and figures.Results: The data of the cost of five different brands of a single antiplatelet drug, Clopidogrel seventy five milligram shows that the annual cost of the costliest among the five brands of this drug is almost three times that of the cheapest brand, or in other words almost 300 percent that of the cheapest brand.Conclusions: The cost differences between the five brands were not negligible. India, with a major part of the population being very sensitive to the cost of medications, the prescribing physician must select the preparation wisely. The most costly preparation of Clopidogrel can significantly add to the the financial stress on the patient’s yearly expenditure. Thus, Pharmaco economic considerations must take a front seat while making a decision to prescribe medicines, especially in a country like India.

Cost comparisons of seven leading brands of the Hypolipidemic drug, Rosuvastatin available in an India city

Background: Hypolipidemic drugs need to be prescribed lifelong for most of the selected patients, once started. Price variation can lead to huge financial strain on the patients, especially when cost associated issues are not considered by the prescribing medical practitioner. This study was conducted to compare the cost, to the patient, of seven most commonly prescribed preparations of different brands of Rosuvastatin ten milligram, in Kolhapur city.Methods: Authors purchased a strip of 10 capsules each of the seven leading brands of Rosuvastatin ten milligrams. The prices of the strip of 10 capsules of each of the seven chosen brands were compared. Finally, the cost of each of these seven brands for one year, was compared directly as well as using percentages. The data was collected, analysed and presented in tabular forms and figures.Results: The data of the cost of seven different brands of a single hypolipidemic drug, Rosuvastatin ten milligram shows that the cost of the costliest among the seven brands of this drug for one year is almost two times that of the cheapest brand, or in other words almost 200 percent that of the cheapest brand.Conclusions: The cost differences between the cheapest and the costliest brands were substantial. The cost of remaining five brands was dispersed in between these two extremes. India, with a major part of the population being highly concerned about the cost of medications, the prescribing medical practitioner must select the preparation wisely . The most costly preparation of Rosuvastatin ten milligram can substantially add to the financial strain on the patient’s yearly expenses. Thus, Pharmaco economic considerations must be a prime concern while making a decision to prescribe medicines, especially in a country like India.

Effects of Wuzhi Soft Capsule Combined with Imatinib Mesylate Tablet on Pharmacokinetics of Imatinib in Rats after Admi- nistration / 中国药房

OBJECTIVE： To study the effects of Wuzhi soft capsule and imatinib mesylate tablet on the pharmacokinetics of imatinib in rats. METHODS： The rats were divided into single administration group and consecutive administration group. The single administration group was divided into imatinib group one （ig administration of blank soybean oil+imatinib suspension 10   mg/kg）， low-dose， medium-dose and high-dose of Wuzhi soft capsule+imatinib group （ig administration of Wuzhi soft capsule solution 134， 268， 536 mg/kg+imatinib suspension 10 mg/kg）， with 6 rats in each group. Each group was given imatinib suspension intragastrically 30 min after intragastric administration of blank soybean oil/Wuzhi soft capsule solution. The consecutive administration group was divided into imatinib group two （ig administration of blank soybean oil+imatinib suspension 10 mg/kg）， Wuzhi soft capsule low-dose+imatinib group （ig administration of Wuzhi soft capsule solution 134 mg/kg+imatinib suspension 10 mg/kg）， with 6 rats in each group. Each group was given blank soybean oil/Wuzhi soft capsule solution intragastrically for consecutive 14 d， once a day； 30 min after last administration， ig imatinib suspension. About 100 μL blood was collected before imatinib， 0.5， 1， 2， 2.5， 3， 4， 5， 6， 8， 12， 24 and 36 h after medication. The plasma concentration of imatinib was determined by HPLC-MS/MS. The pharmacokinetic parameters were fitted by using DAS 2.0 software. RESULTS： After single administration， compared with imatinib group one， cmax， t1/2， AUC0-36 h and AUMC0-36 h in low-dose， medium-dose and high-dose of Wuzhi soft capsule+imatinib group were increased significantly （P＜0.05 or P＜0.01）. After consecutive administration， compared with imatinib group two， cmax， t1/2 and AUMC0-36 h of imatinib+low-dose of Wuzhi soft capsule group were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： Single administration and consecutive administration of Wuzhi soft capsule influence the pharmacokinetics of imatinib， increase plasma concentration of imatinib and prolong half-time.

Cost-effectiveness of newer anti-emetics in the prevention of chemotherapy induced nausea and vomiting: a pharmaco-economic study analysis

Background: Chemotherapy induced Nausea and Vomiting (CINV) is one the most common adverse effects associated with chemotherapeutic management of carcinoma breast. Preventing CINV becomes a vital part in treatment of these cancer patients for better compliance. The conventional regimen of newer 5-HT3 receptor antagonist and dexamethasone along with newer agents - Aprepitant, a NK-1 receptor antagonist and a recently approved atypical antipsychotic, Olanzapine have shown better control of CINV. These newer agents are effective but also very expensive.Methods: The study included carcinoma breast patients scheduled for chemotherapy (n = 55 in each group) who either received aprepitant or olanzapine or a combination of both as the anti-emetic regimen. Considering Cost-Effectiveness Analysis (CEA), the cost included was the cost of anti-emetic agents (sponsor’s perspective) and outcome measured as control of nausea and vomiting - as Complete Protection (CP), Complete Response to Best (CRB) and Incomplete Response (IR) for acute (0-24 hours) and delayed (24-120 hours) phases. The cost effectiveness(CE) ratio for emesis and CINV free days were calculated.Results: CP was seen better during the acute period than the delayed period. With Aprepitant, delayed CRB and IR was seen with 13 (23.6%) and 10 (18.2%) subjects. 16 (29.1%) showed IR with Olanzapine during the delayed period.The average number of Emesis and CINV free days were 4.65, 4.51, 4.89 and 3.38, 3.96, 4.15 for the three groups respectively. The cost required to achieve 1 emesis and 1 CINV free day per subject in the 3 groups was INR 351.19, INR 27.20, INR 339.54 and INR 483.36, INR 30.94, INR 400.60 respectively.Conclusions: The newer anti-emetic even though being expensive at cost, pharmacoeconomically provide better outcomes and seem to have better control rates than the conventional regimen.

Seguridad de las fluoroquinolonas: riesgos habitualmente olvidados para el clínico / Safety of fluoroquinolones: risks usually forgotten for the clinician

Resumen Las quinolonas constituyen una familia de antimicrobianos de amplio uso y si bien son consideradas segura para los pacientes, el conocimiento del perfil de seguridad es necesario para que los profesionales estén alertas a lo que deben vigilar. Sobre el sistema músculo-esquelético, las quinolonas tienen el potencial de dañar cartílagos, provocando incluso muy excepcionalmente rotura de tendón. A nivel endocrino se ha observado hipoglicemia/hiperglicemia, por lo que en pacientes diabéticos se recomienda el control cuidadoso de la glicemia. Las reacciones adversas cardiovasculares son poco frecuentes, pero pueden ir desde alteraciones del ECG como prolongación del QT sin traducción clínica a graves arritmias que pueden ser de riesgo vital. En el sistema nervioso, destaca la aparición de alteraciones del sistema nervioso central y la neuropatía periférica. Durante la evaluación de la seguridad de las quinolonas es importante considerar las potenciales interacciones con otros medicamentos. En niños se prefiere no usar las fluoroquinolonas debido al potencial riesgo de daño a los cartílagos de crecimiento, efectos que no parecen ser tan dramáticos a la luz de la evidencia actual. A pesar del optimismo se debe evaluar la seguridad del tratamiento de estos antimicrobianos en todo paciente pediátrico.

Quinolones are a group of widely used antimicrobials. Although they are considered safe for patients, knowledge of the safety profile is necessary so that professionals become aware of what is necessary to monitor. At the musculoskeletal level, quinolones have the potential to damage cartilage, causing even tendon rupture in infrequent cases. Hypoglycemia / hyperglycemia has been observed at the endocrine level, thus, careful monitoring of glycemia in patients with quinolone is recommended in diabetic patients. At the cardiovascular level, arrhythmias induced by these antimicrobials are rare but severe. At the level of the nervous system, the appearance of alterations of the central nervous system and the peripheral neuropathy are emphasized. When assessing the safety of quinolones, it is important to consider potential interactions with other substances (medical products). In children it is preferred not to use fluoroquinolones because of the potential risk of cartilage damage and growth, effects that do not seem to be so dramatic in the face of new evidence. Despite optimism, the safety of the treatment of these antimicrobials should be evaluated in every pediatric patient.

Listado de medicamentos trazadores/señaladores como herramienta en programas de seguimiento farmacoterapéutico o de farmacoseguridad / List of drug tracers/ markers as a tool in pharmacotherapeutic follow-up or drug-safety programs

Resumen Introducción: los resultados negativos asociados a la medicación (RNM), incluyendo las reacciones adversas a medicamentos (RAM) o problemas de seguridad, son un problema clínico relevante, debido a su alta incidencia y a efectos nocivos en la salud. Un medicamento podría ser considerado como trazador/señalador, debido a: 1) una mayor probabilidad de causar RAM o problemas de seguridad; o 2) su utilización para tratar y por tanto identificar pacientes con RAM. Los listados de medicamentos trazadores podrían ser útiles en los programas de farmacoseguridad o seguimiento farmacoterapéutico (SFT). Objetivo: el objetivo de este trabajo fue estructurar un listado de medicamentos trazadores/ señaladores de los pacientes con mayor riesgo de presentar RNM, el cual podría ser útil para seleccionar pacientes para programas de SFT o farmacoseguridad. Obtención de datos: inicialmente, se realizó una revisión estructurada en PubMed/Medline para identificar medicamentos asociados a la presentación de RAM clasificadas como graves o moderadas y con una prevalencia igual o superior a 10%. Posteriormente, el listado de medicamentos identificados, fue comparado y complementado con medicamentos de alta alerta del Institute for Safe Medication Practices (ISMP) y con medicamentos utilizados para el tratamiento de RAM o antídotos. Resultados: se generó un listado general de 139 medicamentos trazadores/señaladores. Conclusiones: este listado podría ser una herramienta para detectar y seleccionar los pacientes que más se podrían beneficiar de los programas de SFT o farmacoseguridad. Se requiere de la realización de estudios diseñados para evaluar la utilidad práctica de dicho listado.

Abstract Introduction: negative outcomes associated with medication (NOM), including adverse drug reactions (ADRs) or safety problems, are a relevant clinical problem due to their high incidence and harmful effects on health. A drug could be considered a tracer / marker because of: 1) an increased likelihood of causing ADR or safety problems; or 2) its use to treat and therefore identify patients with ADR. Tracer drug listings could be useful in pharmacological safety or pharmacotherapeutic monitoring programs. Objective: the objective of this study was to structure a list of drug tracer / markers of the patients with the highest risk of presenting NOM, which could be useful to select patients for FFT or pharmacological safety programs. Data collection: initially, a structured review was performed in PubMed / Medline to identify drugs associated with the presentation of ADRs classified as severe or moderate and with a prevalence of 10% or greater. Subsequently, the list of identified medications was compared and complemented with high alert medications of the Institute for Safe Medication Practices (ISMP) and medications used to treat ADRs or antidotes. Results: a general listing of 139 drug tracers / markers was generated. Conclusions: this listing could be a tool to detect and select the patients who could most benefit from the FTS or pharmacological safety programs. Studies designed to evaluate the practical usefulness of this listing are required.

Study on the Pharmacokinetics of Recombinant Hirudin Enteric-coated Capsule by Single and Multiple Ad-ministration in Beagle Dogs / 中国药房

OBJECTIVE:To study the pharmacokinetic characteristics of Recombinant hirudin enteric-coated capsule by single and multiple administration in Beagle dogs. METHODS:12 Beagle dogs were divided into single ig group and single iv group by random control method,6 in each group. Recombinant hirudin 0.2 mg/kg was intragastrically administrated or intravenously inject-ed,blood sample was collected;after 2 weeks of cleaning,12 dogs were intragastrically administrated recombinant hirudin 0.2 mg/kg,for 7 d. Sample blood was collected,referred to multiple ig group. Recombinant hirudin concentration in plasma was deter-mined by enzyme-linked immunosorbent assay,and pharmacokinetic parameters were calculated by DAS 2.0 software. RESULTS:The results showed that pharmacokinetics by ig and iv recombinant hirudin in Beagle dogs fitted to two-compartment model,abso-lute bioavailability of ig Recombinant hirudin enteric-coated capsule was(14.908±1.868)%;the pharmacokinetic parameters in sin-gle ig group and multiple ig group were tpeak of(2.105±0.243),(3.000±0.000)h,t1/2β of(8.660±2.965),(14.870±2.710)h, cmax of(10.700±0.872),(12.05±1.587)ng/mL,AUC0-1440 min of(55.250±4.386),(58.978±6.002)ng·h/mL,without statistical significances in two groups(P>0.05). CONCLUSIONS:The ig Recombinant hirudin enteric-coated capsule can be absorbed into the blood to a certain extent. There is no accumulation for ig Recombinant hirudin enteric-coated capsule for several days,and it dose not change the pharmacokinetic characteristics.

Effects of Different Doses of Sufentanil on α1?band of Quantitative Pharmaco?electroencephalography during General Anesthesia Induction by Tracheal Intubation / 中国医科大学学报

Objective To compare the effects of different doses of sufentanil on theα1?band of quantitative pharmaco?electroencephalography (QPEEG)during the induction of general anesthesia by tracheal intubation(TI). Methods Forty selected patients under general anesthesia were randomly divided into two groups,with 20 patients per group. Patients in group Ⅰ were administered 0.2μg/kg sufentanil,whereas patients in group Ⅱ were administered 0.3μg/kg sufentanil. Subsequently,the patients were administered 2 mg/kg propofol and 0.15 mg/kg cisatracurium. HR,MAP,and QPEEG were recorded before induction(T0),after induction(T1),and after insertion of the cannula(T2). Using the method of power spectrum analysis,theα1?band power percentage of QPEEG was calculated. Results In comparison with T0,the values of HR,MAP,andα1?band power percentage in most areas of the brain were both decreased at T1(P0.05). Conclusion The administration of 0.3μg/kg sufentanil during anesthesia induction can effectively depress the cardiovascular response to TI and stabilize theα1?band power per?centage. This suggests that theα1?band power percentage of QPEEG can be an effective means to monitor the depth of sedation.

Medication errors in outpatient care in Colombia, 2005-2013 / Errores de medicación en pacientes atendidos en servicios ambulatorios de Colombia, 2005-2013

Introduction: Medication errors outside the hospital have been poorly studied despite representing an important threat to patient safety. Objective: To describe the characteristics of medication errors in outpatient dispensing pharmacists reported in a pharmaco-surveillance system between 2005 and 2013 in Colombia. Materials and methods: We conducted a descriptive study by reviewing and categorizing medication error reports from outpatient pharmacy services to a national medication dispensing company between January, 2005 and September, 2013. Variables considered included: process involved (administration, dispensing, prescription and transcription), wrong drug, time delay for the report, error type, cause and severity. The analysis was conducted in the SPSS ® software, version 22.0. Results: A total of 14,873 medication errors were reviewed, of which 67.2% in fact occurred, 15.5% reached the patient and 0.7% caused harm. Administration (OR=93.61, CI 95%: 48.510-180.655, p<0.001), dispensing (OR=21.58, CI 95%: 16.139-28.870, p<0.001), transcription errors (OR=5.64; CI 95%: 3.488-9.142, p<0.001), medicines for sensory organs (OR=2.04, CI 95%: 1.519-2.756, p<0.001), anti-infective drugs for systemic use (OR=1.99, CI 95%: 1.574-2.525, p<0.001), confusion generated with the name of the drug (OR=1.28, CI 95%: 1.051-1.560, p=0.014), and trouble interpreting prescriptions (OR=1.32, CI 95%: 1.037-1.702, p=0.025) increased the risk for error reaching the patient. Conclusions: It is necessary to develop surveillance systems for medication errors in ambulatory care, focusing on the prescription, transcription and dispensation processes. Special strategies are needed for the prevention of medication errors related to anti-infective drugs.

Introducción. Los errores de medicación en la atención ambulatoria se han estudiado poco, a pesar de que representan una amenaza importante para la seguridad del paciente. Objetivo. Describir las características de los errores de medicación en atención ambulatoria reportados por un sistema de farmacovigilancia de Colombia entre el 2005 y el 2013. Materiales y métodos. Se hizo un estudio descriptivo en el cual se recopilaron, revisaron y categorizaron los reportes de errores de medicación de pacientes atendidos en un servicio farmacéutico ambulatorio a cargo de una empresa nacional de dispensación de medicamentos, entre enero de 2005 y septiembre de 2013. Se consideraron variables que involucraban el proceso (administración, dispensación, prescripción y transcripción), el medicamento, el tiempo para elaborar el reporte, el tipo de error, su causa y su gravedad. El análisis se hizo con el programa SPSS ® , versión 22.0. Resultados. Se recopilaron 14.873 errores de medicación, de los cuales 67,2 % realmente ocurrió, 15,5 % afectó al paciente y 0,7 % causó daño. Los errores de administración (p<0,001; OR=93,614; IC 95% 48,510-180,655), de dispensación (p<0,001; OR=21,585; IC 95% 16,139-28,870), de transcripción (p<0,001; OR=5,647; IC 95% 3,488-9,142), los relacionados con medicamentos para los órganos de los sentidos (p<0,001; OR=2,046; IC 95% 1,519-2,756), y con los medicamentos de uso sistémico contra infecciones (p<0,001; OR=1,993; IC 95% 1,574-2,525), la confusión en el nombre del fármaco (p=0,014; OR=1,281; IC 95% 1,051-1,560) y los problemas en la interpretación de las prescripciones (p=0,025; OR=1,328; IC 95% 1,037-1,702), aumentaron el riesgo de que el error afectara al paciente. Discusión. Es necesario establecer sistemas de vigilancia específicos para errores de medicación en los servicios ambulatorios, que hagan énfasis en los procesos de prescripción, transcripción y dispensación. Se requieren estrategias específicas para la prevención de los errores de medicación relacionados con antibióticos.

Estudio de utilización de antibióticos en el servicio de consulta externa de un hospital público en Bogotá, D.C. / Study of the use of antibiotics in the outpatient service of a public hospital in Bogotá, D. C.

Se realizó un estudio de utilización de medicamentos sobre hábitos y calidad de la prescripción, con el fin de describir las características y potencial uso no adecuado de los antibióticos en el servicio de consulta externa de un hospital de segundo nivel de la ciudad de Bogotá, D.C. En las 8077 prescripciones analizadas se encontraron 613 (8%) con al menos un antibiótico de uso sistémico. Los antibióticos más dispensados fueron: Amoxicilina, Cefalexina, Ciprofloxacina, Dicloxacilina, Doxiciclina. Se prescribieron combinaciones de dos antibióticos en el 3% de las fórmulas, siendo la más frecuente macrólido-penicilina. Todas las prescripcion esanalizadas cumplieron con los requisitos de calidad y el 0,4% de los tratamientos no tenían el tiempo de duración del tratamiento. La frecuencia de uso de los antibióticos en el servicio de consulta externa fue más baja que en otros estudios. Se identificaron potenciales usos no adecuados como la falta de diagnóstico infeccioso, combinación de antibióticos no documentada, interacciones de medicamentos y falta de información adecuada en la administración de tetraciclinas.

A study on drug use habits and quality of prescribing was conducted to describe the characteristics and potential inadequate use of antibiotics in the outpatient service of one of the Bogota's second-level hospitals. In 8077 prescriptions analyzed it was found 613 (8%) with at least one antibiotic for systemic use. Amoxicillin, Cephalexin, Ciprofloxacin, Dicloxacillin, and Doxycycline were the most dispensed antibiotics. Combinations of two antibiotics were prescribed for 3% of the formulas; the most common of these was macrolide-penicillin. All prescriptions analyzed met the quality requirements and only 0.4% of the treatments did not have the time duration of treatment. The found frequency of use of antibiotics in outpatient services was lower than in other studies. Potential not suitable uses as the lack of infectious diagnosis, antibiotic combination unreported, drug interactions and lack of adequate information on the administration of tetracyclines were identified.

Determination of 1,8-TMP rhein and its pharmacokinetics in rat plasma by HPLC / 中国药理学通报

Aim To develop a HPLC method for the determination of the concentration of 1,8-TMP rhein in rat plasma and study the pharmacokinetics of 1,8-TMP rhein in rat plasma after single dose i. v. administration of 1,8-TMP rhein (2, 4, 8 mg·kg - 1 ). Methods Emodin was used as an internal standard. Plasma sam-ples were extracted with methanol and analyzed by HPLC. The mobile phase was methanol - 0. 1% for-mic acid water (78 ∶ 22, V/ V), with a flow rate of 1. 0 mL·min - 1 and UV 275 nm as the detection wave-length. The plasma concentration of 1,8-TMP rhein in rats was determined by HPLC after single-dose intrave-nous injection in rats with 2,4 and 8 mg·kg - 1 of 1,8-TMP rhein, and the pharmacokinetic parameters were caclulated by DAS 2. 1. Results The result of cali-bration curve was linear over the range of 0. 05 ~ 10. 00 mg·L - 1 (r = 0. 996 2). The lower limit of quantifica-tion was 0. 05 mg · L - 1 . The intra-day and inter-day precision (RSD% ) were both lower than 6% , and the extraction recoveries were higher than 88% , respec-tively. The validated method was successfully applied to a pharmacokinetic study after i. v. administration of 1,8-TMP rhein in rats with a dose of 2,4 and 8 mg· kg - 1 . The T1 / 2 was (68. 35 ± 1. 36), (69. 32 ± 2. 1) and (69. 32 ± 2. 03) min, respectively. The AUC0 - t was ( 101. 03 ± 24. 90 ), ( 144. 79 ± 3. 29 ) and (231. 92 ± 19. 30 ) min · mg · L - 1 , respectively. Conclusion A simple and specific HPLC method for the analysis of 1,8-TMP rhein is successfully developed and applied to a pharmacokinetic study in rat plasma.