Evaluación prospectiva del perfil emético y la eficacia analgésica del ibuprofeno y el metamizol intravenososen el postoperatorio inmediato de la apendicitis agudapediátrica / Prospective evaluation of the emetogenic profile and analgesic efficacy of intravenous ibuprofen and metamizole in the immediate postoperative period of pediatric acute appendicitis

Introducción: En la literatura existen pocas referencias que comparen las distintas alternativas disponibles para controlar el dolor enel postoperatorio inmediato de la apendicitis aguda pediátrica (AAP).Material y métodos: Comparación prospectiva del perfil anal-gésico y emético del ibuprofeno y el metamizol intravenosos en elpostoperatorio inmediato de la AAP, para lo cual se recurre a unamuestra de pacientes operados en 2021 en nuestro centro. Los participantes fueron reclutados a su llegada a Urgencias, obteniéndoseconfirmación histopatológica del diagnóstico en todos ellos. La evaluación del dolor se llevó a cabo cada 8 horas tras la cirugía medianteescalas analógicas visuales validadas, con valoraciones entre los 0 ylos 10 puntos. Se realizó un ANOVA de las medidas repetidas entrelos dos grupos para comparar la evolución del dolor en las 48 horasposteriores a la cirugía.Resultados: La muestra estaba compuesta por un total de 95 pacientes (65% de ellos varones) con una edad media de 9,7 años (DT:3,14). 41 pacientes fueron tratados con ibuprofeno (grupo 1) y 54 conmetamizol (grupo 2). No se hallaron diferencias significativas en lo querespecta al dolor, ni en las comparaciones de las mediciones puntuales,ni en su evolución en las 48 horas posteriores a la cirugía (p= 0,58). Unavez realizado el ajuste correspondiente a la terapia de fluidos recibida,los niños del grupo metamizol tuvieron significativamente más episodioseméticos y necesitaron significativamente más dosis de ondansetrón.Conclusiones: En nuestra cohorte, el ibuprofeno tuvo una eficaciaanalgésica similar y un mejor perfil emético que el metamizol en elpostoperatorio inmediato de la AAP. Se hacen necesarios nuevos estudiosprospectivos, adecuadamente controlados y con mayor tamaño muestralque validen estos hallazgos.(AU)

Background: Literature comparing different alternatives for paincontrol in the immediate postoperative period of pediatric acute appendicitis (PAA) is scarce.Materials and methods: We prospectively compared the analgesicand emetogenic profile of intravenous ibuprofen and metamizole in theimmediate postoperative period of PAA. For this purpose, we used asample of patients operated on in 2021 in our center. Participants wererecruited on arrival at the Emergency Department and histopathologi-cal confirmation of the diagnosis was obtained in all of them. Pain wasevaluated every 8 hours after the surgery with validated visual analogscales ranging from 0 to 10 points. Repeated measures ANOVA wasused to compare the evolution of pain in the 48 hours after surgerybetween the two groups. Results: The sample included 95 patients (65% males) with a meanage of 9.7 years (sd: 3.14). 41 patients were treated with Ibuprofen(group 1) and 54 with metamizole (group 2). No significant differ-ences were found in the level of pain either in the comparisons of pointmeasurements or in its evolution in the 48 hours after surgery (p= 0.58).After adjusting for the received fluid therapy, children in the metamizolegroup had significantly more emetic episodes and needed significantlymore doses of ondansetron. Conclusions: In our cohort, ibuprofen had a similar analgesic ef-ficacy and a better emetogenic profile than metamizole in the immediatepostoperative period of PAA. Future prospective, adequately controlledstudies with larger sample sizes are needed to validate these findings.(AU)

Adecuación de la seguridad del metamizol y agranulocitosis / Adequacy of the safety of metamizole and agranulocytosis

Objetivo: Analizar si la nota informativa de la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS), de 30 de octubre del 2018, sobre agranulocitosis y metamizol contiene la información precisa y necesaria para proteger a los pacientes de la aparición de esta reacción adversa (RA) y si la documentación oficial de los medicamentos con metamizol para médicos, farmacéuticos y población general está adaptada a las directrices de la AEMPS para disminuir el riesgo. Emplazamiento y participantes: Nota informativa, búsqueda bibliográfica, información sobre los medicamentos con metamizol comercializados en España en la Agencia Europea del Medicamento, fichas técnicas, prospectos, base de datos de información sanitaria Bot PLUS y Catálogo de Especialidades Farmacéuticas. Notificación de 4casos de agranulocitosis por metamizol posteriores a la fecha de la nota informativa. Intervenciones y mediciones principales: Comparación de los puntos clave de la nota informativa y de los documentos oficiales sobre metamizol con la bibliografía. Descripción de 4casos de agranulocitosis por metamizol y aplicación del algoritmo de causalidad y gravedad. Resultados: La nota informativa presenta ausencias y dudas respecto a la bibliografía y al uso de metamizol en la práctica asistencial. Los documentos oficiales presentan faltas de actualización, indicaciones no aprobadas y dosis superiores a las recomendadas. La nota informativa no ha frenado la presentación de casos de agranulocitosis por metamizol. Conclusiones: La nota informativa de la AEMPS es mejorable y es necesario actualizar los documentos oficiales de información sobre el metamizol para profesionales sanitarios y pacientes para disminuir el riesgo de agranulocitosis.(AU)

Objective: To analyze whether the drug safety update issued by the Spanish Agency of Medicines and Healthcare Products (AEMPS), dated October 30, 2018, on agranulocytosis and metamizole contains accurate and necessary information to protect patients from the presentation of this adverse reaction (AR) and if the official documentation of medicines containing metamizole for doctors, pharmacists and the general population conforms to the guidelines of the AEMPS to reduce this risk. Setting and participants: Drug safety update, bibliographic search, information at the European Medicines Agency on metamizole drugs marketed in Spain, technical datasheets, leaflets, Bot PLUS Health Information Database and Catalog of Pharmaceutical Specialties. Notification of 4cases of agranulocytosis due to metamizole after the drug safety update was issued. Main interventions and measurements: Comparison of the key points of the drug safety update and official documents on metamizole with the bibliography. Description of the 4cases of agranulocytosis due to metamizole and application of the causality and severity algorithm. Results: The drug safety update contains omissions and contradiction in respect to the bibliography and the actual use of metamizole in healthcare practice. The official documents show a lack of updating, unapproved indications and doses higher than those recommended. The drug safety update has not stopped the presentation of cases of agranulocytosis due to metamizole. Conclusions: The AEMPS drug safety update can be improved and it is necessary to update the official information documents on metamizole for health professionals and patients in order to decrease the risk of agranulocytosis.(AU)

[Adequacy of the safety of metamizole and agranulocytosis]. / Adecuación de la seguridad del metamizol y agranulocitosis.

OBJECTIVE: To analyze whether the drug safety update issued by the Spanish Agency of Medicines and Healthcare Products (AEMPS), dated October 30, 2018, on agranulocytosis and metamizole contains accurate and necessary information to protect patients from the presentation of this adverse reaction (AR) and if the official documentation of medicines containing metamizole for doctors, pharmacists and the general population conforms to the guidelines of the AEMPS to reduce this risk. SETTING AND PARTICIPANTS: Drug safety update, bibliographic search, information at the European Medicines Agency on metamizole drugs marketed in Spain, technical datasheets, leaflets, Bot PLUS Health Information Database and Catalog of Pharmaceutical Specialties. Notification of 4cases of agranulocytosis due to metamizole after the drug safety update was issued. MAIN INTERVENTIONS AND MEASUREMENTS: Comparison of the key points of the drug safety update and official documents on metamizole with the bibliography. Description of the 4cases of agranulocytosis due to metamizole and application of the causality and severity algorithm. RESULTS: The drug safety update contains omissions and contradiction in respect to the bibliography and the actual use of metamizole in healthcare practice. The official documents show a lack of updating, unapproved indications and doses higher than those recommended. The drug safety update has not stopped the presentation of cases of agranulocytosis due to metamizole. CONCLUSIONS: The AEMPS drug safety update can be improved and it is necessary to update the official information documents on metamizole for health professionals and patients in order to decrease the risk of agranulocytosis.

The need for opioid in the postoperative analgesia of dogs undergoing hemilaminectomy due to intervertebral disc extrusion / A necessidade de opioide na analgesia pós-operatória de cães submetidos à hemilaminectomia devido à extrusão do disco intervertebral

The aim of this study was to evaluate the postoperative analgesic effect of protocols with and without the opioid methadone in dogs with intervertebral disc extrusion undergoing decompressive surgery. Sixteen paraplegic dogs with preserved nociception underwent hemilaminectomy/disc fenestration and were randomly assigned to two groups. The analgesic protocol consisted of methadone, meloxicam and dipyrone in Group I (G1), and meloxicam and dipyrone in Group II (G2). The animals were blindly assessed by two observers, using the visual analogue scale (VAS) and the short-form Glasgow Composite Measure Pain Scale (CMPS-SF). Assessments occurred every 2 hours during first 24 hours post-surgery, and every 4 hours afterwards. There was no statistical difference among groups regarding pain scores or analgesic rescues. Both analgesic protocols provided analgesia in the initial 48 hours postoperatively, demonstrating that opioids are not necessary in the postoperative period of dogs undergoing hemilaminectomy and disc fenestration.(AU)

O objetivo deste estudo foi avaliar a analgesia pós-operatória de protocolos com e sem o opioide metadona em cães com extrusão de disco intervertebral submetidos à descompressão cirúrgica. Dezesseis cães paraplégicos com presença de nocicepção foram submetidos à hemilaminectomia/fenestração de disco e distribuídos aleatoriamente em dois grupos. No Grupo I (G1), o protocolo analgésico consistiu em metadona, meloxicam e dipirona e, no Grupo II (G2), por meloxicam e dipirona. Os pacientes foram avaliados de maneira cega por dois avaliadores, com base na escala visual analógica (EVA) e na escala simplificada composta de dor de Glasgow (CMPS-SF). As avaliações ocorreram a cada 2 horas durante as primeiras 24 horas de pós-operatório e, por mais 24 horas, a cada 4 horas. Não houve diferença estatística entre os grupos avaliados em relação à escores de dor e nem a necessidade de resgate analgésico. Ambos os protocolos promoveram analgesia nas 48 horas iniciais de pós-operatório, demonstrando não haver a necessidade do uso de opioide em cães submetidos à hemilaminectomia e fenestração de disco.(AU)

The need for opioid in the postoperative analgesia of dogs undergoing hemilaminectomy due to intervertebral disc extrusion

ABSTRACT: The aim of this study was to evaluate the postoperative analgesic effect of protocols with and without the opioid methadone in dogs with intervertebral disc extrusion undergoing decompressive surgery. Sixteen paraplegic dogs with preserved nociception underwent hemilaminectomy/disc fenestration and were randomly assigned to two groups. The analgesic protocol consisted of methadone, meloxicam and dipyrone in Group I (G1), and meloxicam and dipyrone in Group II (G2). The animals were blindly assessed by two observers, using the visual analogue scale (VAS) and the short-form Glasgow Composite Measure Pain Scale (CMPS-SF). Assessments occurred every 2 hours during first 24 hours post-surgery, and every 4 hours afterwards. There was no statistical difference among groups regarding pain scores or analgesic rescues. Both analgesic protocols provided analgesia in the initial 48 hours postoperatively, demonstrating that opioids are not necessary in the postoperative period of dogs undergoing hemilaminectomy and disc fenestration.

RESUMO: O objetivo deste estudo foi avaliar a analgesia pós-operatória de protocolos com e sem o opioide metadona em cães com extrusão de disco intervertebral submetidos à descompressão cirúrgica. Dezesseis cães paraplégicos com presença de nocicepção foram submetidos à hemilaminectomia/fenestração de disco e distribuídos aleatoriamente em dois grupos. No Grupo I (G1), o protocolo analgésico consistiu em metadona, meloxicam e dipirona e, no Grupo II (G2), por meloxicam e dipirona. Os pacientes foram avaliados de maneira cega por dois avaliadores, com base na escala visual analógica (EVA) e na escala simplificada composta de dor de Glasgow (CMPS-SF). As avaliações ocorreram a cada 2 horas durante as primeiras 24 horas de pós-operatório e, por mais 24 horas, a cada 4 horas. Não houve diferença estatística entre os grupos avaliados em relação à escores de dor e nem a necessidade de resgate analgésico. Ambos os protocolos promoveram analgesia nas 48 horas iniciais de pós-operatório, demonstrando não haver a necessidade do uso de opioide em cães submetidos à hemilaminectomia e fenestração de disco.

Efectividad de la indometacina vs analgésico habitual en el tratamiento del dolor posthisterectomía / Effectiveness of using indomethacin vs usual analgesic in the management of postoperative pain in hysterectomy

Resumen: OBJETIVO: Determinar la efectividad de la indometacina, por vía rectal, en el tratamiento del dolor posthisterectomía versus paracetamol o metamizol administrados por vía intravenosa. MATERIALES Y MÉTODOS: Estudio experimental, comparativo y prospectivo llevado a cabo en el Hospital Central del Estado de Chihuahua entre noviembre y diciembre de 2019. Criterios de inclusión: pacientes histerectomizadas, con expediente clínico completo y de cualquier edad. Criterios de exclusión: pacientes con alteraciones en el umbral del dolor, inconsistencias en el expediente, histerectomía total no ginecológica. Criterios de eliminación: pacientes con limitantes en la información que no permitieron relacionar la variable dependiente con la independiente. El seguimiento del dolor referido se efectuó con la escala análoga del dolor y valoraciones a las 12 y 24 horas posteriores a la cirugía. RESULTADOS: Se reunieron 141 pacientes, que se dividieron en tres grupos. Grupo 1: metamizol intravenoso e indometacina por vía rectal (n = 24). Grupo 2: paracetamol intravenoso e indometacina por vía rectal (n = 19). Grupo 3: paracetamol y metamizol intravenosos (n = 98). La mayoría de las pacientes de los grupos 1 y 2 reportaron, a las 24 h, una escala visual análoga menor de 3 vs las del grupo 3. Diez de 98 pacientes requirieron tratamiento en el servicio de Anestesiología. CONCLUSIÓN: La administración de indometacina por vía rectal a pacientes histerectomizadas demostró menor dolor que con metamizol y paracetamol, y evolución clínica y alta hospitalaria más temprana.

Abstract: OBJECTIVE: To determine the effectiveness of indomethacin in the treatment of post-hysterectomy pain versus paracetamol or metamizole administered intravenously. MATERIALS AND METHODS: Experimental, comparative and prospective study at the Central Hospital of the State of Chihuahua, period November to December 2019, patients undergoing hysterectomy with complete clinical record, any age. Patients with alterations in the pain threshold, inconsistencies in the file, total non-gynecological hysterectomy were excluded, patients with information limitations were eliminated, which did not allow to relate the dependent variable, with the independent one. RESULTS: 141 patients were collected, which were divided into three groups. Group 1: intravenous metamizole and indomethacin rectally (n = 24). Group 2: intravenous paracetamol and indomethacin rectally (n = 19). Group 3: intravenous paracetamol and metamizole (n = 98). Most of the patients in groups 1 and 2 reported, at 24 hours, a visual analog scale of less than 3 vs those of group 3. Ten of 98 patients required treatment in the Anesthesiology service. CONCLUSION: The administration of indomethacin rectally in postoperative patients of hysterectomy has been shown to reduce pain more effectively than conventional analgesics such as metamizole and paracetamol, relating to clinical evolution and early hospital discharge.

Active metabolites of dipyrone induce a redox-dependent activation of the ion channels TRPA1 and TRPV1.

INTRODUCTION: The nonopioid analgesic and antipyretic dipyrone (metamizol) is frequently used worldwide. Dipyrone is a prodrug, and the metabolites 4-N-methylaminoantipyrine (MAA) and 4-aminoantipyrine (AA) seem to induce analgesia and antipyresia in part by inhibiting cyclooxygenase. In mice, however, the analgesic effect of dipyrone also seems to depend on the ion channel TRPA1. In this study, we explored the effects of dipyrone and its active metabolites on recombinant and native TRPA1 and TRPV1 channels. METHODS: Constructs human (h) TRPA1 and TRPV1 were expressed in HEK293 cells, and dorsal root ganglion neurons were isolated from adult mice. Effects of dipyrone, MAA, and AA were explored by means of whole-cell patch clamp recordings and ratiometric calcium imaging. RESULTS: Dipyrone failed to activate both hTRPA1 and hTRPV1. However, both MAA and AA evoked small outwardly rectifying membrane currents and an increase of intracellular calcium in cells expressing hTRPA1 or hTRPV1. MAA also sensitized both channels and thus potentiated inward currents induced by carvacrol (hTRPA1) and protons (hTRPV1). MAA-induced activation was inhibited by the antioxidant 10-mM glutathione included in the pipette, and the mutant constructs hTRPA1-C621/C641/C665S and hTRPV1-C158A/C391S/C767S were insensitive to both MAA and AA. Mouse dorsal root ganglion neurons exhibited a marginal calcium influx when challenged with MAA. CONCLUSION: The metabolites MAA and AA, but not dipyrone itself, activate and sensitize the nociceptive ion channels TRPA1 and TRPV1 in a redox-dependent manner. These effects may be relevant for dipyrone-induced analgesia and antipyresia.

[Fatal Outcome of Agranulocytosis after Re-Exposure to Metamizole and Cefepime-Induced Encephalopathy]. / Agranulozytose nach Metamizol-Reexposition und Cefepim-induzierte Enzephalopathie mit fatalem Ausgang.

Fatal Outcome of Agranulocytosis after Re-Exposure to Metamizole and Cefepime-Induced Encephalopathy Abstract. We present the case of an 83-year-old female patient who died as a result of likely drug-induced complications, namely agranulocytosis caused by metamizole and cefepime-induced encephalopathy. Agranulocytosis precipitated a cascade of events that eventually led to death. As prescription of metamizole has increased over the past decades, it is important to keep in mind its serious adverse drug reactions. Metamizole must be stopped immediately at the onset of symptoms such as fever, mucositis and sore throat, and re-exposure in patients who have previously developed leukopenia under metamizole must be avoided. This can be achieved by meticulous documentation in the medical records and the use of an emergency or allergy alert card which the patient carries at all times. When using cefepime, renal function should be closely monitored, especially in multimorbid geriatric patients, and the dose should be adjusted accordingly.

Which agent should be used to reduce ischemia-reperfusion injury after testicular torsion: a comparative animal experiment.

INTRODUCTION: Testicular torsion is an acute urological emergency that causes severe damage of testis. In order to prevent testicular damage, early diagnosis and surgical intervention is essential. Also pain management in both pre-operative and postoperative periods remains a challenging entity. OBJECTIVE: In this study, we aimed to determine the possible positive effects of three different analgesics (ibuprofen, metamizole, and paracetamol), which are widely used in clinical practice on testicular tissue, in addition to pain control. STUDY DESIGN: Forty prepubertal rats (180-210 g) were divided into five experimental groups. Group 1 was sham group in which the left testis was brought out through a scrotal incision and then replaced in the scrotum without torsion. Group 2 was control group (only 0.9% NaCl was applied). Also in group 3, paracetamol, in group 4, ibuprofen, and in group 5, metamizole sodium was applied 1 h after the torsion. Torsion duration was planned as 4 h for all groups. RESULTS: In the biochemical evaluation, malondialdehyde (MDA), myeloperoxidase (MPO), and total nitrate (NO) levels were measured in the testicular tissue. All groups were compared with group 2 (control group). In group 3, although the MDA level was lower and the MPO level was found to be higher, these were not statistically significant. In group 4, the NO level was low but statistically significant. Histological findings were evaluated due to Cosentino's classification, and the scores of group 4 were better than all groups. DISCUSSION: In this study, severe damage was observed at the end of torsion period of 4 h. This is in line with previous published data. The beneficial effects of all three drugs have been observed. CONCLUSIONS: Biochemical results did not clearly highlight any agents. According to pathology results, metamizole was better than paracetamol and the most ideal analgesic preparation was observed as ibuprofen.

Síndrome de Nicolau. Manejo conservador. Caso clínico / Nicolau syndrome, Conservative management: Clinical case

Introducción: el síndrome de Nicolau, embolia cutis o dermatitis livedoide, es una reacción adversa poco frecuente a la administración de inyección intramuscular, subcutánea o intraarticular de medicamentos, inicia con dolor intenso y eritema que evoluciona a lesión livedoide que se torna hemorrágica, progresa a necrosis isquémica de piel y tejidos más profundos. Caso clínico: niño de 7 meses de edad, luego de inyección intramuscular de metamizol sódico presenta llanto continuo, seguido de lesión purpúrica afectando espalda, glúteo, muslo y pierna derechos, evolucionando hasta cicatrización total en 18 semanas. Conclusión: el síndrome de Nicolau, condición iatrogénica por inyección de múltiples medicamentos, produce lesión necrótica en área de irrigación de vasos afectados. El conocimiento de este síndrome facilitaría su prevención, al igual que su diagnóstico y manejo tempranos

Introduction: Nicolau syndrome, embolism cutis or livedoid dermatitis, is a rare adverse reaction to the administration of intramuscular, subcutaneous or intra-articular injection of drugs, begins with intense pain and erythema that progresses to a livedoid lesion that becomes hemorrhagic, progresses to ischemic necrosis of skin and deeper tissues. Clinical case: A 7-month-old boy, after intramuscular injection of sodium metamizole, presented continuous crying followed by a purpuric lesion affecting the right back, gluteus, thigh and leg, evolving to total healing in 18 weeks. Conclusion: Nicolau Syndrome, iatrogenic condition by injection of multiple drugs, produces necrotic lesion in irrigated area of affected vessels. The knowledge of this syndrome would facilitate its prevention, as well as its early diagnosis and management.

Respondiendo a la interrogante: ¿el metamizol es o no un antiinflamatorio no esteroideo? / Answering the question: is metamizole a non-steroidal anti-inflammatory or not?

Resumen: El objetivo de este artículo es determinar la importancia del metamizol como analgésico en México, al conocer la frecuencia de su uso y los mecanismos de acción y así clasificar adecuadamente al medicamento dentro de la farmacopea de analgésicos. Pocos fármacos generan discusión sobre su filiación, pero el metamizol, desde que salió al mercado en 1922 hasta el día de hoy, se mantiene sin definirse claramente. Comúnmente cuando se busca una clasificación de los antiinflamatorios no esteroideos (AINE), se clasifica al metamizol dentro de los mismos como derivados de la pirazolona. Se debe comenzar entonces con los aspectos farmacológicos para relacionar las semejanzas y diferencias con otros AINEs y poder sacar conclusiones adecuadas. Aun así, el medicamento es de los más utilizados por los médicos en los hospitales de segundo y tercer nivel (82%), aunque la mayoría no sabe en realidad cuál es su mecanismo de acción (91%), por ello, la importancia de conocer el mecanismo de acción de este fármaco.

Abstract: The aim of this article is to know the importance of metamizol as analgesic in Mexico, knowing the frequency of their use and the mechanisms of action and to adequately classify the drug in the pharmacopoeia of painkillers. Few drugs generate discussion about their parentage but metamizol from that hits the market in 1922 until today, it has no clearly defined. Commonly when NSAIDs rated seeks to metamizol is classified within the same as pyrazolone derivatives. We then start with the pharmacological aspects and later to know the similarities and differences with other NSAIDs and can draw appropriate conclusions. Even so, the medicine is one of the most used by physicians in second and third level hospitals (82%), although most do not really know what their mechanism of action is (91%), so the importance of knowing the mechanism of action of this drug.

Identificación de reacciones adversas por dipirona en pacientes de un hospital de tercer nivel / Identification of adverse drug reactions in patients treated with dipyrone in a third level hospital

Resumen Introducción: la dipirona es un antipirético, analgésico y antiespasmódico, posicionado como una de las primeras opciones en el manejo del dolor. El objetivo de esta investigación fue establecer la incidencia de efectos adversos relacionados al uso de dipirona en pacientes internados en un hospital de tercer nivel en la ciudad de Pereira -Risaralda durante 2016. Métodos: estudio descriptivo que incluyó pacientes con cualquier efecto adverso relacionado con el uso de dipirona. Se utilizó la clasificación de reacciones adversas de Rawlins y Thompson. La relación de causalidad se calculó con la escala de Naranjo. Resultados: se evaluaron 59 pacientes con reacciones adversas por el uso de dipirona, con una edad media de 44,4 ± 21,6 años y el 52,5 % eran mujeres. La mayoría de las reacciones se presentaron en el servicio de cirugía (52,5 %). La indicación más frecuente para su uso fue traumatismo (39 %), seguida de algún procedimiento quirúrgico (25,4 %). La reacción reapareció en 28,8 % de los casos tras una nueva administración de dipirona en la misma hospitalización. Se presentó un caso de granulocitopenia. La incidencia de reacciones adversas fue 1,4 por cada 1 000 pacientes. Conclusión: las reacciones adversas relacionadas con el uso de dipirona son un hallazgo poco frecuente a pesar del amplio uso del medicamento. La toxicidad hematológica se debe tener en cuenta a la hora de prescribir dipirona. Se deben mejorar los protocolos de seguridad del paciente con el fin de disminuir las posibles reacciones adversas relacionados con la administración de medicamentos.

Abstract Background. Dipyrone is an antipyretic, analgesic and antispasmodic, positioned as one of the first options in pain management. The aim was to establish the incidence of adverse effects related to the use of dipyrone in patients hospitalized in a third level hospital in the city of Pereira- Colombia during 2016. Methods: A descriptive study that included patients with any adverse effect related to the use of dipyrone. The classification of adverse reactions of Rawlins and Thompson was used. The causal relationship was calculated with Naranjo scale. Results: A total of 59 patients were evaluated for adverse reactions with the use of dipyrone, with a mean age of 44.36 ± 21.6 years and 52.5% were women. The reactions occurred mainly in surgical patients (52.5%). The most frequent indication for its use was trauma in 39 % of cases, followed by some surgical procedure (25.4%). In 28.8% of the cases, the event reappeared after a new administration of dipyrone during the same hospitalization. A case of granulocytopenia was presented. The incidence of adverse events with dipyrone was 1.4 per 1000 patients. Conclusion: Adverse reactions related to the use of dipyrone are a rare finding despite the wide use of the drug. Hematological toxicity should be considered when prescribing dipyrone. Patient safety protocols should be improved in order to reduce possible adverse events related to the administration of medications.

[Comparative study of the effect of two analgesic techniques in postoperative pain control in pediatric surgery]. / Estudio comparativo de dos técnicas analgésicas en el postoperatorio de Cirugía Pediátrica.

OBJECTIVE: The study purpose was to evaluate the analgesic efficacy of the association of paracetamol + metamizol versus tramadol in pediatric surgery. METHODS: A prospective, randomized and double-blinded study of 60 patients between 3 and 8 years, undergoing abdominal surgery in the ambulatory unit. Patients were divided into 2 groups who received paracetamol plus metamizol (Group I) or tramadol (Group II), prior to the end of the procedure. The anesthetic technique in all cases consisted of general anesthesia balanced. The study compared the pain intensity according to the Wong-Baker scale, the need of rescue analgesia, and the side effects every hour in the postoperative period. The statistical analysis was performed using the chi-square test and T-Student test. RESULTS: The analgesia time for Group I was 202 ± 25 minutes and 215 ± 17 minutes for Group II without statistical significance. There was no significant differences (p= 0.233) in the pain scores; only 3 children in the first group had more than 4 points on the Wong-Baker scale versus 5 children in the tramadol group. The overall side effects were significantly higher (p< 0.05) in Group II, 5 patients presented vomiting compared to no child in Group I. The average dose of morphine chloride was 0.6 ± 0.2 mg. CONCLUSIONS: Both techniques provide adequate pain control in the postoperative period of abdominal ambulatory surgery in pediatric patients. However, children treated with tramadol presented a greater number of side effects compared to the NSAIDs group.

OBJETIVO: Evaluar la eficacia analgésica de la asociación paracetamol + metamizol frente a tramadol en Cirugía Pediátrica. MATERIAL Y METODOS: Se realiza un estudio prospectivo, randomizado y a doble ciego, se seleccionaron 60 pacientes de entre 3 y 8 años programados para cirugía abdominal ambulatoria, divididos en 2 grupos, al grupo I se les administró paracetamol y metamizol intravenosos y al grupo II tramadol intravenoso, previos a la finalización de la intervención. La técnica anestésica consistió en anestesia general balanceada. Se valoró en el periodo postoperatorio la intensidad del dolor según la escala de Wong-Baker, la necesidad de analgesia de rescate y los efectos indeseables. El análisis estadístico se realizó mediante el test de Chi-cuadrado y la t-Student. RESULTADOS: El tiempo de analgesia para el grupo I fue de 202 ± 25 minutos y para el grupo II 215 ± 17 minutos sin significación estadística. Solo 3 niños en el grupo I presentaron valores superiores a 4 en la escala de Wong-Baker y 5 en el grupo II sin diferencias significativas (p= 0,233). En el grupo II presentaron vómitos 5 pacientes frente a ningún niño en el grupo I con diferencias estadísticamente significativas (p< 0,05). La dosis media de cloruro mórfico fue de 0,6 ± 0,2 mg. CONCLUSIONES: Ambas técnicas proporcionan una analgesia adecuada en el postoperatorio de la cirugía abdominal ambulatoria. Destaca un mayor número de efectos secundarios en el grupo del tramadol frente al grupo de los AINEs.

[Non-opioid analgesics]. / Neopioidní analgetika.

Non-opioid analgesics are commonly used to treat mild and moderate acute and chronic pain. They can be used as monotherapy; however, they have greater efficacy in combination with weak and strong opioids. Unlike opioids, long-term use of non-steroidal anti-inflammatory drugs does not lead to physical dependence. One of the main disadvantages of the NSA is the risk of gastrointestinal side effects, especially bleeding into the digestive tract. This is increased especially in ulcerative disease and in higher doses, but also in the elderly (over 65 years), also with concomitant administration of corticosteroids, anticoagulants or other NSAIDs.

Descripción y cuantificación de riesgos atribuidos a analgésicos antiinflamatorios no esteroides no selectivos consumidos por la población mexicana / Description and quantification of risks attributed to non-selective non-steroidal anti-inflammatory drugs consumed by Mexican population

Resumen OBJETIVO Analizar las reacciones adversas a medicamentos asociadas con la administración de antiinflamatorios no esteroides (AINEs) no selectivos reportadas al Centro Nacional de Farmacovigilancia durante el periodo 2011-2014. MATERIAL Y MÉTODO Estudio en el que para el análisis descriptivo se utilizó la base de datos del Centro Nacional de Farmacovigilancia 2011-2014 que contiene las reacciones adversas a medicamentos asociadas con la administración de analgésicos provenientes de los diferentes integrantes del Programa Permanente de Farmacovigilancia, que se agruparon de acuerdo con edad y sexo del paciente, procedencia de la reacción adversa a medicamentos, principio activo sospechoso, gravedad y causalidad de la reacción. RESULTADOS 4553 reacciones adversas a medicamentos se asociaron con la administración de un AINE (3.9%). El metamizol fue el más reportado con 21.1% del total de reacciones adversas registradas para este grupo de medicamentos. CONCLUSIONES El metamizol fue el medicamento con más reacciones adversas a medicamentos reportadas. Las reacciones dermatológicas de importancia (necrólisis epidérmica tóxica, síndrome de Stevens-Johnson y síndrome de Lyell) se manifestaron mayormente con nimesulida.

Abstract OBJECTIVE To analyze drug-adverse reactions related to the administration of non-selective non-steroidal anti-inflammatory drugs (NSAIDS) reported to the National Pharmacovigilance Center from 2011 to 2014. MATERIAL AND METHOD A study was done in which for the descriptive analysis was used the database of the National Pharmacovigilance Center 2011-2014 containing the drug-adverse reactions related to the administration of analgesic drugs coming from the different members of the Permanent Program of Pharmacovigilance, that were grouped according to: age and sex of patient, proceeding of the drug-adverse reaction, suspect active principle, severity and causality of reaction. RESULTS 4553 drug-adverse reactions were related to the administration of an NSAID (3.9%). Metamizol was the most reported with 21.1% of the total of adverse reaction registered for this group of drugs. CONCLUSIONS Metamizol was the drug with more drug-adverse reactions reported. The dermatological reactions of importance (toxic epidermal necrolysis, Stevens-Johnson syndrome and Lyell syndrome) were higher reported with nimesulide.

Chitosan/waste coffee-grounds composite: An efficient and eco-friendly adsorbent for removal of pharmaceutical contaminants from water.

Waste coffee-grounds (WCG), a poorly explored source of biocompounds, were combined with chitosan (Cs) and poly(vinyl alcohol) (PVA) in order to obtain composites. Overall, WCG showed a good interaction with the polymeric matrix and good dispersibility up to 10 wt-%. At 5 wt-% WCG, the composite exhibited a noticeable enhancement (from 10 to 44%) of the adsorption of pharmaceuticals (metamizol (MET), acetylsalicylic acid (ASA), acetaminophen (ACE), and caffeine (CAF)) as compared to the pristine sample. The highest removal efficiency was registered at pH 6 and the removal followed the order ASA > CAF > ACE > MET. For all pharmaceuticals, the adsorption kinetics was found to follow the pseudo-second order model, while the adsorption mechanism was explained by the Freundlich isotherm. Reuse experiments indicated that the WCG-containing composite has an attractive cost-effectiveness since it presented a remarkable reusability in at least five consecutive adsorption/desorption cycles.

Pharmacokinetics and pharmacodynamics of metamizol in co-administration with morphine under acute and chronic treatments in arthritic rats.

OBJECTIVE: To investigate the relationship between metamizol pharmacokinetics and the antinociceptive effect produced after subcutaneous administration of metamizol (177.8 mg/kg) alone or in combination with morphine (3.2 mg/kg), under acute and chronic treatments. METHODS: Antinociception was assessed using the pain-induced functional impairment model in rat (PIFIR). Serial blood samples were collected from the same animals to study the pharmacokinetics of metamizol. KEY FINDINGS: The co-administration of the drugs in single dose, confirmed the potentiation of their individual antinociceptive effects. When the drugs were administered alone following the chronic schedule, a pronounced tolerance development to their antinociceptive effects was found, whereas it was significantly attenuated when they were administered together. Metamizol pharmacokinetics was unaltered by the presence of morphine. Plasma concentrations of 4-methylaminoantipyrine, an active metabolite markedly decreased under chronic administration. CONCLUSIONS: The mechanism involved in the potentiation of the antinociceptive effect produced by the combination, cannot be explained by the interaction of morphine on metamizol pharmacokinetics. Other pharmacokinetic interactions along with known pharmacodynamic interactions in which metamizol active metabolites contribute, should be considered. The frequency of administration enhances tolerance development and induces metamizol elimination process.

Effect of tramadol on metamizol pharmacokinetics and pharmacodynamics after single and repeated administrations in arthritic rats.

Combined administration of certain doses of opioid compounds with a non-steroidal anti-inflammatory drug can produce additive or supra-additive effects while reducing unwanted effects. We have recently reported that co-administration of metamizol with tramadol produces antinociceptive effect potentiation, after acute treatment. However, none information about the effect produced by the combination after chronic or repeated dose administration exists. The aims of this study were to investigate whether the antinociceptive synergism produced by the combination of metamizol and tramadol (177.8 + 17.8 mg/kg, s.c. respectively) is maintained after repeated treatment and whether the effects observed are primarily due to pharmacodynamic interactions or may be related to pharmacokinetics changes. Administration of metamizol plus tramadol acute treatment significantly enhanced the antinociceptive effect of the drugs given alone (P < 0.05). Nevertheless, this effect decreased about 53% after the chronic treatment (3 doses per day, for 4 days). No pharmacokinetic interaction between metamizol and tramadol was found under acute treatment (P > 0.05). The mechanism involved in the synergism of the antinociceptive effect observed with the combination of metamizol and tramadol in single dose cannot be attributed to a pharmacokinetic interaction, and other pharmacodynamic interactions have to be considered. On the other hand, when metamizol and tramadol were co-administered under repeated administrations, a pharmacokinetic interaction and tolerance development occurred. Differences found in metamizol active metabolites' pharmacokinetics (P < 0.05) were related to the development of tolerance produced by the combination after repeated doses. This work shows an additional preclinical support for the combination therapy. The clinical utility of this combination in a suitable dose range should be evaluated in future studies.

Postoperative analgesia for supratentorial craniotomy.

OBJECTIVES: The prevalence of moderate to severe pain is high in patients following craniotomy. Although optimal analgesic therapy is mandatory, there is no consensus regarding analgesic regimen for post-craniotomy pain exists. This study aimed to investigate the effects of morphine and non-opioid analgesics on postcraniotomy pain. PATIENTS AND METHODS: This prospective, randomized, double blind, placebo controlled study included eighty three patients (ASA 1, II, and III) scheduled for elective supratentorial craniotomy. Intravenous dexketoprofen, paracetamol and metamizol were investigated for their effects on pain intensity, morphine consumption and morphine related side effects during the first 24h following supratentorial craniotomy. Patients were treated with morphine based patient controlled analgesia (PCA) for 24h following surgery and randomized to receive supplemental IV dexketoprofen 50mg, paracetamol 1g, metamizol 1g or placebo. The primary endpoint was pain intensity, secondary endpoint was the effects on morphine consumption and related side effects. RESULTS: When the whole study period was analyzed with repeated measures of ANOVA, the pain intensity, cumulative morphine consumption and related side effects were not different among the groups (p>0.05). CONCLUSION: This study showed that the use of morphine based PCA prevented moderate to severe postoperative pain without causing any life threatening side effects in patients undergoing supratentorial craniotomy with a vigilant follow up during postoperative 24h. Although we could not demonstrate statistically significant effect of supplemental analgesics on morphine consumption, it was lower in dexketoprofen and metamizol groups than control group.