Perfil prescriptivo de corticoides en el servicio de urgencias del Hospital Odontológico de la ciudad de Formosa, Argentina / Prescriptive Profile of Corticoids in the Emergency Department of the Dental Hospital of the City of Formosa, Argentina

Objetivo: identificar el perfil prescriptivo de corticoides en pacientes que asistieron al Servicio de Urgencias del Hospital Odontológico de la ciudad de Formosa, Argentina. Métodos: se realizó un estudio transversal, observacional y descriptivo, se analizaron las prescripciones de corticoides realizadas por odontólogos que atendieron en el Servicio de Urgencias del Hospital Odontológico de la ciudad de Formosa desde marzo 2019 a febrero 2020. Las variables de estudio fueron: características demográficas del paciente, diagnóstico clínico odontológico, corticoide prescrito, dosis y forma farmacéutica. Resultados: de un total de 9.635 historias clínicas, se observaron 3.244 prescripciones de corticoides (33,6%). De acuerdo a los corticoides prescritos, se halló a la dexametasona para vía intramuscular y además se utilizó dexametasona en tratamientos combinados con dipirona para vía intramuscular e ibuprofeno para vía oral. Los diagnósticos relacionados con prescripción de estos medicamentos fueron: pulpitis, periodontitis apical aguda, flemón/absceso, entre otras. De acuerdo al valor intrínseco terapéutico potencial, los fármacos prescritos en el hospital odontológico son de valor elevado, esto significa que demostraron eficacia para el tratamiento, el diagnóstico o la prevención de enfermedades del ser humano. Conclusiones: el estudio de la utilización de medicamentos en el Hospital Odontológico de la ciudad de Formosa permitió observar situaciones donde los corticoides no están indicados. Además, se señala la prescripción excesiva de la vía intramuscular. A partir de los resultados obtenidos es necesario realizar una retroalimentación a los prescriptores, por lo que se sugieren intervenciones para elaborar propuestas de solución a los problemas identificados y formular políticas de medicamentos.

Objective: to identify the prescriptive profile of corticosteroids in patients who were treated at the Emergency Service of the Dental Hospital of the City of Formosa, Argentina. Methods: a cross-sectional, observational, and descriptive study was carried out, and corticosteroid prescriptions made by dentists who attended the Emergency Service of the Dental Hospital of the City of Formosa, from March 2019 to February 2020 were analyzed. The study variables were: demographic characteristics of the patient, dental clinical diagnosis, corticosteroid prescribed, dose, and pharmaceutical form. Results: Of 9,635 medical records, 3,244 corticosteroid prescriptions (33.6%) were observed. According to the prescribed corticosteroids, dexamethasone was found for the intramuscular route, and dexamethasone was also used in combined treatments with dipyrone for the intramuscular route and ibuprofen for the oral route. The diagnoses related to the prescription of these medications were: pulpitis, acute apical periodontitis, phlegmon/abscess, trauma, pericoronitis, hypersensitivity and alveolitis. According to the potential therapeutic intrinsic value, the drugs prescribed in the dental hospital are of high value, which means that they have demonstrated efficacy for the treatment, diagnosis or prevention of diseases that affect humans. Conclusions: the study of the use of drugs in the Dental Hospital of the City of Formosa allowed us to observe situations where corticosteroids are not indicated. In addition, the excessive prescription of the intramuscular route is pointed out. Based on the results obtained, it is necessary to provide feedback to the prescribers, so it is suggested to continue with different interventions to develop proposals for solutions to the identified problems and formulate drug policies.

Real world evidence of the use of metamizole (dipyrone) by the Brazilian population. A retrospective cohort with over 380,000 patients

ABSTRACT Objective To determine under which health conditions metamizole (dipyrone) is used as a single drug or as fixed-dose combination. Methods Two retrospective cohorts of Brazilian patients treated with metamizole between January 2015 and December 2017 were analyzed: a metamizole-based cohort (Cohort 1) and a symptoms-based cohort (Cohort 2). Anonymized patient data was obtained from Amil Clinical Data Warehouse. The number of patients with symptoms was described by age and sex. Results The sample size of the two cohorts consisted of 384,668 patients. In patients using metamizole (Cohort 1), the most common reason for medication was the treatment of some form of pain (81%), followed by fever (19%). Headache was the most common (19%) specified pain class, followed by sore throat (8%), muscular pain (6%), and abdominal pain (5%). In adult patients (n=276,279; 71.8%), metamizole was used as a monotherapy or associated with another drug, for any sort of pain, in over 88% of the patients. General pain was the main reason for metamizole use in children (61%). Conclusion Real world evidence to evaluate Brazilian patients' therapeutic options is unusual and yet to be more explored using digital tools enabling better data registration. The present study confirmed that metamizole is widely used as a non-anti-inflammatory drug, and also showed the management of pain and fever as the most frequent indications in all age groups studied. Registry in Clinical Trials Database: REBEC Database: 10507

Requisitos de bioisenção com base no Sistema de Classificação Biofarmacêutica no Brasil e no mundo / Biowaiver requirements based on the Biopharmaceutical Classification System in Brazil and worldwide

O acesso a medicamentos pode ser facilitado por programas globais de desenvolvimento farmacêutico, mas há necessidade de que as agencias regulatórias e as indústrias farmoquímicas e farmacêuticas interajam e haja um consenso quanto as exigências para o registro de medicamentos. Este artigo examinou a legislação especifica sobre bi isenção com base no Sistema de Classificação Biofarmacêutica, comparando os cenários do Brasil e do mundo. A partir dessa análise, identificou os entraves a aplicação dos critérios internacionais na realidade regulatória nacional, identificando algumas fragilidades da legislação, como no caso de pro-fármacos. Analisaram-se os critérios de cinco organismos regulatórios (Agência Europeia de Medicamentos, Food and Drug Administration, Health Canada, Conselho Internacional para Harmonização de Requisitos Técnicos para Medicamentos de Uso Humano e Organização Mundial da Saúde) frente aos requisitos da Agência Nacional de Vigilância Sanitária, pontuando as diferenças e o que já se encontra pacificado no tocante a classe do Sistema de Classificação Biofarmacêutica aceita, a comparabilidade entre formulação teste e de referência, solubilidade, permeabilidade intestinal e perfil de dissolução in vitro. Concluiu--se que a Agência Nacional de Vigilância Sanitária deve internalizar os preceitos e critérios da bioisenção com base no Sistema de Classificação Biofarmacêutica por meio de um novo marco regulatório. Além disso, para que esse marco regulatório seja bem-sucedido e produza resultados palpáveis, em especial na área de saúde publica e vigilância sanitária, a agência brasileira deve estar aberta ao diálogo com o setor regulado e as inovações e orientações da academia, sem desviar o foco de sua missão institucional.

Access to medicines can be facilitated by global pharmaceutical development programs, but there is a need for regulatory agencies and the pharmochemical and pharmaceutical industries to interact and to have a consensus on the requirements for drug registration. This article examined the specific legislation concerning to biowaiver based on the Biopharmaceutical Classification System, comparing the scenario in Brazil and worldwide. Based on this analysis, it identified the obstacles to the application of international criteria in the national regulatory reality, identifying some weaknesses of the legislation, as in the case of prodrugs. The criteria of five regulatory bodies (European Medicines Agency, Food and Drug Administration, Health Canada, International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use and World Health Organization) were analyzed in relation to the requirements of the Brazilian Health Regulatory Agency (Anvisa), pointing out the differences and what has already been settled regarding the accepted class of the Biopharmaceutical Classification System, the comparability between test and reference formulations, solubility, intestinal permeability and in vitro dissolution profile. It was concluded that Anvisa should internalize the percepts and criteria of the biowaiver based on Biopharmaceutical Classification System, through a new regulatory framework. Moreover, for this regulatory framework to be successful and produce tangible results, especially in the area of public health and health surveillance, Anvisa must be open to dialogue with the regulated sector and to innovations and guidance from academia, without losing focus of its institutional mission.

Factores clínicos y demográficos asociados con la mortalidad por dengue en Colombia: estudio de casos y controles / Demographic and clinical factors associated with dengue mortality in Colombia: a case-control study

Resumen: Objetivo: Identificar factores demográficos y clínicos asociados con la mortalidad por dengue grave en cinco departamentos de Colombia. Material y métodos: Análisis secundario de un estudio de casos y controles basado en pacientes admitidos de 2009 a 2013. Los casos fueron pacientes que murieron por dengue y los controles fueron pacientes con dengue grave sobrevivientes a la enfermedad. Se utilizó el procedimiento de Mantel-Haenszel para identificar los factores. Resultados: Analizando 58 casos y 121 controles, cuatro factores fueron asociados con la mortalidad por dengue: administración hospitalaria de dipirona (RMa=6.38 IC95% 2.41-16.86) y de acetaminofén (RMa=0.25 IC95% 0.10-0.61), presencia de comorbilidad (RMa=3.52 IC95% 1.51-8.18) y consulta previa por el mismo padecimiento (RMa=3.99 IC95% 1.63-9.77). Conclusiones: La administración de dipirona en pacientes con dengue grave se asoció con un aumento del riesgo de mortalidad. Si se considera que la dipirona fue retirada del mercado en 20 países por sus efectos secundarios, se puede desaconsejar su uso en el manejo del dengue.

Abstract: Objective: To identify demographic and clinical factors associated with mortality due to severe dengue in five departments in Colombia. Materials and methods: Case-control study with patients admitted between 2009 and 2013. The cases were patients who died from dengue and the controls where patients with severe dengue who survived the disease. A multivariate analysis using the Mantel-Haenszel procedure identified risk factors associated with dengue mortality. Results: We analyzed 58 cases and 121 controls and identified four factors: in-hospital administration of dypirone (ORa=6.38 95%CI 2.41-16.86) and paracetamol (ORa=0.25 95%CI 0.10-0.61), comorbidities (ORa=3.52 95%CI 1.51-8.18), and a prior visit to the hospital (ORa=3.99 95%CI 1.63-9.77). Conclusions: Administration of dypirone in patients with severe dengue was associated with a higher risk of mortality. Considering that 20 countries have banned dipyrone because of its adverse effects, we advise against its use.

Erupção fixa bolhosa generalizada após reexposição à dipirona: relato de caso e revisão da literatura / Generalized bullous fixed drug eruption after reexposure to dipyrone: a case report and literature review

A erupção fixa à droga (EFD) é uma reação de hipersensibilidade tardia a medicamentos caracterizada por máculas ou pápulas eritematosas, violáceas ou acastanhadas, bem demarcadas, que aparecem após uso de uma medicação, e reaparecem na mesma localização após exposições repetidas. A erupção fixa à droga bolhosa generalizada (EFDBG) é uma variante rara da EFD que foi recentemente incluída pelo RegiSCAR no grupo das farmacodermias graves. Apresenta-se através de lesões cutâneas generalizadas características de EFD, com formação de bolhas, geralmente em pacientes com história prévia de EFD. Os principais medicamentos envolvidos na EFDBG são antibióticos e anti-inflamatórios não esteroidais. O diagnóstico é clínico, entretanto, a biópsia cutânea na fase aguda e o teste de contato após a recuperação do paciente, podem auxiliar a investigação. O tratamento requer geralmente apenas a suspensão do fármaco suspeito e medidas de suporte. Relatamos um caso de EFDBG em adolescente após reexposição à dipirona (metamizol) apesar da história prévia de hipersensibilidade a esta medicação. O objetivo deste relato é alertar sobre a importância do diagnóstico da EFDBG e ressaltar os principais pontos para o diagnóstico diferencial com a síndrome de Stevens-Johnson (SSJ)/necrólise epidérmica tóxica (NET).

Fixed drug eruption (FDE) is a delayed drug hypersensitivity reaction characterized by erythematous, violaceous or brownish well-demarcated macules or papules that appear after use of a medication and reappear at the same site after repeated exposures. Generalized bullous fixed drug eruption (GBFDE) is a rare FDE variant that has been recently included by RegiSCAR in the group of severe cutaneous adverse reactions to drugs. GBFDE presents as generalized cutaneous lesions characteristic of FDE, with blistering, usually in patients with a previous history of FDE. The main drugs involved in GBFDE are antibiotics and nonsteroidal anti-inflammatory drugs. The diagnosis is clinical, but some tests can help the investigation, such as skin biopsy in the acute phase and patch testing after patient recovery. Treatment usually requires suspension of the suspected drug and some supportive measures. We report a case of GBFDE after reexposure to dipyrone (metamizole) in an adolescent with a previous history of hypersensitivity to this drug. The aim of this report is to warn about the importance of diagnosing GBFDE and to highlight the main points for differential diagnosis with Stevens- Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).

Implantação de um protocolo de manejo de dor e redução do consumo de opioides na unidade de terapia intensiva: análise de série temporal interrompida / Pain management protocol implementation and opioid consumption in critical care: an interrupted time series analysis

RESUMO Objetivo: Avaliar o impacto de um protocolo de manejo da dor e redução do consumo de opioides no consumo geral de opioides e nos desfechos clínicos. Métodos: Estudo em centro único, quasi-experimental, retrospectivo, de coortes antes e depois. Utilizamos uma série temporal interrompida para analisar as alterações no nível e na tendência de utilização de diferentes analgésicos. Foram usadas comparações bivariadas nas coortes antes e depois, regressão logística e regressão quantílica para estimativas ajustadas. Resultados: Incluímos 988 pacientes no período pré-intervenção e 1.838 no período pós-intervenção. O consumo de fentanil teve ligeiro aumento gradual antes da intervenção (β = 16; IC95% 7 - 25; p = 0,002), porém diminuiu substancialmente em nível com a intervenção (β = - 128; IC95% -195 - -62; p = 0,001) e, a partir de então, caiu progressivamente (β = - 24; IC95% -35 - -13; p < 0,001). Houve tendência crescente de utilização de dipirona. A duração da ventilação mecânica foi significantemente menor (diferença mediana: - 1 dia; IC95% -1 - 0; p < 0,001), especialmente para pacientes mecanicamente ventilados por períodos mais longos (diferença no 50º percentil: -0,78; IC95% -1,51 - -0,05; p = 0,036; diferença no 75º percentil: -2,23; IC95% -3,47 - -0,98; p < 0,001). Conclusão: Um protocolo de manejo da dor conseguiu reduzir o consumo de fentanil na unidade de terapia intensiva. Esta estratégia se associou com menor duração da ventilação mecânica.

ABSTRACT Objective: To evaluate the impact of an opioid-sparing pain management protocol on overall opioid consumption and clinical outcomes. Methods: This was a single-center, quasi-experimental, retrospective, before and after cohort study. We used an interrupted time series to analyze changes in the levels and trends of the utilization of different analgesics. We used bivariate comparisons in the before and after cohorts as well as logistic regression and quantile regression for adjusted estimates. Results: We included 988 patients in the preintervention period and 1,838 in the postintervention period. Fentanyl consumption was slightly increasing before the intervention (β = 16; 95%CI 7 - 25; p = 0.002) but substantially decreased in level with the intervention (β = - 128; 95%CI -195 - -62; p = 0.001) and then progressively decreased (β = - 24; 95%CI -35 - -13; p < 0.001). There was an increasing trend in the utilization of dipyrone. The mechanical ventilation duration was significantly lower (median difference: - 1 day; 95%CI -1 - 0; p < 0.001), especially for patients who were mechanically ventilated for a longer time (50th percentile difference: -0.78; 95%CI -1.51 - -0.05; p = 0.036; 75th percentile difference: -2.23; 95%CI -3.47 - -0.98; p < 0.001). Conclusion: A pain management protocol could reduce the intensive care unit consumption of fentanyl. This strategy was associated with a shorter mechanical ventilation duration.

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.

Estudo da dor no período pós-operatório de cirurgia de catarata: utilização de dipirona no intraoperatório / Study on immediate postoperative pain following cataract surgery: intraoperative endovenous administration of dipyrone

Resumo Objetivos: Quantificar a dor dos pacientes submetidos a cirurgia de facoemulsificação sob anestesia tópica e anestesia tópica mais dipirona e avaliar se há correlação da dor com o tempo operatório, a graduação da catarta e a Energia Ultrassônica Dissipada Acumulada. Métodos: Cento e quatro olhos de 52 pacientes foram submetidos a cirurgia de catarata por facoemulsificação. Um olho foi submetido a anestesia tópica associado à sedação. O outro olho foi submetido a anestesia anterior acrescida de 1g de dipirona venosa. 15 minutos e 24 horas após a cirurgia, uma Escala Visual de Dor era respondida. Registraram-se a graduação da catarata, tempo cirúrgico, energia ultrassônica. Resultados: Dor no grupo sem dipirona 15 minutos e 24 horas apresentou decréscimo com correlação estatística significativa (p=0,004). Não houve significância estatística na redução da dor no grupo submetido à infusão de dipirona. Pacientes com cataratas de maior graduação apresentaram dor maior no pós-operatório (p=0,046). Conclusão: Ausência de redução significativa da dor com a dipirona apresentou resultados semelhantes a outros estudos. Redução da dor 24 horas após a cirurgia no grupo sem o analgésico pode ser devido à subjetividade da dor. Pacientes com cataratas de grau mais avançados apresentam dor mais intensa.

Abstract Objectives: Evaluate the effect of intraoperative endovenous administration of dipyrone on postoperative pain in patients submitted to phacoemulsification by correlating pain scores with duration of surgery and the amount of cumulative dissipated energy (CDE) delivered to the eye. Methods: The sample consisted of 104 eyes from 52 patients submitted to phacoemulsification under topic anesthesia and sedation. In each patient, one eye was treated intraoperatively with 1g dipyrone. Information was collected on cataract grade/type, duration of surgery and CDE. Postoperative pain was scored on a visual analog scale at 15 min and 24 hours. Results: Between 15 min and 24 hours, pain decreased significantly (p=0.004) among patients not treated with dipyrone, but no change was observed in patients receiving dipyrone. Caratact severity was positively associated with postoperative pain (p=0.046). Conclusion: The absence of a measurable effect of dipyrone on pain scores matched the literature. The decrease in pain scores at 24 hours among patients not treated with dipyrone may be explained by the influence of subjective psychological factors on pain perception. Higher grades of cataract were associated with greater postoperative pain.

Pethidine in low doses versus dipyrone for pain relief in labor: a randomized controlled trial / Petidina em doses baixas versus dipirona para alívio da dor no trabalho de parto: um ensaio clínico randomizado

Abstract Objective To compare low doses of pethidine with dipyrone in labor analgesia. Methods In a randomized prospective study conducted by Universidade de Fortaleza, in the state of Ceará, Brazil, between May and December 2016, 200 full-term parturients, with very painful uterine contractions and exhibiting uterine cervix dilatation ≥ 5 cm, were selected to receive a single intravenous dose of either 0.25 mg/kg of pethidine (n = 100) or of 25 mg/kg of dipyrone (n = 100). Pain was assessed using the visual analogue scale. The data were analyzed using the Student t-test, the chi-square test and the likelihood ratio. Results There was a significant improvement in pain in 35% of the parturients. Both drugs presented a similar analgesic effect 1 hour after the intervention (p = 0.692). There was no analgesic effect during the evaluation of the second hour after the intervention with pethidine or dipyrone. There were no adverse effects, such as maternal drowsiness, nausea or vomiting, related to the drugs used. Conclusion Pethidine in low doses and dipyrone presented equivalent analgesia during labor. Public Registry of Clinical TrialsRBR-4hsyy4.

Resumo Objetivo Comparar doses baixas de petidina com dipirona na analgesia de parto. Métodos Em um estudo prospectivo randomizado realizado pela Universidade de Fortaleza, Ceará, Brasil, entre maio e dezembro de 2016, 200 parturientes a termo, com contrações uterinas muito dolorosas e apresentando dilatação do colo uterino ≥ 5 cm, foram selecionadas para receber dose única intravenosa de 0,25 mg/kg de petidina (n = 100) ou 25 mg/kg de dipirona (n = 100). A dor foi avaliada pela escala visual analógica. Os dados foram analisados por meio dos testes t de Student, qui-quadrado e razão de verossimilhança. Resultados Houve melhora significativa da dor em 35% das parturientes. Ambas as drogas apresentaram efeito analgésico semelhante 1 hora após a intervenção (p = 0.692). Inexistiu efeito analgésico durante a avaliação da segunda hora após a intervenção com a petidina ou com a dipirona. Não houve efeitos adversos, como sonolência, náuseas ou vômitos maternos, relacionados aos medicamentos utilizados. Conclusão A petidina em doses baixas e a dipirona apresentaram analgesia equivalente durante o trabalho de parto. Registro público de testes clínicosRBR-4hsyy4.

Effects of dipyrone on the digestive tract

Dipyrone (metamizole), acting through its main metabolites 4-methyl-amino-antipyrine and 4-amino-antipyrine, has established analgesic, antipyretic, and spasmolytic pharmacological effects, which are mediated by poorly known mechanisms. In rats, intravenously administered dipyrone delays gastric emptying (GE) of liquids with the participation of capsaicin-sensitive afferent fibers. This effect seems to be mediated by norepinephrine originating from the sympathetic nervous system but not from the superior celiac-mesenteric ganglion complex, which activates β2-adrenoceptors. In rats, in contrast to nonselective non-hormonal anti-inflammatory drugs, dipyrone protects the gastric mucosa attenuating the development of gastric ulcers induced by a number of agents. Clinically, it has been demonstrated that dipyrone is effective in the control of colic-like abdominal pain originating from the biliary and intestinal tracts. Since studies in humans and animals have demonstrated the presence of β2-adrenoceptors in biliary tract smooth muscle and β2-adrenoceptor activation has been shown to occur in dipyrone-induced delayed GE, it is likely that this kind of receptors may participate in the reduction of smooth muscle spasm of the sphincter of Oddi induced by dipyrone. There is no evidence that dipyrone may interfere with small bowel and colon motility, and the clinical results of its therapeutic use in intestinal colic appear to be due to its analgesic effect.

Volume de dipirona para via oral versus tipo de conta-gotas, temperatura e ângulos de gotejamento / The volume of dipyrone for oral use versus dropper type, temperature and drip angles / Volumen de dipirona (metamizol) para vía oral versus tipo cuentagotas, temperatura y ángulo de goteo

Objetivo: determinar as diferenças entre volume e número de gotas de dipirona (via oral) por mililitro controlando algumas variáveis. Método: trata-se de um estudo experimental, com abordagem quantitativa, que foi realizado a partir de dados obtidos em experimentos realizados em laboratório, com dois tipos de conta-gotas, temperaturas de 5o e 35o Celsius, além da temperatura ambiente (30o Celsius), de laboratório e os ângulos de 90°, 60° e 45° utilizados para dispensar dipirona. Resultados: com base nos dados coletados, considerou-se que o ângulo de maior confiança para atingir o volume de 20 gotas por cada ml é o ângulo de 90o com o conta-gotas de vidro; em relação à temperatura, a maior confiança no volume de gotas desejado foi alcançada no intervalo de 5o e 30oCelsius. Conclusão: os resultados indicam a necessidade de seguir rigorosamente as orientações do fabricante para que se possa atingir a dose certa na administração de medicamento.

Objective: to determine the differences between volume and number of drops of dipyrone (oral) per milliliter, while controlling some variables. Method: this study applied quantitative analysis to data obtained in laboratory experiments with two types of droppers, temperatures of 5o and 35o Celsius, in addition to ambient temperature (30o Celsius), and the 90°, 60° and 45° angles used to dispense dipyrone. Results: based on the data collected, it was considered that, with the glass dropper, the angle of greatest confidence to achieve the volume of 20 drops per ml is 90o. In relation to temperature, the highest confidence in the desired volume of drops was achieved in the 5o to 30o Celsius interval. Conclusion: the results indicate the need to follow manufacturer's guidelines strictly, so as to achieve the correct dose for drug administration.

Objetivo: determinar las diferencias entre volumen y número de gotas de dipirona (vía oral) por mililitro controlando algunas variables. Método: se trata de un estudio experimental, con enfoque cuantitativo realizado con datos obtenidos en experimentos realizados en laboratorio, con dos tipos de cuentagotas, temperaturas de 5o y 35o Celsius, temperatura ambiente (30° Celsius) de laboratorio y los ángulos de 90°, 60° y 45° para gotear dipirona. Resultados: con base en los datos recolectados, se consideró que el ángulo de mayor confianza para alcanzar el volumen de 20 gotas por cada ml es el ángulo de 90o con el cuentagotas de vidrio. Respecto a la temperatura, la mayor confianza en el volumen de gotas deseado fue alcanzada en el intervalo de 5o y 30o Celsius. Conclusión: los resultados indican la necesidad de seguir rigurosamente las orientaciones del fabricante para alcanzar la dosis correcta en la administración de medicamentos.

Análisis de la incidencia de eventos adversos relacionados a aplicación de dipirona / Analysis of the incidence of adverse events related to the administration of dipyrone

Abstract Introduction: Notwithstanding the widespread use of dipyrone, its association with adverse events has reduced its clinical use, with Agranulocytosis being the most studied adverse event, and apparently of primary clinical impact. Studies in Latin America have disputed these claims. Objective: To analyze the incidence and reports of adverse events associated with the use of dipyrone in a high complexity hospital. Materials and methods: Descriptive observational study of an incident cohort. Population: Patients receiving dipyrone during their hospital stay. Quantitative analysis of incidents and description of dipyrone-associated adverse events. Results: Incidence of global adverse events=0.3% (in 48,946 doses of dipyrone prescribed to 2747 patients). No cases of Agranulocytosis. A total 100% non-severe adverse events. (All were associated with toxidermia). Conclusion: A low incidence of dipyrone-associated adverse events is reported. Optimal reporting of institutional adverse events is controversial, and the recommendation is to measure any adverse events with a more rigorous follow-up of patients using dipyrone, and a clear and specific standardization of the guidelines for improved prescription and medical control.

Resumen Introducción: A pesar del amplio espectro de uso de la dipirona, su asociación a eventos adversos ha reducido su empleo clínico, siendo la agranulocitosis el evento adverso más estudiado, y al parecer de mayor impacto clínico. Estudios en América Latina han controvertido dichas afirmaciones. Objetivo: Analizar la incidencia y reporte de eventos adversos asociados al uso de dipirona en un hospital de alta complejidad. Materiales y métodos: Estudio observacional descriptivo de una cohorte Incidente. Población: Pacientes usuarios de dipirona durante su estancia hospitalaria. Análisis cuantitativo de Incidencias, y descriptivo de los casos incidentes de adversos relacionados al uso de dipirona. Resultados: Incidencia de Eventos Adversos Globales=0,3% (En 48.496 dosis de dipirona formuladas en 2.747 pacientes). Ningún caso de Agranulocytosis. 100% de eventos adversos no severos (Todos asociados a reacción toxidérmica). Conclusiones: Se reporta una baja incidencia de eventos adversos relacionados al uso de dipirona. Se controvierte la óptima ejecución de los reportes de eventos adversos institucionales. Se sugiere la realización de la medición de eventos adversos posterior a un más riguroso seguimiento de los pacientes usuarios de este medicamento, y a una estandarización clara y puntual de pautas para una mejor prescripción y control médico luego de su formulación.

Dipyrone-related granulocytopenia. Case report / Granulocitopenia por dipirona: reporte de caso

Abstract Introduction: Dipyrone has been positioned in several countries as one of the first over-the-counter options for pain management. Its possible adverse effects are known worldwide; among them, agranulocytosis is the most lethal, with a mortality of approximately 10% and an associated risk of 1 per 1,000,000 patients. Clinical findings, interventions, and outcomes: A case of a patient who, after 23 days of using dipyrone for pain management, developed a progressive drop in leukocyte count. Other potential causes of the event were ruled out. After dipyrone discontinuation, leukocyte counts returned to their normal values. Conclusion: The probable diagnosis of granulocytopenia as a dipyrone-related adverse drug reaction was established. Although rare, dipyrone-related granulocytopenia, may occur in patients who use this medication for long periods.

Resumen Introducción: La dipirona se ha posicionado en varios países como una de las primeras opciones de venta libre al público para el manejo del dolor. Sus posibles efectos adversos son conocidos a nivel mundial; entre ellos, la agranulocitosis es la más letal con una mortalidad aproximada del 10% y un riesgo asociado de 1 por cada 1.000.000 pacientes. Hallazgos clínicos, intervención y resultados: Se presenta un caso de una paciente que luego de recibir 23 días seguidos dipirona para el manejo del dolor presentó disminución progresiva de los leucocitos documentados en el hemograma. Se descartaron otras posibles causas de dicho evento. Luego de suspender la administración de la dipirona los leucocitos volvieron a sus valores normales. Conclusión: Se estableció la sospecha de diagnóstico probable de granulocitopenia como reacción adversa medicamentosa por dipirona. La granulocitopenia por dipirona aunque poco frecuente, se puede presentar en pacientes que la reciben por largos periodos de tiempo.

Reacción de anafilaxia grave por dipirona sin antecedente de hipersensibilidad. Informe de caso / Severe anaphylaxis reaction from dipyrone without a history of hypersensitivity. Case report

Introduction: The safety of dipyrone has been the object of numerous debates, since severe allergic reactions to it can occur with an estimated incidence of 1 in 5000 parenteral administrations. Clinical findings: We report the case of one patient who, after an infusion with dipyrone, presented coughing, pharynx itch, dyspnea, generalized cyanosis, and decreased consciousness. The diagnosis of anaphylactic shock without a history of hypersensitivity to the medication was made, and despite treatment with orotracheal intubation, adrenaline, hydrocortisone, sodium chloride, and sodium bicarbonate, it was fatal for the patient. Conclusion: Cases of severe hypersensitivity without antecedents can be present in patients, which makes it important to recognize this risk in our patients.

Introducción: La seguridad de la dipirona ha sido objeto de numerosos debates, ya que pueden aparecer reacciones alérgicas graves cuya incidencia estimada es de 1 en 5.000 administraciones parenterales. Hallazgos clínicos: Se reporta un caso de una paciente que luego de una infusión con dipirona presenta tos, prurito faríngeo, disnea, cianosis generalizada y deterioro del estado de conciencia. Se hizo el diagnóstico de shock anafiláctico sin antecedentes previos de hipersensibilidad al medicamento, que a pesar del tratamiento con intubación orotraqueal, adrenalina, hidrocortisona, cloruro de sodio, y bicarbonato de sodio, resultó fatal. Conclusión: pueden presentarse casos de grave hipersensibilidad en pacientes sin antecedentes de ésta, lo que hace importante reconocer este riesgo en nuestros pacientes.

Dipyrone in association with atropine inhibits the effect on gastric emptying induced by hypoglycemia in rats

Atropine (AT) and dipyrone (Dp) induce a delay of gastric emptying (GE) of liquids in rats by inhibiting muscarinic receptors and activating β2-adrenergic receptors, respectively. The objective of the present study was to determine the effects of pretreatment with AT and Dp, given alone or in combination, on the effect of hypoglycemia in the liquid GE in rats. Male Wistar adult rats (280-310 g) were pretreated intravenously with AT, Dp, AT plus Dp or their vehicle and then treated 30 min later with iv insulin or its vehicle (n=8-10 animals/group). Thirty min after treatment, GE was evaluated by determining, in awake rats, the percent gastric retention (%GR) of a saline meal labeled with phenol red administered by gavage. The results indicated that insulin induced hypoglycemia in a dose-dependent manner resulting in a significant reduction in %GR of liquid only at the highest dose tested (1 U/kg). Pretreatment with AT significantly increased %GR in the rats treated with 1 U/kg insulin. Surprisingly, after pretreatment with AT, the group treated with the lowest dose of insulin (0.25 U/kg) displayed significantly lower %GR compared to its control (vehicle-treated group), which was not seen in the non-pretreated animals. Pretreatment with Dp alone at the dose of 40 mg/kg induced an increase in %GR in both vehicle and 0.25 U/kg-treated rats. A higher dose of Dp alone (80 mg/kg) significantly reduced the effect of a marked hypoglycemia induced by 1 U/kg of insulin on GE while in combination with AT the effect was completely abolished. The results with AT suggest that moderate hypoglycemia may render the inhibitory mechanisms of GE ineffective while Dp alone and in combination with AT significantly overcame the effect of hypoglycemia on GE.

Mortalidad en pacientes menores de edad con diagnóstico de dengue y su relación con el uso de Dipirona / Mortality in minor patients with diagnosis of dengue and its relationship with the use of Dipirone

Introducción: El dengue es una de las diez causas de hospitalización más frecuentes en los servicios de urgencias de pediatría, en la atención sintomática se utiliza la Dipirona como antipirético, la guía clínica de manejo del dengue de la Organización Panamericana de la Salud (OPS) evidencia restricciones para su uso en pacientes con dengue y según la Guía de Atención Clínica Integral del paciente con dengue, no se debe administrar en pacientes pediátricos. Objetivo: Determinar la relación de la Dipirona con casos de mortalidad en menores de 16 años con dengue en el Meta. Materiales y métodos: Se realizó un estudio de casos y controles basado en la mortalidad por dengue en menores de edad reportados al Sistema de Vigilancia en Salud Pública del departamento del Meta, años 2008 a 2011. Resultados: La razón de las ventajas (OR) evidencia que la mortalidad por dengue es 17,6 veces mayor en menores de edad que recibieron Dipirona con un intervalo de confianza de 95% entre 3,7-84,5 y un valor de P de 0,0002. Conclusión: El grupo de casos que recibió Dipirona en su tratamiento presentó una mayor mortalidad, la revisión de literatura no evidencia resultados sobre la relación de la Dipirona y mortalidad en niños con dengue, se debe seguir estudiando el fenómeno para contar con mayor evidencia científica.

Introduction: Dengue is one of the ten most frequent causes of hospitalization in the emergency department of pediatrics where Dipyrone is used as an antipyretic in the symptomatic care. The clinical management guide for dengue of the Panamerican Health Organization (PHO) evidences restrictions for its use in patients with dengue, and according to the Integral Clinical Care Guide for patients with dengue, it should not be administered in pediatric patients. Objective: To determine the relationship between the uses of Dipyrone with the cases of mortality in children under 16 who suffered from dengue in Meta. Materials and methods: A case-control study was conducted based on mortality from dengue in minors reported to the Surveillance System in Public Health in the department of Meta, from 2008 to 2011. Results: The odds ratio (OR) shows that dengue mortality is 17.6 times greater in children Dipyrone treated with a confidence interval of 95% between 3.7 to 84.5 and a P value of 0.0002. Conclusion: The case group who received Dipyrone in their treatment had a higher mortality. There is no evidence or results in the literature review about the relationship of Dipyrone and mortality in children with dengue. This phenomenon should continue to be studied to have greater scientific evidence.

Effect of selective beta-adrenoceptor blockade and surgical resection of the celiac-superior mesenteric ganglion complex on delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine, and antipyrine in rats

There is evidence for participation of peripheral β-adrenoceptors in delayed liquid gastric emptying (GE) induced in rats by dipyrone (Dp), 4-aminoantipyrine (AA), and antipyrine (At). The present study aimed to determine whether β-adrenoceptors are involved in delayed GE induced by phenylpyrazole derivatives and the role of the prevertebral sympathetic nervous system in this condition. Male Wistar rats weighing 220-280 g were used in the study. In the first experiment rats were intravenously pretreated with vehicle (V), atenolol 30 mg/kg (ATE, β1-adrenergic antagonist), or butoxamine 25 mg/kg (BUT, β2-adrenergic antagonist). In the second experiment, rats were pretreated with V or SR59230A 2 mg/kg (SRA, β3-adrenergic antagonist). In the third experiment, rats were subjected to surgical resection of the celiac-superior mesenteric ganglion complex or to sham surgery. The groups were intravenously treated with saline (S), 240 µmol/kg Dp, AA, or At, 15 min after pretreatment with the antagonists or V and nine days after surgery. GE was determined 10 min later by measuring the percentage of gastric retention (%GR) of saline labeled with phenol red 10 min after gavage. The %GR (means±SE, n=6) values indicated that BUT abolished the effect of Dp (BUT+Dp vs V+Dp: 35.0%±5.1% vs 56.4%±2.7%) and At (BUT+At vs V+At: 33.5%±4.7% vs 52.9%±2.6%) on GE, and significantly reduced (P<0.05) the effect of AA (BUT+AA vs V+AA: 48.0%±5.0% vs 65.2%±3.8%). ATE, SRA, and sympathectomy did not modify the effects of treatments. These results suggest that β2-adrenoceptor activation occurred in delayed liquid gastric emptying induced by the phenylpyrazole derivatives dipyrone, 4-aminoantipyrine, and antipyrine. Additionally, the released neurotransmitter did not originate in the celiac-superior mesenteric ganglion complex.

Avaliação da Função Renal e Alterações Morfológicas em Ratos Tratados com Dipirona em Diferentes Doses / Evaluation of Renal Function and Morphological Changes in rats Treated with Dipyrone in Different Dosing

A dipirona é um fármaco muito utilizado para o tratamento da febre e da dor, entretanto, seus efeitos em doses altas podem levar a danosirreversíveis e até letais. Na presente investigação foram utilizados 32 ratos albinos machos da linhagem Wistar. Um grupo (1) recebeu uma dose única, 5.000 mg/Kg de dipirona por gavagem e o outro grupo (2) administração uma vez ao dia, por quatro dias consecutivos, de 600mg/Kg de dipirona. Ao final de quatro dias, para o grupo 2 e após 3 horas de ingestão do medicamento para o grupo 1, os animais foram eutanasiados em câmara de CO2, conforme a aprovação do Comitê de Ética Animal do Centro Universitário Barão de Mauá (CEPAn). Foram avaliados os parâmetros ureia e creatinina e a histopatologia renal. Os resultados dos escores hemorragia glomerular, congestão renal e processo inflamatório foram estatisticamente significativos nos três parâmetros analisados para dose única; congestão renal e processo inflamatório para dose múltipla. O marcador de função renal, ureia apresentou diferença estatística significativa com a dose única. Os resultados do modelo experimental atestam que a metodologia aplicada foi capaz de demonstrar as alterações histopatológicas do grupo tratado com dipirona dose única assim como alterações na dosagem de ureia e a preservação das características normais do grupo controle. O mesmo não ocorreu com o grupo tratado com doses múltiplas.

Dipyrone is a drug widely used for the treatment of fever and pain, but their effects at high doses can lead to irreversible and even lethal damages.In the present study it was used 32 male albino rats of Wistar strain. First group received a single dose 5.000 mg/kg by gavage dipyrone and the second given once daily for four consecutive days of 600 mg/kg Dipyrone. At the end of four days, for group 2 and 3 hours after ingestion of the drug for group 1, the animals were euthanized in a CO2 chamber, as the approval of the Baron of Maua University Center (Cepan) Animal Ethics Committee. The urea and creatinine parameters and renal histopathology were evaluated. The results of the scores glomerular bleeding, renal congestion and inflammation were statistically significant in all parameters analyzed for single dose; renal congestion and inflammation to multiple dose. The marker of renal function, urea statistically significant difference with the single dose. The results of the experimental model show that the methodology was able to demonstrate the histopathological changes in the group treated with single dose dipyrone as well as changes in the levels of urea and the preservation of the normal characteristics of the control group. This did not occur with the group treated with multiple doses.

Perfil de uso y rango de dosis de analgésicos en un hospital de cuarto nivel en Bogotá / Profile of use and dose range of painkillers on a fourth-level hospital in Bogotá

Introducción: El dolor es uno de los síntomas más frecuentes e importantesen el paciente hospitalizado, con una frecuencia hasta de 76.9 porciento. El adecuado control del mismo es uno de los objetivos terapéuticos más buscados. Para lograr este objetivo, frecuentemente suelen usarse dosis inadecuadas de analgésicos, lo cual ocasiona reacciones adversas en los pacientes. El objetivo de este trabajo fue identificar los analgésicos de mayor uso en el paciente adulto hospitalizado y el rango de dosis de los mismos en un hospital de cuarto nivel de la ciudad de Bogotá. Métodos: Estudio observacional descriptivo de corte transversal en pacientes hospitalizados mayores de 18 años, con prescripción de analgésicos; seleccionados por muestreo aleatorio estratificado según servicio, entre julio a diciembre de 2013. Se evaluaron los analgésicos y las dosis prescritas, comparándolas con las dosis diarias máximas descritas para cada uno. El análisis de las variables sociodemográficas y farmacológicos serealizó con STATA 12. Resultados: Se evaluaron 355 historias clínicas depacientes, encontrando 555 prescripciones de analgésicos. Los más usados fueron acetaminofén en 186 casos (33,5 porciento) y tramadol en 167 (30,1 porciento). El uso de tramadol y acetaminofén se encontró en un rango de dosis adecuado en el 99,4 porciento y 90,9 porciento respectivamente. Los otros opiáceos utilizdos diferentes a tramadol, se encontraron en el rango de dósis según indica la literatura.Conclusiones: Los analgésicos más utilizados en el paciente hospitalizado pertenecen al escalón I y II de la escala del manejodel dolor de la OMS, siendo los más frecuentes acetaminofén y tramadol. Eluso de antiinflamatorios no esteroideos fue escaso, siendo el más relevanteentre estos, diclofenaco. Las dosis utilizadas de analgésicos en general fueron adecuadas, pero para dipirona se observó sobredosificación muy frecuente.Elanalgésico para el cual hay un mayor porcentaje de casos de subdosificación fue butilbromuro de hioscina.

Introduction: Pain is one of the most common and important symptomsinpatients, with a frequency of up to 76.9%. Proper control of the same is oneof the most sought therapeutic targets. To achieve this goal, often inadequatedoses of analgesics used, which causes adverse reactions in patients. The aim ofthis study was to identify the most widely used analgesics adult inpatient and thedose range of them at a hospital in fourth level of Bogota. Methods: Descriptiveobservational cross-sectional study inpatients over 18 years with prescriptionpainkillers, selected by stratified random sampling according to service, fromJuly to December 2013. Painkillers and prescribed doses were evaluated andcompared with the maximum daily doses described for each one. The analysisof the sociodemographic and pharmacological variables was performed usingSTATA 12, Results: Medical records of 355 patients were evaluated, finding555 prescription painkillers. The most used were acetaminophen in 186 cases(33.5%) and tramadol 167 (30.1%). The use of tramadol and acetaminophenwas found an appropriate range of doses in 99.4% and 90.9% respectively. Twocases with 4 prescription painkillers and a case with 5 concurrent analgesicswere found. Conclusions: The most commonly used in hospitalized patientsanalgesics belonging to stage I and II of the scale of pain management WHO,being the two main acetaminophen and tramadol. The use of NSAIDs wasrare, the most important among these, diclofenac. Analgesic doses used weregenerally adequate, but dipyrone overdosing very frequently observed. Theanalgesic for which there is a higher percentage of cases of underdosing washyoscine butylbromide.