Drug-related problems in cardiac neonates under intensive care / Problemas relacionados a medicamentos em neonatos cardiopatas sob terapia intensiva

ABSTRACT Objective: To determine the frequency and nature of the Drug Related Problems (DRP) in neonates with cardiac diseases admitted to an Intensive Care Unit. Methods: This prospective cross-sectional study was developed at the Neonatal Intensive Care Unit (NICU) of a teaching maternity hospital in Brazil from January 2014 to December 2016. All neonates diagnosed with any heart disease (congenital heart disease, cardiomyopathy, arrhythmias, etc.) and who were admitted to the NICU for more than 24 hours with at least one prescribed drug were included in the study. Demographic and clinical data were collected from the records of the institution's clinical pharmacy service. DRP and their respective interventions were independently reviewed and classified by two pharmacists. DRP classification was performed through the Pharmaceutical Care Network Europe v6.2 system. Results: 122 neonates were included in the study. The frequency of neonates exposed to DRP was 76.4% (confidence interval of 95% [95%CI] 65.9-82.0), with a mean of 3.2±3.8 cases/patient. In total, 390 DRP were identified, of which 49.0% were related to "treatment effectiveness", 46.7% to "adverse reactions" and 1.0% to "treatment costs". The medicines most involved in DRP were Vancomycin (10.2%; n=46), Meropenem (8.0%; n=36) and Furosemide (7.1%; n=32). Pharmacists performed 331 interventions, of which 92.1% were accepted by physicians and nurses. Conclusions: The study showed that DRP are very frequent in patients with cardiac diseases hospitalized in the NICU, predominating problems related to the effectiveness and safety of the drug treatment.

RESUMO Objetivo: Determinar a frequência e a natureza dos problemas relacionados a medicamentos (PRMs) em neonatos cardiopatas internados em uma unidade de terapia intensiva. Métodos: Trata-se de um estudo transversal prospectivo desenvolvido na Unidade de Terapia Intensiva Neonatal (UTIN) de uma maternidade de ensino do Brasil, de janeiro de 2014 a dezembro de 2016. Todos os neonatos diagnosticados com alguma doença cardíaca (cardiopatias congênitas, cardiomiopatias, arritmias etc.) e internados na UTIN por período superior a 24 horas, com pelo menos um medicamento prescrito, foram incluídos no estudo. Dados demográficos e clínicos foram coletados a partir dos registros do serviço de farmácia clínica da instituição. Os PRMs e suas respectivas intervenções foram revisadas e classificadas independentemente por dois farmacêuticos. A classificação dos PRMs foi realizada por meio do sistema Pharmaceutical Care Network Europe versão 6.2. Resultados: Cento e vinte e dois neonatos foram incluídos no estudo. A frequência de neonatos expostos a PRM foi de 76,4% (intervalo de confiança de 95% [IC95%] 65,9-82,0), com média de 3,2±3,8 casos por paciente. Ao todo, 390 PRM foram identificados, sendo que 49,0% estiveram relacionados à "efetividade do tratamento", 46,7% a "reações adversas" e 1,0% a "custos do tratamento". Os medicamentos mais envolvidos em PRM foram: vancomicina (10,2%; n=46), meropenem (8,0%; n=36) e furosemida (7,1%; n=32). Os farmacêuticos realizaram 331 intervenções, sendo 92,1% aceitas por médicos e enfermeiros. Conclusões: O estudo mostrou que PRMs são muito frequentes em pacientes cardiopatas internados em UTIN, predominando problemas relacionados à efetividade e segurança do tratamento medicamentoso.

Uso inapropiado de diuréticos: Algunas características no tan conocidas / Diuretic misuse: Some not so well known characteristics

Entre las situaciones asociadas al uso inapropiado de diuréticos se encuentran los intentos por descencer rápidamente de peso, comunes en los desordenes de la alimentación, y los intentos por enmascarar el consumo de otras sustancias, en el caso de las competencias deportivas. El uso sin indicación ni supervisión médica de estos fármacos genera un desbalance electrolítico, que puede manifestarse con hiponatremia, hipocalemia, hipocalcemia e hipomagnesemia, hipercalemia, entre otras alteraciones. El objetivo de este trabajo fue investigar las caracteríscas del uso inapropiado de diuréticos a partir de la casuística del CENATOXA. Se realizó un estudio descriptivo restrospectivo sobre los análisis ingresados al CENATOXA con solicitud de investigación cualitativa de diuréticos en orina, entre los años 2002 y 2016. En dicho período ingresaron al CENATOXA 138 casos, de los cuales el 56 % resultó positivo para algún diurético. Del total de casos con resultado positivo, el 93,5 % fueron mujeres entre 25 y 55 años de edad y predominó la etiología intencional. Los diuréticos mayoritariamente encontrados fueron hidroclorotiazida y furosemida. El perfil de diuréticos hasta el año 2008 (hidroclorotiazida = 68% de los casos positivos) se diferenció del hallado entre 2009 y 2016 (furosemida + hidroclorotiazida = 60% de los casos positivos). Se observó recurrencia en el uso inapropiado en el 8% de los casos. El uso simultáneo de más de un diurético y la recurrencia son factores que pueden contribuir a la aparición de toxicidad. Estos resultados sugieren que el uso inapropiado de diuréticos es una situación que debería ser ob­servada más atentamente para establecer mejor su alcance y sus riesgos.

Among the situations associated with diuretics misuse are the attempts to lose weight fast, frequently observed in eating disorders, and the attempts to mask the consumption of other substances, in the case of sports competitions. The use of these drugs with no medical indication or supervision generates an electrolyte imbalance, leading to hyponatremia, hypokalemia, hypocalcemia and hypomagnesemia, hyperkalemia, among other alterations. The objective of this work was to investigate the characteristics of diuretics misuse from the CENATOXA database, where the qualitative investigation of diuretics in urine is per­formed. A descriptive retrospective study was conducted on the cases admitted to the CENATOXA with a request for qualitative diuretic investigation, between 2002 and 2016. During this period, 138 urine samples were received at the CENATOXA and 56% were positive for at least one diuretic. Of all cases with positive results, 93.5% were women between 25 and 55 years of age, and intentional etiology predominated. The most detected diuretics were hydrochlorothiazide and furosemide. The diuretic misuse pattern detected up to 2008 (hydrochlorothiazide = 68% of positive cases) differed from that detected between 2009 and 2016 (furosemide + hydrochlorothiazide = 60% of positive cases). Recurrence in misuse was observed in 8% of the cases. The simul­taneous misuse of more than one diuretic and the recurrence are factors that can contribute to the onset of toxicity. These results suggest that diuretic misuse is a situation that should be observed more closely to better assess its consequences and its risks.

Furosemida en el control de la hipertensión arterial posparto en preeclámpticas severas / Furosemide in the control of postpartum hypertension in severe preeclamptic women

RESUMEN OBJETIVO: Establecer la utilidad de la furosemida en el control de la hipertensión arterial posparto en preeclámpticas severa. MÉTODOS: Se realizó un estudio de casos y controles en el Hospital Central "Dr. Urquinaona", Maracaibo, Venezuela. Se incluyeron pacientes con preeclampsia severa, las cuales durante el posparto fueron asignadas al azar para ser tratadas con furosemida, alfametildopa y cloruro de potasio oral (grupo A) o alfa-metildopa oral (grupo B) por 48 horas. Los parámetros evaluados fueron: variaciones en los valores de presión arterial y frecuencia cardiaca, persistencia de hipertensión, parámetros de laboratorio y efectos adversos. RESULTADOS: Para el análisis final estaban disponibles los datos de 198 pacientes en el grupo A y 197 pacientes en el grupo B en cada uno de los grupos. Luego de 48 horas de tratamiento se observaron disminuciones estadísticamente significativas en los valores de presión arterial sistólica y diastólica entre las pacientes tratadas con furosemida y las pacientes del grupo control (p < 0,0001). Se observó persistencia de la hipertensión en 52 pacientes (26,3 %) del grupo A y en 134 pacientes (68,0 %) del grupo B (p < 0,0001). No se encontraron diferencias entre los grupos en la frecuencia cardiaca, valores de laboratorio y efectos adversos (p = ns). CONCLUSIÓN: La furosemida produce disminuciones significativas en los valores promedios de presión arterial sistólica y diastólica, al igual que en la frecuencia de persistencia de hipertensión postparto en preeclámpticas severas.

ABSTRACT OBJECTIVE: To establish the utility of furosemide in the control of postpartum blood pressure in severe preeclamptic patients. METHODS: A case-control study was conducted at the Central Hospital "Dr. Urquinaona", Maracaibo, Venezuela. Patients diagnosed with severe preeclampsia were included, who during the postpartum period were randomized to be treated with furosemide, alpha-methyldopa and oral potassium chloride (group A) or oral alpha-methyldopa (group B) for 48 hours. The parameters evaluated were: variations in blood pressure and heart rate values, the persistence of hypertension, laboratory parameters and adverse effects related to treatment. RESULTS: Data of 198 patients in group A and 197 patients in group B in each of the groups were available for the final analysis. After 48 hours of treatment, statistical significant decreases were observed in the values of systolic and diastolic blood pressure between patients treated with furosemide and patients in the control group (p <0.0001). Persistence of hypertension was observed in 52 patients (26.3 %) of group A and in 134 patients (68.0 %) of group B (p < 0.0001). No differences were found between the groups in heart rate, laboratory values and adverse effects (p = ns). CONCLUSION: Furosemide produces significant decreases in the mean values of systolic and diastolic blood pressure, as well as in the frequency of persistence of postpartum hypertension in severe preeclamptic patients.

Furosemide-induced pseudoporphyria in a patient with chronic kidney disease: case report / Pseudoporfiria induzida por furosemida em paciente com doença renal crônica: relato de caso

ABSTRACT Introduction: Pseudoporphyria is a rare photodermatosis with characteristics similar to those of porphyria cutanea tarda, without, however, presenting abnormalities in porphyrin metabolism. Its etiology is related to chronic kidney disease, ultraviolet radiation and certain medications. The aim of the present study is to describe a case of furosemide-related pseudoporphyria in a patient with chronic kidney disease. Case description: A 76-year-old male patient with stage 4 chronic kidney disease and in continuous use of furosemide presented ulcerated lesions with peripheral erythema and central hematic crust in the legs. On a skin infection suspicion, treatment with quinolone and neomycin sulfate was initiated, without improvement. A biopsy of the lesion was performed, with histopathological examination demonstrating findings compatible with porphyria, although the patient did not present high porphyrin levels. The diagnosis of furosemide-induced pseudoporphyria was then established, with medication suspension, and there was a significant improvement of the lesions. Discussion: There are few cases of pseudoporphyria described, but it is believed that this condition is underdiagnosed, especially in patients with chronic kidney disease. Both clinical and histopathological findings closely resemble porphyria, differentiating it from normal levels of porphyrin in plasma, urine, or feces. Conclusions: Although the lesions are mostly benign, they may increase the morbidity and mortality of these patients, so a proper diagnosis and early treatment are extremely important.

RESUMO Introdução: A pseudoporfiria é uma fotodermatose rara com características semelhantes às da porfiria cutânea tardia, sem, no entanto, apresentar anormalidades no metabolismo da porfirina. Sua etiologia está relacionada a doença renal crônica, radiação ultravioleta e determinados medicamentos. O objetivo do presente trabalho é descrever um caso de pseudoporfiria relacionada a furosemida em paciente portador de doença renal crônica. Descrição do caso: Paciente masculino, 76 anos, com doença renal crônica estágio 4 e em uso contínuo de furosemida, apresentou lesões ulceradas com eritema periférico e crosta hemática central nas pernas. Por suspeita de infecção de pele, foi iniciado tratamento com quinolona e sulfato de neomicina, sem melhora. Foi realizada então biópsia da lesão, com exame histopatológico demonstrando achados compatíveis com porfiria, sem, no entanto, o paciente apresentar níveis elevados de porfirinas. Foi então estabelecido o diagnóstico de pseudoporfiria induzida por furosemida, com suspensão de medicação , e houve melhora significativa das lesões. Discussão: Há poucos casos de pseudoporfiria descritos, mas acredita-se que essa condição seja subdiagnosticada, principalmente em pacientes com doença renal crônica. Tanto achados clínicos quanto histopatológicos se assemelham muito à porfiria, diferenciando desta por níveis normais de porfirina no plasma, na urina ou nas fezes. Conclusões: Embora as lesões sejam majoritariamente benignas, podem aumentar a morbimortalidade desses pacientes, por isso um diagnóstico adequado e tratamento precoce são de extrema importância.

Vasculitis leucocitoclástica cutánea por posible hipersensibilidad a medicamento de uso crónico en el marco de una infección por virus de la hepatitis C / Leukocytoclastic cutaneous vasculitis due to possible hypersensitivity to cronic drug use in connection with an infection of hepatitis C virus

INTRODUCCIÓN: La Vasculitis leucocitoclástica cutánea (VLC) es una inflamación vascular, habitualmente de vénulas post-capilares. Posee baja incidencia. El signo más frecuente es púrpura palpable (PP). Puede ser primario, o secundario a infecciones, enfermedades sistémicas o fármacos. LaVLC por fármacos es un trastorno poco definido y difícilmente demostrable, la evidencia actual sugiere como criterio principal: asociación temporal fármaco-lesión. PRESENTACIÓN DE CASO CLÍNICO: Mujer, 60 años, antecedentes de Hipertensión Arterial (HTA) en tratamiento, alérgica a Enalapril,Metamizol, y Atenolol, ex-consumidora de anfetaminas, acudió a Urgencias Hospital Las Higueras (HLH), por cuadro de una semana de evolución de lesiones purpúricas, solevantadas, no pruriginosas, ubicadas desde tercio inferior del muslo al pie en extremidades inferiores (EEII), dolorosas EVA 9/10, atenuado con el frío. Lesiones evolucionaron a necrosis durante estadía intrahospitalaria. EcoDoppler descartó trombosis venosa profunda. Función hepática normal. Serología destacó Virus Hepatitis C (VHC) positivo confirmado por Instituto de Salud pública (ISP). Biopsia confirma VLC. Nuevo antecedente reveló inicio reciente de tratamiento con Furosemida; paciente suspendió medicamento. Egresó tras 29 días hospitalizada con dolor leve y lesiones de EEII en regresión. DISCUSIÓN:VLC es una entidad clínico-patológica de difícil abordaje, muchos casos resultan de etiología desconocida aun después de una detallada historia clínica. Es discutible si este caso de VLC se desencadenó por VHC o Furosemida, muchos casos son provocados por hipersensibilidad a medicamentos sumado a infección subyacente. Si bien la Furosemida, medicamento de alta prescripción en patologías GES, ha demostrado ser seguro, es necesaria la administración cuidadosa en pacientes con antecedentes de hipersensibilidad

INTRODUCTION: Leukocytoclastic cutaneous vasculitis (LCV) is a vascular inflamation, usually of post-capillary veins. It has low incidence. The most common sign is palpable purpura. It can be primary or secondary to infections, systemic diseases or drugs. Drug-induced LCV is poorly defined and a difficult to prove disorder. Current evidence suggests as the main criteria: drug-injury temporal association. CASE-REPORT: Female, 60 years old, history of arterial hypertension (AHT) in treatment; allergic to Enalapril, (Metamizol) Dipyrone, and Atenolol; former consumer of amphetamines. Attended to Hospital Las Higueras (HLH) Emergency on 04.18.2014, due to nonpruritic up thrust purpuric lesions, painful EVA 9/10 and attenuated with cold, located from the lower third of the thigh to the foot in lower limbs, one week of evolution. Lesions evolved to necrosis during hospital stay. Doppler ultrasound ruled out deep vein thrombosis. Normal liver function. Serology shows positive HCV confirmed later by IPH. Dermatological biopsy confirms LCV. New data reveals recent onset of treatment with Furosemida; patient stopped taking medication. Patient was discharged after 29 days in hospital with mild pain and lesions in lower limbs in regression. DISCUSION: LCV is a clinicopathological entity of difficult approach. A large number of cases are of unknown etiology entity even after a detailed medical history. It is debatable whether this event was triggered by HCV or Furosemide, because many cases are caused by drug hypersensitivity coupled with an underlying infection. Though furosemide, high prescription drug in GES pathologies, has been proven safe, careful administration in patients with known hypersensitivity is necessary

Recurrent aborted sudden cardiac death with seizures and rhabdomyolysis due to bulimia-induced hypokalemia: Report of one case / Muerte súbita abortada recurrente con convulsiones y rabdomiolisis causada por hipokalemia: Informe de una paciente con bulimia

Recurrent vomiting due to bulimia associated with abuse of furosemide and laxatives causing severe hypokalemia may result in recurrent aborted sudden cardiac death (SCD) and seizures. We report a 25-year-old female with a history of bulimia associated with abuse of furosemide and laxatives since the age of 15 years, migraine since puberty, renal abscesses at age 20 y, and rhabdomyolysis of unknown cause at age 24 y. She experienced aborted SCD due to severe hypokalemia with symptomatic seizures at 21 and 25 years of age. Bulimia patients additionally taking laxatives or furosemide are at particular risk of SCD and rhabdomyolysis and require periodic determination of electrolytes, potassium substitution, and adequate psychiatric therapy and surveillance.

Los vómitos recurrentes debidos a bulimia, asociados a abuso de furosemida y laxantes que causan hipokalemia severa, pueden llevar a muerte súbita abortada y convulsiones. Informamos una mujer de 25 años con una historia de bulimia asociada a abuso de furosemida y laxantes desde los 15 años, migrañas desde la pubertad, abscesos renales a los 20 años y rabdomiolisis de causa desconocida a los 24 años. La paciente tuvo dos episodios de muerte súbita abortada con convulsiones a los 21 y 25 años, debido a hipokalemia severa. Los pacientes con bulimia y abuso de furosemida y laxantes tienen un riesgo mayor de tener muerte súbita y rabdomiolisis, requieren de controles periódicos de electrolitos y tratamiento psiquiátrico.

Furosemida e risco de lesão renal aguda em pacientes com insuficiência cardíaca descompensada / Furosemide and risk of acute renal injury in decompensated heart failure patients

JUSTIFICATIVA E OBJETIVOS: Diuréticos têm sido importantes no tratamento da insuficiência cardíaca (IC). Os objetivos deste estudo foram estimar a incidência e os fatores preditores de lesão renal aguda (LRA) em portadores de IC descompensada tratados com diuréticos.MÉTODO: Estudo prospectivo com 66 portadores de IC descompensada em uso de diuréticos seguidos por um período de 30 dias. LRA foi definida como elevação da creatinina sérica 50% superior à creatinina da admissão. RESULTADOS: A incidência de LRA foi de 39,4%. Preditores de desenvolvimento de LRA encontrados foram: diagnóstico de IC classe funcional IV, OR = 3,15; IC a 95%: 1,12 - 8,82; dose de furosemida por via venosa, OR = 1,07; IC a 95%: 1,02 - 1,12 e a interação classe funcional IV e dose de furosemida venosa,OR = 1,03; IC a 95%: 1,01 - 1,04. O preditor independente de LRA foi dose de furosemida venosa (OR = 1,09; IC a 95%: 1,01- 1,17). Dose de furosemida venosa total se correlacionou com a creatinina máxima do internamento (rho = 0,69; p < 0,01). O tempo de uso de furosemida venosa apresentou correlação com a creatinina máxima da internação (rho = 0,73; p < 0,01).CONCLUSÃO: A incidência de LRA encontrada foi de 39,4%.Pertencer à classe IV de IC e dose de furosemida venosa associou-se a LRA. Dose de furosemida venosa foi preditora independente para desenvolvimento de LRA, com forte correlação com a creatinina máxima durante a internação, bem como o seu tempo de uso em dias.

BACKGROUND AND OBJECTIVES: Diuretics have been important in the treatment of heart failure (HF). The aims of this study are to estimate the incidence and predictors of acute kidney injury (AKI) in patients with decompensated heart failure treated with diuretics.METHOD: A prospective study of 66 patients with decompensated HF on diuretic therapy followed by a period of 30 days. AKI has been defined as an increase in serum creatinine over 50% compared to the basal serum creatinine. RESULTS: The incidence of AKI was 39.4%. Predictors of AKI were: diagnosis of HF class IV, OR = 3.15, 95% CI: 1.12 to 8.82, dose of intravenous furosemide, OR = 1.07, CI 95%: 1.02 to 1.12 and interaction HF class IV/ dose of intravenous furosemide, OR = 1.03, 95% CI: 1.01 to 1.04. Dose of intravenous furosemide was the only independent predictor of AKI inmultivariate analysis (OR = 1.09, 95% CI: 1.01 - 1.17). Total intravenous dose of furosemide had correlated with maximum creatinine during follow-up (rho = 0.69, p < 0.01). The time ofuse of intravenous furosemide had correlated with the maximum serum creatinine during hospitalization (rho = 0.73, p < 0.01).CONCLUSION: The incidence of AKI was 39.4%. Class IV HF and dose of intravenous furosemide were associated with AKI. Dose of intravenous furosemide was independent predictor for AKI. Total dose of furosemide and time counted in days of furosemide use had a strong correlation with maximum serum creatinine during hospitalization.

Furosemide is associated with acute kidney injury in critically ill patients

Acute kidney injury (AKI) is common in critically ill patients. Diuretics are used without any evidence demonstrating a beneficial effect on renal function. The objective of the present study is to determine the incidence of AKI in an intensive care unit (ICU) and if there is an association between the use of furosemide and the development of AKI. The study involved a hospital cohort in which 344 patients were consecutively enrolled from January 2010 to January 2011. A total of 132 patients (75 females and 57 males, average age 64 years) remained for analysis. Most exclusions were related to ICU discharge in the first 24 h. Laboratory, sociodemographic and clinical data were collected until the development of AKI, medical discharge or patient death. The incidence of AKI was 55% (95%CI = 46-64). The predictors of AKI found by univariate analysis were septic shock: OR = 3.12, 95%CI = 1.36-7.14; use of furosemide: OR = 3.27, 95%CI = 1.57-6.80, and age: OR = 1.02 (95%CI = 1.00-1.04). Analysis of the subgroup of patients with septic shock showed that the odds ratio of furosemide was 5.5 (95%CI = 1.16-26.02) for development of AKI. Age, use of furosemide, and septic shock were predictors of AKI in critically ill patients. Use of furosemide in the subgroup of patients with sepsis/septic shock increased (68.4%) the chance of development of AKI when compared to the sample as a whole (43.9%).

Stability of furosemide and aminophylline in parenteral solutions / Estabilidade de furosemida e aminofilina em soluções parenterais

Parenteral solutions (PS) are one of the most commonly used drug delivery vehicles. Interactions among the drug, components in the drug's formulation, and the PS can result in the formation of inactive complexes that limit efficacy or increase side effects. The aim of this work was to evaluate possible interactions between the drugs and PS, assess drug stability and to identify degradation products after 20 h at room temperature. Furosemide (FSM) and Aminophylline (APN) were added to PS containing either 20 percent mannitol or 0.9 percent NaCl at pH 6.5-7.5 and 10-11. Their behavior was studied individually and as an admixture, after 1 h oxidation with H2O2, using a spectrophotometer and HPLC. Individually, FSM and APN added to 20 percent mannitol and 0.9 percent NaCl solutions had the highest stability at pH 10-11. When FSM and APN were combined, the behavior of FSM was similar to the behavior observed for the drug individually in the same solutions. With the drugs combined in 20 percent mannitol pH 10-11, HPLC showed that both drugs were stable after a 20 h period yielding two distinct peaks; in oxidized samples, the elution profile showed four peaks with retention times unrelated to the untreated samples.

Soluções parenterais de grande volume são frequentemente utilizadas no ambiente hospitalar para a veiculação de fármacos. No entanto, possíveis incompatibilidades entre as estruturas dos fármacos, em diferentes veículos de administração, podem gerar possíveis associações antagônicas ou sinérgicas, resultando em alterações das propriedades físico-químicas, consequentemente, dos efeitos farmacológicos e das respostas clínicas esperadas. Este artigo avaliou a estabilidade e a possível formação de produtos de degradação entre os fármacos furosemida e aminofilina quando estes foram veiculados em soluções parenterais, após o preparo e após o período de 20 h. Furosemida e aminofilina foram adicionadas às soluções de 20 por cento manitol e 0,9 por cento NaCl nos valores de pH 6,5-7,5 e 10-11. A estabilidade dos fármacos foi avaliada individualmente, combinada e após degradação com peróxido de hidrogênio através de espectrofotometria de UV e HPLC. Furosemida e aminofilina individualmente avaliadas mostraram alta estabilidade em ambas as soluções estudadas nos valores de pH 10-11. Quando os fármacos foram combinados o comportamento da furosemida foi similar ao observado na ausência de aminofilina. Os fármacos combinados em 20 por cento manitol pH10-11 por HPLC foram estáveis após o período de 20 h. Após degradação o perfil de cromatograma encontrado foi diferente do observado na ausência de degradação mostrando que o método é indicativo de estabilidade.

Bloqueo AV completo, reversible, en relación a hiperkalemia grave por enalapril y espironolactona: caso clínico / Complete atrioventricular block, reversible, related to serious hyperkalemia due to enalapril and spironolactone: case report

La hiperkalemia es una de las principales complicaciones potenciales del uso de drogas del tipo IECA, bloqueadores ARAII y antagonistas del receptor de aldosterona, en relación a su dosis, su eventual uso combinado y la función renal del paciente. A continuación se reporta el caso de un paciente de 71 años de edad, hipertenso y diabético que se encontraba en tratamiento con Enalapril 10 mg c/12 h y Furosemida 40 mg a/ 12 h, que sufre una bloqueo aurículo ventricular de 3º grado, secundario a una hiperkalemia de 8.53 mEq/l.

Histological study on the effect of furosemide on renal cortex of mice with hepatic fibrosis Secondary to schistosoma mansoni infection

Schistosoma mansoni is a documented factor for the acquisition of hepatic fibrosis, with further edema and ascites. Recent researches suggested that diuretic treatment in patients with hepatic fibrosis could result in renal impairment. To evaluate the changes in renal cortex after injection of furosemide in mice with hepatic fibrosis secondary to Schistosoma mansoni infection. Sixteen adult male mice were divided into 2 groups. Non-infected mice [group I], were further subdivided into two subgroups [a and b]. Subgroup [Ia] mice were untreated and subjected as negative controls while subgroup [II] mice were injected daily with furosemide for 14 successive days. The other 8 mice [group II], were infected with Schistosoma mansoni and left for 8 weeks for induction of hepatic fibrosis. Then, group II mice were subdivided into two subgroups [a and b]. Subgroup [IIa] mice were untreated and served as positive controls for liver fibrosis. Mice of subgroup [IIb] were injected with the same dose of furosemide for successive 14 days. All animals were sacrificed and samples from livers and kidneys were collected, stained and examined. Mice of subgroup [IIa] showed focal glomerular changes in the form of either proliferation or atrophy. Fusion of foot processes of podocytes with deposition of dense bodies appeared with electron microscopic study. Mice of subgroup [IIb] showed massive glomerular and tubular damage. Glomerular capillary obliteration, subendothelial humps, destructed foot processes and cellular vacuolations were manifested. Renal tubules showed destructed microvilli and cellular damage. Interstitial lymphocytic infiltration and interstitial renal fibrosis were also demonstrated. Furosemide possessed renal cortical damaging effect when administered in mice with hepatic fibrosis

Technological development of 40mg furosemide tablets: equivalence and bioavaibility study in dogs

Furosemide (40mg) was administered to 20 street dogs, 10 males and 10 females, in two different pharmaceutical forms: (1) compressed furosemide 40mg formulated at the Federal University of Pernambuco (UFPE-tablet), and (2) a commercial formulation with equal bioequivalence produced by the Laboratory for Pharmaceutical Technology of Pernambuco State (LAFEPE), the LAFEPE-furosemide. The study aimed to evaluate the kinetics of dissolution of the UFPE-tablet in order to analyze the behavior of bioavailability of the best formulation for veterinary use. The plasmatic concentrations of furosemide for the determination of parameters of pharmacological kinetics were analyzed by high-performance liquid chromatographic method (HPLC). The in vitro study accomplished through physiochemical analyses demonstrated that the formulas of the furosemide tablets attained the pharmaceutical requirements in agreement with USP 23 and the Brazilian Pharmacopoeia. The evaluation accomplished in dogs with UFPE-tablets given in only dose demonstrated uniformity in blood levels indicating stability in maintenance of the pharmaceutical formulation and efficiency in absorption of the active compound. These values are not significantly different in relation to the 5 percent confidence limit. Regarding maximum concentration (Tmax) time and global bioavaibility assessed by AUC means, there were no considerable differences as well. UFPE-furosemide displayed 743.492µg/mL.h as AUC average value whereas LAFEPE-furosemide had an average of 537.284µg/mL.h.

Furosemida (40mg) foi administrada a 20 cães de rua (cães SRD), 10 machos e 10 fêmeas, em duas formas farmacêuicas distintas: (1) furosemida comprimido 40mg formulada na Universidade Federal de Pernambuco (UFPE-comprimido) e (2) uma formulação comercial bioequivalente produzida pelo Laboratório de Tecnologia Farmacêutica do Estado de Pernambuco (LAFEPE-furosemida). O estudo objetivou avaliar a cinética de dissolução do UFPE-comprimido para analisar o comportamento da liodisponibilidade dos comprimidos buscando a melhor formulação para uso veterinário. As concentrações plasmáticas de furosemida para determinação de parâmetros farmacocinéticos, foram analisadas por cromatografia líquida de alto desempenho (HPLC). O estudo in vitro realizado através de análises físico-químicas demonstrou que as fórmulas dos comprimidos de furosemida preencheram os requisitos farmacêuticos de acordo com USP 23 e a Farmacopéia Brasileira. Avaliações realizadas em cães da formulação UFPE-comprimidos administrados em dose única, demonstrou uma uniformidade nos níveis sangüíneos indicando estabilidade na manutenção da forma farmacêutica e eficiência na absorção do princípio ativo. Estes valores não são significativamente diferentes em relação ao limite de confiança de 5 por cento. Em relação a concentração de máximo (Tmax) e ao tempo de biodisponibilidade global avaliados por meios de AUC, não houve nenhuma diferença considerável. O comprimido UFPE-furosemide exibiu AUC de 743.492µg/mL.h e o LAFEPE-furosemide teve uma média de 537.284µg/mL.h.

Hipokalemia, hipovolemia y repercusión electrocardiográfica secundarias a ingesta prolongada de furosemida: Caso clínico / Hypokalemia, hypovolemia and electrocardiographic changes due to furosemide abuse: Report of one case

Hypokalemia (serum K+ < 3.5 mEq/1) is a potentially serious adverse effect of diuretic ingestión. We report a 27 year-old woman admitted with muscle weakness, a serum potassium of 2.0 mEq/1, metabolic alkalosis and EKG abnormalities simulating cardiac ischemia, that reverted with potassium chloride administration. She admitted high dose furosemide self-medication for edema. Glomerular filtration rate, tubular sodium reabsortion, potassium secretion, the renin-aldosterone system, total body water distribution and capillary permeability, were studied sequentially until 90 days after her admission. There was hyperactivity of the renin-aldosterone axis, reduction in extracellular and intracellular volumes, normal capillary permeability and high sodium tubular reabsorption, probably explained by a "rebound" salt retention associated with her decreased extracellular volume.

Nefrocalcinose associada provavelmente com abuso de furosemida: relato de caso e revisão de literatura / Nephrocalcinosis probably associated with furosemide abuse: case report and review

Introdução: Nefrocalcinose tem sido descrita em neonatos e crianças que fazem uso de furosemida em altas doses por longo período de tempo. Relatamos aqui um caso de nefrocalcinose em uma mulher adulta após o uso de furosemida por dez anos. Relato de caso: Paciente de 27 anos, sexo feminino, admitida com queixa de edema, tendo feito uso de furosemida 40 a 120mg por dez anos. Ultra-sonografia diagnosticou nefrocalcinose, mostrando aumento difuso da ecogenicidade das pirâmides renais. Tratada com suspensão do furosemida. Evolução mostrou regressão do edema e nefrocalcinose persistente. Conclusão: Nefrocalcinose medular associada com abuso de furosemida por tempo prolongado em adulto é relatada e feita revisão de literatura sobre oassunto.

Introduction: Nephrocalcinosis has been described in neonates and infants who used furosemide in high doses for extended periods of time. We report here a case of nephrocalcinosis in an adult female after taking furosemide for ten years. Case report: A 27 year-old, female, admitted for edema took 40to 120 mg of furosemide per day for ten years. Nephrocalcinosis was diagnosed by ultrasonography, which showed a diffuse increase in echogenicity pyramids. Treatment was a furosemide suspension. Evolution showed regression of edema and persistent nephrocalcinosis. Conclusion: A case of medullary nephrocalcinosis associated with long-term furosemide abuse in adults is described and a review of the literature is presented.

Evaluation of tracheal wash of horses with exercise-induced pulmonary hemorrhage treated with furosemide

Avaliaram-se os efeitos da furosemida sobre o lavado traqueal de eqüinos portadores de hemorragia pulmonar induzida pelo exercício (HPIE). Nove animais foram distribuídos em três grupos experimentais: grupo-controle, formado por três eqüinos hígidos e não portadores da doença; grupo 1, com três eqüinos portadores e não submetidos a tratamento; e grupo 2, com três eqüinos portadores da doença e tratados com furosemida na dose de 1mg/kg, quatro horas antes da atividade atlética. As amostras do lavado traqueal foram obtidas duas horas após o exercício físico e sua avaliação demonstrou que o uso do medicamento reduziu a severidade da HPIE, refletida pela redução no número relativo de hemossiderófagos (de 7,8 por cento no grupo 1 para 4,2 por cento no grupo 2) e no número de eritrócitos (de 77666 x 10³/ml no grupo 1 para 8000x10³/ml no grupo 2).

Efecto de un incremento en la diuresis sobre la absorción y retención de algunos nutrientes en ratas / Effect of an increase in diuresis on absorption and retention of some nutrients in rats

Estudios previos en ratas han demostrado que la administración del diurético furosemida aumenta la pérdida urinaria de electrolitos y nutrientes, causando un efecto negativo sobre las reservas de los mismos. Una alternativa para proteger esas reservas es incrementar la absorción intestinal. Así, se evaluó la absorción, pérdidas urinarias y reservas corporales de nitrógeno, calcio, magnesio, sodio, potasio y cinc, en cuatro grupos de ratas: control, y tres grupos experimentales que consumieron furosemida en concentraciones de 0,5; 1,0 y 1,5 mg/g de dieta, durante 23 días. El diurético causó poliuria dosis dependiente, disminución en el consumo de alimento, la eficiencia y el crecimiento. También, provocó un aumento en las pérdidas urinarias del nitrógeno y minerales. La absorción de nitrógeno, calcio y cinc no se modificó, mientras que la del magnesio, sodio y potasio aumentó ligeramente. Se determinó que la absorción no compensó las pérdidas urinarias. Así, la furosemida afectó negativamente la retención de nutrientes y electrolitos, provocando una reducción en las reservas corporales de los mismos. Este diurético tiene un efecto negativo sobre el estado nutricional en ratas, causado por la reducción en el consumo de alimento, así como en la utilización de los nutrientes consumidos. La reducción en la utilización de los nutrientes asociada con este diurético, puede ser explicada en parte, por una pobre retención de nutrientes por el riñón, que no puede ser compensada por un incremento en la absorción intestinal.

Previous studies have shown that, in rats, the administration of the diuretic furosemide increases diuresis as well as urinary loss of electrolytes and essential nutrients. This loss has a negative effect on electrolytes and nutrient reserves. Since one alternative to help protect these reserves is to increase intestinal absorption, the purpose of this study was to evaluate the absorption, urinary loss and tissue reserves of nitrogen, calcium, magnesium, sodium, potassium and zinc in rats offered 0, 0.5, 1.0 and 1.5 mg furosemide per g diet, daily during 23 days. The diuretic caused a dose dependent polyuria, a reduction in food intake, growth and feed efficiency. In addition, those rats had increased urinary loss of nitrogen and minerals. Nitrogen, calcium and zinc absorption were not affected, but magnesium, sodium and potassium increased slightly. Intestinal absorption could not compensate for urinary loss. In general, this study showed that in rats, this diuretic had a negative effect on nutritional status caused by a reduction in food intake and also in the utilization of the nutrients consumed. The reduction in nutrient utilization associated with this diuretic may be partly explained by a poor nutrient retention by the kidney which was not compensated by an increase in intestinal absorption.

Nível de tiamina no miocárdio, área transversa e número de núcleos de cardiomiócitos de ratos em uso de furosemida / Myocardial thiamine level, cardiomyocyte cross-sectional area and nuclei number in furosemide-treated rats

Objetivo: Avaliar os níveis miocárdicos de tiamina e área transversa e número de núcleos de cardiomiócitos de ratos em uso de furosemida. Métodos: 24 ratos foram estratificados em 4 grupos: 2 grupos receberam furosemida por via intraperitoneal e 2 receberam solução salina, por 21 dias. Dois destes grupos receberam ração-padrão, e 2 ração pobre em tiamina. Os níveis miocárdicos de tiamina foram avaliados por: dosagem de tiamina pirofosfato (TPP) por HPLC, e medidas de atividade da transcetolase miocárdica(ATm) e do efeito da tiamina pirofosfato (ETPP). Métodos estereológicos foram utilizados para a obtenção da área transversa (Acmy) e número de núcleos (Ncmy) dos cardiomiócitos. Resultados: as médias e desvios-padrão de TPP, ATm, ETPP, Acmy e Ncmy foram, respectivamente: Grupo 1 - 133,7 maior ou menor que 17,9ng/100 microlitro de tecido homogeneizado; 173 maior ou menor que 20 micrograma.hexose/ml/h; 3,6 maior ou menor que 1,9 por cento; 808 maior ou menor que 8 milhões; Grupo 2 - 160,2 maior ou menor que 23,2ng/100 microlitro de tecido homogeneizado; 1634 maior ou menor que 137 micrograma.hexose/ml/h; 2,2 maior ou menor que 1,4 por cento; 961 maior ou menor que 59 micrometro2; 63 maior ou menor que 2 milhões; Grupo 3 - 73,5 maior ou menor que 8,6ng/100 microlitro de tecido homogeneizado; 715 maior ou menor que 123 micrograma.hexose/ml/h; 39,8 maior ou menor que 9,8 milhões por cento; 963 maior ou menor que 2 micrometro2; 59 maior ou menor que 4 milhões Grupo 4 - 82,1 maior ou menor que 9ng/100 microlitro de tecido homogeneizado; 863 maior ou menor que 75 micrograma.hexose/ml/h; 26,2 maior ou menor que 11,9 por cento; 1061 maior ou menor que 33 micrometro2; 63 maior ou menor que 5 milhões. Conclusão: A furosemida não reduziu o nível de tiamina no miocárdio, nem alterou a área transversa e o número de núcleos de cardiomiócitos nos animais estudados.

La hiperuricemia es un marcador del umbral anaeróbico en la insuficiencia cardíaca crónica / Hyperuricemia is a marker for anaerobic threshold in chronic cardiac failure

Background: Patients with chronic cardiac failure often have elevated plasma uric acid levels, that are associated to a dismal prognosis. Aim: To investigate possible metabolic mechanisms to explain elevated uric acid levels in these patients. Patients and methods: Eighteen patients with chronic cardiac failure aged 61 ñ 10 years old, without gout or renal failure and not using high doses of diuretics (equal or less than 80 mg/day furosemide or 50 mg/day hydrochlorothiazide) were studied. Plasma uric acid levels were correlated with anaerobic threshold, maximal oxygen uptake, plasma noradrenaline and creatinine and left ventricular ejection fraction, measured radioisotopically. Results: Mean maximal oxygen uptake was 16.6 ñ 4.2 ml/kg/min. There was a negative correlation between uric acid levels and maximal oxygen uptake or maximal oxygen uptake/body surface area (r=0.521 and -0.533 respectively, p<0.05). Patients with uric acid levels over 7 mg/dl had a lower anaerobic threshold than patients with lower levels (9.81 ñ 2.41 and 13.08 ñ 3.28 ml/kg/min respectively, p<0.05). No significant differences in maximal oxygen uptake were observed in these two groups of patients (15.5 ñ 4.24 and 18.08 ñ 3.86 ml/kg/min respectively). Uric acid levels did not correlate with plasma noradrenaline, creatinine or lefi ventricular ejection fraction. Conclusions: These results suggest that a defect in cellular oxygenation contributes to the elevation of plasma uric acid levels in patients with chronic cardiac failure

Reacciones adversas e interacciones medicamentosas en pacientes con edema cerebral / Adverse drug reactions and drug interactions in patients with brain edema

Se realizó un estudio en la Unidad de Cuidados Intensivos e Intermedios del Hospital Clinicoquirúrgico Docente "Saturnino Lora" de Santiago de Cuba, con el objetivo de evaluar reacciones adversas e interacciones medicamentosas detectadas en el tratamiento del edema cerebral. Se aplicó el método de vigilancia intensiva del paciente hospitalizado, adaptado a las condiciones experimentales en una muestra de 65 pacientes. Los datos obtenidos se evaluaron por medio de los algoritmos de Naranjo y de Karch-Lasagna, así como la relación beneficio-riesgo de cada tratamiento y el procesamiento estadístico apropiado. Se detectaron 114 reacciones adversas y 40 interacciones medicamentosas; eventos que luego de relacionarlos con aspectos clínicos y demográficos, se analizaron farmacológicamente. Se proponen medidas terapéuticas al personal del servicio