Ocorrência de carcinoma espinocelular labial não melanocítico em usuários crônicos de hidroclorotiazida / Occurrence of non-melanoma labial squamous cell carcinoma in chronic users of hydrochlorothiazide

Diversos autores desenvolveram estudos acerca da potencial associação entre a etiocarcinogênese do carcinoma espinocelular não melanocítico (CECNM) labial e o uso crônico da hidroclorotiazida (HCTZ). Objetivo: A atual revisão objetivou investigar a relação do diurético HCTZ e o risco de CECNM labial. Métodos: Realizou-se uma revisão de literatura nas bases de dados LILACS, PUBMED/MEDLINE e Periódico CAPES, em que foram incluídos artigos em inglês, português e francês, publicados no período de 2017 a 2022. Foram propostos 60 documentos e, dentre esses, 30 foram selecionados para compor a amostra no estudo. Resultados: Foi evidenciada uma relação entre o uso da HCTZ e a ocorrência de CENM com relação dose cumulativa devido às alterações provocadas pelo fármaco, no entanto, em virtude da heterogeneidade de desenhos metodológicos e concentração dos estudos em populações semelhantes, existem limitações quanto à confiabilidade dessas informações. Conclusão: Identificou-se uma desproporção entre a ocorrência e relevância do CENM e a produção científica vigente, demonstrando a necessidade de estudos com metodologias padronizadas que abranjam diferentes especificidades socioeconômicas e demográficas.(AU)

Several authors have developed studies about a potential association between the etiocarcinogenesis of non-melanocytic lip squamous cell carcinoma (NMSCC) and the chronic use of hydrochlorothiazide (HCTZ). Objective: The current study aimed to investigate the relation between the diuretic HCTZ and the risk of lip NMSCC. Methods: A literature review was carried out in the LILACS, PUBMED/MEDLINE and CAPES Periodical databases, which included articles in English, Portuguese and French, published between 2017 and 2022. Sixty documents were collected and, among these, 30 were selected to compose the sample in the study. Results: There was evidence of a relationship between the use of HCTZ and the occurrence of MSCC with a cumulative dose relationship due to changes caused by the drug, however, because of the heterogeneity of methodological designs and concentration of studies in similar populations, there are limitations regarding the reliability of this information. Conclusion: A disproportion between the occurrence and relevance of the NMSCC and the current scientific production was identified, demonstrating the need for studies with standardized methodologies that cover different demographic socioeconomic specificities.(AU)

Intraoperative management of potentially fatal arrhythmias after anesthesia induced by severe hypokalemia: A case report / 北京大学学报(医学版)

Severe hypokalemia is defined as the concentration of serum potassium lower than 2.5 mmol/L, which may lead to serious arrhythmias and cause mortality. We report an unusual case of potentially fatal ventricular arrhythmias induced by severe hypokalemia in a patient undergoing laparoscopic partial nephrectomy in Peking University Third Hospital due to irregular use of indapamide before operation. Indapamide is a sulfonamide diuretic with vasodilative and calcium antagonistic effects, which enhances sodium delivery to the renal distal tubules resulting in a dose-related increase in urinary potassium excretion and decreases serum potassium concentrations. The electrolyte disorder caused by the diuretic is more likely to occur in the elderly patients, especially those with malnutrition or long-term fasting. Hence, the serum potassium concentration of the patients under indapamide therapy, especially elderly patients, should be monitored carefully. Meanwhile, the potassium concentration measured by arterial blood gas analysis is different from that measured by venous blood or laboratory test. According to the previous research, the concentration of potassium in venous blood was slightly higher than that in arterial blood, and the difference value was 0.1-0.5 mmol/L. This error should be taken into account when rapid intravenous potassium supplementation or reduction of blood potassium level was carried out clinically. In the correction of severe hypokalemia, the standard approach often did not work well for treating severe hypokalemia. The tailored rapid potassium supplementation strategy shortened the time of hypokalemia and was a safe and better treatment option to remedy life-threatening arrhythmias caused by severe hypokalemia with a high success rate. Through the anesthesia management of this case, we conclude that for the elderly patients who take indapamide or other potassium excretion diuretics, the electrolyte concentration and the general volume state of the patients should be comprehensively measured and fully evaluated before operation. It may be necessary for us to reexamine the serum electrolyte concentration before anesthesia induction on the morning of surgery in patients with the history of hypokalemia. For severe hypokalemia detected after anesthesia, central venous cannulation access for individualized rapid potassium supplementation is an effective approach to reverse the life-threatening arrhythmias caused by severe hypokalemia and ensure the safety of the patients.

Use of Diuretics is Associated with Higher Risk of Sarcopenia in Older Adults with Hypertension

Abstract Background: Sarcopenia is a disease that involves skeletal muscle mass loss and is highly prevalent in the older adult population. Moreover, the incidence of sarcopenia is increased in patients with hypertension. Objectives: The study aimed to evaluate the association between the classes of the drugs used for arterial hypertension treatment and the presence or absence of sarcopenia. Methods: 129 older adults with hypertension were evaluated by the researchers who registered the participants medication for arterial hypertension treatment. Sarcopenia level was measured by anthropometric parameters, muscular strength, and functional capacity. The data were analyzed by one-way ANOVA followed by post-hoc test and Fisher's exact test; statistical significance was set at 0.05. Results: Age was not different between women with different levels of sarcopenia, but significant differences were observed between men with absent sarcopenia (66.8±4.2 years) and men with probable sarcopenia (77.0±10.2 years). Individuals with absent sarcopenia showed higher handgrip strength (men: 33.8±7.4, women: 23.2±4.6 Kgf) in comparison with those with sarcopenia (men with probable sarcopenia: 9.5±3.3 Kgf, women with probable, confirmed, and severe sarcopenia: 11.7±2.5, 12.2±3.0, 11.8±1.8 Kgf, respectively). The analysis showed an association between the type of medication and degree of sarcopenia; diuretics were significantly associated with probable sarcopenia, and angiotensin II receptor blockers (alone or in combination with diuretics) was associated with absence of sarcopenia. Conclusion: In conclusion, handgrip strength was a good method to diagnose sarcopenia, and diuretics were associated with increased risk of sarcopenia in older adults with hypertension.

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.

Determinação de estimulantes, esteroides anabolizantes, diuréticos e laxante por HPLC-DAD e LC-MS/MS em suplementos alimentares adulterados disponíveis no Brasil / Determination of stimulants, anabolic steroids, diuretics and laxative by HPLC-DAD and LC-MS/MS in adulterated dietary supplements available in Brazil

A adulteração de suplementos alimentares pela adição de substâncias farmacologicamente ativas e um problema que vem se agravando nos últimos anos. Essas substâncias são adicionadas intencionalmente nos produtos, com objetivo de melhorar a sua eficácia, sem que essa adição seja devidamente informada nos rótulos. O consumo de suplementos adicionados de substâncias farmacologicamente ativas nao declaras nos rótulos e, alem de um problema de saúde pública, um risco a carreira de atletas profissionais, quando se trata de doping no esporte. Neste trabalho foram desenvolvidos métodos analíticos baseados em cromatografia líquida para detecção de 19 substâncias farmacologicamente ativas em amostras de suplementos alimentares, nos niveis de contaminação cruzada e adulteração. Para tal, empregou-se a cromatografia líquida de alta eficiência acoplada a detector de arranjo de diodos (HPLC-DAD) e a cromatografia líquida acoplada a espectrometria de massas sequencial (LC-MS/MS). As substâncias investigadas apresentam ação androgênica e anabólica (i.e. testosterona, metiltestostetona, propionato de testosterona, decanoato de testosterona, trembolona, estanozolol, dehidroepiandrosterona, androstenediona, decanoato de nandrolona, oxandrolona e metasterona), estimulante (i.e. cafeína), anorexigena (i.e. sibutramina), diurética (i.e. amilorida, bumetanida, furosemida, hidroclorotiazida e clortalidona) e laxante (i.e. fenolftaleina). Entre os métodos de preparo de amostra avaliados (Quechers e extração sólido-líquido seguida de uma etapa de precipitação de proteína), a extração sólido-líquido empregando metanol como solvente extrator e ZnSO4 como agente precipitante apresentou-recuperação acima de 80% para todas as substâncias avaliadas, sendo selecionado para o fim deste estudo. Os métodos analíticos propostos apresentaram limites de detecção e de quantificação na faixa de contaminação, foram seletivos e lineares com r2 superior a 0,99 na faixa de concentração de interesse para todas as substâncias e valores de recuperação, precisão e exatidão dentro dos valores aceitáveis. Um conjunto amostral representativo dos suplementos alimentares comercializados no Brasil, constituído por 230 amostras, foi analisado sendo que mais de 25% do conjunto amostra foram positivos para cafeína (48), sibutramina (14), fenolftaleína (2) e furosemida (3), isoladas ou associadas entre si. Os métodos desenvolvidos utilizaram um preparo de amostra simples e apresentaram resultados satisfatórios para a investigação de possível adulteração ou contaminação com 19 das substâncias de interesse. Dos 58 suplementos alimentares adulterados, apenas 11 podem ser considerados adulterados por contaminação cruzada. Os demais, são consideradas adições dolosas por parte dos fabricantes com objetivo de melhorar a eficiência dos seus produtos. Os resultados aqui apresentados indicam a necessidade de ações mais efetivas por parte das autoridades sanitárias no sentido de fiscalizar com mais eficiência a produção e a comercialização desses produtos e alertar a população para que fiquem atentos a possível adulteração de suplementos alimentares e aos riscos associados ao consumo desses produtos

The adulteration of dietary supplements by the addition of pharmacologically active substances is a serious issue, which is aggravating steadily. These substances are added intentionally in various products, with the aim of improving their effectiveness, but without proper labeling stating so. In addition to a public health problem, the consumption ofsupplements added with undeclared pharmacologically active substances also represents a career risk for professional athletes when it comes to doping in sport. In the present work, analytical methods based on liquid chromatography were developed for the detection of 19 pharmacologically active substances in dietary supplement samples at the levels of crosscontamination and adulteration. For this purpose, high performance liquid chromatography/diode array detector (HPLC-DAD) and liquid chromatography/tandem mass spectrometry (LC-MS/MS) were used. The investigated substances comprise of androgenic and anabolic effects (ie testosterone, testosterone propionate, testosterone decanoate, trenbolone, stanozolol, dehydroepiandrosterone, androstenedione, nandrolone decanoate, oxandrolone and metasterone), stimulant (ie caffeine), anorexigenic (ie sibutramine), diuretic (ie amiloride, bumetanide, furosemide, hydrochlorothiazide and chlorthalidone) and laxative (ie phenolphthalein). Among the sample preparation methods evaluated (Quechers and solidliquid extraction followed by a protein precipitation step), solid-liquid extraction using methanol as extraction solvent and ZnSO4 as the precipitating agent has been chosen as it has shown recovery values above 80% for all evaluated substances. The proposed analytical methods had limits of detection and quantification within the contamination range, they were also selective and linear showing r2 values higher than 0.99 in the concentration range of interest for all substances and accuracy within acceptable values. A representative sampling of dietary supplements marketed in Brazil, consisting of 230 samples, was analyzed and more than 25% have shown to be positive for caffeine (48), sibutramine (14), phenolphthalein (2) and furosemide (3), isolated or associated with each other. The methods developed used a simple sample preparation and presented satisfactory results for the investigation of possible adulteration or cross-contamination for the 19 of the substances of interest. From a total of 58 adulterated dietary supplements, only 11 could be considered adulterated by crosscontamination. The remaining are considered to be intentional additions by manufacturers in order to improve the efficiency of their products. The results presented in this study indicate the need for more effective measures by the health authorities towards the production and marketing of these products so that the general public is aware of their potential adulteration and the risks associated with their consumption

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.

Avaliação de potássio, sódio e cálcio em neonatos com displasia broncopulmonar em uso de diuréticos / Evaluation of potassium, sodium and calcium in neonates with bronchopulmonary dysplasia using diuretics

Os diuréticos, no tratamento da Displasia Broncopulmonar (DBP), têm como função diminuir a retenção hídrica e auxiliar a reabsorção do edema intersticial dos pulmões. É uma doença crônica causada pela inflamação da membrana pulmonar e sua morbidade é mais comum em recém-nascidos com extremo baixo peso (EBP). O tratamento com diuréticos incluem os de alça, os tiazídicos e os poupadores de potássio. Objetivo: analisar possíveis efeitos da terapia com diuréticos sobre os íons de cálcio, sódio e potássio de amostras de sangue e urina dos neonatos diagnosticados com Displasia Broncopulmonar. Resultados: As concentrações séricas de sódio apresentaram variações abaixo dos valores mínimos de referência sendo suas alterações creditadas ao uso farmacológico. Outros resultados apresentaram limitações sendo um dificultador do estudo. Palavras-chave: displasia broncopulmonar; prematuridade; diuréticos; eventos adversos

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.

Edema pulmonar agudo por hidroclorotiazida: una reacción adversa poco conocida / Hydrochlorothiazide-induced acute pulmonary edema: a rare adverse reaction

In Chile, hydrochlorothiazide is frequently prescribed as first line antihypertensive therapy. Among it’s well known adverse reactions are: electrolytic disorders, hyperuricemia, dyslipidemia, agranulocytosis and azotemia. Acute pulmonary edema is a rare and potentially lethal adverse effect. Only 50 cases have been reported since 1968. In this article, we discuss a case of a 70 year old woman who, one hour after the ingestion of hydrochlorotiazide, presented acute and progressive dyspnea. Her clinical and radiologic findings are compatible with non-cardiogenic acute pulmonary edema.

En Chile, la hidroclorotiazida se utiliza ampliamente como terapia de primera línea en la hipertensión arterial esencial. Entre los efectos adversos más conocidos destacan: trastornos hidroelectrolíticos, hiperuricemia, dislipidemia, azotemia, entre otros. El edema pulmonar agudo es un efecto adverso infrecuente y potencialmente grave. Desde 1968, se han reportado 50 casos clínicos en la literatura. En este artículo presentamos el caso clínico de una mujer de 70 años atendida en el Hospital Santiago Oriente quien, una hora posterior a la ingesta de hidroclorotiazida, presenta disnea aguda progresiva. El estudio clínico y radiológico es compatible con edema pulmonar agudo no cardiogénico.

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.

Alteraciones hidroelectrolíticas en pacientes tratados con diuréticos / Electrolytes disturbances in patients treated with diuretics

a) Introducción y objetivos: Los diuréticos son fármacos que han demostrado su utilidad en el trtamiento de la hipertensión arterial. Los objetivos de este estudio fueron analizar la prevalencia de las alteraciones hidroelectrolíticas en pacientes ambulatorios tratados con diuréticos y su asociación con el tipo de diuréticos utilizados. b) Métodos: Se evaluaron en forma prospectiva 93 pacientes adultos mayores de 31 años. La edad promedio fue de 66.3 años. La tensión arterial media fue de 127/76 mmHg. Se analizaron los siguientes parámetros: sodio, potasio, cloro, magnesio, bicarbonato, urea plasmática, creatinina sérica, calcio, fosforo y ácido úrico en sangre. c) Resultados: De los 93 pacientes, el 96 por ciento recibían diuréticos por hipertensión arterial. De ellos 64 por ciento recibían tiazidas, 11 por ciento indapamida, 6 por ciento furosemida, 5 por ciento clortalidona y 4 por ciento la combinación de tiazidas y amiloride. la alteración más frecuente encontrada fue la hiperazoemia en 28 por ciento, hiponatremia en 8.6 por ciento, hipokalemia en 4.3 por ciento de los casos. No presentaron hiponatremia ni hipokalemia ninguno de los pacientes tratados con indapamida. Los valores de cloro se encontraron por debajo de su valor normal en 11 por ciento, no observándose cambios significativos en los valores de calcio, fosforo, magnesio y ácido úrico. Once pacientes presentaron valores elevados de bicarbonato. d) Conclusiones: La alteración hidroelectrolítica más frecuentemente encontrada en nuestra población fue la hiperazoemia seguida de hiponatremia, siendo infrecuente la hipokalemia. Los diuréticos constituyen importantes herramientas terapéuticas en el manejo de la hipertensión arterial. Su utilización es segura y efectiva como monoterapia en pacientes con hipertensión arterial.

a) Background and Objectives: Diretics have demonstrated their utility for the management of hypertension. The goals of this study were to analyze the prevalence of electrolytes disturbances in ambulatory patients treated with diretics and the type of diuretics used. b) Methods: We prospectively evaluated 93 adults patients older than 31 years old. their mean age was 66.3 years and mean arterial blood pressure was 127/76 mmHg. The varialbes evaluated were: sodium, potassium, chlorine, magnesium, bicarbonte, blood urea nitrogen (BUN) serum cretinine, calcium, phosphorus and uric acid. c) Results: Ninety six percent of the patients received diuretics for the management of hypertension. Sixty four percent of the patients were treated with hydrochlorothiazide, 11 percent indapamide, 6 percent furosemide, 5 percent clortalidone and 4 percent the combination of thiazide with amiloride. The most common abnormality was increased blood urea nitrogen (BUN) seen in 28 percent of the patients, hyponatremia in 8.6 percent and hypokalemia in 4.3 percent. The majority of our patients were treated with thiazides. No patients treated with indapamide had hypnatremia or hypokalemia. The chlorine value was below the normal range in 11 percent of our patients. We haven't seen significant changes in serum calcium, phosphorus, and magnesium. Bicarbonate was elevated in 11 of 30 patients. d) Conclusions: In summary, the most common abnormality ound in our population was the increased BUN. Hyponatremia was mild and hypokalemia was exceptinal. Diuretics are important therapeutic tools for tretment of hypertension. The use of these drugs are safe and effective for the treatment of patients with hypertension.

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%).

Preference of patient information leaflets over standard drug monographs by patients prescribed hydrochlorothiazide, nifedipine and enalapril / Preferencia por los prospectos de información al paciente en lugar de las monografías estándar sobre medicamentos, por parte de los pacientes a quienes se les ha prescrito hidroclorotiazida, nifedipina y analapril

Standard drug monographs (SDMs) have been described as deficient in providing information in a manner simplified enough for patient reading. The aim of this study was to design patient information leaflets for hydrochlorothiazide, nifedipine and enalapril with content indicated by patients as relevant and to evaluate them against the SDM. Patient information leaflet (PIL) for each drug was designed to contain information on name, use of drug, how it works, how it is to be taken, common side effects, storage, missed dose action, things to avoid and when to contact the physician. Appropriateness was assessed by 10 practising pharmacists. For each drug, 40 patients were recruited, of which 20 were given SDM and 20 PIL. The knowledge of each participant was examined before and after exposure to SDM or PIL, as well as opinion on ease of reading and attractiveness using Pearson's Chi-square analysis. The results showed that both SDM and PIL improved knowledge of common side effects when compared with responses before exposure (χ² = 24.26for SDM and 27.64 for PIL, p < 0.001) with no difference between the groups. Respondents receiving PILs were better able to recall "things to avoid" after exposure to PIL (χ² =10.85, p < 0.001). After exposure to SDM or PIL, the respondents who received PIL were more aware of when to contact the physician, compared to the SDM group (χ² = 8.41, p < 0.01). When compared with SDM, respondents receiving PIL were more likely to indicate that PIL was easy to read (χ² = 20.00, p < 0.001), attractive (χ² = 12.45, p < 0.001) and they were more likely to recommend distribution of their reading material to other patients (χ² = 22.11, p < 0.001). We conclude that there is benefit in designing information leaflets that simplify language and medication information contained in SDMs, including better understanding of precautions to take while on medication and when to consult physicians.

Las monografías de medicamentos estandarizadas se han considerado deficientes a la hora de proporcionar información de manera suficientemente simple para que el paciente pueda entenderlas. El objetivo de este estudio fue disenar prospectos con información sobre la hidroclorotiazida, la nifedipina y el analapril con contenidos indicados como relevantes por los pacientes, y evaluarlos en comparación con las monografías estandarizadas de medicamentos (MEM). El prospecto de información para el paciente (PIP) fue disenado de modo que apareciera información sobre el nombre del medicamento, su uso, modo de operar, manera de tomarse, efectos secundarios comunes, almacenamiento, qué hacer en caso de perder una dosis, cosas que deben evitarse, y cuando debe contactarse el médico. Se evaluó la adecuación por parte de 10 farmacéuticos practicantes. Para cada medicamento, se reclutaron 40 pacientes, a 20 de los cuales se les dio monografías (MEM), en tanto que a 20 se les ofreció prospectos (PIP). El conocimiento de cada participante se examinó antes y después de la exposición a MEM o PIP, así como la opinión en cuanto a facilidad de lectura y grado de atracción, usando el análisis del Chi-cuadrado de Pearson. Los resultados mostraron que tanto MEM como PIP mejoraron el conocimiento sobre los efectos secundarios comunes, cuando se hacía una comparación con las respuestas antes de la exposición (χ² = 24.26para MEMy 27.64para PIP, p < 0.001) sin diferencia entre los grupos. Los encuestados que recibieron prospectos pudieron recordar mejor las "cosas a evitar" luego de la exposición a PIP (χ² =10.85, p < 0.001). Después de la exposición a MEM o PIP, los encuestados con PIP tenían mayor conciencia en cuanto a cuando contactar a un médico, en comparación con el grupo MEM (χ² = 8.41, p < 0.01). Cuando se les comparó con el grupo MEM, los encuestados que recibieron PIP mostraron por una parte mayor probabilidad de indicar que PIP era más fácil de leer (χ² = 20.00, p < 0.001) y atractivo (χ² = 12.45, p < 0.001), y por otra, una mayor tendencia a recomendar la distribución de su material de lectura a otros pacientes (χ² = 22.11, p < 0.001). Se llegó a la conclusión de que es beneficioso disenar prospectos que simplifiquen el lenguajey la información médica contenida en las monografias estándar del medicamento, incluyendo una mejor comprensión de las precauciones a tomar mientras se está bajo medicación, y sobre cuándo consultar al médico.

Efeito do extrato aquoso de cabelo de milho (Zea mays L. ) sobre a excreção renal de água e eletrólitos e pressão arterial em ratos Wistar anestesiados / Effect of aqueous extract of corn silks (Zea mays L. ) on the renal excretion of water and electrolytes and arterial pressure in anesthetized Wistar rats

O milho (Zea mays L.) possui nos estigmas (cabelo de milho) substâncias que o tornam diurético, podendo ser importante no controle da hipertensão. No presente estudo, foi investigado o efeito do extrato aquoso (EA) do cabelo de milho sobre o fluxo renal de água (V) e eletrólitos e a pressão arterial (PA) em ratos Wistar anestesiados. Foram realizados 3 grupos: I) Controle - administração intragástrica (AI) de 1mL de água destilada; II) AI de 1 mL de EA de cabelo de milho a 20 por cento e III) AI de 1 mL de solução contendo furosemida. Canulou-se a artéria carótida esquerda para mensuração da PA, de 10 em 10 minutos, e a bexiga urinária, para mensuração de V de 30 em 30 minutos e da carga excretada dos íons sódio (Qe (Na+)) e potássio (Qe (K+)). Protocolo experimental: quatro períodos de 30 minutos cada: basal (avaliação dos parâmetros basais) e experimentais (Ex) 1, 2 e 3 (30, 60 e 90 minutos após a AI, respectivamente). O Grupo I não apresentou alterações significativas entre os períodos nos parâmetros analisados (p>0,05). O Grupo II apresentou aumento significativo (p<0,05) em V, em Qe (Na+) e em Qe (K+) nos períodos Ex2 e Ex3, com redução significativa na PA (p<0,05) em Ex2 e Ex3. Conforme esperado, o Grupo III apresentou aumento significativo em V nos períodos Ex2 (p<0,05) e Ex3 (p<0,001), aumento em Qe (Na+) em Ex1 (p<0,05), Ex2 (p<0,001) e Ex3 (p<0,001) e aumento em Qe (K+) em Ex2 (p<0,05) e Ex3 (p<0,001), com redução significativa na PA (p<0,05) em Ex2 e Ex3. Os dados mostram que o EA do cabelo de milho possui efeito diurético, porém não age como um diurético "de alça", uma vez que não levou à expoliação de potássio e nem a uma excreção tão acentuada de sódio quanto à furosemida.

The corn (Z. mays) has in its stigmas (corn silks) substances that make it diuretic, which may be important in hypertension control. In this study, the effect of aqueous extract (AE) of corn silks on the renal flow of water (V) and electrolytes and arterial pressure (AP) was investigated in anesthetized Wistar rats. Three groups were tested: I) Control - intragastric administration (IA) of 1mL of distilled water, II) IA of 1 mL of AE of corn silks at 20 percent and III) IA of 1 mL of a solution containing furosemide. Cannulation was performed in the left carotid artery to measure AP, at every 10 minutes, and in the urinary bladder to measure V, at every 30 minutes, and the excreted load of ions sodium (Qe (Na+)) and potassium (Qe (K+)). Experimental protocol: four periods of 30 minutes each: basal (evaluation of basal parameters) and experimental (Ex) 1, 2 and 3 (30, 60 and 90 minutes after IA, respectively). Group I had no significant differences between periods for the analyzed parameters (p>0.05). Group II presented a significant increase (p<0.05) in V, Qe (Na+) and Qe (K+) in periods Ex2 and Ex3, with significant reduction in AP (p<0.05) in Ex2 and Ex3. As expected, Group III had a significant increase in V in periods Ex2 (p<0.05) and Ex3 (p<0.001), an increase in Qe (Na+) in Ex1 (p<0.05), Ex2 (p<0.001) and Ex3 (p<0.001) and an increase in Qe (K+) in Ex2 (p<0.05) and Ex3 (p<0.001), with an important reduction in AP (p<0.05) in Ex2 and Ex3. These data show that AE of corn silks has a diuretic effect but does not act as a loop diuretic since it did not lead to potassium loss or marked sodium loss, compared to furosemide.

Acute-Onset Bilateral Myopia and Ciliochoroidal Effusion Induced by Hydrochlorothiazide

The authors experienced two cases of hydrochlorothiazide (HCTZ)-induced acute-onset bilateral myopia and shallowing of the anterior chambers. Two middle-aged women taking HCTZ, a sulfa derivative, visited our clinic complaining of acute bilateral visual deterioration. Both had good visual acuity without corrective lenses before taking HCTZ. A complete ophthalmologic examination revealed bilateral myopic shift, intraocular pressure elevation, shallowing of the anterior chambers, choroidal effusions, radiating retinal folds, and conjunctival chemosis. Approximately one week after HCTZ discontinuance, all ocular changes disappeared completely. Physicians should be aware of the adverse ocular effects of HCTZ and should manage patients accordingly.

Paracentesis evacuante en pacientes cirróticos con ascitis a tensión: revisión del tema / Therapeutic paracentesis in cirrhotic patients: a review

El desarrollo de ascitis es la complicación más frecuente del paciente con cirrosis hepática y generalmente marca el paso hacia la descompensación, con lo cual empeora el pronóstico y se deteriora la calidad de vida. Los estudios clínicos demuestran que aproximadamente el 50%de los pacientes cirróticos con ascitis no complicada mueren a los 2 años y que el 50% de los que desarrollan ascitis refractaria mueren a los 6 meses si no reciben tratamiento. Las medidas terapéuticas actuales en el paciente cirrótico con ascitis se encaminan a mantener un balance negativo de sodio, mediante la restricción del consumo de sal y el uso de diuréticos. Tales medidas pueden ser insuficientes en el caso de la ascitis a tensión, por lo que se requiere un tratamiento que mejore rápidamente la sintomatología y restaure la funcionalidad del paciente, además de medidas de soporte para prevenir la acumulación de líquido en la cavidad peritoneal y por ende reducir las enfermedades asociadas. Por lo anterior, la paracentesis evacuante seguida de fármacos diuréticos es el tratamiento de elección en los pacientes con ascitis a tensión.

The development of ascites is the most frequent complication of patients with hepatic cirrhosis; usually it leads to decompensation which is associated with worsening prognosis and deterioration of life quality. Clinical studies reveal that approximately 50%of cirrhotic patients with uncomplicated ascites die within two years while 50%of those with refractory ascites, if left untreated, die within six months. Currently, therapeutic measures in cirrhotic patients with ascites are designed to maintain a negative balance of sodium, which is achieved by a restricted salt intake and the use of diuretics. In the case of tense ascites those measures may be insufficient and, therefore, a treatment is required that quickly controls symptoms and improves function. Such treatment must be accompanied by support measures to prevent fluid accumulation in the peritoneal cavity, thus reducing the risk of associated diseases. Paracentesis of great volumes followed by diuretics is considered as the therapy of choice for managing patients with tense ascites.