Insulin autoimmune syndrome in an occidental woman: a case report and literature review

SUMMARY Insulin autoimmune syndrome (IAS, Hirata's disease) is a rare hypoglycemic disorder characterized by spontaneous hypoglycemia associated with extremely high circulating insulin levels and positive anti-insulin antibody results. Thus far, most cases have been reported in Asian countries, notably Japan, with few cases reported in western countries. As a possible cause, it is associated with the use of drugs containing sulfhydryl radicals, such as captopril. This report refers to a 63-year-old female Brazilian patient with a history of postprandial hypoglycemia. After extensive investigation and exclusion of other causes, her hyperinsulinemic hypoglycemia was considered to have likely been induced by captopril. Most cases of IAS are self-limiting. However, dietary management, corticosteroids, plasmapheresis, and rituximab have already been used to treat patients with IAS. In our case, after discontinuation of captopril, an initial decrease in insulin autoantibody levels was observed followed by improvement in episodes of hypoglycemia. Although it is a rare disease, IAS should be considered in the differential diagnosis of endogenous hyperinsulinemic hypoglycemia. Patients with suspected IAS must be screened for autoimmunity-related drugs for insulin. Initial clinical suspicion of IAS can avoid unnecessary costs associated with imaging examinations and/or invasive surgical procedures.

Mucosal-dominant pemphigus vulgaris in a captopril-taking woman with angioedema

AbstractWe describe a 39-year-old woman with an apparent captopril-induced, contact mucosal-dominant pemphigus vulgaris and angioedema, who took captopril during a bout of arterial hypertension. This exposure suggests that captopril and pathophysiology of angioedema stimulated the development of pemphigus vulgaris, which was diagnosed using the novel, indirect immunofluorescence BIOCHIP mosaic, with the modification to detect serum IgG4 autoantibodies. We discuss the patient, who experienced a chain of events leading to the active stage of pemphigus vulgaris, and review concepts of pemphigus vulgaris inducible by drugs and pathological immunity.

Severa hiponatremia induzida pela associação de fluoxetina, hidroclorotiazida e captopril em paciente jovem / Severe hyponatremia induced by the association of fluoxetine, hydrochlorothiazide and captopril in a young patient

Descrevemos um caso de hiponatremia grave, com um dos níveis séricos de sódio mais baixos da literatura, secundário ao uso de fluoxetina, captopril e hidroclorotiazida. Paciente do sexo feminino, 45 anos, portadora de hipertensão arterial , vinha assintomática em uso de hidroclorotiazida e captopril, quando, há um mês da internação. iniciou-se fluoxetina devido sintomas de depressão. Paciente foi internada por rebaixamento de nível de consciência, com tomografia computadorizada de crânio evidenciando edema cerebral...

We describe a case of severe hyponatremia, with some of the lowest levels of sodium in the literature, secondary to the use of fluoxetine, captropil and hydrochlorothiazide. A 45-year-old female patient suffering from arterial hypertension who was being treated with hydrochlorothiazide and captopril was asymptomatic until one month prior to hospitalization when treatment with fluoxetine was initiated due to depressive symptoms. The patient was hospitalized due to a lower level of consciousness. A CT scan of the skull revealed cerebral edema...

Potenciais interações medicamentosas em prescrições de um hospital-escola de Porto Alegre / Potential drug interactions among prescriptions of a teaching hospital in Porto Alegre

Introdução: Relatos das prevalências de interações medicamentosas em hospitais brasileiros são escassos. Objetivos: Descrever a prevalência de interações medicamentosas potenciais entre os fármacos prescritos nas enfermarias clínicas e cirúrgicas de um hospital-escola. secundariamente, descrever as características dessas interações e relacionar a sua ocorrência com o número de medicamentos prescritos e a idade dos pacientes. Pacientes e Métodos: Os dados foram coletados durante uma semana de out/2007, de 2a a 6a feira, a partir da última ficha de prescrição encontrada nos prontuários, envolvendo 128 fichas de prescrição com 10,5±4,1 fármacos. Os pacientes tinham 58,6±16,9 anos e 51,2% eram homens. A doença cardiovascular foi a enfermidade principal (23,4%) e a comorbidade (42,5%) mais frequentemente encontrada. A análise das interações foi feita através de consulta a um sistema interativo (Micromedex®). Resultados: 485 interações foram encontradas, estando presentes em 79,7% (IC95%: 72,6-86,8) das fichas de prescrição (média 3,8). A interação mais frequente foi captopril/dipirona (9,7%), seguida por dipirona/furosemida (4,5%), e os fármacos mais envolvidos foram dipirona (29,3%) e captopril (21,2%). A maioria das interações tinha mecanismo farmacodinâmico (65,5%), gravidade moderada (55,5%), começo tardio (61,3%) e bom embasamento científico (71,1%). A prevalência de interações esteve associada fortemente com o número de fármacos prescritos (r=0,65, p<0,001) e fracamente com a idade do paciente.

Introduction: Reports of the prevalence of drug interactions in Brazilian hospitals are scarce. Aims: To describe the prevalence of potential drug interactions among the medical drugs prescribed in the clinical and surgical units of a teaching hospital. Secondarily, to describe the characteristics of drug interactions and relate their occurrence to the number of prescribed medications and patient age. Patients and Methods: The data were collected from Monday to Friday of a week in Oct 2007, starting from the last prescription form found in the medical charts, and involved 128 prescription forms with 10.5±4.1 drugs. The patients’ mean age was 58.6±16.9 years and 51.2% were males. Cardiovascular disease was the main disease (23.4%) and the most frequently found comorbidity (42.5%). The analysis of interactions was done through consultation with an interactive system (Micromedex®). Results: 485 cases of drug interactions were found, being present in 79.7% (CI95%: 72.686.8) of the prescription forms (mean 3.8). The most frequent interaction was captopril/dipyrone (9.7%), followed by ipyrone/furosemide (4,5%), and the most frequently involved drugs were dipyrone (29.3%) and captopril (21.2%). Most of the interactions had a pharmacodynamic mechanism (65.5%), moderate severity (55.5%), late onset (61.3%), and a good scientific basis (71.1%). The prevalence of interactions was strongly associated with the number of drugs prescribed (r=0.65, p<0.001) and weakly associated with patient age.

Angiotensin converting enzyme inhibitors and aortic arch obstructive malformations.

We describe two newborn infants with aortic arch obstructive malformations who became anuric after initiation of captopril. Since angiotensin converting enzyme inhibitors can alter renal blood flow by reduction in angiotensin II and blocking autoregulation phenomenon, it is important to use them with great caution in neonates with aortic arch obstructive malformations, while monitoring their renal function closely.

Análise da cápsula de captopril manipuladas em farmácias / Analysis of compounded captopril capsules

Cápsulas de captropil 25mg elaboradas em quatro farmácias de manipulação localizadas no vale do Itajaí e na região norte do estado de Santa Catarina, foram analisadas em relação ao peso médio, teor de captropil e limite de dissulfeto de captopril, por HPLC em comparação com comprimidos de uma especialidade farmacêutica.Todas as amostras analisadas foram aprovadas quanto ao teor médio de captopril e limite de dissulfeto de captopril, indicando a qualidade da matéria-prima utilizada.Por outro lado, das quatro amostras adquiridas em farmácias de manipulação, duas foram reprovadas no ensaio de peso médio, provavelmente devido a problemas durante o encapsulamento.Estes dados denotam a necessidade da implementação do controle do processo a fim de garantir a qualidade dos produtos manipulados

Hipertensión renovascular: caso clínico / Renal vascular hypertension: clinical case

Se presenta un caso de hipertensión secundaria de causa renovascular, detectado en una mujer diabética de 74 años con historia de hipertensión severa de 28 años de evolución conocida, acentuada en los últimos 3 meses. En el caso analizado, la arteriografía renal fue normal pero el cintigrama demostró la existencia de isquemia renal bilateral frente al uso de captopril. Debe recordarse que a pesar de que la arteriografía es el "gold standar"para el diagnóstico de la hipertensión renovascular, su sensibilidad no es 100 por ciento, especialmente en los casos en que existe enfermedad de pequeños vasos. Dentro del estudio de esta paciente hubiese sido ideal realizar un exámen con ecografía Doppler, el que, asociado al cintigrama, aumenta el rendimiento diagnóstico en los casos de hipertensión por estenosis de los vasos intrarrenales. Se aprovecha el caso para analizar brevemente el diagnóstico de la hipertensión renovascular: sospecha clínica; exámenes de laboratorio; imágenes y estudio funcionales. Desde el punto de vista terapéutico, el tratamiento quirúrgico es el más indicado en las estenosis ateroescleróticas de la arteria renal y la angioplastía en las de naturaleza fibromuscular

Therapeutic trial of effective erythropoietin suppression in children affected with beta-thalassemia major: a three-year follow-up

A Three-year follow up study was conducted on 45 regularly transfused beta-thalassemic children; 23 of them were also given captopril therapy [6.25-12.5mg b.i.d.]. The aim was to evaluate the efficacy of captopril in inducing more effective suppression of erythropoiesis. Twenty age and sex matched controls were included at the end of study. All thalassemics were evaluated for their blood pressure [BP], hemoglobin [Hb], blood urea, serum creatinine, alkaline phosphatase, alanine aminotransferase, reticulocytic index [RI], serum ferritin, serum erythropoietin [sEpo] and serum transferrin receptors [s Tfr]; at the start and at the end of the study. Results showed that subjects given captopril, after 3 years therapy, had lower sEpo, sTfr and RI [31, 9, and 1.41 versus 60 mU/ml, 16 microg/ml, 2.3 respectively]; less incidence of splenomegaly [39 versus 77%]; higher height velocity and weight values; compared to thalassemics without captopril therapy [P<0.05]. Captopril used in regularly transfused beta-thalassemics could induce better suppression of endogenous erythropoiesis with reasonable cost, fair compliance and no side effects

Captopril associado a didroclorotiazida no tratamento da hipertensäo leve e moderada / Association of captopril and hydrochlorothiazide in mild and moderate hypertension. A Brazilian multicenter study

Objetivo - Avaliar a eficácia e tolerabilidade da associação de captopril 50mg com hidrocloratiazida 25 mg em hipertensos com pressão arterial diastólica (PAD) entre 95 e 115mmHg. Métodos - Estudo aberto, multicêntrico, não comparativo. Na fase inicial, durante 2 semanas, os pacientes receberam placebo, seguida de ½ comprimido da associação. Os pacientes foram avaliados após 4,8 e 12 semanas. Após 8 semanas de tratamento, naqueles em que a PAD foi >90mmHg, foi prescrito um comprimido/dia. Resultados - Foram analisados 433 pacientes, com idades de 47+10 anos, sendo 30 por cento mulheres e 76 por cento brancos. As pressões sistólica/diastólica iniciais foram de 156+16/103+11 mmHg, após 14 dias de placebo, 156+15/103+9 mmHg (p>0,05) e, após 4,8 e 12 semanas, mostraram progressiva redução (p<0,05) para 143+14/95+11, 140+13/91+9 e 134+11/86+8 mmHg. O controle pressórico foi observado em 45, 67 e 88 por cento (p<0,05), após 4,8 e 12 semanas. Tosse foi o sintoma mais importante registrado em 7 por cento dos pacientes em placebo e 12 por cento nos que usavam a associação. A tolerabilidade foi considerada boa por 98 por cento dos pacientes. Conclusão - A associação de captopril com hidroclotiazida é eficaz e tem boa tolerabilidade, sendo prescrita em dose única diária em monoterapia, para hipertensos leves e moderados.

Angiotensin converting enzyme inhibitors and cough--a north Indian study.

Cough is an important side effect of Angiotensin Converting Enzyme Inhibitor (ACEI) therapy. The incidence of cough was investigated in a prospective 8 week study in 250 hypertensive patients receiving ACEI alone or in combination with other agents. Enalapril (5-20 mg/day), Lisinopril (5-20 mg/day), Captopril (25-75 mg/day) or Ramipril (5-15 mg/day) was prescribed to patients, who were followed up at weekly visits. Cough developed in 73 of the 250 patients i.e. an incidence of 29.2%. Females had a higher incidence of cough as compared to males--37.9% versus 15.5% (p < 0.001) and there was no significant difference in the cough incidence in the various age groups. A dry, non-productive cough developed in all patients within 4 weeks of ACEI initiation. Increased nocturnal intensity of cough was reported by 79.4% patients. Cough incidence was 34.4%, 24.3% and 18.1% in patients on Enalapril, Ramipril and Lisinopril, respectively. Cough was not dose related and was not related to smoking. There was no statistically significant difference among patients on ACEI alone or in combination with beta blockers, calcium channel blockers or diuretics. Of the 18 patients with ACEI induced cough who received Indomethacin, 50 mg bid, 8 reported complete cure and cough was reduced in intensity in the remaining ten.

Uso de captopril durante a gestaçäo e suas repercussöes sobre o feto e o recém-nascido: relato de caso / Neonatal and fetal effects of captopril use in pregnancy: case report

Os inibidores da enzima conversora da angiotensina tem sido largamente utilizados para o controle da hipertensao, mas o uso destes durante a gestacao pode provocar obito fetal, retardo de crescimento intra-uterino, sequencia de oligamnio, hipotensao e insuficiencia renal aguda no periodo neonatal e persistencia de canal arterial. O objetivo e chamar a atencao para os possiveis efeitos neonatais do uso desta droga durante a gestacao. Os autores descrevem um caso de uso de captopril durante a gestacao, cujo RN apresentou insuficiencia renal aguda logo apos o nascimento e persistencia de canal arterial necessitando de tratamento clinico...

Nifedipine, captopril, metoprolol and nifedipine with metoprolol in hypertensive crisis in non-intensive care setting.

In 102 cases of severe hypertension (DBP > or = 115 mm Hg), with or without acute complications, efficacy and safety of SL Nifedipine 10 mg (NIF), SL Captopril 25 mg (CAP), IV Metoprolol 15 mg (MET) and SL NIF + IV MET were studied in an inpatient trial. Maximum mean percent reduction in SBP was 13.3, 9.7, 15.7 and 19.9 and in DBP was 21.2, 13.9, 12.5 and 20.4 with NIF, CAP, MET and NIF + MET respectively. A safe DBP of < or = 110 mm Hg (Kaplan) was achieved in 90, 61, 72.2 and 95.2 percent of patients. A statistically significant fall in DBP was observed at 5 minutes with all regimens except CAP which was at 15 minutes. Mild side effects observed were palpitations and flushing (NIF n = 4), taste disturbances (CAP n = 3), heaviness of head (CAP n = 1) and giddiness (MET n = 2, NIF + MET n = 2). The trial data suggest that hypertensive crisis can be managed, without intensive care facility, with all four regimens; this implies significant cost containment.

Assessment of renal artery stenosis with captopril renography followed by its treatment with angioplasty

To review the important pathophysiological changes in renal haemodynamics and in the rennin-angiotensin-aldosterone axis in response to significant renal artery stenosis and the effect of an angiotensin-converting enzyme inhibitor [captopril] on the function of the affected kidney. Hypertension due to renal artery stenosis is the most common of the curable forms of hypertension. Its early identification can best be accomplished by angiography which is invasive and inadvisable as a routine test. Captopril renography is accepted as the least invasive screening test available. Our experience with captopril renography as a screening test for renal artery stenosis as an aid to selecting patients for angiography and angioplasty is described. Twenty-nine hypertensive patients presenting with a suspicion of renal artery stenosis were studied with 99mTc-diethylenetriaminepentaacetic acid renography both before and after captopril administration. The test has been found to have a good sensitivity [100%] and a good specificity [89%]. Our results confirm the value of the test in selecting patients for angiography

Reversible neonatal renal failure associated with maternal use of captopril

We report a case of neonatal hypotension and reversible renal failure in a newborn, delivered to a mother who was known to have hypertension. The mother required a battery of anti-hypertensives including captopril, through pregnancy until delivery. We agree with other reports that there is a possible association of acute neonatal renal failure following maternal use of captopril

Efectos del captopril en el apetito y la ingestión de alcohol en alcohólicos / Effects of captopril in appetite and alcohol consumption in alcoholics

El captopril ha mostrado la propiedad de disminuir el consumo de alcohol de ratas y también en un ensayo con un grupo de voluntarios sanos. Dada la importancia de esta proyección en la terapéutica de los alcohólicos, decidimos probar sus efectos en un grupo de ellos. La muestra fue un grupo de 14 alcohólicos diagnosticados según criterios DSM-III-R. El ensayo terapéutico fue randomizado, doble ciego y se usó placebo y captopril durante 12 semanas. Los resultados mostraron que ambos tratamientos redujeron significativamente: las cantidades de tragos estándar de alcohol ingeridas, el número de días de embriagueces semanales y de días de apetito alcohólico por semana y la intensidad del apetito. En este período, se embriagaron sólo el 43 por ciento de las veces que sintieron apetito, la gran mayoría de las veces con un apetito de intensidad leve o moderada, y a veces sin apetito. Concluimos que el efecto del captopril y del placebo son semejantes, que el apetito por alcohol no parece decisivo en la ingesta y que la motivación de los pacientes, el apoyo de su familia y del grupo profesional que los atendieron, explicaría los resultados favorables obtenidos

Ramipril vs captopril in mild to moderate hypertension.

Ramipril 5 mg once daily was compared to Captopril 50 mg twice daily in a randomised, double-blind, parallel group study in 60 patients with a diastolic blood pressure between 95 to 120 mmHg over a period of 2 months. Both drugs in the dose regimen used in this study exerted a similar anti-hypertensive effect at the end of 2 months of treatment resulting in a fall of supine diastolic blood pressure with Ramipril = 19.27 +/- 3.34 mmHg and Captopril = 19.15 +/- 2.63, in patients receiving the drugs without the diuretic. The mean fall in supine diastolic blood pressure 4 hours after the first dose of Ramipril was 6.5 mmHg and Captopril 8 mmHg. None of the patients developed first dose hypotension or orthostatic hypotension and there was no significant alteration of the heart rate in either group. The serum K+ levels remained unchanged in both groups of patients. Both drugs were well tolerated and there were no adverse effects observed on the liver, kidney, blood sugar or haemopoietic system. Based on the results of this study, it can be concluded that the antihypertensive efficacy of 5 mg ramipril in a once daily dose is equivalent to 50 mg captopril given twice daily. However an appreciably greater number of patients reported improvement in the "quality of life' parameters with ramipril as compared to captopril. Thus for the routine treatment of mild to moderate arterial hypertension, ramipril offers reliable antihypertensive efficacy in a once daily dose, thereby helping to improve patient compliance and making the treatment more economical.

Estudo aberto comparativo captopril + hidroclorotiazida versus clortalidona para tratamento da hipertensäo primária leve e moderada / An open comparative study of captopril + hydrochlorothiazide versus chlorthalidone for the treatment of mild and moderate primary hypertension

Objetivo - Comparar o efeito anti-hipertensivo e alterações metabólicas da associação captopril + hidroclorotiazida (C+HCTZ) contra clortalidona (CT) para tratamento de hipertensão arterial primária leve e moderada. Métodos - cinqüenta e cinco pacientes que tiveram a sua medicação anti-hipertensiva suspensa por 15 dias ou sem tratamento prévio, foram randomizados para tratamentos com a associação captopril 50mg + hidroclorotiazida 25mg (n=29) ou clortalidona 50mg (n=26). A avaliação clínica foi realizada previamente à medicação e mensalmente durante 3 meses e os exames laboratoriais foram feitos no início e ao final do estudo. Resultados - A pressão arterial (PA) no período placebo não foi diferente entre os grupos (C+CHTZ: 161 ± 25/102 ± 6 - CT: 155 ± 18/101 ± 6 mmHg), porém a diminuição da pressão diastólica já no 1° mês foi estatisticamente significante no grupo C+HCTZ (89±8 mmHg) comparado ao grupo CT (94±8 mmHg, p<0,05). O perceptual de queda da PA diastólica em média, de 12% no grupo C+HCTZ e no grupo CT variou de 7 (1° e 2° mês) a 11% (3° mês). Embora sem diferença estatística, obteve-se normalização pressórica em 69% dos pacientes com captopril associado ao diurético e, em 50%, com clortalidona. Observou-se uma redução significativa da potassemia com clortalidona (4,2±0,7 para 3,7±0,4 mEq/L, p<0,01) e manutenção dos níveis de potássio com associação captopril e tiazídico. Este último tratamento também reduziu significativamente os níveis de colesterol (219±39 mg/dl para 202±39 mg/dl, p<0,04). Conclusão - Os resultados mostraram que a associação de captopril com dose baixa de tiazídico normaliza a PA em 69% de pacientes portadores de hipertensão arterial primária leve e moderada e age mais rapidamente que a clortalidona no controle pressórico, apresentando efeito metabólico benéfico de reduzir os níveis de colesterol sem alterar a potassemia

Purpose - To compara the antihypertensive and metabolic effects of captopril combined with hydrochlorothiazide (C+HCTZ) versus chlorthalidone (CT) in mild and moderate primary hypertensive patients. Methods - Fifty five patients, whithout treatment or treated with 15 days placebo were randomized for treatment with the combination of captopril 50mg and hydrochlorothiazide 25mg (n=29) against chlorthalidone (n=26). The clinical evaluation was done during placebo and monthly throughout three months, and the laboratory tests were done before and at the end of the study. Results - The blood pressure were similar between groups during placebo period (C+HCTZ: 161±25/102±6 - CT: 155±18/101±6 mmHg); the diastolic blood pressure decreases significantly at first month already in the group C+HCTZ (89±8 mmHg) comparad to group CT (94±8 mmHg, p<0,05). The percentile diastolic and mean blood pressure dropped, in average, 12% in C+HCTZ group and in CT varied between 7 (1st and 2nd month) to 11% (3rd month). Without statistical difference, the blood pressure normalization was obtained in 69% of the patients with the association captopril and diuretic and in 50% of the patients in the chlorthalidone group. It was observed a significant reduction of potassium in patients treated with chlorthalidone (4,2±0,7 to 3,7±0,4 mEq/L, p<0,01) that was not observed with the captopril and the thyazide associated. The last treatment also significantly reduced the cholesterol levels (219±39mg/dl to 202±39mg/dl, p<0,04). Conclusion - Our results indicate that captopril combined with low diuretic dose normalize the blood pressure in 69% mild to moderate primary hypertensive patients, and acts faster than chlorthalidone in this control. In addition has metabolic benefits reducing cholesterol levels with no alteration in potassium levels

Comparaçäo de captopril e Enalapril em pacientes com insuficiência cardíaca crônica severa / Comparison of captopril and Enalapril in patients with severe chronic heart failure

A fim de avaliar o conceito de que a açäo de longa duraçäo é uma propriedade vantajosa dos inibidores da enzima conversora da angiotensina no tratamento da insuficiência cardíaca severa escolhemos e randomizamos 42 pacientes para o tratamento com um inibidor de curta açäo (Captopril, 150mg/dia) ou com um inibidor de açäo prolongada (Enalapril, 40mg/dia), durante um a três meses, enquanto a terapia com digoxina e diuréticos era mantida constante. Os grupos de tratamento possuíam características hemodinâmicas e clínicas similares na avaliaçäo inicial e respostas iniciais similares com relaçäo à inibiçäo da enzima conversora. Durante a terapia prolongada, captopril e Enalapril produziram reduçäo similares na pressäo arterial sistólica, mas os efeitos hipotensivos do Enalapril foram mais prolongados e persistentes do que aqueles do Captopril. Consequentemente, embora os pacientes de ambos os grupos melhorassem hemodinamicamente e clinicamente durante o estudo, observou-se hipotensäo sintomática séria (síncope e pré-sincope) primeiramente naqueles pacientes tratados com Enalapril. A hipotensäo prolongada provavelmente também contribuiu para o declínio do clearance de creatinina (P < 0,05) e a destacada retençäo de potássio (P < 0,05) observada nos pacientes tratados com Enalapril, mas näo naqueles tratados com Captopril. Concluímos que quando säo utilizadas doses altas e fixas de inibidores da enzima conversora no tratamento de pacientes com insuficiência cardíaca crônica, severa, os agentes de longa açäo podem produzir efeitos hipotensores prolongados que podem comprometer as funçöes cerebrais e renais e, conseqüentemente, levar desvantagem quando comparados com agentes de curta açäo