RESUMO
STUDY OBJECTIVE: To assess the efficacy and safety of intravenous (IV) chlorothiazide versus oral metolazone when added to loop diuretics in patients with acute decompensated heart failure (ADHF) and loop diuretic resistance. DESIGN: Retrospective cohort study. SETTING: Large urban academic medical center. PATIENTS: Adults admitted with ADHF between 2005 and 2015 who had loop diuretic resistance, defined as administration of IV furosemide at a dose of 160 mg/day or higher (or an equivalent dose of IV bumetanide), during hospitalization, and who then received at least one dose of IV chlorothiazide (88 patients) or oral metolazone (89 patients) to augment diuresis. MEASUREMENTS AND MAIN RESULTS: The primary efficacy end point was a change in 24-hour net urine output (UOP) from before to after thiazide-type diuretic administration, and the study was designed to test for the noninferiority of metolazone. Safety end points included changes in renal function and electrolyte concentrations. The mean dose of IV loop diuretic therapy (in IV furosemide equivalents) at baseline (before thiazide-type diuretic administration) was higher in the chlorothiazide group (mean ± SD 318.9 ± 127.7 vs 268.4 ± 97.6 mg/day in the metolazone group, p=0.004), but net UOP was similar (mean ± SD 877.0 ± 1189.0 ml in the chlorothiazide group vs 710.6 ± 1145.9 ml in the metolazone group, p=0.344). Mean doses of chlorothiazide and metolazone were 491 ± 282 mg and 5.8 ± 3.5 mg, respectively. Following thiazide-type diuretic administration, net UOP improved to a similar degree (2274.6 ± 1443.0 ml vs 2030.2 ± 1725.0 ml in the chlorothiazide and metolazone groups, respectively, p=0.308). For the primary efficacy end point, metolazone met the threshold for noninferiority by producing a net UOP of 1319.6 ± 1517.4 ml versus 1397.6 ± 1370.7 ml for chlorothiazide (p=0.026 for noninferiority). No significant differences in renal function were observed between the groups. Although hypokalemia was more frequent in the chlorothiazide group (75% with chlorothiazide vs 60.7% with metolazone, p=0.045), no significant differences in the rates of severe hypokalemia or other electrolyte abnormalities were observed between the groups. CONCLUSION: Oral metolazone was noninferior to IV chlorothiazide for enhancing net UOP in patients with ADHF and loop diuretic resistance and was similarly safe with regard to renal function and electrolyte abnormalities. Given the significant cost disparity between the two agents, these findings suggest that oral metolazone may be considered a first-line option in this patient population.
Assuntos
Clorotiazida/uso terapêutico , Diuréticos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Metolazona/uso terapêutico , Doença Aguda , Administração Intravenosa , Administração Oral , Adulto , Idoso , Clorotiazida/efeitos adversos , Estudos de Coortes , Resistência a Medicamentos , Feminino , Humanos , Masculino , Metolazona/efeitos adversos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To report our experience in treating infants and toddlers with central diabetes insipidus (DI) with thiazide diuretics. STUDY DESIGN: A retrospective chart review of all infants and toddlers who were treated with thiazide diuretics for central DI at the Mayo Clinic between 1996 and 2014. RESULTS: Our cohort consisted of 13 patients. The median age at the start of therapy was 6 months (IQR, 1-14 months). Eight patients were given chlorothiazide at a starting dose of 5-10 mg/kg/day, and 5 patients were treated with hydrochlorothiazide at a starting dose of 1-2 mg/kg/day. The median age at the cessation of thiazide therapy was 18 months (IQR, 11.5-39 months). The main reason for stopping was the lack of continued response, in addition to hypernatremia. There was no hospitalization secondary to hyponatremia and only 1 hospitalization secondary to hypernatremia while receiving thiazide therapy. Calcium was checked periodically in 7 of the 13 patients, and 2 of these 7 patients had persistent hypercalcemia. CONCLUSION: Thiazide diuretics appear to be safe and effective in treating infants with central DI. They can be continued after the introduction of solid food, and until a lack of response is observed.
Assuntos
Diabetes Insípido Neurogênico/tratamento farmacológico , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico , Glicemia/análise , Cálcio/sangue , Clorotiazida/uso terapêutico , Feminino , Humanos , Hidroclorotiazida/uso terapêutico , Lactente , Recém-Nascido , Masculino , Potássio/sangue , Estudos RetrospectivosRESUMO
Fatty acids play an important role in regulating insulin secretion, but the mechanisms are unclear. We report a case of a novel splice site mutation in the short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) gene associated with hyperinsulinism. This mutation resulted in a nearly complete absence of immunoreactive protein and a decrease in fibroblast SCHAD activity.
Assuntos
3-Hidroxiacil-CoA Desidrogenases/genética , Hiperinsulinismo/genética , 3-Hidroxiacil-CoA Desidrogenases/metabolismo , Clorotiazida/uso terapêutico , Diazóxido/uso terapêutico , Diuréticos , Humanos , Hiperinsulinismo/tratamento farmacológico , Lactente , Masculino , Mutação Puntual , Inibidores de Simportadores de Cloreto de Sódio/uso terapêuticoRESUMO
La hipertension arterial (HTA) es un factor de riesgo para enfermedad cardiovascular y es considerada como un problema de salud pública. La HTA constituye una sobrecarga de presión, que induce en el corazón una serie de modificaciones anatómicas y funcionales para compensar esta sobrecarga y esto se logra a través de la hipertrofia del ventrículo izquierdo (HVI). La HVI constituye un factor de riesgo independiente para mortalidad cardiovascular en pacientes con HTA; por consiguiente, la utilización de diferentes fármacos antihipertensivos, pueden reducir y/o revertir la HVI. Evaluar la eficacia de la combinación de bisoprolol con hidroclorotiazida en la reducción de la presión arterial (PA) y masa del ventrículo izquierdo (MVI), en pacientes con HTA y compararlo con el uso de un IECA. El presente estudio clínico controlado y doble ciego, evaluó la regresión de la HVI, en 19 pacientes hipertensos asignados al azar en dos: grupo A (n=10) recibió la combinación de bisoprolol con hidroclorotiazida y el grupo B (n=9) recibió enalapril, durante 6 meses, 16 pacientes completaron el estudio. Se observó reducción significativa de la MVI al 3er y 6to mes de tratamiento en los pacientes tratados con la combinación de bisoprolol con hidroclorotiazida (p<0,05). La reducción de la HVI en los pacientes tratados enalapril ocurrió al 6to mes y no fue significativo (p>0,05). Ambos medicamentos redujeron la PA (p<0,05) 7 pero esta fue mayor en el grupo A (bisoprolol con hidroclorotiazida). La combinación de bisoprolol con hidroclorotiazida es más efectiva en la reducción de la PA y MVI en pacientes con HTA estadio I y II que el enalapril
Assuntos
Humanos , Masculino , Adolescente , Adulto , Feminino , Pessoa de Meia-Idade , Bisoprolol , Clorotiazida , Eficácia , Enalapril , Hipertensão/diagnóstico , Hipertensão/terapia , Pressão Sanguínea , Farmacologia , Terapêutica , VenezuelaRESUMO
Se comunica una paciente de 44 años de edad que presentaba lesiones kaposiformes profusas, manifestación cutánea infrecuente del síndrome antifosfolípido. Se describen las características clínicas, los hallazgos de laboratorio, así como el tratamiento de esta enfermedad multisistémica (AU)
Assuntos
Humanos , Adulto , Feminino , Síndrome Antifosfolipídica/diagnóstico , Anticorpos Antifosfolipídeos , Trombose/etiologia , Doença Medicamentosa , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/complicações , Fenotiazinas/efeitos adversos , Procainamida/efeitos adversos , Clorpromazina/efeitos adversos , Hidralazina/efeitos adversos , Clorotiazida/efeitos adversos , Etossuximida/efeitos adversos , Fenitoína/efeitos adversos , Penicilinas/efeitos adversos , Quinina/efeitos adversos , Quinidina/efeitos adversos , Anticoncepcionais Orais/efeitos adversos , Anticoncepcionais Orais Hormonais/efeitos adversos , Anticoncepcionais Orais Sintéticos/efeitos adversos , Estreptomicina/efeitos adversos , Pirimetamina/efeitos adversos , Interferon-alfa/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversosRESUMO
Se comunica una paciente de 44 años de edad que presentaba lesiones kaposiformes profusas, manifestación cutánea infrecuente del síndrome antifosfolípido. Se describen las características clínicas, los hallazgos de laboratorio, así como el tratamiento de esta enfermedad multisistémica
Assuntos
Humanos , Adulto , Feminino , Anticorpos Antifosfolipídeos , Doença Medicamentosa , Síndrome Antifosfolipídica/diagnóstico , Trombose , Anticoncepcionais Orais Sintéticos/efeitos adversos , Bloqueadores dos Canais de Cálcio , Clorotiazida , Clorpromazina , Anticoncepcionais Orais , Anticoncepcionais Orais Hormonais , Etossuximida , Fenitoína/efeitos adversos , Hidralazina , Interferon-alfa , Penicilinas , Fenotiazinas , Procainamida , Pirimetamina , Quinidina , Quinina , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/tratamento farmacológico , EstreptomicinaRESUMO
A 2-month-old child with infantile hypophosphatasia had hypercalcemia (3.49 mmol/L (14 mg/dl)), nephrocalcinosis, and diminished bone mineral content. Hypercalcemia was corrected with calcitonin. Hypercalciuria and bone demineralization abated with chlorothiazide. Hypercalcemia is hypothesized to be related to normal bone resorption in conjunction with impaired bone mineralization. Chlorothiazide may alleviate this impairment.
Assuntos
Reabsorção Óssea/tratamento farmacológico , Calcitonina/uso terapêutico , Clorotiazida/uso terapêutico , Hipofosfatasia/tratamento farmacológico , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico , Cálcio/urina , Diuréticos , Feminino , Humanos , Hipercalcemia/prevenção & controle , Hipofosfatasia/complicações , Hipofosfatasia/metabolismo , Lactente , Nefrocalcinose/complicações , Nefrocalcinose/tratamento farmacológico , Nefrocalcinose/metabolismoRESUMO
STUDY OBJECTIVE: To determine whether long-term oral diuretic therapy would improve the pulmonary function of preterm infants with bronchopulmonary dysplasia. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Level III intensive care nursery. INTERVENTION: We randomly selected 43 stable patients with oxygen-dependent bronchopulmonary dysplasia to receive either orally administered spironolactone and chlorothiazide or placebo. These drugs were continued until the patients no longer required supplemental oxygen. Both groups received furosemide as needed. MEASUREMENTS AND RESULTS: Each infant had pulmonary function tests at study entry, 4 weeks after study entry, 1 week and 8 weeks after being weaned to room air and off study drugs, and at 1 year of corrected age. Pulmonary function tests include dynamic pulmonary compliance, airway resistance, thoracic gas volume, and maximal expiratory flow at functional residual capacity; most of the infants had functional residual capacity measured. Between the first and second pulmonary function tests (while the infants were receiving diuretic or placebo), the infants in the diuretic group had a significant improvement in dynamic pulmonary compliance (46%; p < 0.001) and airway resistance (31%; p < 0.05); there were no changes in compliance or resistance in the placebo group. Although patients in both the diuretic and the placebo groups required progressively less supplemental oxygen, by 4 weeks after study entry the patients in the diuretic group needed less supplemental oxygen than did those in the placebo group (p < 0.01). There were no significant differences in results of serial pulmonary function tests in either group after discontinuation of diuretic therapy. Despite the significant differences in pulmonary function between the two groups, there was no significant difference between them in the total number of days that supplemental oxygen was required. Significantly more infantsin the placebo group received more than 10 doses of furosemide on an as-needed basis. CONCLUSIONS: Long-term diuretic therapy in stable infants with oxygen-dependent bronchopulmonary dysplasia, after extubation, improves their pulmonary function and decreases their fractional inspired oxygen requirement, but does not decrease the number of days that they require supplemental oxygen. The improvement in pulmonary function associated with diuretic therapy is not maintained after treatment is discontinued.
Assuntos
Displasia Broncopulmonar/tratamento farmacológico , Clorotiazida/uso terapêutico , Espironolactona/uso terapêutico , Análise de Variância , Displasia Broncopulmonar/fisiopatologia , Displasia Broncopulmonar/terapia , Clorotiazida/farmacologia , Método Duplo-Cego , Quimioterapia Combinada , Furosemida/uso terapêutico , Humanos , Lactente , Recém-Nascido , Oxigenoterapia , Estudos Prospectivos , Mecânica Respiratória/efeitos dos fármacos , Espironolactona/farmacologiaRESUMO
We studied the effects of orally administered theophylline and diuretics (chlorothiazide and spironolactone) on pulmonary mechanics in 16 infants with bronchopulmonary dysplasia. Their gestational age (mean +/- SD) was 28.5 +/- 3.4 weeks, and postnatal age at the time of study 19.5 +/- 10.7 weeks. The infants were randomized to two groups. Group 1 received successively placebo, theophylline, and theophylline plus diuretics; Group 2 received theophylline, placebo, and placebo plus diuretics on successive 4-day periods. Pulmonary function was measured before beginning the study (baseline) and at the end of each 4-day period. No significant changes in pulmonary function were noted after treatment with placebo. After treatment with theophylline, dynamic compliance (Cdyn) increased from baseline (mean +/- SD) 0.075 +/- 0.017 to 0.091 +/- 0.028 mL/cm H2O/cm (P less than 0.01), airway resistance (Raw) decreased from 67.19 +/- 36.71 to 41.44 +/- 22.50 cm H2O/L/sec (P less than 0.001), maximal expiratory flow at functional residual capacity (VmaxFRC) increased from 0.261 +/- 0.240 to 0.357 +/- 0.299 thoracic gas volume (TGV)/sec (P less than 0.01), and time constant decreased from 0.312 +/- 0.224 to 0.275 +/- 0.247 sec (P less than 0.02). After treatment with combined placebo and diuretics, Cdyn increased to 0.103 +/- 0.023 mL/cm H2O/cm (P less than 0.05), Raw decreased to 31.76 +/- 24.90 cm H2O/L/sec (P less than 0.001), VmaxFRC increased to 0.638 +/- 0.595 TGV/sec (P less than 0.02), and time constant decreased to 0.180 +/- 0.141 sec (P less than 0.05). After treatment with combined theophylline and diuretics, Cdyn increased to 0.118 +/- 0.017 mL/cm H2O/cm (P less than 0.001), Raw decreased to 35.98 +/- 25.85 cm H2O/L/sec (P less than 0.02), VmaxFRC increased to 0.479 +/- 0.377 TGV/sec (P less than 0.02), and time constant decreased to 0.180 +/- 0.137 sec (P less than 0.01). We conclude that theophylline and diuretics have additive effects on the improvement of pulmonary function in infants with bronchopulmonary dysplasia.
Assuntos
Displasia Broncopulmonar/tratamento farmacológico , Clorotiazida/uso terapêutico , Pulmão/efeitos dos fármacos , Espironolactona/uso terapêutico , Teofilina/uso terapêutico , Administração Oral , Ensaios Clínicos como Assunto , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Lactente , Recém-Nascido , Medidas de Volume Pulmonar , Ventilação Pulmonar/efeitos dos fármacos , Distribuição AleatóriaRESUMO
The antidiuretic effect of two prostaglandin synthetase inhibitors, ibuprofen (25 mg/kg/day) and indomethacin (2 mg/kg/day), was studied in patients aged 8 to 18 years with hereditary nephrogenic diabetes insipidus. Ibuprofen (studied in five patients) did not have demonstrable effects on urine volume, free water clearance, or osmolar clearance, but fractional excretion of sodium decreased from a mean of 0.38% to 0.19% (P less than 0.05). In contrast, indomethacin (studied in three patients) was associated with a decrease in mean urine volume from 5.8 to 2.8 mL/min and a decrease in mean free water clearance from 3.1 to 1.1 mL/min (both P less than 0.05). Fractional excretion of sodium decreased from 0.77% to 0.27% (P less than 0.01) and was accompanied by an increase in serum urea nitrogen level (P less than 0.01) and a decrease in urea nitrogen clearance (P less than 0.025). Thus, prostaglandin synthetase inhibitors are not uniformly effective in treatment of nephrogenic diabetes insipidus. The inhibitory effect of indomethacin on urine volume and free water clearance in our patients may have been mediated by an enhancement of antidiuretic hormone (ADH)-stimulated cyclic adenosine monophosphate generation, or by increased ADH-independent water reabsorption resulting from an increase in solute reabsorption and consequent medullary hypertonicity.
Assuntos
Inibidores de Ciclo-Oxigenase , Diabetes Insípido/tratamento farmacológico , Ibuprofeno/uso terapêutico , Indometacina/uso terapêutico , Adolescente , Nitrogênio da Ureia Sanguínea , Criança , Clorotiazida/uso terapêutico , Ensaios Clínicos como Assunto , Diabetes Insípido/genética , Diurese/efeitos dos fármacos , Quimioterapia Combinada , Humanos , Capacidade de Concentração Renal/efeitos dos fármacos , Masculino , Natriurese/efeitos dos fármacos , Concentração Osmolar , UrinaRESUMO
A prospective study of 99 premature infants with severe respiratory distress syndrome who were randomly assigned to receive diuretic treatment with either furosemide or chlorothiazide was analyzed to examine the relationship of diuretic administration and diuresis to survival and to the duration and degree of mechanical ventilatory support. Subjects were given a diuretic, usually beginning on the second or third day of life, if they had not initiated the expected spontaneous diuresis and did not show pulmonary improvement. Infants given furosemide experienced a postnatal weight loss nearly identical to that in infants who were deemed not to need a diuretic; infants given chlorothiazide lost weight more slowly and had significantly greater body weight on postnatal days 4 and 5. Four factors were independently correlated with improved survival: furosemide usage, high birth weight, low initial mean airway pressure, and the absence of intraventricular hemorrhage. Ventilator mean airway pressure on the seventh day of life and duration of mechanical ventilation were both related to diuresis. These data provide additional evidence for the importance of water homeostasis in determining the course of respiratory distress syndrome in premature infants and indicate that furosemide administration is beneficial when spontaneous diuresis does not occur. Furosemide may be particularly effective if combined with early closure of the ductus arteriosus.
Assuntos
Diurese/efeitos dos fármacos , Doenças do Prematuro/fisiopatologia , Pulmão/fisiopatologia , Síndrome do Desconforto Respiratório do Recém-Nascido/fisiopatologia , Clorotiazida/uso terapêutico , Ensaios Clínicos como Assunto , Permeabilidade do Canal Arterial/tratamento farmacológico , Permeabilidade do Canal Arterial/mortalidade , Permeabilidade do Canal Arterial/fisiopatologia , Furosemida/uso terapêutico , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/tratamento farmacológico , Doenças do Prematuro/mortalidade , Estudos Prospectivos , Respiração Artificial , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Síndrome do Desconforto Respiratório do Recém-Nascido/mortalidadeRESUMO
The antihipertensive effect of a diuretic (dihidrochlorothiazide 100-200 mgr.), a betablocker (propranolol 20-180 mgr.) and the vasodilating agent minoxidil (25-70 mgr.), administered daily during 10-16 weeks, was asessed in 18 patients with refractory arterial hypertension (RAH). The arterial blood pressure (mm. of Hg.) differences obtained at the end of a 2 weeks diuretic period and at the end of the triple theraphy period was --53.1 +/- 18.1, p less than or equal to 0.001 (mean, standard deviation and significance) and --26.5 +/- 11.8, p less than or equal to 0.001, for clinostatic sistolic and diastolic pressures, respectively and --45.7 +/- 24.1, p less than or equal to 0.001 and --21.6 +/- 40 (p less than or equal to 0.001) for orthostatic sistolic and diastolic pressures, respectively. 66.6% of cases normalized the blood pressure at the end of the protocol. No significant changes were observed in body weight and pulse rate. In 94.4, 66.6 and 16.6% of cases appeared hypertricosis lanuginosa; edema or palpitations, respectively, as theraphy related symptoms. RAH is an entity of poor prognosis and difficult therapheutic management. In this study a significant antihipertensive response was achieved, which was superior to the one obtained in a similar population treated with other regimens in the same clinic. Despite the opposed attitude to continue the treatment exihibited by most female patients, we believe that minoxidil has enriched the therapheutic armamentarium of this dreadfull type of hypertension.
Assuntos
Anti-Hipertensivos/uso terapêutico , Clorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Minoxidil/uso terapêutico , Propranolol/uso terapêutico , Pirimidinas/uso terapêutico , Clorotiazida/administração & dosagem , Quimioterapia Combinada , Humanos , Minoxidil/administração & dosagem , Propranolol/administração & dosagem , Resistência Vascular/efeitos dos fármacosRESUMO
The case of a 28 year-old man in whom diabetes insipidus appeared 24 hours after Pantopaque myelography is reported. This unusual complication, not previously reported, probably was caused by a hypersensitivity reaction or mechanical-irritative effect on the hypothalamic-hipophyseal area produced by suprasellar Pantopaque droplets, demonstrated by skull x-rays. The patient improved after being treated with steroids. Some serious complications of myelography can be prevented by avoiding supratentorial spillage of Pantopaque.
Assuntos
Diabetes Insípido/etiologia , Iodobenzenos/efeitos adversos , Iodofendilato/efeitos adversos , Mielografia/efeitos adversos , Adulto , Clorotiazida/uso terapêutico , Diabetes Insípido/tratamento farmacológico , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Masculino , Prednisona/uso terapêutico , Crânio/diagnóstico por imagemRESUMO
The interaction of three diuretics with bilirubin-albumin complexes was studied using the peroxidase assay, erythrocyte uptake, and sephadex gel filtration. On a molar basis, each diuretic was as potent or more potent than sulfisoxazole in displacing bilirubin from albumin. Furosemide and ethacrynic acid, when used at the recommended dosage (1 mg/kg), would probably not produce a significant increase in free bilirubin in most infants. Chlorothiazide could introduce a significant risk to jaundiced infants because of the higher dosage required.