RESUMO
Hyponatremia is one of the most common electrolyte disorders encountered in the elderly. We present the case of an 81-year-old man who developed hyponatremia due to isolated hypoaldosteronism occurring after licorice withdrawal. He had severe hypokalemia with hypertension and was diagnosed with pseudoaldosteronism. He had been taking a very small dose of licorice as a mouth refresher since his early adulthood. Five months after licorice withdrawal, he developed hypovolemic hyponatremia, which was resolved with administration of fludrocortisone acetate. Our experience with this case suggests that isolated hypoaldosteronism occurring after licorice withdrawal should be considered as a potential cause of hyponatremia in elderly patients.
Assuntos
Medicamentos de Ervas Chinesas , Glycyrrhiza , Hipoaldosteronismo/diagnóstico , Hiponatremia/diagnóstico , Antissépticos Bucais , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Fludrocortisona/análogos & derivados , Fludrocortisona/uso terapêutico , Humanos , Hipoaldosteronismo/sangue , Hipoaldosteronismo/complicações , Hipoaldosteronismo/tratamento farmacológico , Hiponatremia/sangue , Hiponatremia/complicações , Hiponatremia/tratamento farmacológico , MasculinoRESUMO
Nanoemulsions aimed at dermal drug delivery are usually stabilised by natural lecithins. However, lecithin has a high tendency towards self-aggregation and is prone to chemical degradation. Therefore, the aim of this study was to develop nanoemulsions with improved structure and long-term stability by employing a natural sucrose ester mixture as sole surfactant. A thorough comparison between the novel sucrose stearate-based nanoemulsions and corresponding lecithin-based nanoemulsions revealed that the sucrose ester is superior in terms of emulsifying efficiency, droplet formation as well as physical and chemical stability. The novel formulations exhibited a remarkably homogeneous structure in cryo TEM investigations, as opposed to the variable structure observed for lecithin-based systems. The in vitro skin permeation rates of lipophilic drugs from sucrose stearate nanoemulsions were comparable to those obtained with their lecithin-based counterparts. Furthermore, it was observed that addition of γ-cyclodextrin led to enhanced skin permeation of the steroidal drug fludrocortisone acetate from 9.99±0.46 to 55.10±3.67 µg cm(-2) after 24 h in the case of sucrose stearate-based systems and from 9.98±0.64 to 98.62±24.89 µg cm(-2) after 24 h in the case of lecithin-based systems. This enhancement effect was significantly stronger in formulations based on lecithin (P<0.05), which indicates that synergistic mechanisms between the surfactant and the cyclodextrin are involved. Cryo TEM images suggest that the cyclodextrin is incorporated into the interfacial film, which might alter drug release rates and improve the droplet microstructure.
Assuntos
Sistemas de Liberação de Medicamentos , Emulsões/química , Excipientes/química , Sacarose/análogos & derivados , Tensoativos/química , gama-Ciclodextrinas/química , Abdome/fisiologia , Administração Cutânea , Animais , Anti-Inflamatórios/análise , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Ciclodextrinas/análise , Ciclodextrinas/química , Ciclodextrinas/metabolismo , Composição de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Estabilidade de Medicamentos , Emulsões/análise , Emulsões/metabolismo , Excipientes/análise , Excipientes/metabolismo , Fludrocortisona/análogos & derivados , Fludrocortisona/análise , Fludrocortisona/química , Fludrocortisona/metabolismo , Modelos Químicos , Nanopartículas/química , Tamanho da Partícula , Permeabilidade , Pele/metabolismo , Absorção Cutânea , Solubilidade , Sacarose/química , Sacarose/metabolismo , Propriedades de Superfície , Tensoativos/metabolismo , Suínos , gama-Ciclodextrinas/metabolismoRESUMO
The severe side effects of glucocorticoids prevent long term management of hearing loss. Alternative steroid treatments that minimize or eliminate these effects would significantly benefit therapeutic control of hearing disorders. A steroid treatment study of autoimmune mouse hearing loss was conducted to determine the efficacy of combining aldosterone and prednisolone at low doses. An assessment also was made of low dose fludrocortisone, a synthetic mineralocorticoid that also has a slight glucocorticoid effect. MRL/MpJ-Fas(lpr) mice were tested for baseline ABR thresholds at 3 months of age and then treated with aldosterone (3.0 µg/kg) or prednisolone (1.0 mg/kg) to determine the lowest effective dose of each. Other mice were given the two steroids in combination at doses of Pred 0.5 mg+Aldo 1.5 µg; Pred 1.0 mg+Aldo 3.0 µg; or Pred 1.5 mg+Aldo 5.0 µg. Mice were retested with ABR at 1 and 2 months to determine the efficacy of the different steroid treatments in controlling hearing loss. Another series of mice were given the synthetic mineralocorticoid fludrocortisone at low (2.8 µg/kg) or high (10 µg/kg) doses and retested at monthly intervals for 3 months. Autoimmune mouse hearing loss developed in untreated controls. This threshold elevation was not prevented by prednisolone at 1 mg/kg or by aldosterone at 3 µg/kg when each was given alone. However, the two steroids combined at these doses effectively controlled hearing loss. The fludrocortisone treatments also were effective at low doses in preventing or reversing the autoimmune mouse hearing loss. This efficacy of combined steroids at low doses suggests the potential for reducing the side effects of glucocorticoids in the therapeutic control of hearing disorders.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Perda Auditiva/tratamento farmacológico , Esteroides/uso terapêutico , Estimulação Acústica/métodos , Aldosterona/uso terapêutico , Análise de Variância , Animais , Limiar Auditivo/efeitos dos fármacos , Doenças Autoimunes/complicações , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Quimioterapia Combinada/métodos , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Fludrocortisona/análogos & derivados , Fludrocortisona/uso terapêutico , Perda Auditiva/etiologia , Perda Auditiva/imunologia , Perda Auditiva/fisiopatologia , Camundongos , Camundongos Endogâmicos MRL lpr , Prednisolona/uso terapêutico , Fatores de TempoAssuntos
Catecolaminas/fisiologia , Morte Súbita Cardíaca/etiologia , Cardiopatias/etiologia , Transtornos Psicofisiológicos/fisiopatologia , Estresse Fisiológico/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Animais , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Cálcio/metabolismo , Cardiotônicos/uso terapêutico , Catecolaminas/antagonistas & inibidores , Catecolaminas/toxicidade , Gatos , Cultura , Cães , Eletrocardiografia , Emoções , Ergocalciferóis/toxicidade , Fludrocortisona/análogos & derivados , Fludrocortisona/toxicidade , Sistema de Condução Cardíaco/fisiopatologia , Cardiopatias/induzido quimicamente , Cardiopatias/fisiopatologia , Cardiopatias/psicologia , Desamparo Aprendido , Humanos , Hipotálamo/fisiopatologia , Imobilização/efeitos adversos , Camundongos , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio Atordoado/etiologia , Miocárdio Atordoado/fisiopatologia , Miocárdio Atordoado/psicologia , Miocárdio/patologia , Necrose , Sistema Nervoso Parassimpático/fisiopatologia , Transtornos Psicofisiológicos/psicologia , Ratos , Estresse Fisiológico/complicações , Estresse Fisiológico/psicologia , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/fisiopatologia , Tiroxina/toxicidade , Nervo Vago/fisiopatologiaRESUMO
CASE REPORT: A 24-year-old woman suffering from post-influenza otitis media infection was initially treated with several series of a steroid (Elocon) and a combination of steroids and antibiotics (Atecortin, Dicortineff) without significant medical benefit. The isolated bacterial strains were identified as Staphylococcus homis and Staphylococcus epidermidis. Specific phage therapy applied sequentially over a period of three weeks resulted only in a partial reduction in inflammation and limited improvement in overall health condition. Oral application of lactoferrin (LF; 50-mg daily oral doses for seven days with two-week intervals) led to a complete clearance of both bacterial strains and full recovery of the patient. The recovery was associated with increased myelopoiesis and a sustained elevation of serum endogenous LF. In conclusion, specific bacteriophage therapy combined with the administration of lactoferrin proved to be effective in the treatment of antibiotic-resistant external ear infection.
Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Farmacorresistência Bacteriana/efeitos dos fármacos , Lactoferrina/uso terapêutico , Otite Média/tratamento farmacológico , Adulto , Antivirais/uso terapêutico , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Fludrocortisona/análogos & derivados , Fludrocortisona/uso terapêutico , Gramicidina/uso terapêutico , Humanos , Neomicina/uso terapêutico , Otite Média/microbiologia , Otite Média/virologia , Penicilina G/uso terapêutico , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus hominis/efeitos dos fármacos , Resultado do TratamentoRESUMO
Potassium depletion induced by dietary potassium restriction causes sodium retention while potassium supplementation augments urinary sodium excretion. The role of external potassium balance in modulating mineralocorticoid-induced sodium retention in humans is unknown. Accordingly, eight healthy subjects were studied at the Clinical Research Center receiving a constant diet providing (per kg body wt) sodium 2.5 mmol, potassium 1.1 mmol daily. After establishing basal sodium and potassium balance over three days, each subject received 9 alpha-fludrocortisone 0.4 mg/day for 10 days. Subjects were studied twice, four to eight weeks apart, in a double blind, randomized crossover design receiving either placebo or additional KCl (80 mmol/day) over the 10 day study period. Serum potassium concentrations were unchanged from basal values on KCl while the values fell (4.1 +/- 0.1 vs. 3.4 +/- 0.1 mmol/liter, P = 0.01) on placebo. Urinary sodium excretion decreased with fludrocortisone administration in both groups, but this decrease reached significance only in the placebo group. Furthermore, during fludrocortisone administration the sodium excretion rates on KCl were significantly higher compared to the values noted on placebo (134 +/- 8 vs. 112 +/- 13 mmol/day, P = 0.01). Body weight recorded after 10 days of fludrocortisone administration was higher on placebo compared to KCl (72.3 +/- 2.8 vs. 71.6 +/- 2.8 kg, P = 0.01). Plasma renin activity, and aldosterone concentrations decreased on fludrocortisone while atrial natriuretic peptide levels increased. These studies suggest that amelioration of hypokalemia attenuates mineralocorticoid-induced sodium retention. Therefore, potassium depletion may contribute to the mineralocorticoid-induced sodium retention.
Assuntos
Mineralocorticoides/efeitos adversos , Potássio/uso terapêutico , Sódio/metabolismo , Adulto , Aldosterona/sangue , Feminino , Fludrocortisona/efeitos adversos , Fludrocortisona/análogos & derivados , Hemodinâmica , Humanos , Masculino , Natriurese/efeitos dos fármacos , Potássio/sangue , Potássio/urina , Circulação Renal , Renina/sangue , Sódio/sangueRESUMO
We have previously shown that high dose cortisol (F; 240 mg/day)-induced Na+ retention and systolic blood pressure (BP) increases are not inhibited by the glucocorticoid (type II) receptor antagonist RU486. Adequacy of type II receptor blockade with RU486 was clearly demonstrated, indicating that the Na+ retention was not mediated through the glucocorticoid receptor. Spironolactone (Sp: 400 mg/day), in a preliminary assessment, also did not inhibit F-induced Na+ retention. The purpose of this study was to determine whether the Na+ retention produced by F administration is mediated by the type I receptor by comparing the effects of F to a potent type I agonist [9 alpha-fludrohydrocortisone (9 alpha FF)] with and without Sp administration. The effects of the two agonists and Sp on urinary K excretion and BP were also compared. Normal male volunteers, on a constant daily diet for 10 days, received either F (240 mg/day) or 9 alpha FF (3.0 mg/day) with or without Sp (400 mg/day) for the last 5 days. The mean cumulative reductions in Na+ excretion during the 5 days compared to baseline values before hormone administration were 255 +/- 38 and 494 +/- 81 mmol/5 days for F (n = 9) and 9 alpha FF (n = 5), respectively (P = 0.01). Sp (n = 5) completely inhibited 9 alpha FF-induced Na+ retention (494 +/- 81 vs. -37 +/- 130 mmol/5 days; P less than 0.01), but had no effect (n = 5) on F-induced Na+ retention (255 +/- 38 vs. 193 +/- 50 mmol/5 days; P = NS). After the expected first day kaliuresis, the effects of both steroids on net cumulative urinary K+ excretion were minimal. Systolic BP was increased by F, but not 9 alpha FF, and Sp did not inhibit this increase. A 2-fold greater Sp-inhibitable Na(+)-retaining effect of the mineralocorticoid demonstrates that the failure of Sp to block F-induced Na+ retention is not due to inadequate type I receptor blockade. Based on these findings and earlier studies, we conclude that high dose (stress level) F-induced Na+ retention and systolic BP increase are not mediated by either the mineralo- or glucocorticoid receptor in normal man.
Assuntos
Hidrocortisona/farmacologia , Receptores de Esteroides/fisiologia , Sódio/metabolismo , Retenção Urinária/induzido quimicamente , Adulto , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Relação Dose-Resposta a Droga , Fludrocortisona/análogos & derivados , Fludrocortisona/farmacologia , Humanos , Hidrocortisona/administração & dosagem , Rim/fisiologia , Rim/ultraestrutura , Masculino , Potássio/metabolismo , Receptores de Mineralocorticoides , Receptores de Esteroides/efeitos dos fármacos , Sódio/sangue , Sódio/urina , Espironolactona/farmacologia , Retenção Urinária/fisiopatologia , Retenção Urinária/urinaRESUMO
In order to investigate the possible role of mineralocorticoid in the regulation of digoxin-like substance (DLS), 9 alpha-fluorocortisol (9-F) was administered to 6 healthy men and urinary excretion of DLS was measured. The administration of 0.6 mg of 9-F caused slight increases in body weight and blood pressure and significant decreases in urinary Na excretion, plasma renin activity and plasma aldosterone, which indicate the expansion of extracellular fluid (ECF) volume by 9-F administration. Urinary excretion of DLS decreased significantly from the baseline level of 43.3 +/- 2.6 (SEM) to 29.8 +/- 5.1 (SEM) ng/day; digoxin equiv. after 9-F. These results suggest that a large dose of mineralocorticoid may suppress DLS despite an increase in the ECF volume.