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1.
Expert Opin Pharmacother ; 21(4): 435-444, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31957506

RESUMEN

Introduction: Chronic subdural hematoma (CSDH) is a common neurosurgical disease, whose incidence has been steadily increasing with our aging population. While not common, CSDH can also occur in children. CSDH is often associated with traumatic head injury, but its underlying mechanism remains poorly understood. The first line treatment for CSDH is surgery. However, surgery is contraindicated in some patients and has a high rate of recurrence. Effective non-surgical treatment is therefore highly desirable.Areas covered: This review discusses the pathogenesis of CSDH and drugs that have been used to treat CSDH either as monotherapy or an adjuvant to surgery, including controlled clinical trials.Expert opinion: The pathophysiology of CSDH remains poorly understood. Developing effective drug treatments is therefore challenging. Most drugs discussed in this review are evaluated in small clinical studies without sufficient sample size and controls for confounding variables. More controlled clinical trials are therefore needed to carefully evaluate drugs for the non-surgical treatment of CSDH, especially for drugs targeting specific pathogenic pathways of CSDH.


Asunto(s)
Hematoma Subdural Crónico/tratamiento farmacológico , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Atorvastatina/administración & dosificación , Atorvastatina/uso terapéutico , Diuréticos/administración & dosificación , Diuréticos/uso terapéutico , Hematoma Subdural Crónico/epidemiología , Hematoma Subdural Crónico/etiología , Humanos , Incidencia , Recurrencia , Resultado del Tratamiento
2.
Expert Opin Drug Saf ; 19(1): 59-67, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31795777

RESUMEN

Introduction: The objective of this study was to review the current status of drug-induced hypomagnesemia and its adverse effects on cardiovascular disease (CVD) and hypertension. Since magnesium is a potent vasodilator, which modulates vasomotor tone, peripheral blood flow, and hypertension, its deficiency could have significant cardiovascular and blood pressure (BP) effects.Areas covered: Studies have shown that several factors can contribute to magnesium deficiency including age, diet, disease, and certain drugs such as diuretics and proton-pump inhibitors (PPIs). For an updated perspective of drug-induced hypomagnesemia, a Medline search of the English language literature was conducted between 2010 and 2019 using the terms diuretics, proton-pump inhibitors, hypomagnesemia, cardiovascular disease, hypertension, and 35 pertinent papers were retrieved.Expert opinion: The data showed that magnesium deficiency is difficult to occur since it is plentiful in green leafy vegetables, cereals, nuts, and the drinking water. However, magnesium deficiency can occur with the use of diuretics for the treatment of hypertension and heart failure, or the use of PPIs for the treatment of gastroesophageal reflux disease. Therefore, magnesium deficiency should be detected and treated to prevent the aggravation of hypertension and the onset of CVD and serious cardiac arrhythmias including torsades de points.


Asunto(s)
Diuréticos/efectos adversos , Deficiencia de Magnesio/inducido químicamente , Inhibidores de la Bomba de Protones/efectos adversos , Animales , Arritmias Cardíacas/inducido químicamente , Presión Sanguínea/efectos de los fármacos , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/fisiopatología , Diuréticos/administración & dosificación , Humanos , Hipertensión/etiología , Deficiencia de Magnesio/complicaciones , Deficiencia de Magnesio/diagnóstico , Inhibidores de la Bomba de Protones/administración & dosificación
3.
Expert Opin Pharmacother ; 21(1): 85-96, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31714803

RESUMEN

Introduction: Urolithiasis is a common, highly recurrent disease with increasing prevalence worldwide. There are many dietary and pharmacological measures to prevent kidney stones.Areas covered: Herein, the authors explore medical expulsive therapy as well as pharmacological therapies to prevent/treat urolithiasis.Expert opinion: All stone formers should be advised to increase their fluid intake sufficiently to achieve a urine volume of at least 2.5 L/day. In the case of hypercalciuria, a thiazide diuretic should be prescribed while in cases of hypocitraturia, potassium citrate should be given. In the case of hyperoxaluria, the treatment depends on the type of hyperoxaluria. Pyridoxine or calcium supplements with a meal can be offered. For uric acid stone formers, alkali therapy is the standard of care whereas allopurinol can be beneficial in hyperuricosuric stone formers. For cystine stone formers, increased fluid intake, restriction of sodium and animal protein ingestion, and urinary alkalinization are the standard therapies used. Cystine binding thiol drugs such as tiopronin and D-penicillamine are reserved for patients where a conservative approach fails. For struvite stone formers, optimal management is the complete stone removal. Acetohydroxamic acid may be offered only after surgical options have been exhausted, for patients with residual stones but it has many side effects.


Asunto(s)
Cálculos Renales/prevención & control , Urolitiasis/tratamiento farmacológico , Alopurinol/administración & dosificación , Calcio/administración & dosificación , Suplementos Dietéticos , Diuréticos/administración & dosificación , Humanos , Factores de Riesgo
4.
Med Klin Intensivmed Notfmed ; 115(1): 37-42, 2020 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-29327197

RESUMEN

Acute kidney injury (AKI) occurs in 30-50% of all intensive care patients. Renal replacement therapy (RRT) has to be initiated in 10-15%. The early in-hospital mortality is about 50%. Up to 20% of all survivors develop chronic kidney disease after intensive care discharge and progress to end-stage kidney disease within the next 10 years. For timely initiation of prophylactic or therapeutic interventions, it is crucial to exactly determine the actual kidney function, i. e., glomerular filtration rate (GFR), and to gain insight into the further development of kidney function. Traditionally, renal function has been estimated using serum levels of creatinine or urea. Unfortunately, both are notoriously unreliable and insensitive in intensive care patients. Cystatin C has fewer non-GFR determinants when compared to creatinine and is more sensitive and accurate to detect early decreases of GFR. At present, new functional tests are discussed, namely the furosemide stress test (FST) and renal functional reserve (RFR). The FST consists of an intravenous infusion of 1.0-1.5 mg/kgBW furosemide to critically ill patients with AKI. An increase in urine output to >100 ml/h is indicative of a GFR >20 ml/min and almost certainly excludes progression to AKI stage III and need for RRT. Estimation of RFR can be made by short-term oral or intravenous administration of a high protein load. A subsequent increase in GFR defines the presence and the magnitude of functional reserve which can be activated. Loss of RFR is an indicator of loss of functioning nephron mass and incomplete recovery following AKI. Both FST and RFR can help to improve diagnosis and care of high-risk patients with acute and chronic kidney disease.


Asunto(s)
Lesión Renal Aguda , Diuréticos , Furosemida , Pruebas de Función Renal , Lesión Renal Aguda/diagnóstico , Creatinina , Diuréticos/administración & dosificación , Furosemida/administración & dosificación , Humanos , Riñón/fisiopatología , Terapia de Reemplazo Renal
5.
Crit Care Resusc ; 21(4): 258-64, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31778632

RESUMEN

OBJECTIVE: To compare the physiological and biochemical effects of a single intravenous dose of furosemide or acetazolamide in critically ill patients. DESIGN: Single centre, pilot randomised controlled trial. SETTING: Large tertiary adult intensive care unit (ICU). PARTICIPANTS: Twenty-six adult ICU patients deemed to require diuretic therapy. INTERVENTION: Single dose of intravenous 40 mg furosemide or 500 mg acetazolamide. MAIN OUTCOME MEASURES: Data were collected on urine output, cumulative fluid balance, and serum and urine biochemistry for 6 hours before and 6 hours after diuretic administration. RESULTS: Study patients had a median age of 55 years (IQR, 50-66) and median APACHE III score of 44 (IQR, 37-52). Furosemide caused a much greater increase in-urine output and much greater median mass chloride excretion (121.7 mmol [IQR, 81.1-144.6] v 23.3 mmol [IQR, 20.4-57.3]; P < 0.01) than acetazolamide. Furosemide also resulted in a progressively more negative fluid balance while acetazolamide resulted in greater alkalinisation of the urine (change in median urinary pH, +2 [IQR, 1.75-2.12] v 0 [IQR, 0-0.5]; P = 0.02). In keeping with this effect, furosemide alkalinised and acetazolamide acidified plasma (change in median serum pH, +0.03 [IQR, 0.01-0.04] v -0.01 [IQR, -0.04 to 0]; P = 0.01; change in median serum HCO3-, +1.5 mmol/L [IQR, 0.75-2] v -2 mmol/L [IQR, -3 to 0]; P < 0.01). CONCLUSIONS: Furosemide is a more potent diuretic and chloriuretic agent than acetazolamide in critically ill patients, and achieves a threefold greater negative fluid balance. Compared with acetazolamide, furosemide acidifies urine and alkalinises plasma. Our findings imply that combination therapy might be a more physiological approach to diuresis in critically ill patients.


Asunto(s)
Acetazolamida/farmacología , Acetazolamida/farmacocinética , Enfermedad Crítica/terapia , Diuréticos/farmacología , Diuréticos/farmacocinética , Furosemida/farmacología , Furosemida/farmacocinética , Acetazolamida/administración & dosificación , Adulto , Anciano , Diuréticos/administración & dosificación , Electrólitos/sangre , Furosemida/administración & dosificación , Humanos , Infusiones Intravenosas , Persona de Mediana Edad , Proyectos Piloto , Resultado del Tratamiento , Urodinámica/efectos de los fármacos , Equilibrio Hidroelectrolítico/efectos de los fármacos
6.
Yakugaku Zasshi ; 139(11): 1457-1462, 2019.
Artículo en Japonés | MEDLINE | ID: mdl-31685742

RESUMEN

Recently, there have been reports that the combination of renin angiotensin inhibitors, diuretics, and non-steroidal anti-inflammatory drugs increases the risk of acute kidney injury (AKI). This combination has been dubbed the "Triple Whammy". However, there have been no reports about its chronic effects on the kidney. In this study, we investigated the chronic effects of the "Triple Whammy" on kidney function. There were 203 outpatients who were prescribed this combination in our hospital for 5 years. We excluded patients who could also confirm the combination in the previous year and patients for whom laboratory data were unavailable, thus, leaving a target patient group of 95 patients. The average estimated glomerular filtration rate (eGFR) decreased significantly from 62.6 to 58.9 mL/min/1.73 m2 immediately after administering the combination (p<0.01). Although no patients were diagnosed with AKI within 90 days after being administered the combination, 7.4% of patients exhibited a ≥25% reduction in eGFR compared with that before commencing the combination. Correlation analysis of gender, age, past renal function, and renal function change demonstrated that eGFR before administration of the combination negatively correlated with changes in eGFR (p<0.01). Considering the effects of individual differences, eGFR changes before and after administering the combination were compared using a case-crossover design and eGFR after administering the combination was found to be significantly reduced (p<0.01). Therefore, it appears that the "Triple Whammy" may cause not only AKI but also chronic renal degeneration.


Asunto(s)
Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antiinflamatorios no Esteroideos/efectos adversos , Diuréticos/efectos adversos , Tasa de Filtración Glomerular/efectos de los fármacos , Insuficiencia Renal Crónica/inducido químicamente , Lesión Renal Aguda/inducido químicamente , Anciano , Anciano de 80 o más Años , Antagonistas de Receptores de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Antiinflamatorios no Esteroideos/administración & dosificación , Estudios Cruzados , Diuréticos/administración & dosificación , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/fisiopatología
7.
Pan Afr Med J ; 33: 251, 2019.
Artículo en Francés | MEDLINE | ID: mdl-31692700

RESUMEN

Introduction: Acute Heart Failure (AHF) is a specific syndromic disorder grouping several heterogeneous clinical conditions frequently seen in the emergency department. This study aimed to describe the epidemiological, clinical, therapeutic and prognostic features of patients with AHF admitted to the emergency department. Methods: We conducted a prospective, descriptive study in the emergency department. It included all patients admitted with AHF. We studied the epidemiological, clinical, therapeutic and prognostic features of these patients. Results: The study enrolled 180 patients with AHF admitted to the emergency department. Sex ratio was 1.27. The average age of patients was 66±12 years. Eighty-two percent of patients were hypertensive and 69% were known diabetic patients. The causes of decompensation included primarily hypertensive crisis (61.7% of patients), acute coronary syndrome (24% of patients). Respiratory support was mainly provided by CPAP (Continuous Positive Airway Pressure) in 73.3% of cases. Pharmacological treatment was based on nitrate derivatives (70% of cases) and diuretic (40.5% of cases). Acute heart failure incidence at one month was 21.7% (n=39 patients) and mortality rate at 3 months was 13.3%. Conclusion: Patients with AHF treated in the emergency department mainly had hypertensive crisis. Treatment is primarily based on CPAP, vasodilators and diuretics. Recurrence rate and mortality rate were high.


Asunto(s)
Síndrome Coronario Agudo/complicaciones , Presión de las Vías Aéreas Positiva Contínua/métodos , Insuficiencia Cardíaca/epidemiología , Hipertensión/complicaciones , Síndrome Coronario Agudo/epidemiología , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Diuréticos/administración & dosificación , Servicio de Urgencia en Hospital , Femenino , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/terapia , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Nitratos/administración & dosificación , Pronóstico , Estudios Prospectivos , Recurrencia , Túnez , Adulto Joven
8.
Rev Cardiovasc Med ; 20(3): 111-120, 2019 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-31601085

RESUMEN

Randomized controlled trials have demonstrated the benefits of guideline-directed medical therapy in the outpatient setting for treatment of chronic heart failure. However, the benefits of continuation (or discontinuation) of major chronic heart failure therapies when treating acute heart failure during hospitalization are less clear. Real and anticipated worsening renal function, hyperkalemia and hypotension are the three major reasons for discontinuation of renin-angiotensin-aldosterone system inhibitors during hospitalization, and a failure to resume renin-angiotensin-aldosterone system inhibitors before discharge could worsen cardiovascular outcomes. Available data, mostly observational, shows that continuation or initiation of renin-angiotensin-aldosterone system inhibitors appears efficacious, safe, and well tolerated in majority of acute heart failure patients during hospitalization. Worsening renal function portends poor prognosis only if associated with congestion in acute heart failure, and clinicians should not de-escalate diuretic therapy routinely for worsening renal function.


Asunto(s)
Antagonistas de Receptores de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Síndrome Cardiorrenal/tratamiento farmacológico , Diuréticos/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Admisión del Paciente , Sistema Renina-Angiotensina/efectos de los fármacos , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Síndrome Cardiorrenal/diagnóstico , Síndrome Cardiorrenal/mortalidad , Síndrome Cardiorrenal/fisiopatología , Toma de Decisiones Clínicas , Diuréticos/efectos adversos , Esquema de Medicación , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Humanos , Factores de Riesgo , Resultado del Tratamiento
9.
Am Surg ; 85(10): 1171-1174, 2019 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-31657318

RESUMEN

Avoiding excess fluid administration is necessary when managing critically ill surgical patients. The aim of this study was to delineate the current practices of IV electrolyte (IVE) replacement in a surgical ICU and quantify their contribution to the fluid balance (FB) status. Patients admitted to the surgical ICU over a six-month period were reviewed. Patients undergoing dialysis and those with ICU stay <72 hours were excluded. A total of 248 patients were included. The median age was 60 years, and 57 per cent were male. Overall, 1131 patient ICU days were analyzed. The median daily FB was 672 mL. IVEs were administered in 62 per cent of ICU days. In days that IVEs were used, negative FB was significantly less likely to be achieved (62% vs 69%, P = 0.02). The most commonly administered IVE was calcium (32% of ICU days); however, the largest volume of IVE was administered in the form of phosphorus (median 225 mL). Diuretics were administered in 17 per cent of ICU days. Patients who received diuretics were significantly more likely to receive IVE (70% vs 61%, P = 0.02). Administration of IVE may contribute to the daily positive FB of surgical ICU patients. Implementation of practices that can ameliorate this effect is encouraged.


Asunto(s)
Enfermedad Crítica , Electrólitos/administración & dosificación , Infusiones Intravenosas/métodos , Procedimientos Quirúrgicos Operativos , Equilibrio Hidroelectrolítico , Calcio/administración & dosificación , Diuréticos/administración & dosificación , Femenino , Fluidoterapia/efectos adversos , Fluidoterapia/métodos , Humanos , Infusiones Intravenosas/estadística & datos numéricos , Unidades de Cuidados Intensivos , Sulfato de Magnesio/administración & dosificación , Masculino , Persona de Mediana Edad , Fósforo/administración & dosificación , Potasio/administración & dosificación , Estudios Retrospectivos
10.
Int J Clin Pharmacol Ther ; 57(12): 603-606, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31657712

RESUMEN

Residual renal function and diuresis preservation are associated with improved volume control and lower mortality in peritoneal dialysis (PD). Loop diuretics are used to maintain diuresis, although their optimal dosage remains unclear. This study aimed to compare the pharmacodynamics of a 250-mg and a 500-mg dose of oral furosemide in PD patients. 12 patients with a diuresis > 100 mL per day were randomized in a crossover pattern to successively receive an oral dose of 250 mg and 500 mg of furosemide. Twelve-hour natriuresis and diuresis were measured before and after each furosemide dose. Fractional excretion of sodium (FENa) and absolute sodium excretion increased after each dose, although these rises were not statistically significantly different (5.8% (250 mg) vs. 6.9% (500 mg), p = 0.57 for FENa and 42.6 mmol/12h (250 mg) vs. 70.8 mmol/12h (500 mg), p = 0.07 for absolute sodium excretion). Urinary volume was significantly increased after the 500-mg dose, whilst the difference did not reach statistical significance after the 250-mg dose. Furthermore, the higher dose was associated with a greater increase in diuresis than the lower dose (226 mL (250 mg) vs. 522 mL (500 mg), p = 0.04). Furosemide could be used at oral single doses reaching 500 mg in PD patients requiring greater volume control.


Asunto(s)
Diuréticos/administración & dosificación , Diuréticos/farmacocinética , Furosemida/administración & dosificación , Furosemida/farmacocinética , Diálisis Peritoneal , Diuresis , Humanos , Natriuresis
11.
Lancet ; 394(10208): 1540-1550, 2019 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-31533906

RESUMEN

BACKGROUND: Spironolactone is effective at reducing blood pressure in patients with uncontrolled resistant hypertension. However, the use of spironolactone in patients with chronic kidney disease can be restricted by hyperkalaemia. We evaluated use of the potassium binder patiromer to allow more persistent use of spironolactone in patients with chronic kidney disease and resistant hypertension. METHODS: In this phase 2 multicentre, randomised, double-blind, placebo-controlled study, we enrolled participants aged 18 years and older with chronic kidney disease (estimated glomerular filtration rate 25 to ≤45 mL/min per 1·73 m2) and uncontrolled resistant hypertension from 62 outpatient centres in ten countries (Bulgaria, Croatia, Georgia, Hungary, Ukraine, France, Germany, South Africa, the UK, and the USA). Patients meeting all eligibility criteria at the final screening visit were stratified by local serum potassium measurement (4·3 to <4·7 mmol/L vs 4·7 to 5·1 mmol/L) and history of diabetes. Participants were randomly assigned (1:1) with an interactive web response system to receive either placebo or patiromer (8·4 g once daily), in addition to open-label spironolactone (starting at 25 mg once daily) and their baseline blood pressure medications. Participants, the study team that administered treatments and measured blood pressure, and the investigators were masked to assigned treatment groups. Dose titrations were permitted after 1 week (patiromer) and 3 weeks (spironolactone). The primary endpoint was the between-group difference at week 12 in the proportion of patients on spironolactone. Efficacy endpoints and safety were assessed in all randomised patients (intention to treat). The study was registered with Clinicaltrials.gov, NCT03071263. FINDINGS: Between Feb 13, 2017, and Aug 20, 2018, we screened 574 patients. 295 (51%) of 574 patients met all inclusion criteria and were randomly assigned to spironolactone in addition to double-blind treatment with either placebo (n=148) or patiromer (n=147). At week 12, 98 (66%) of 148 patients in the placebo group and 126 (86%) of 147 patients in the patiromer group remained on spironolactone (between-group difference 19·5%, 95% CI 10·0-29·0; p<0·0001). Adverse events were mostly mild or moderate in severity and occurred in 79 (53%) of 148 patients in the placebo group and 82 (56%) of 147 patients in the patiromer group. INTERPRETATION: In patients with resistant hypertension and chronic kidney disease, patiromer enabled more patients to continue treatment with spironolactone with less hyperkalaemia. Persistent spironolactone enablement in this population of patients has clinical relevance for the treatment of resistant hypertension. FUNDING: Relypsa, a Vifor Pharma Group Company.


Asunto(s)
Diuréticos/administración & dosificación , Hipertensión/tratamiento farmacológico , Polímeros/administración & dosificación , Espironolactona/administración & dosificación , Adulto , Anciano , Diuréticos/efectos adversos , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Hiperpotasemia/prevención & control , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Potasio/sangre , Insuficiencia Renal Crónica/complicaciones , Espironolactona/efectos adversos , Resultado del Tratamiento
12.
J Vet Intern Med ; 33(5): 2319-2326, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31397944

RESUMEN

BACKGROUND: Public pressure exists in the United States to eliminate race-day furosemide administration despite its efficacy in decreasing the severity of equine exercise pulmonary hemorrhage (EIPH). No effective alternative prophylaxis strategies have been identified. OBJECTIVE: To investigate alternative protocols to race-day furosemide that might mitigate EIPH. ANIMALS: Seven fit Thoroughbreds with recent EIPH. METHODS: Double-blinded placebo-controlled Latin square crossover using a treadmill followed by a blinded placebo-controlled crossover study at a racetrack. First, horses exercised supramaximally to fatigue 24 hours after initiating 5 EIPH prophylaxis protocols: 0.5 and 1.0 mg/kg furosemide IV 24 hours pre-exercise with and without controlled access to water, and 24 hour controlled access to water. Effects were compared to those measured after giving a placebo 24 hours pre-exercise, and 0.5 mg/kg furosemide IV 4 hours pre-exercise. Bronchoalveolar lavage (BAL) erythrocyte count was determined 45-60 minutes postexercise after endoscopy to assign an EIPH score. Data were analyzed using linear mixed effects models. The most promising protocol from the treadmill study was further evaluated in 6 horses using endoscopy and BAL after 1100 m simulated races. RESULTS: Intravenous furosemide (0.5 mg/kg) administered 24 hours pre-exercise combined with controlled access to water decreased the severity of EIPH on the treadmill and at the racetrack. CONCLUSION AND CLINICAL IMPORTANCE: Administering 0.5 mg/kg furosemide 24 hours pre-racing combined with controlling water intake may be a strategy to replace race-day furosemide administration for the management of EIPH. A larger study is indicated to further evaluate whether this protocol significantly mitigates EIPH severity.


Asunto(s)
Furosemida/farmacología , Hemorragia/veterinaria , Enfermedades de los Caballos/prevención & control , Animales , Líquido del Lavado Bronquioalveolar/citología , Estudios Cruzados , Diuréticos/administración & dosificación , Diuréticos/farmacología , Recuento de Eritrocitos , Femenino , Furosemida/administración & dosificación , Hemorragia/prevención & control , Caballos , Enfermedades Pulmonares/prevención & control , Enfermedades Pulmonares/veterinaria , Masculino
13.
Medicine (Baltimore) ; 98(35): e16617, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31464898

RESUMEN

It is unclear whether strategies targeting negative fluid balance are associated with facilitated early fascial closure. The present study investigated the effects of fluid removal therapy on early facial closure of open abdomen patients.A prospective study was conducted in patients who underwent open abdomen management with vacuum-assisted and mesh-mediated fascial traction technique. Therapeutic diuresis with torasemide was applied to cause negative fluid balance in the treatment group. The study and follow-up periods were 7 and 180 days, respectively. The observational indices included the intra-abdominal pressure, the number of days to closure, the type of closure, the septic complications, the duration of ventilation support, the duration of initial hospital stay, and the duration of intensive care unit (ICU) stay.A total of 27 patients were divided into the treatment (16 patients) and control (11 patients) groups. The median intra-abdominal pressure (IAP) of the patients of the control and the treatment groups was significantly lower at day 7 compared with the baseline value (P < .0001). IAP was lower in the treatment group compared with that noted in the control group, following day 4 of the fluid removal therapy (P < .05). The percentage weight loss in the treatment group was between 4.80% and 10.88%. The early closure rates were significantly higher in the treatment group compared with those in the control group (75.0% vs 18.2%, P = .0063).Fluid removal therapy combined with vacuum-assisted and mesh-mediated fascial traction provided a high early fascial closure rate for open abdomen patients.


Asunto(s)
Abdomen/cirugía , Técnicas de Cierre de Herida Abdominal/instrumentación , Diuréticos/administración & dosificación , Terapia de Presión Negativa para Heridas/instrumentación , Torasemida/administración & dosificación , Cicatrización de Heridas , Adulto , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Mallas Quirúrgicas , Resultado del Tratamiento
14.
World J Gastroenterol ; 25(26): 3283-3290, 2019 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-31341355

RESUMEN

Since the 1970s, non-selective beta-blockers (NSBB) have been used to prevent variceal upper bleeding in advanced cirrhotic patients. However, several recent studies have raised the doubt about the benefit of NSBB in end-stage cirrhotic patients. In fact, they suggested a detrimental effect in these patients that even reduced survival. All of these studies have been assembled to compose the "window therapy hypothesis", in which NSBB would have traditional indication to be initiated to prevent variceal upper bleeding; however, treatment should be stopped (or not be initiated) in patients with end-stage cirrhosis. NSBB would reduce the cardiac reserve of these patients, worsening systemic perfusion and prognosis. However, it should be emphasized that these studies present important bias issues, and their results also suggested that diuretic treatment may also be behind the effects observed. In this opinion review, we changed the point of view from NSBB to diuretic treatment, based on a physiopathogenic approach of circulatory parameters of cirrhotic patients studied, and based on diuretic effect in blood pressure lowering and in other hypervolemic disease, as heart failure. We suggest a "diuretic window hypothesis", composed by an open window in hypervolemic phase, an attention window when patient present in a normal plasma volume phase, and a closed window during the plasma hypovolemic phase.


Asunto(s)
Diuréticos/administración & dosificación , Enfermedad Hepática en Estado Terminal/complicaciones , Várices Esofágicas y Gástricas/tratamiento farmacológico , Hemorragia Gastrointestinal/prevención & control , Cirrosis Hepática/complicaciones , Antagonistas Adrenérgicos beta/administración & dosificación , Enfermedad Hepática en Estado Terminal/mortalidad , Enfermedad Hepática en Estado Terminal/patología , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/mortalidad , Medicina Basada en la Evidencia/métodos , Gastroenterología/métodos , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/mortalidad , Humanos , Cirrosis Hepática/mortalidad , Cirrosis Hepática/patología , Pronóstico , Análisis de Supervivencia , Resultado del Tratamiento
15.
AAPS PharmSciTech ; 20(5): 208, 2019 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-31161450

RESUMEN

Individualized medicines for pediatrics are a useful alternative if there is no correct dosage marketed for this segment (easy to swallow, adequate volume and content, correct composition for pediatrics, good organoleptic properties, etc.). Its validation process must ensure quality testing: its content uniformity, physical (homogeneity after shaking), chemical, and microbiological stability. Some of these attributes are checked by the recommendations of European Pharmacopoeia (Ph. Eur.), International Conference of Harmonization (ICH), and National Formularies but others are not. The aim of this study is to develop a general high-demanding strategy to ensure the final quality of liquid dosage forms testing and developing standard operating processes (SOPs) for the elaboration of individualized oral liquid medicines for pediatric use. Furosemide was used as an example of the validation of an individualized liquid solution for pediatric use. Three SOPs were selected according to their composition and the recommendations of liquid dosage forms for pediatric use. Quality attributes according to National Formularies, Ph. Eur., and ICH were tested: pH, organoleptic properties, uniformity of mass of delivered dose from multidose containers, and chemical stability. In this study, a general high-demanding strategy was elaborated to validate oral liquid dosage forms, including validation of the analytical method used to test their quality. A second part focuses on the elaboration of liquid formulations for pediatrics with the highest standards of quality taking into account CQAs that were not contemplated by official compendial such as content uniformity and physical stability.


Asunto(s)
Excipientes/normas , Furosemida/normas , Pediatría/normas , Medicina de Precisión/normas , Administración Oral , Niño , Diuréticos/administración & dosificación , Diuréticos/normas , Composición de Medicamentos/métodos , Composición de Medicamentos/normas , Excipientes/administración & dosificación , Furosemida/administración & dosificación , Humanos , Pediatría/métodos , Soluciones Farmacéuticas/administración & dosificación , Soluciones Farmacéuticas/normas , Medicina de Precisión/métodos
17.
Heart Vessels ; 34(12): 1952-1960, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31114959

RESUMEN

According to the "chloride theory" for heart failure (HF) pathophysiology, manipulation of the serum chloride concentration is an important therapeutic target. This study determined the short- and long-term effects of acetazolamide (Diamox), a potential chloride-regaining diuretic, on peripheral blood, serum electrolytes, and renal function. Effects of low-dose Diamox (250-500 mg/day) were evaluated in 30 HF patients for whom Diamox was added as de-novo/add-on decongestion therapy for acutely worsening HF (n = 18) or as modification therapy for serum hypochloremia in stable HF ( < 100 mEq/L; n = 12). Peripheral hematologic tests were performed at baseline, and at short- ( ≤ 10 days) and long-term ( ~ 60 days) time-points. In all 30 study patients of both groups, the serum chloride concentration increased in the short-term and even further over the long-term. The serum potassium concentration constantly decreased throughout the study period. Both the blood urea nitrogen and serum creatinine concentrations increased in the short-term, but returned to baseline levels over the long-term. Responders to Diamox (n = 13; defined by HF resolution and body weight loss ≥ 1 kg) in the decongestion group exhibited reduced serum b-type natriuretic peptide levels and a markedly increased serum chloride concentration, but the hemoglobin/hematocrit and serum creatinine concentrations did not change after treatment. In conclusion, acetazolamide is a potent candidate "chloride-regaining diuretic" for treating HF patients under the "chloride theory". Its effect to enhance the serum chloride concentration occurred within 10 days and persisted for at least ~ 60 days. Plasma volume and renal function were preserved under adequate diuretic treatment with acetazolamide.


Asunto(s)
Acetazolamida/administración & dosificación , Cloruros/sangre , Insuficiencia Cardíaca/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Diuréticos/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Volumen Sistólico/fisiología , Factores de Tiempo , Resultado del Tratamiento
18.
J Med Food ; 22(4): 393-407, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30990753

RESUMEN

Although leaves of Anchietea salutaris are used in Brazilian traditional medicine, there is no available data in the literature proving its efficacy and safety. Thus, the aim of the study was to perform a meticulous botanical, phytochemical, toxicological, and pharmacological investigation of A. salutaris in Wistar rats. At first, a morphoanatomical characterization of Anchietea pyrifolia leaves and stems was performed. Then, a purified infusion (ethanol-soluble fraction obtained from A. pyrifolia [ESAP]) was obtained followed by its chemical profile elucidation. Furthermore, an acute toxicity test was performed, and the acute and prolonged diuretic and hypotensive effects were also evaluated in Wistar rats. Finally, the vasodilatory responses of ESAP in mesenteric vascular beds were investigated. The main secondary metabolites identified from ESAP were O-glycosylated flavonoids, chlorogenic acids, and phenylpropanoic acid derivatives. ESAP did not promote any toxic effects in female rats nor increased urinary excretion in male rats after a single exposure. However, ESAP significantly reduced renal elimination of sodium, potassium, and chloride after prolonged treatment. An ESAP highest dose promoted significant acute hypotension without affecting blood pressure levels after prolonged use. Furthermore, its cardiovascular effects seem to be related with the calcium-activated potassium channel activation in resistance vessels.


Asunto(s)
Antihipertensivos/administración & dosificación , Hipertensión/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Violaceae/química , Animales , Antihipertensivos/efectos adversos , Antihipertensivos/química , Presión Sanguínea/efectos de los fármacos , Brasil , Diuréticos/administración & dosificación , Diuréticos/efectos adversos , Diuréticos/química , Femenino , Humanos , Hipertensión/genética , Hipertensión/metabolismo , Hipertensión/fisiopatología , Masculino , Extractos Vegetales/efectos adversos , Extractos Vegetales/química , Hojas de la Planta/química , Canales de Potasio Calcio-Activados/genética , Canales de Potasio Calcio-Activados/metabolismo , Ratas Wistar
19.
J Vet Emerg Crit Care (San Antonio) ; 29(3): 279-287, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30983126

RESUMEN

OBJECTIVE: To describe the frequency of renal tubular vacuolization (RTV) as a surrogate of osmotic nephrosis and assess hyperosmolar agents as predictors of RTV severity. DESIGN: Retrospective study (February 2004-October 2014). SETTING: Veterinary teaching hospital. ANIMALS: Fifty-three client-owned, critically ill dogs that had a postmortem examination. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The frequency, severity, and location of RTV were determined in small group of critically ill dogs postmortem. Logistic regression was performed to assess cumulative 6% HES (670/0.75) and mannitol dose as predictors for RTV severity with presenting serum creatinine concentration, cumulative furosemide dose, and duration of hospitalization as covariates. RTV was noted in 45 (85%) of 53 critically ill dogs and was most commonly located to the medullary rays (68%). Cumulative 6% HES (670/0.75) dose (P = 0.009) and presenting serum creatinine concentration (P = 0.027) were significant predictors of RTV severity. For every 1 mL/kg increase in 6% HES (670/0.75) dose that a dog received, there was 1.6% increased chance of having more severe RTV (OR 1.016; 95% CI 1.004-1.029). In addition, for every 88.4 µmol/L (1 mg/dL) increase in presenting serum creatinine, there was a 22.7% increased chance of having more severe RTV (OR 1.227; 95% CI 1.023-1.472). Cumulative mannitol (P = 0.548) and furosemide (P = 0.136) doses were not significant predictors of RTV severity. CONCLUSION: In a small group of critically ill dogs, there was a high frequency of RTV identified on postmortem examination. Administration of 6% HES (670/0.75) and presenting serum creatinine concentration were significant predictors of RTV severity. Larger prospective studies are needed to determine the etiology and significance of RTV in dogs.


Asunto(s)
Lesión Renal Aguda/veterinaria , Enfermedades de los Perros/patología , Lesión Renal Aguda/sangre , Lesión Renal Aguda/patología , Animales , Autopsia/veterinaria , Creatinina/sangre , Cuidados Críticos , Enfermedad Crítica , Diuréticos/administración & dosificación , Enfermedades de los Perros/sangre , Perros , Femenino , Furosemida/administración & dosificación , Hospitales Veterinarios , Derivados de Hidroxietil Almidón/administración & dosificación , Masculino , Sustitutos del Plasma/administración & dosificación , Estudios Prospectivos , Estudios Retrospectivos
20.
J Cancer Res Clin Oncol ; 145(7): 1835-1843, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31006846

RESUMEN

INTRODUCTION: Based on the observation of beneficial effects on cancer metabolism, microenvironment, or VEGF-signaling, several non-anticancer drugs have been discussed as useful in renal cell carcinoma (RCC). In the present study, we investigated the prognostic impact of concomitant medication in RCC and correlated comedication with cell-cycle and proliferation activity in corresponding surgical specimen. METHODS: A total of 388 patients who underwent surgery for localized RCC were included. The individual medication was evaluated according to substance classes. Tissue microarrays from corresponding tumor specimen were immunohistochemically (IHC) stained for Cyclin D1 and Ki67 and semi-quantitatively evaluated. Uni- and multivariate analyses were used to compare survival outcomes. For the comparison of IHC expression according to medication subgroups, Kruskal-Wallis analysis was performed. RESULTS: Median follow-up was 57.93 months (95% CI 53.27-69.43) and median OS accounted for 181.12 months (129.72-237.17). Univariate analysis identified pathological standard variables (T-stage > T2, Grading > G2, L1, N1, M1, sarcomatoid subtype, necrosis) as significant determinants of OS. Moreover, statin use (p = 0.009) and sartan use (p = 0.032) were significantly associated with improved OS. Multivariate analysis identified M1-stage (p < 0.001), statin and sartan use (p = 0.003 and p = 0.033, respectively) as independent prognosticators of survival. Expression of Ki67 was significantly reduced in patients with statin use (p = 0.013), while Cyclin D1 expression showed no correlation with comedication. CONCLUSIONS: Concomitant intake of statins and sartans identifies as an independent predictor of OS in RCC, and reduced Ki67 expression was significantly associated with statin use. Further evaluation of drug repurposing approaches with these substances in RCC appear warranted.


Asunto(s)
Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Preparaciones Farmacéuticas/administración & dosificación , Adolescente , Antagonistas Adrenérgicos beta/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Diuréticos/administración & dosificación , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Adulto Joven
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