Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new furosemide research articles will be listed here shortly after becoming available to us.
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Medical research on furosemide
Off-label drug use in children.
Indian J Pediatr. 2008 Sep 22;
Jain SS, Bavdekar SB, Gogtay NJ, Sadawarte PA
OBJECTIVES: To determine the extent and nature of off-label drug use in children admitted to a pediatric general ward in a tertiary health care centre METHODS: Consecutive patients aged 1 mo-12 years admitted to the general wards in a tertiary care center in Mumbai over a two-month period were prospectively enrolled in the study. British National Formulary [BNF] version 2005 was used to ascertain if the drug use was "off-label". The off-label use was categorized as: administration of a greater/lesser dose, administration at a higher/lower frequency than indicated, administration for indications not described, administration of a drug not licensed for use in that age group and/ or use of alternative routes of administration. Descriptive statistics was used for calculating the off-label drug use. RESULTS: Two thousand prescriptions received by 600 subjects (M:F= 1.47:1) were analyzed. One thousand and forty-five (50.62%) prescriptions were off-label. The off-label drug use rate was 1.74+/-1.56 per patient. The maximum rate of off-label drugs was in infants (2.33/patient). 'alteration in dosage' was by far the commonest reason for off-label use; followed by 'age' and 'indication'. Furosemide (i. v.), diazepam (i.v), cefotaxime (i.v), ethambutol (tab) and prednisolone (tab) were the five commonest off-label drugs used in the study population. CONCLUSIONS: Off-label drug use was highly prevalent in general pediatric ward of a tertiary care hospital in India.
Massive bilateral pleural effusion associated with use of pioglitazone.
Clin Ther. 2008 Aug; 30(8): 1485-9
Chen YW, Chen YC, Wu CJ, Chen HH
Background: Pioglitazone is a peroxisome proliferatoractivated receptor-gamma agonist that decreases insulin resistance in type 2 diabetes mellitus. However, it has been associated with fluid retention, peripheral edema, and congestive heart failure, which has become of particular concern. There are no reports in the literature of severe pleural effusions in a patient with normal cardiac function. Case summary: A 54-year-old Asian woman weighing 77 kg developed massive bilateral pleural effusion after receiving pioglitazone (30 mg QD) in combination with glimepiride 2 mg BID and metformin 500 mg TID. Despite treatment with furosemide (20 mg intravenously at 12-hour intervals for 4 days) and a decrease in weight from 77 to 72 kg, the effusion persisted. However, it began to decrease after pioglitazone was discontinued, and it had resolved completely when the patient was evaluated on follow-up 1 month later in the outpatient department. Conclusions: This article reports a case of massive bilateral pleural effusion found in a patient with normal cardiac function who was receiving pioglitazone. After the drug was discontinued, the effusion resolved completely, indicating a probable adverse drug reaction.
Can J Rural Med. 2008; 13(3): 121-8
Bosomworth J
Rural management of acute cardiogenic pulmonary edema should be based on avoidance of adverse outcomes such as in-hospital mortality, the need for intensive care unit care, and the need for intubation and mechanical ventilation. Current evidence suggests that early noninvasive continuous positive airway pressure and early aggressive preload reduction with intravenous nitroglycerin are first-line interventions. Afterload reduction with sublingual captopril, with or without nitroglycerin, improves outcomes and is a second-line intervention. Furosemide is associated with adverse outcomes when used alone and should be given only after vasodilator therapy as a third-line intervention. Inotropes should be used only with demonstrably poor perfusion as they do not improve outcomes and may indeed be associated with increased mortality. Concurrent vasodilator therapy should be considered as soon as possible. Morphine should not be used as it is associated with adverse outcomes. If sedation is desirable, benzodiazepines should be considered.
Hypersensitivity to Furosemide.
South Med J. 2008 Sep 9;
Dalton CI, Pacheco MS
J Pain Symptom Manage. 2008 Sep 12;
Mercadante S, Villari P, Ferrera P, David F, Intravaia G
Peripheral edema is a common feature in populations with advanced cancer, although it is seldom recognized. Diuretics are commonly employed and may show some benefit, but there are insufficient clinical trial data to draw useful conclusions about their clinical use. The aim of this prospective study was to evaluate the efficacy and tolerability of high-dose furosemide and small-volume hypertonic saline solution infusion in reducing leg edema in patients with advanced cancer treated unsuccessfully with diuretics. A prospective study was performed in a consecutive sample of 24 patients admitted at a pain relief and palliative care unit over a period of 18 months. To be eligible to enter the trial, advanced cancer patients had to have diffuse bilateral leg edema unresponsive to common doses of diuretics. A solution of 60 mEq of NaCl, 250mg of furosemide, and 150mL of normal saline, were infused over 20 minutes. The treatment was repeated twice a day for two days and eventually continued on the basis of the clinical outcome. Circumferences were measured at the foot, ankle, calf, and thigh before starting the treatment (T(0)) and at intervals of 24 hours (T(1) and so on). At the same intervals, diuresis was determined. Patients were asked to score their sensation of leg weakness/heaviness on a numerical scale from 0 to 10, before (T(0)) and after the treatment (T(end)). An appreciable improvement in the sensation of weakness/heaviness (score reduction of at least two points) was recorded in all the patients. A small decrease in leg circumferences at the different sites was found, and a mean of 3600mL/day of diuresis was recorded. These observations suggest that high-dose furosemide and small-volume saline may be an effective strategy for the treatment of peripheral edema in patients with advanced cancer.
Acute kidney injury in pediatric stem cell transplant recipients.
Semin Nephrol. 2008 Sep; 28(5): 481-7
Dicarlo J, Alexander SR
Because respiratory dysfunction after hematopoietic stem cell transplantation is a manifestation of a continuum of dysfunction temporarily induced by the transplant process, a proactive rather than reactive approach might prevent or attenuate its progression to acute respiratory distress syndrome. Organ dysfunction in this population results from cytokine-driven processes, of which the first manifestation includes fluid accumulation. We describe a multistep protocol that first targets fluid balance control, both through restriction of intake and through augmentation of output using dopamine and furosemide infusions. If these steps fail to stem the tide of water accumulation, we advocate the relatively early use of continuous renal replacement therapy, its use triggered by a continued increase in body weight (>10% above baseline), an increasing c-reactive protein level, and an increasing oxygen need. Renal function parameters do not figure in this protocol. We recommend continuous renal replacement therapy at 35 mL/kg/h (2,000 mL/1.73 m(2)/h), a dose that allows adequate flexibility in fluid management and that may provide effective clearance of proinflammatory (and anti-inflammatory) mediators that drive the evolving dysfunction. Proactive intervention improves the clinical status such that the transition to mechanical ventilation may proceed smoothly or in some cases even may be avoided altogether.
Intraindividual Comparison of Image Quality in MR Urography at 1.5 and 3 Tesla in an Animal Model.
Rofo. 2008 Sep 8;
Regier M, Nolte-Ernsting C, Adam G, Kemper J
PURPOSE: Experimental evaluation of image quality of the upper urinary tract in MR urography (MRU) at 1.5 and 3 Tesla in a porcine model. MATERIALS AND METHODS: In this study four healthy domestic pigs, weighing between 71 and 80 kg (mean 73.6 kg), were examined with a standard T 1w 3D-GRE and a high-resolution (HR) T 1w 3D-GRE sequence at 1.5 and 3 Tesla. Additionally, at 3 Tesla both sequences were performed with parallel imaging (SENSE factor 2). The MR urographic scans were performed after intravenous injection of gadolinium-DTPA (0.1 mmol/kg body weight (bw)) and low-dose furosemide (0.1 mg/kg bw). Image evaluation was performed by two independent radiologists blinded to sequence parameters and field strength. Image analysis included grading of image quality of the segmented collecting system based on a five-point grading scale regarding anatomical depiction and artifacts observed (1: the majority of the segment (> 50 %) was not depicted or was obscured by major artifacts; 5: the segment was visualized without artifacts and had sharply defined borders). Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were determined. Statistical analysis included kappa-statistics, Wilcoxon and paired student t-test. RESULTS: The mean scores for MR urographies at 1.5 Tesla were 2.83 for the 3D-GRE and 3.48 for the HR 3D-GRE sequence. Significantly higher values were determined using the corresponding sequences at 3 Tesla, averaging 3.19 for the 3D-GRE (p = 0.047) and 3.92 for the HR 3D-GRE (p = 0,023) sequence. Delineation of the pelvicaliceal system was rated significantly higher at 3 Tesla compared to 1.5 Tesla (3D-GRE: p = 0.015; HR 3D-GRE: p = 0.006). At 3 Tesla the mean SNR and CNR were significantly higher (p < 0.05). A kappa of 0.67 indicated good interobserver agreement. CONCLUSION: In an experimental setup, MR urography at 3 Tesla allowed for significantly higher image quality and SNR compared to 1.5 Tesla, particularly for the visualization of the pelvicaliceal system.
J Physiol. 2008 Sep 4;
Banke TG, Gegelashvili G
The furosemide-sensitive potassium chloride co-transporter (KCC2) plays an important role in establishing the intracellular chloride concentration in many neurons within the central nervous system. Consequently, modulation of KCC2 function will regulate the reversal potential for synaptic GABAergic inputs, thus setting the strength of inhibitory transmission. We show that tonic activation of group I metabotropic glutamate receptors (mGluRs) regulates inhibitory synaptic strength via modulation of KCC2 function in pyramidal neurons of the hippocampal CA3 area. Specifically, group 1 mGluRs signal via activation of a protein kinase C-dependent pathway to alter KCC2 activity, thereby altering the intracellular chloride concentration, and thus inhibitory synaptic input. This interaction between the glutamatergic and chloride transport systems highlights a novel homeostatic mechanism whereby ambient glutamate levels directly regulate the inhibitory synaptic tone by setting the activity level of KCC2. Thus, mGluRs are poised to play a pivotal role in providing a direct interplay between the excitatory and inhibitory systems in the hippocampus.
Neurosurg Focus. 2008 Sep; 25(3): E22
Kahle KT, Staley KJ
Seizures that occur during the neonatal period do so with a greater frequency than at any other age, have profound consequences for cognitive and motor development, and are difficult to treat with the existing series of antiepileptic drugs. During development, gamma-aminobutyric acid (GABA)ergic neurotransmission undergoes a switch from excitatory to inhibitory due to a reversal of neuronal chloride (Cl()) gradients. The intracellular level of chloride ([Cl()](i)) in immature neonatal neurons, compared with mature adult neurons, is about 20-40 mM higher due to robust activity of the chloride-importing Na-K-2Cl cotransporter NKCC1, such that the binding of GABA to ligand-gated GABA(A) receptor-associated Cl() channels triggers Cl() efflux and depolarizing excitation. In adults, NKCC1 expression decreases and the expression of the genetically related chloride-extruding K-Cl cotransporter KCC2 increases, lowering [Cl()](i) to a level such that activation of GABA(A) receptors triggers Cl() influx and inhibitory hyperpolarization. The excitatory action of GABA in neonates, while playing an important role in neuronal development and synaptogenesis, accounts for the decreased seizure threshold, increased seizure propensity, and poor efficacy of GABAergic anticonvulsants in this age group. Bumetanide, a furosemide-related diuretic already used to treat volume overload in neonates, is a specific inhibitor of NKCC1 at low doses, can switch the GABA equilibrium potential of immature neurons from depolarizing to hyperpolarizing, and has recently been shown to inhibit epileptic activity in vitro and in vivo in animal models of neonatal seizures. The fundamental role of NKCC1 in establishing excitatory GABAergic neurotransmission in the neonate makes it a tempting target of a novel mechanism-based anticonvulsant strategy that could utilize the well-known pharmacology of bumetanide to help treat neonatal seizures.
Am J Physiol Regul Integr Comp Physiol. 2008 Aug 27;
Lazartigues E, Sinnayah P, Augoyard G, Gharib C, Johnson AK, Davisson RL
To address the relative contribution of central and peripheral angiotensin II (ANG II) type 1A receptors (AT1A) to blood pressure and volume homeostasis, we generated a transgenic mouse model (NSE-AT1A) with brain-restricted over-expression of AT1A receptors. These mice are normotensive at baseline but have dramatically enhanced pressor and bradycardic responses to intracerebroventricular (ICV) ANG II or activation of endogenous ANG II production. Here our goal was to examine the water and sodium intake in this model under basal conditions and in response to increased ANG II levels. Baseline water and NaCl (0.3 M) intakes were significantly elevated in NSE-AT1A compared to non-transgenic littermates, and bolus ICV injections of ANG II (200 ng in 200 nL) caused further enhanced water intake in NSE-AT1A. Activation of endogenous ANG II production by sodium depletion (10 days low sodium diet followed by furosemide, 1 mg sc) enhanced NaCl intake in NSE-AT1A mice compared to wildtypes. Fos immunohistochemistry, used to assess neuronal activation, demonstrated sodium depletion-enhanced activity in the AV3V region of the brain in NSE-AT1A mice compared to control animals. The results show that brain-selective over-expression of AT1A receptors results in enhanced salt appetite and altered water intake. This model provides a new tool for studying the mechanisms of brain AT1A -dependent water and salt consumption. Key words: thirst, sodium appetite, transgenic mice, circumventricular organs, volume homeostasis.