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  1. Van Siang Lian Mang P, Hui JC, Tan RSJ, Hasan MS, Choo YM, Abosamak MF, et al.
    Eur J Pediatr, 2023 Jan;182(1):1-8.
    PMID: 36251063 DOI: 10.1007/s00431-022-04655-w
    The diuretic effect of the combined furosemide and aminophylline/theophylline among pediatric patients remains unclear. The primary aim of this systematic review was to examine the clinical diuretic effects (urine output and fluid balance) of co-administration of furosemide and aminophylline/theophylline as compared to furosemide alone in pediatric population. Ovid MEDLINE, CENTRAL, and EMBASE were searched from its inception until March 2022 for observational studies and randomized controlled trials (RCTs) comparing the administration of furosemide versus furosemide and aminophylline/theophylline in pediatric population. Case reports, case series, commentaries, letters to editors, systematic reviews, and meta-analyses were excluded. Five articles with a total sample population of 187 patients were included in this systematic review. As compared to the furosemide alone, our pooled data demonstrated that co-administration of furosemide and aminophylline/theophylline was associated with higher urine output (mean difference: 2.91 [90% CI 1.54 to 4.27], p 
    Matched MeSH terms: Furosemide/pharmacology; Furosemide/therapeutic use
  2. Balasegaram M, Damodaran A
    Med J Malaya, 1971 Dec;26(2):133-6.
    PMID: 4260860
    Matched MeSH terms: Furosemide/administration & dosage*; Furosemide/pharmacology
  3. Dauw J, Lelonek M, Zegri-Reiriz I, Paredes-Paucar CP, Zara C, George V, et al.
    ESC Heart Fail, 2021 Dec;8(6):4685-4692.
    PMID: 34708555 DOI: 10.1002/ehf2.13666
    AIMS: Although acute heart failure (AHF) with volume overload is treated with loop diuretics, their dosing and type of administration are mainly based upon expert opinion. A recent position paper from the Heart Failure Association (HFA) proposed a step-wise pharmacologic diuretic strategy to increase the diuretic response and to achieve rapid decongestion. However, no study has evaluated this protocol prospectively.

    METHODS AND RESULTS: The Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure (ENACT-HF) study is an international, multicentre, non-randomized, open-label, pragmatic study in AHF patients on chronic loop diuretic therapy, admitted to the hospital for intravenous loop diuretic therapy, aiming to enrol 500 patients. Inclusion criteria are as follows: at least one sign of volume overload (oedema, ascites, or pleural effusion), use ≥ 40 mg of furosemide or equivalent for >1 month, and a BNP > 250 ng/L or an N-terminal pro-B-type natriuretic peptide > 1000 pg/L. The study is designed in two sequential phases. During Phase 1, all centres will treat consecutive patients according to the local standard of care. In the Phase 2 of the study, all centres will implement a standardized diuretic protocol in the next cohort of consecutive patients. The protocol is based upon the recently published HFA algorithm on diuretic use and starts with intravenous administration of two times the oral home dose. It includes early assessment of diuretic response with a spot urinary sodium measurement after 2 h and urine output after 6 h. Diuretics will be tailored further based upon these measurements. The study is powered for its primary endpoint of natriuresis after 1 day and will be able to detect a 15% difference with 80% power. Secondary endpoints are natriuresis and diuresis after 2 days, change in congestion score, change in weight, in-hospital mortality, and length of hospitalization.

    CONCLUSIONS: The ENACT-HF study will investigate whether a step-wise diuretic approach, based upon early assessment of urinary sodium and urine output as proposed by the HFA, is feasible and able to improve decongestion in AHF with volume overload.

    Matched MeSH terms: Furosemide
  4. Ng KT, Yap JLL
    Anaesthesia, 2018 Feb;73(2):238-247.
    PMID: 28940440 DOI: 10.1111/anae.14038
    Loop diuretics remain a fundamental pharmacological therapy to remove excess fluid and improve symptom control in acute decompensated heart failure. Several recent randomised controlled trials have examined the clinical benefit of continuous vs. bolus furosemide in acute decompensated heart failure, but have reported conflicting findings. The aim of this review was to compare the effects of continuous and bolus furosemide with regard to mortality, length of hospital stay and its efficacy profile in acute decompensated heart failure. All parallel-arm randomised controlled trials from MEDLINE, EMBASE, PubMed and the Cochrane Database of Systematic Reviews from inception until May 2017 were included. Cross-over randomised controlled trials, observational studies, case reports, case series and non-systematic reviews that involved children were excluded. Eight trials (n = 669) were eligible for inclusion. There was no difference between furosemide continuous infusion and bolus administration for all-cause mortality (four studies; n = 491; I2 = 0%; OR 1.65; 95%CI 0.93-2.91; p = 0.08) or duration of hospitalisation (six studies; n = 576; I2 = 71%; mean difference 0.27; 95%CI -1.35 to 1.89 days; p = 0.74). Continuous infusion of intravenous furosemide was associated with increased weight reduction (five studies; n = 516; I2 = 0%; mean difference 0.70; 95%CI 0.12-1.28 kg; p = 0.02); increased total urine output in 24 h (four studies; n = 390; I2 = 33%; mean difference 461.5; 95%CI 133.7-789.4 ml; p < 0.01); and reduced brain natriuretic peptide (two studies; n = 390; I2 = 0%; mean difference 399.5; 95%CI 152.7-646.3 ng.l-1 ; p < 0.01), compared with the bolus group. There was no difference in the incidence of raised creatinine and hypokalaemia between the two groups. In summary, there was no difference between continuous infusion and bolus of furosemide for all-cause mortality, length of hospital stay and electrolyte disturbance, but continuous infusion was superior to bolus administration with regard to diuretic effect and reduction in brain natriuretic peptide.
    Matched MeSH terms: Furosemide/administration & dosage*; Furosemide/therapeutic use*
  5. Khan YH, Sarriff A, Adnan AS, Khan AH, Mallhi TH
    Clin Exp Nephrol, 2017 Dec;21(6):1011-1023.
    PMID: 28271257 DOI: 10.1007/s10157-017-1397-6
    INTRODUCTION: Diuretic therapy has been the mainstay of treatment in chronic kidney disease (CKD) patients, primarily for hypertension and fluid overload. Apart from their beneficial effects, diuretic use is associated with adverse renal outcomes. The current study is aimed to determine the outcomes of diuretic therapy.
    METHODOLOGY: A prospective observational study was conducted by inviting pre-dialysis CKD patients. Fluid overload was assessed by Bioimpedance analysis (BIA).
    RESULTS: A total 312 patients (mean age 64.5 ± 6.43) were enrolled. Among 144 (46.1%) diuretic users, furosemide and hydrochlorothiazide (HCTZ) were prescribed in 69 (48%) and 39 (27%) patients, respectively, while 36 (25%) were prescribed with combination therapy (furosemide plus HCTZ). Changes in BP, fluid compartments, eGFR decline and progression to RRT were assessed over a follow-up period of 1 year. Maximum BP control was observed with combination therapy (-19.3 mmHg, p 
    Matched MeSH terms: Furosemide/pharmacology; Furosemide/therapeutic use
  6. Rajasekaran A, Sivakumar V
    Nephrolepis cordifolia rhizome (sword fern) juice was investigated for diuretic activity in wistar rats. Different parameters viz. total urine volume (corrected for water intake during the test period), urine concentration of electrolytes such as sodium, potassium and chloride have been evaluated. Rhizome juice of Nephrolepis cordifolia (100 mg/kg), the reference drug, furosemide (20 mg/kg) was administrated orally to male Wistar rats and their urine output was quantitated at several intervals of time after the dose. After single dose of the rhizome juice of Nephrolepis cordifolia, urine output was significantly increased. Increase in urinary levels of Na+, K+ and Cl- was also observed after the administration of rhizome juice.
    Matched MeSH terms: Furosemide
  7. Ng KT, Velayit A, Khoo DKY, Mohd Ismail A, Mansor M
    J Cardiothorac Vasc Anesth, 2018 10;32(5):2303-2310.
    PMID: 29454528 DOI: 10.1053/j.jvca.2018.01.004
    OBJECTIVE: Fluid overload is a common phenomenon seen in intensive care units (ICUs). However, there is no general consensus on whether continuous or bolus furosemide is safer or more effective in these hemodynamically unstable ICU patients. The aim of this meta-analysis was to examine the clinical outcomes of continuous versus bolus furosemide in a critically ill population in ICUs.

    DATA SOURCES: MEDLINE, EMBASE, PubMed, and the Cochrane Database of Systematic reviews were searched from their inception until June 2017.

    REVIEW METHODS: All randomized controlled trials, observational studies, and case-control studies were included. Case reports, case series, nonsystematic reviews, and studies that involved children were excluded.

    RESULTS: Nine studies (n = 464) were eligible in the data synthesis. Both continuous and bolus furosemide resulted in no difference in all-cause mortality (7 studies; n = 396; I2 = 0%; fixed-effect model [FEM]: odds ratio [OR] 1.15 [95% confidence interval (CI) 0.67-1.96]; p = 0.64). Continuous furosemide was associated with significant greater total urine output (n = 132; I2 = 70%; random-effect model: OR 811.19 [95% CI 99.84-1,522.53]; p = 0.03), but longer length of hospital stay (n = 290; I2 = 40%; FEM: OR 2.84 [95% CI 1.74-3.94]; p < 0.01) in comparison to the bolus group. No statistical significance was found in the changes of creatinine and estimated glomerular filtration rate between both groups.

    CONCLUSIONS: In this meta-analysis, continuous furosemide was associated with greater diuretic effect in total urine output as compared with bolus. Neither had any differences in mortality and changes of renal function tests. However, a large adequately powered randomized clinical trial is required to fill this knowledge gap.

    Matched MeSH terms: Furosemide/administration & dosage*
  8. Khor, K.H., Jessie-Bay, J.X.
    Jurnal Veterinar Malaysia, 2018;30(1):15-19.
    MyJurnal
    Myxomatous Mitral Valve Disease is a degenerative condition of the mitral valves leaflets. A 10-year-old
    male castrated Shih Tzu was presented with primary complaint of coughing. Clinical examination revealed normal
    heart rate, respiratory rate and rectal temperature. Systolic murmur Grade IV/VI was heard at the left heart apex.
    Thoracic radiographic findings were cardiomegaly with the vertebral heart score of 11.0 and had evidence of
    cardiogenic pulmonary edema. Echocardiographic examination revealed thickening mitral valves with evidence of
    moderate regurgitation observed. Based on the findings obtained, the dog was diagnosed with Myxomatous Mitral
    Valve disease stage C2. Dog was treated with benazepril (0.5mg/kg), pimobendan (0.2mg/kg) with a combination of
    furosemide (2mg/kg). Frusemide was gradually removed from the treatment regime as coughing improved over time.
    The dog was no longer lethargy and even gained weight.
    Matched MeSH terms: Furosemide
  9. Muniandy RK, Sinnathamby V
    BMJ Case Rep, 2012;2012.
    PMID: 22922924 DOI: 10.1136/bcr-2012-006562
    A 16-month-old child developed a brief generalised tonic-clonic fitting episode and vomiting at home, after accidental ingestion of traditional massage oil. As the patient presented with clinical features of salicylate toxicity, appropriate management was instituted. He was admitted to the intensive care unit for multiorgan support. The child was discharged well 1&emsp14;week after the incident. Methyl-salicylate is a common component of massage oils which are used for topical treatment of joint and muscular pains. However, these massage oils may be toxic when taken orally. Early recognition of the salicylate toxicity is very important in producing a good patient outcome.
    Matched MeSH terms: Furosemide/therapeutic use
  10. Asmah BJ, Wan Nazaimoon WM, Norazmi K, Tan TT, Khalid BA
    Horm. Metab. Res., 1997 Nov;29(11):580-3.
    PMID: 9479560 DOI: 10.1055/s-2007-979105
    The effect of thyroid hormones on the renin-angiotensin-aldosterone system has not been fully resolved. Highly specific immunoassays for measurement of renin, aldosterone, free T4 (fT4), free T3 (fT3) and ultrasensitive TSH enables a direct and more accurate measurement of these hormones. We investigated the relationship between plasma renin, aldosterone and thyroid hormones in the basal state and after intravenous frusemide. This is a cross-sectional study involving 37 patients with thyrotoxicosis, 42 rendered euthyroid with normal fT4, fT3 and TSH levels, 17 with euthyroid levels of fT4 and fT3 but suppressed TSH, and 11 with hypothyroidism. Basal plasma renin was significantly higher in thyrotoxicosis (63.4 +/- 9.8 microU/ml, mean +/- SEM) compared to euthyroid (32.7 +/- 4.4 microU/ml) and hypothyroid (26.7 +/- 9.8 microU/ml). Basal plasma renin for euthyroid with suppressed TSH (41.0 +/- 7.4 microU/ml) was significantly higher than hypothyroid (p = 0.02). Basal plasma aldosterones were not significantly different except for suppressed TSH (157.7 +/- 13 pg/ml), which was higher than normal (109.9 +/- 10.4 pg/ml; p = 0.04). Following frusemide, plasma renin and aldosterone were significantly increased in all groups. Plasma renin was highly correlated to fT3 (r = 0.405, p < 0.001), total T3 (r = 0.359, p < 0.001), fT4 (r = 0.331, p < 0.001) and TSH (r = 0.300, p < 0.001) in the basal state, but less to total T4 (r = 0.248, p < 0.01). Plasma renin correlated poorly to serum aldosterone (r = 0.212, p < 0.03). This study clearly showed that regulation of renin was mainly influenced by fT3, and that aldosterone response to frusemide was blunted in thyrotoxicosis despite normal electrolytes.
    Matched MeSH terms: Furosemide/administration & dosage
  11. Adam Y, Somchit MN, Sulaiman MR, Nasaruddin AA, Zuraini A, Bustamam AA, et al.
    J Ethnopharmacol, 2009 Jul 6;124(1):154-8.
    PMID: 19375494 DOI: 10.1016/j.jep.2009.04.014
    Orthosiphon stamineus has been used in traditional medicine for centuries especially to treat diseases of the urinary system.
    Matched MeSH terms: Furosemide/pharmacology
  12. Khairul Azman Mohd. Khalid, Hussain Imam Mohd Ismail, Mohd Sham Kasim
    MyJurnal
    The diagnosis of tuberculous meningitis (TBM) demands a high index of suspicion. The prognosis depends on the stage of the disease the diagnosis is made and how early the treatment is instituted. The outcome of the disease is very poor when the diagnosis and treatment are late. This is what happened to this child, a 7-year-old Malay girl who presented at stage III TBM. The diagnosis was confirmed by a positive culture of M. tuberculosis from the cerebrospinal fluid (CSF). The delay in the diagnosis in this child had catastrophic consequences. She had hydrocephalus at presentation; however ventricular drainage was not done because parental consent was not obtained. She was started on acetazolamide and frusemide, and daily lumbar puncture in an attempt to reduce the raised intracranial pressure (ICP) in addition to anti-tuberculous chemotherapy. However when she showed no improvement, an external lumbar drain was inserted. The CSF was checked daily and the level of protein and glucose became normal after 6 weeks. The CT scan showed improvement of the hydrocephalus. However, the girl remained severely disabled after treatment and had to be fed via nasogastric tube and needed constant nursing care.
    Matched MeSH terms: Furosemide
  13. Wahab IA, Akbar B, Zainal ZA, Che Pa MF, Naina B
    Malays J Med Sci, 2019 Mar;26(2):77-87.
    PMID: 31447611 MyJurnal DOI: 10.21315/mjms2019.26.2.9
    Background: Studies have shown that the use of medicines with anti-cholinergic (Ach) properties can increase elderly patients' risk of experiencing falls, confusion, and longer hospital stays (LOS). These adverse effects are preventable with appropriate intervention. Little is known about the use of medicines with Ach properties and their impact on Malaysian elderly patients. This study aimed to investigate the use of medicines with Ach properties and their impact on fall risk, confusion, and longer LOS among hospitalised elderly patients.

    Methods: This study utilised a cross-sectional design and was conducted at a single centre where convenience sampling was employed to collect data from elderly patients (> 60 years) admitted to geriatric and medical wards at Hospital Tuanku Ja'afar during a 2-month period (July 2017-August 2017). Patients were excluded from this study if their hospital admission was planned for an elective procedure or if neurocognitive and hepatic impairment were diagnosed prior to the hospital admission. Medicines with Ach properties were identified and classified according to the anti-cholinergic drug scale (ADS). Univariate and multiple logistic regression statistical analyses were performed to assess its impacts on falls, confusion, and LOS.

    Results: A total of 145 elderly patients with a mean age of 71.59 years old (SD = 8.02) were included in the study. Fifty-two percent of the participants were female, and the average hospital stay was 6 days (SD = 2.09). Medicines with Ach properties were administered in 62% (n = 90) of the cases. The most commonly prescribed medicine with Ach properties was furosemide (n = 59), followed by ranitidine (n = 44), warfarin (n = 23), and methylprednisolone (n = 22). Compared to patients who did not receive medicines with Ach properties, patients who received them had a significantly higher risk of falls [odds ratios (OR) = 2.61; 95%CI: 1.18, 5.78; P = 0.018], confusion (OR = 3.60; 95%CI: 1.55, 8.36; P = 0.003), and LOS (OR = 4.83; 95%CI: 2.13, 10.94; P < 0.001). Multiple comorbidities also showed a significantly increased risk of falls (OR = 3.03; 95%CI: 1.29, 7.07; P = 0.010).

    Conclusion: Medicines with Ach properties had a significant impact on elderly patients' health. Strategies for rationally prescribing medicines with Ach properties to Malaysian elderly patients need to be improved and be recognised as an important public health priority.

    Matched MeSH terms: Furosemide
  14. Fan PC, Lai TH, Hor CC, Lee MT, Huang P, Sieghart W, et al.
    Neuropharmacology, 2018 09 15;140:1-13.
    PMID: 30016665 DOI: 10.1016/j.neuropharm.2018.07.017
    Novel treatments against migraine are an urgent medical requirement. The α6 subunit-containing GABAA receptors (α6GABAARs) are expressed in trigeminal ganglia (TG), the hub of the trigeminal vascular system (TGVS) that is involved in the pathogenesis of migraine. Here we reveal an unprecedented role of α6GABAARs in ameliorating TGVS activation using several pharmacological approaches in an animal model mimicking pathological changes in migraine. TGVS activation was induced by intra-cisternal (i.c.) instillation of capsaicin in Wistar rats. Centrally, i.c. capsaicin activated the trigeminal cervical complex (TCC) measured by the increased number of c-Fos-immunoreactive (c-Fos-ir) TCC neurons. Peripherally, it elevated calcitonin gene-related peptide immunoreactivity (CGRP-ir) in TG and depleted CGRP-ir in the dura mater. Pharmacological approaches included a recently identified α6GABAAR-selective positive allosteric modulator (PAM), the pyrazoloquinolinone Compound 6, two α6GABAAR-active PAMs (Ro15-4513 and loreclezole), an α6GABAAR-inactive benzodiazepine (diazepam), an α6GABAAR-selective antagonist (furosemide), and a clinically effective antimigraine agent (topiramate). We examined effects of these compounds on both central and peripheral TGVS responses induced by i.c. capsaicin. Compound 6 (3-10 mg/kg, i.p.) significantly attenuated the TCC neuronal activation and TG CGRP-ir elevation, and dural CGRP depletion induced by capsaicin. All these effects of Compound 6 were mimicked by topiramate, Ro15-4513 and loreclezole, but not by diazepam. The brain-impermeable furosemide antagonized the peripheral, but not central, effects of Compound 6. These results suggest that the α6GABAAR in TG is a novel drug target for TGVS activation and that α6GABAAR-selective PAMs have the potential to be developed as a novel pharmacotherapy for migraine.
    Matched MeSH terms: Furosemide/pharmacology
  15. Konopacka A, Qiu J, Yao ST, Greenwood MP, Greenwood M, Lancaster T, et al.
    J Neurosci, 2015 Apr 01;35(13):5144-55.
    PMID: 25834041 DOI: 10.1523/JNEUROSCI.4121-14.2015
    The Na-K-2Cl cotransporter 2 (NKCC2) was thought to be kidney specific. Here we show expression in the brain hypothalamo-neurohypophyseal system (HNS), wherein upregulation follows osmotic stress. The HNS controls osmotic stability through the synthesis and release of the neuropeptide hormone, arginine vasopressin (AVP). AVP travels through the bloodstream to the kidney, where it promotes water conservation. Knockdown of HNS NKCC2 elicited profound effects on fluid balance following ingestion of a high-salt solution-rats produced significantly more urine, concomitant with increases in fluid intake and plasma osmolality. Since NKCC2 is the molecular target of the loop diuretics bumetanide and furosemide, we asked about their effects on HNS function following disturbed water balance. Dehydration-evoked GABA-mediated excitation of AVP neurons was reversed by bumetanide, and furosemide blocked AVP release, both in vivo and in hypothalamic explants. Thus, NKCC2-dependent brain mechanisms that regulate osmotic stability are disrupted by loop diuretics in rats.
    Matched MeSH terms: Furosemide/pharmacology
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