Furosemide Given by Inhalation Ameliorates Acute Exacerbation of Asthma

Previous studies have suggested that inhaled furosemide may have a protective effect against a wide variety of bronchoconstrictor agents, but a therapeutic effect has not been established in acute exacerbation of asthma. The purpose of this study was to investigate whether inhaled furosemide would exhibit any therapeutic benefit in acute asthma. We conducted a double-blind, placebo-controlled, randomized study in 40 patients with acute mild or moderate exacerbation of asthma. All patients received intravenous (IV) aminophylline 250 mg for 90 min and IV hydrocortisone 100 mg at entry. After randomization, 3 patients were excluded from the final analysis. At 30 min after starting IV aminophylline, 20 patients were given inhaled furosemide 20 mg and 17 patients received normal saline as placebo-control. Both inhalations were given by a jet nebulizer. The baseline forced expiratory volume at 1 sec (FEV₁), peak expiratory flow rate (PEFR), and serum concentration of theophylline did not differ between the two groups. An increase in FEV₁ in the furosemide group by 28.2 ± 5.9% (mean ± SE) was noted at 60 min, and this was significantly higher than in the control group. PEFR at 60 min was also significantly higher in the furosemide group than in control group. We conclude that inhaled furosemide has a bronchodilator effect on mild to moderate exacerbation of asthma when it is used with IV theophylline. Inhaled furosemide may benefit certain acute asthma patients, especially those suffering complications from the adverse effects of β₂-agonists.     

Changes in element concentrations induced by agonist in pig pancreatic acinar cells

 Changes in electrolytes of pig pancreatic acinar cells following application of gastrin-cholecystokinin (CCK) were investigated using the technique of X-ray microanalysis of hydrated and dehydrated sections of freshly frozen pancreas. After stimulation by CCK (10^–9 M), Na and Cl increased significantly in the cytoplasm [Na, from 10 mmol/kg wet wt. (48 mmol/kg dry wt.) to 19 mmol/kg (95 mmol/kg); Cl, from 22 mmol/kg (105 mmol/kg) to 49 mmol/kg (245 mmol/kg)] as well as in the luminal interspace [Na, from 53 mmol/kg (189 mmol/kg) to 65 mmol/kg (283 mmol/kg); Cl, from 65 mmol/kg (232 mmol/kg) to 102 mmol/kg (443 mmol/kg)]. In the secretory granules Cl increased significantly from 30 mmol/kg (86 mmol/kg) to 67 mmol/kg (203 mmol/kg). K decreased significantly from 120 mmol/kg (571 mmol/kg) to 81 mmol/kg (405 mmol/kg) in the cytoplasm, while both increased from 38 mmol/kg (109 mmol/kg) to 58 mmol/kg (176 mmol/kg) in the granules and from 46 mmol/kg (164 mmol/kg) to 48 mmol/kg (209 mmol/kg) in the luminal interspace. Ca increased significantly in the cytoplasm as well as in the luminal interspace, and decreased significantly in the secretory granules. CCK evoked Ca release from secretory granules in the secretory pole of acinar cells. The values were measured from dehydrated sections, and agreed well with those from hydrated sections. The effect of furosemide, an inhibitor of the Na⁺-K⁺-2Cl^–co-transporter, on the ion transport of acinar cell was studied. When furosemide (10^–5 M) was added to the external solution, the cytoplasmic Cl and Ca concentrations decreased significantly, while there was a little decrease in Na and K concentrations under the secretory condition. These results indicate that Na⁺-K⁺-2Cl^–co-transport, and Na⁺, Cl^–and K⁺ exits into the lumen are involved in the mechanism of ion secretion in pig pancreatic acinar cells. Received: 17 January 1996 / Accepted: 12 March 1996     

Effect of various diuretics on membrane voltage of macula densa cells. Whole-cell patch-clamp experiments

The tubuloglomerular feedback mechanism is inhibited by diuretics such as furosemide. For the macula densa (MD) cells similar transport systems, as present in thick ascending limb (TAL) cells, have been suggested. To examine this further, membrane voltages (V _m) of MD cells were recorded with the fast or slow wholecell patch-clamp method. The effects of diuretics on voltages and the conductance properties of these cells were examined. V _m of MD cells measured with the whole-cell patch-clamp method were as high as those in TAL cells: –72±1 mV (n=21). An increase in the extracellular K⁺ concentration by 15 mmol/l depolarized V _m of MD cells by 11±1 mV (n=18). Ba²⁺ (1 mmol/ l) reversibly depolarized MD cells by 10±2 mV (n= 10). Thus, MD cells possess a K⁺ conductance that could allow for the recycling of K⁺ taken up by the Na⁺-2 Cl^–-K⁺ cotransporter. MD cells hyperpolarized reversibly upon addition of the loop diuretics furosemide, piretanide and torasemide, whereas muzolimine and hydrochlorothiazide, neither one acting on this cotransport system in other preparations including the TAL, had no effect on V _m. MD cells most likely possess the same cotransport system as the TAL cells, which drives NaCl reabsorption in the TAL and serves as sensor for the tubular NaCl concentration in MD cells.     

Assessment of high-energy phosphorus compounds in the rat kidney by in situ31P nuclear magnetic resonance spectroscopy: effect of ischemia and furosemide

Summary ³¹P nuclear magnetic resonance (NMR) spectroscopy of the in situ rat kidney was performed by a surface coil method, and the effects of ischemia and furosemide infusion were assessed.³¹P NMR spectra of the kidney subjected to 30 min of ischemia returned completely to the pre-ischemic level after 60 min of reperfusion. But the³¹P NMR spectra after 60 min of ischemia did not recover, even after 120 min of reperfusion. Levels of -ATP and inorganic phosphate (Pi) decreased and the chemical shift of Pi increased after intravenous infusion of furosemide. This increase in chemical shift might signal an alkalotic change in intracellular pH. Furosemide infusion prior to ischemia is thought to protect the kidney from injury induced by 60 min of warm ischemia. The chemical shift of Pi returned to the pre-ischemic level earlier than -ATP and Pi. In conclusion, according to the findings of³¹P NMR spectroscopy, furosemide infusion prior to ischemia may be effective in protecting the kidney against ischemic injury. But the change in Pi peak and the causes of the dissociation of Pi and -ATP should be examined further.     

Comparison of the diuretic effect and absorption of a single dose of furosemide and free and the fixed combinations of furosemide and triamterene in healthy male adults

Summary The absorption and diuretic effect of furosemide 40 mg alone (F), and of the free (F+T) and the fixed (FT) combinations of furosemide 40 mg and triamterene 50 mg have been compared in 12 healthy young men.A slight reduction in the area under the concentration-time curve (AUC) of plasma furosemide was found for the fixed combination (AUC₄₈₀) F 2.58 g · h · ml^–1; F+T 2.46 g · h · ml^–1; FT 1.97 g · h · ml^–1. There was a significant reduction in the AUC₄₈₀ of plasma triameterene (F+T 204.9 g · h · l^–1; FT 130.2 g · h · l^–1). Sodium excretion after F+T and FT was more pronounced than after F (F+T 302 mmol; FT 311 mmol; F 259 mmol). When compared to F alone, there was a reduction in the 24-hour potassium excretion after F+T as well as after FT (F 121 mmol; F+T 104 mmol; FT 107 mmol).It is concluded that the absorption of triamterene was significantly reduced after ingestion of the fixed combination tablet. However, in healthy male adults this had no influence on its natriuretic and potassium-sparing effect as compared to the free combination.     

Influence of meloxicam on furosemide pharmacokinetics and pharmacodynamics in healthy volunteers

Fifteen healthy male volunteers participated in an open, multiple-dose study to investigate a possible interaction between furosemide and meloxicam, a new non-steroidal anti-inflammatory agent (NSAID). The study comprised three treatment periods. First, furosemide (40 mg) was administered as a single oral daily dose for 3 days. A wash-out day was followed by the administration of meloxicam (15 mg) as a single oral daily dose for 10 days. Thereafter, meloxicam and furosemide were administered concomitantly at the same doses as described above, for 3 days. The effect of concomitant ingestion of meloxicam and furosemide on furosemide-induced diuresis, urine and serum electrolytes, and furosemide pharmacokinetics was determined, after both single and repeated administration of furosemide. Estimates of the (furosemide + meloxicam)/(furosemide alone) mean ratio of the variable AUC(0-) for plasma furosemide and the cumulative sodium excretion (0–8 h) were 97.4% (90% confidence interval 89.7–106%) and 88% (90% confidence interval 82–94%), respectively. The study results indicate that meloxicam does not affect the pharmacokinetics of furosemide in healthy volunteers, nor does it affect furosemide-induced diuresis or serum electrolytes. The cumulative urinary electrolyte excretion after concomitant administration of meloxicam and furosemide is somewhat lower than after administration of furosemide alone, in particular for the period 0–8 h after administration of furosemide. This effect of meloxicam on furosemide dynamics is small, and is probably not clinically relevant in healthy volunteers under the dosing regime studied.     

静脉泵入与静脉注射速尿治疗重度充血性心力衰竭的疗效比较

目的通过比较静脉泵入与静脉注射速尿（呋塞束）治疗重度充血性心力衰竭（congestive heart failure，CHF）的临床效果．为充血性心力衰竭的治疗提供新的方法。方法50例重度心力衰竭患者被随机分为静脉泵入组与静脉注射组，各25例。两组均给予心力衰竭常规治疗，静脉泵入组速给予速尿100mg·d^-1，10mg·h^-1持续静脉泵入10h。静脉注射组给予速尿100mg·d^-1，2次静脉注射。7天后观察治疗前后患者临床表现及左室射血分数（left ventricular ejection fraction．LVEF）、心输出量（cardiac output，CO）、心搏量（stroke volume，SV）、心脏指数（cardiac index，CI）的变化。结果静脉泵入组总有效率为92％．静脉注射组的68％，差异有显著性（P〈0．05）。静脉泵入组LVEF、CO、SV、CI改善明显优于静脉注射组（P〈0．05）。结论静脉泵入速尿治疗重度心力衰竭的疗效明显优于静脉注射。     

持续静脉微量注射呋塞米对充血性心力衰竭患者的疗效观察

目的观察对比持续静脉微量注射呋塞米对严重充血性心力衰竭(CHF)患者疗效是否优于传统的间断注射疗效,对患者血浆B型钠尿肽前体(pro-LPBN)浓度的影响。方法在常规防重构、强心、扩血管的基础上,观察分析70例NYHA心功能Ⅲ~Ⅳ级患者,分为持续静脉微量注射呋塞米组(观察组)35例和间断注射呋塞米组(对照组)35例,两组使用呋塞米剂量大致相同,比较两组治疗前后尿量、血压波动、血液电解质浓度、超声心动图心功能指标、症状缓解时间的差别,并对两组患者治疗前后的血浆pro-LPBN进行测定。结果观察组治疗后尿量多于对照组,LVEF改善显著优于对照组,症状缓解时间短于对照组(P<0.01或0.05);观察组治疗后pro-LPBN水平显著低于对照组(P<0.05);血压和血液电解质浓度无显著差异(P>0.05)。结论持续静脉微量注射呋塞米治疗严重CHF,疗效明显优于传统的间断静脉注射法。     

不同剂量甘露醇单用或合用速尿治疗颅高压的疗效观察

目的观察不同剂量甘露醇单用或合用速尿治疗颅高压的疗效。方法对60例各种原因行脑外科手术后出现颅内压增高的患者、依据使用不同剂量甘露醇单用或加用速尿而分为半量甘露醇(0.5 g/kg)组(A组)、全量甘露醇(1.0 g/kg)组(B组)、半量甘露醇 速尿(20 mg)组(C组)及全量甘露醇 速尿(20 mg)组(D组),通过颅内压监测,观察各组降低颅内压的效率、血浆渗透压及肾功能改变。结果(1)在降低颅内压的有效率、颅内压反跳率、药效持续时间上,C、D组明显优于A、B组(均P<0.05);降压幅度4组间差异无显著性。(2)连续降颅压治疗第5 d及第7 d时,各组均出现血浆渗透压的升高,与C组相比,B、D组升高更明显(P<0.05~0.01)。(3)连续使用甘露醇第5 d、7 d,与C组相比,B、D组血尿素氮、肌酐明显升高(均P<0.05)。结论半量甘露醇 速尿治疗颅内压增高疗效佳、安全性高。     

多巴胺联合速尿持续泵入治疗顽固性心衰中利尿剂抵抗的疗效观察

目的探讨持续静脉泵人多巴胺和呋塞米（速尿）对顽固性心衰的疗效。方法将58例顽固性心力衰竭患者随机分为观察组和对照组,分别为30例和28例。观察组在常规抗心力衰竭治疗的基础上联合多巴胺和速尿持续静脉泵人,连续应用6d：对照组常规抗心力衰竭治疗基础上单纯持续静脉泵入速尿。观察两组治疗后临床症状、体征及心功能指标等方面的变化。结果观察组临床总有效25例,总有效率为83.3％;对照组临床总有效15例,总有效率为53．6％。两组比较差异有统计学意义（P〈0．05）;两组治疗后左室射血分数、左室舒张末内径比较,差异均有统计学意义（P均〈0．05）。结论在常规治疗基础上持续静脉泵人多巴胺和速尿对存在利尿剂抵抗的顽同性心力衰竭疗效显著。