坦索罗辛联合托特罗定或呋塞米治疗输尿管下段结石的比较研究

目的比较坦索罗辛联合托特罗定或呋塞米在治疗输尿管下段结石上的疗效。方法将120例输尿管下段结石患者随机分为3组,A组给予坦索罗辛0.4 mg,1次/日;B组在A组基础上,给予托特罗定2 mg,2次/日;C组在A组基础上,给予呋塞米20 mg,2次/日。每5天复查1次,直至治疗后第15天。结果三组间排石率无显著性差异（P=0.277）。在结石排出时间上,C组显著短于A组（P=0.004）和B组（P=0.001）,A组与B组间无显著性差异（P=0.958）。结论在坦索罗辛的基础上联用托特罗定或呋塞米并不能提高输尿管结石的排石率,但联用呋塞米能更快地促进结石排出。     

Comparison between fluxes of potassium and of chloride in astrocytes in primary cultures

Transport processes operating in astrocytes were examined by measuring unidirectional fluxes of⁴²K and³⁶Cl in primary cultures of mouse astrocytes, at steady-state with respect to ion composition. The total K⁺ uptake rate was 2025 nmol·mg⁻¹ protein·min⁻¹. This rate was not influenced by furosemide (2 mM), an inhibitor of Cl⁻ uptake and K⁺-K⁺ exchange, or acetazolamide (0.1 mM), a carbonic anhydrase inhibitor. Ouabain (1 mM) inhibited the uptake rate by 541 nmol·mg⁻¹·min⁻¹. The equilibrated K⁺ content was determined to be 696 nmol·mg⁻¹. The rate constant for efflux was 2.76 min⁻¹. This equals an efflux rate of 1921 nmol·mg⁻¹·min⁻¹, i.e. a similar value as the influx. Furosemide and ouabain did not inhibit the efflux. The eequilibrated Cl⁻ contents was found to be 167 nmol·mg⁻¹ and it decreased in furosemide-treated cells to 68.1 nmol·mg⁻¹. The total Cl⁻ uptake was 35 nmol.mg⁻¹ and it was inhibited by furosemide or bumetanide by 27 nmol·mg⁻¹·min⁻¹. The means resting membrane potential was found to be—77.4 mV. From these data we conclude: (1) that the K⁺ uptake rates are high, as can be expected from estimates based on literature data for K⁺ conductance in mammalian glial cells in situ; and (2) that the cells possess a very low relative Cl⁻ permeability.     

A Quantitative Method of Evaluating the Diuretic Response to Furosemide in Rats

Furosemide effects are usually evaluated by measuring the urinary excretion rate of Na⁺ (UV_Na) in humans. In the present study, however, UV_Na showed a nonlinear relationship with urine flow rate after intravenous injection of furosemide in rats. In contrast, when the urinary excretion rate of (Na⁺ + K⁺) (UV_Na+K) was plotted against the urine flow rate, a linear regression line was observed, with small interindividual variations in normal rats and in rats with uranyl nitrate-induced acute renal failure (ARF). Piretanide, a loop diuretic, also showed a similar relationship, while other types of diuretics revealed different slope values for the relationship. Although the urinary excretion rate of Cl^– (UV_C1) vs UV_Na+K is expected to show a linear relationship in normal rats, the correlation coefficient of the linear regression line was smaller than that of the urine flow rate vs UV_Na+K. Further, the slope of UV_C1 vs UV_Na+K was slightly different in ARF rats. Therefore, UV_Na+K provides a better quantitative measure of diuretic response to loop diuretics than UV_Na or UV_C1.     

Aspects on pharmacokinetics of some diuretics

Abstract: This review summarizes the present knowledge of some commonly used diuretics. Bendroflumethiazide and bumetanide are completely absorbed from the gut while the uptake of hydrochlorothiazide, chlorthalidone and furosemide averages about 65%. The degree of uptake of amiloride and spironolactone is unknown but exceeds 50%. Plasma t 1/2 of bumetanide and furosemide are approximately 1 h. The clinically important phase of the plasma concentration of bendroflumethiazide has a t 1/2 of 3 h, although a slower phase with a t 1/2 of 9 h has been described. Hydrochlorothiazide and amiloride, often used in combination, both have a t 1/2 of about 10 h. Canrenone, an active metabolite of spironolactone, has a t 1/2 of 15–20 h. Chlorthalidone is eliminated very slowly with a t 1/2 of about two days. This is partly caused by an extensive binding to carbonic anhydrase in the erythrocytes. The protein binding of bendroflumethiazide, bumetanide, canrenone and furosemide is approximately 95%. The binding of chlorthalidone and hydrochlorothiazide is about 75 and 40% respectively. All mentioned diuretics except spironolactone are in part eliminated renally, mainly via tubular secretion. This is the major elimination route for amiloride and hydrochlorothiazide, while it constitutes one third to two thirds for bendroflumethiazide, bumetanide and furosemide. Spironolactone is exclusively eliminated as metabolites.     

Pharmacokinetics of furosemide in man after intravenous and oral administration. Application of moment analysis

Summary Furosemide 40 mg was administered to 8 healthy subjects as an i.v. bolus dose, as 1 tablet in the fasting state, and as 1 tablet and a solution after food intake. The i.v. data gave a total body clearance of 162±10.8 ml/min and a renal clearance of 117±11.3 ml/min; the volume of distribution at steady state was 8.3±0.61. Oral administration gave a bioavailability of the tablet (fasting) of 51%. Food intake slightly reduced the bioavailability, but not to a significant extent. There was no significant difference in availability between the tablet and the solution. Moment analysis gave a mean residence time after the i.v. dose, MRT_i.v., of 51±1.5 min. The mean absorption times (MAT) for all oral doses were significantly longer than the MRT_i.v., indicating absorption rate-limited kinetics of furosemide. On average, food delayed the absorption by 60 min. The MAT for the tablet in the postprandial state was significantly longer than for the solution, indicating dissolution rate-limited absorption of the tablet.     

Spironolactone further reduces urinary albumin excretion and plasma B-type natriuretic peptide levels in hypertensive type II diabetes treated with angiotensin-converting enzyme inhibitor

1. Over the course of treatment with angiotensin-converting enzyme inhibitor (ACEI), plasma levels of aldosterone have been shown to increase and this increase would blunt the effectiveness of the ACEI (aldosterone escape phenomenon). 2. In the present study, we assessed a potential renal benefit of additional aldosterone blockade with spironolactone in hypertensive diabetic patients treated with ACEI showing the phase of aldosterone escape. 3. The present clinical study was a randomized prospective study to assess difference between the clinical effects of spironolactone and furosemide. Thirty hypertensive type II diabetics (DM2) with a urinary alubumin:creatinine ratio (ACR) above 30 mg/g creatinine (showing albuminuria) and plasma B-type natriuretic peptide (BNP) levels above 100 pg/mL (showing mild heart failure) were treated with an ACEI (imidapril 5 mg/day) for 1 year and then randomly divided into two groups, one group receiving additional spironolactone (25 mg/day) treatment and the other receiving furosemide (20 mg/day) treatment. Blood pressure, ACR and plasma BNP levels were monitored in both groups. 4. Treatment with the ACEI reduced ACR initially but, in 1 year, ACR tended to increase. Additional spironolactone treatment progressively reduced ACR, whereas furosemide treatment did not show any effect. Plasma BNP levels were reduced by ACEI and were further reduced by additional spironolactone treatment, but not furosemide treatment. Blood pressure levels in both groups were comparable. 5. In conclusion, additional therapy with spironolactone in ACEI treatment exerts a renoprotective, as well as cardioprotective, effect in hypertensive diabetes.     

Abolition of the negative endocochlear potential as a consequence of the gentamicin-furosemide interaction

The DC endocochlear potential and the AC cochlear potential in response to a 4 kHz tone were recorded in pigmented guinea pigs before and during ototoxic damage induced by sequential administration of the aminoglycoside antibiotic, gentamicin, and the loop diuretic, furosemide. Within 4 h significant diminution of the amplitude of the AC cochlear potential was accompanied by an almost complete abolition of the negative diffusion potential revealed by either furosemide administration or terminal anoxia. Thus, one of the effects of this interaction appears to involve a reduction in the potassium permeability of the cochlear partitions.     

Comparison of the pharmacodynamic effect of muzolimine and furosemide in patients with advanced chronic renal insufficiency

Summary In a double blind cross-over study of 11 patients suffering from advanced chronic renal failure, the diuretic effect of single oral dose of muzolimine 240 mg and furosemide 240 mg was compared. The patients were stratified according to a serum creatinine of approximately 4/8 and 12 mg/dl, or a mean endogenous creatinine clearance of 21.7 ml/min/1.73 m², 8.2 ml/min/1.73 m² and 5.4 ml/min/1.73 m². Urine volume and sodium excretion were studied biometrically using a 3-factor variance analysis. Urine excretion in all groups tended to be greater after muzolimine than after furosemide. The cumulative sodium excretion after muzolimine was significantly greater. In the groups with a creatinine clearance of 8.2 or 5.4 ml/min/1.73 m², the duration of the time- response curve of muzolimine was greater than that of furosemide. Thus, even in advanced renal insufficiency, both substances had a saluretic effect. Muzolimine appeared to be significantly more effective than furosemide in causing natriuresis in patients with a serum creatinine of 4 to 8 mg/dl.     

Evaluation of Prehospital Use of Furosemide in Patients with Respiratory Distress

Objective. To evaluate the appropriateness of prehospital use of furosemide. Methods. All patients over 18 years old receiving prehopsital furosemide were retrospectively identified, andcases were matched to subsequent hospital records. Data collected included ED andhospital primary andsecondary diagnoses, brain-type natriuretic peptide (BNP) levels andfinal disposition. Furosemide was considered appropriate when the primary or secondary ED or hospital diagnoses included congestive heart failure (CHF) or pulmonary edema, or the BNP was > 400. Furosemide was considered inappropriate when none of the diagnoses included CHF, when the BNP was < 200, or when an order for IV fluid hydration was given. Furosemide was considered potentially harmful when the diagnoses included sepsis, dehydration or pneumonia, without a diagnosis of CHF or BNP > 400. Results. Of the 144 included patients, a primary or secondary diagnosis of CHF was reported in 42% and17% patients, respectively. The initial BNP was > 400 in 44% of the 120 patients in which this lab test was obtained. Sixty patients (42%) did not receive a diagnosis of CHF, 30 (25%) patients had a BNP < 200, and33 (23%) had an order for IV fluid hydration. A diagnosis of sepsis, dehydration or pneumonia without a diagnosis of CHF or a BNP > 400 occurred in 17% of patients. Seven of the 9 deaths did not receive a diagnosis of CHF. Furosemide was considered appropriate in 58%, inappropriate in 42% andpotentially harmful in 17% of patients. Conclusions. In this EMS system, prehospital furosemide was frequently administered to patients in whom its use was considered inappropriate, andnot uncommonly to patients when it was considered potentially harmful. EMS systems should reconsider the appropriateness of prehospital diuretic use.