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1.
Diuretics, such as furosemide, are routinely administered to dogs with congestive heart failure (CHF). Traditionally, dose and determination of efficacy primarily are based on clinical signs rather than quantitative measures of drug action. Treatment of human CHF patients increasingly is guided by quantification of urine sodium concentration (uNa) and urine volume after diuretic administration. Use of these and other measures of diuretic responsiveness is associated with decreased duration of hospitalization, complication rates, future rehospitalization, and mortality. At their core, loop diuretics act through natriuresis, and attention to body sodium (Na) stores and handling offers insight into the pathophysiology of CHF and pharmacology of diuretics beyond what is achievable from clinical signs alone. Human patients with low diuretic responsiveness or diuretic resistance are at risk for difficult or incomplete decongestion that requires diuretic intensification or other remedial strategies. Identification of the specific etiology of resistance in a patient can help tailor personalized interventions. In this review, we advance the concept of loop diuretic responsiveness by highlighting Na and natriuresis. Specifically, we review body water homeostasis and congestion in light of the increasingly recognized role of interstitial Na, propose definitions for diuretic responsiveness and resistance in veterinary subjects, review relevant findings of recent studies, explain how the particular cause of resistance can guide treatment, and identify current knowledge gaps. We believe that a quantitative approach to loop diuretic usage primarily involving natriuresis will advance our understanding and care of dogs with CHF.  相似文献   

2.
Diuretic renal scintigraphy is commonly used in human medicine to differentiate obstructive from nonobstructive pyelectasia. In order to determine normal parameters, 99mTc-DTPA renal scintigraphy was performed twice in 20 healthy adult Mongrel dogs. Each dog was injected with either 3.0 mg/kg furosemide or an equivalent volume of saline 4.5 min following injection of the radiopharmaceutical. The following parameters were evaluated: (1) global and individual glomerular filtration rate (GFR); (2) time of peak (TOP) of the time-activity curve (TAC); (3) shape of the TAC; (4) individual kidney excretion half-time (T1/2); (5) proportion of maximum activity measured at end of study (8 min); (6) time of onset; and (7) duration of the effect of the diuretic. Most TAC in the diuretic renography group showed a steep drop in the curve following administration of the diuretic compared with a gradual slope in the saline control group. There was a statistically significant difference in T1/2 between the control renograms (median 10.25 min, range 4.41-18.07 min) and the diuretic renograms (median 4.16 min, range 3.62-5.90 min). There was a statistically significant difference in percentage maximum activity between the control renograms (median 65.25%, range 48.27-93.68%) and the diuretic renograms (median 48.54%, range 35.64-58.76%). Median time of onset of the diuretic effect was 1.10 min (0.20-2.40 min), and median duration was 0.83 min (0.30-2.35 min).  相似文献   

3.
The purpose of this study was to develop a protocol for diuretic renal scintigraphy (renography) in cats and describe normal findings. 99mTc‐DTPA renal scintigraphy was performed twice in 10 healthy cats. Furosemide or saline were injected 4.5 min after radiopharmaceutical administration for the diuretic or control scan, respectively. A dynamic acquisition was performed for 8 min. The following parameters were evaluated: (1) global and individual glomerular filtration rate (GFR); (2) shape of the time–activity curve (TAC); (3) time of peak (TOP); (4) individual kidney excretion half‐time (T1/2) of the radiopharmaceutical; (5) percentage of maximum activity measured at the end of the study. Global GFR in the control studies (2.79±0.83 ml/min/kg, mean±SD) did not differ significantly from the diuretic scans (2.34±0.51 ml/min/kg). The shape of most (16/20) TAC of diuretic renograms was similar to those of control renograms. The TOP of the diuretic renogram curves was 3.06±0.58 min, and did not differ from that of the control scans (3.01±0.61 min). T1/2 of the diuretic renograms was significantly shorter (5.15±0.83 min) than that of the control renograms (6.31±1.50 min). A significantly lower percentage of maximum activity was present at the end of the study in diuretic renograms (median: 47.25%; range: 33.60–59.60%) compared with control renograms (63.40%; 30.00–69.40%). Diuretic renal scintigraphy is a noninvasive and fast procedure to perform in cats. The applicability of this technique needs to be investigated in patients with significantly impaired renal function and obstructive uropathies.  相似文献   

4.
研究五皮口服液的利尿作用,通过给水负荷模型小鼠灌服不同剂量的五皮口服液,观察给药后的排尿量,以评价五皮口服液的利尿效果。给药后4 h内,与阴性对照组排尿量1.18 g±0.42 g比较,五皮口服液高、中剂量组(13.5 g生药/kg、6.75 g生药/kg体重)排尿量分别为1.78 g±0.42 g、1.73 g±0.60 g,均极显著增加(P<0.01),低剂量组(3.375 g生药/kg体重)的排尿量为1.34 g±0.91 g,显著增加(P<0.05)。结果表明,五皮口服液具有显著利尿作用。  相似文献   

5.
Right atrioventricular valve insufficiency and bilateral congestive heart failure were identified in a carpet python (Morelia spilota variegata) with the aid of colour Doppler echocardiography, electrocardiography and radiography. The snake failed to respond to diuretic therapy and was euthanased. Based on this case, it appears that bilateral congestive failure is feasible in univentricular animals with lesions restricted to one side of the heart. Loop diuretic therapy may be inappropriate in non-crocodilian reptiles because reptiles lack a loop of Henle.  相似文献   

6.
The pharmacokinetics and the biliary and urinary excretions following intravenous administration of furosemide (5 mg/kg) were investigated in the anesthetized dogs with normal and experimentally reduced renal function. After the administration, furosemide caused diuretic and choleretic response, and was excreted into urine and bile at almost similar rate to plasma concentration decay in normal dogs. Half maximum diuretic response was obtained at 1.5 micrograms/ml of plasma concentration and 100 micrograms/min of urinary excretion rate of furosemide. Acute renal failure was produced in dogs by the intravenous administration of mercuric chloride (HgCl2, 2 mg/kg). In HgCl2-treated dogs, the prolongation of half life (T1/2 beta) and the decrease in plasma clearance were noted with the decreased diuretic response. These changes in parameters appeared to be associated with the decrease in excretion of furosemide into the urine, but not into the bile. Plasma level-diuretic response relationship was extensively shifted to the right in HgCl2-treated dogs, while urinary dose-response relationship did not change significantly between two groups. These results suggest that the decreased response to furosemide in HgCl2-treated dogs seems to be due to the decreased renal clearance rather than to the subsensitivity to furosemide on the site of action.  相似文献   

7.
Concentrations of the potent diuretic bumetanide were determined by a sensitive high performance liquid chromatographic procedure in plasma and urine from horses following intravenous and intramuscular administration of a dose rate of 15 micrograms/kg. The elimination half-life was found to be 6.3 min, the volume of distribution at steady state 68 ml/kg and the total plasma clearance 10.9 ml/min/kg. The onset of diuresis occurred within 15 min and diuresis was no longer apparent 1 h after i.v. administration. Given by the intramuscular (i.m.) route, bumetanide was rapidly absorbed; bioavailability was 70-80%. i.m. administration of bumetanide prolonged its plasma half-life (11-27 min) and enhanced and prolonged its diuretic effect.  相似文献   

8.
Diuretics are a mainstay of therapy in dogs with heart failure. In dogs with advanced heart failure, moderate to high doses of loop diuretics such as furosemide are used with diminishing effects as profound activation of neuroendocrine systems promote signs of congestive heart failure. The loop diuretic torsemide has several characteristics that make it suitable for treatment of advanced heart failure including longer half-life, increased potency of diuretic action, and anti-aldosterone effects. This case report details the administration of torsemide in 3 dogs with advanced heart failure and apparent furosemide resistance.  相似文献   

9.
Torasemide is a new loop diuretic that combines the effects of furosemide and spironolactone. There are no reports on the effects of torasemide in cats and dogs. This study compared the diuretic effects of furosemide and torasemide in cats and dogs. Cats with pressure overload cardiac hypertrophy were given oral placebo, torasemide 0.3 mg/kg, or furosemide 1 mg/kg or 3 mg/kg. Control and mitral regurgitation dogs were given oral placebo, torasemide 0.2 mg/kg, and furosemide 2 mg/kg for 7 days. Urine samples were obtained at baseline and 1, 2, 3, 4, 5, 6, 8, 12, and 24 hr after each drug dose. Urine volume and urine Na(+) and K(+) were measured. Both furosemide and torasemide increased urine volume 1 hr after administration. Furosemide caused a dose-dependent increase in urine volume that peaked at 2-3 hr in cats and dogs. The diuretic effect of furosemide disappeared 6 hr after administration, while that of torasemide peaked 2-4 hr after administration and persisted for 12 hr in cats and dogs. In MR dogs, torasemide for 7 days significantly decreased urine potassium excretion. Plasma aldosterone increased with torasemide, whereas there was no change with furosemide. In conclusion, about 1/10 concentration of torasemide was as potent as furosemide and had a longer diuretic effect in cats and dogs. These data suggest that torasemide is useful for treating congestive heart failure or edema in cats and dogs.  相似文献   

10.
SUMMARY Responses (473) were collated from a questionnaire sent to 5054 veterinarians in Australia enquiring about drug preferences for treating cardiac disease in dogs and cats. When treating a small breed dog with endocardiosis and mild left congestive heart failure, 74% of 472 respondents used a diuretic, 67% a theophylline derivative, 27% a vasodilator and 20% a positive inotrope. Frusemide was the preferred diuretic and digoxin the preferred inotrope, but vasodilator use varied. Low sodium diets were “often recommended” by 71% of respondents. Propranolol was preferred to diltiazem for treating feline hypertrophic cardiomyopathy. Digoxin was clearly preferred for treating supraventricular dysrhythmias, while lignocaine and digoxin were preferred equally for ventricular dysrhythmias. Respondents appeared more willing than US veterinarians to use theophylline derivatives and prasozin, and less inclined to employ nitrates, hydralazine, inotropes other than digoxin, and low sodium diets.  相似文献   

11.
The correlation between pharmacokinetics and dynamics of furosemide was investigated in anaesthetized dogs. After intravenous administration (i.v.) of furosemide (5 mg/kg), the plasma concentration declined rapidly with bioexponential decay. The half-life (t1/2 beta) of the late phase of elimination was 0.931 +/- 0.187 h and the apparent volume of distribution at steady state was 0.25 +/- 0.043 l/Kg. The total clearance (Cltot) was 0.435 +/- 0.031 l/h/kg, in which the renal clearance was 0.260 +/- 0.020 (about 60% of Cltot). The change in rate of urinary excretion of furosemide was similar to the plasma concentration decay curve. The diuretic effect of furosemide was accompanied by an extreme increase in the excretion rate of sodium and chloride, but not potassium. The relationships between the diuretic response and the plasma concentration or the urinary excretion rate of furosemide was depicted by sigmoidal dose-response curves in both cases. The half-maximum effect was obtained at 1.5 micrograms/ml of plasma concentration or at 80 micrograms/min of excretion rate of furosemide.  相似文献   

12.
This study shows the development of two major deformities in the non-stenosed kidney of the 2K-1C Goldblatt model; namely the widening of the LIS and the enlargement of the basilar interdigitations of the proximal tubule cells. These deformities were much less in the 2K-1C animals treated with the angiotensin I converting enzyme inhibitor (AICEI) cilazapril. From these findings it is suggested that the non-stenosed kidney is operating under the diuretic effect of the elevated systemic blood pressure (SBP) via an increase in the renal interstitial hydrostatic pressure (RIHP). Therefore, the AII antidiuretic effect is masked by the diuretic effect of the elevated SBP. The suggested rise in urine output fits well with the idea that kidneys lose water and sodium when SBP increases enormously. Therefore, in this model of hypertension, the non-stenosed kidney tries to lower SBP by losing water and sodium, an excretion behavior which is opposite to that of the stenosed kidney. Thus, the rise in SBP in this model is probably due to an increase in the vascular peripheral resistance rather than fluid accumulation.  相似文献   

13.
目的：初探大叶斑鸠菊的药效。方法：将大叶斑鸠菊制成浓度为1 g生药/mL的提取液,通过抑菌试验、利尿试验及对鸡肾肿的治疗试验,考察其药效。结果：大叶斑鸠菊提取液对大肠杆菌、沙门氏菌、巴氏杆菌有一定抑制作用,最小抑菌浓度均为0.25 g/mL,对金黄色葡萄球菌无抑制效果;有一定利尿作用;饲喂0.4、0.5、0.6 g/mL不同剂量大叶斑鸠菊提取液,2次/d,鸡肾肿明显减轻,鸡的存活率提高,分别为42.86%、71.43%和85.71%。结论：大叶斑鸠菊具有一定抑菌作用、利尿作用,对鸡肾肿有较好的治疗效果。  相似文献   

14.
A pharmacokinetic/pharmacodynamic modelling approach was used to determine a dosage regimen which maximizes diuretic efficiency of torasemide in dogs. Kinetic profiles of plasma concentration, torasemide excretion rate in urine (TERU) and diuresis were investigated in 10 dogs after single oral administrations at 3 dose levels, 0.2, 0.8 and 1.6 mg/kg, and an intravenous injection of 0.2 mg/kg. Endogenous regulation was evidenced by a proteresis loop between TERU and diuresis. To describe the diuresis–time profile, TERU served as input into a turnover model with inhibition of loss of response, extended by a moderator acting on both loss and production of response. Estimated maximum inhibition of loss of response, Imax, was 0.984 showing that torasemide is an efficacious diuretic able to suppress almost total water reabsorption. A TERU50, value producing half of Imax, of 1.45 μg/kg/h was estimated from the model. Pharmacokinetic and pharmacodynamic parameters were used to simulate the torasemide dose–effect relationship after oral administration. Model predictions were in good agreement with diuresis measured in a validation study conducted in 10 dogs, which were administered oral doses of 0.15, 0.4, 0.75, 1.5 and 4.5 mg/kg for 5 days. Finally, oral dose associated with the highest daily diuretic efficiency was predicted to be 0.1 mg/kg.  相似文献   

15.
The use of the diuretic furosemide made it possible to obtain samples of urine from cattle for leptospiral isolations. The drug was injected IV at a dose level of 0.8 mg/kg for heifers and 0.5 mg/kg for calves. The average time to first voiding in heifers was 19 minutes. The average time from the first to the second voiding was 17 minutes. The average time to the first voiding in four calves was 12 minutes; the average time from the first to the second voiding was 10 minutes. A decrease in urinary osmolarity provoked by furosemide created a more favorable condition for the survival of leptospires. Leptospires were isolated in 24 (72.7%) of 33 weekly cultural attempts with the aid of furosemide in three experimentally infected adult cattle. Serovar hardjo was isolated in 16 (57.1%) of 28 weekly cultural attempts with aid of the diuretic in four experimentally infected calves. The recovery frequency was 28.5% from the first voiding and 50% from the second. Leptospires were not isolated from urine obtained from the calves by manual stimulation. Untoward side effects that might have been attributable to furosemide were not observed. Furosemide appears to be well suited to obtain urine samples from cattle for leptospiral isolation.  相似文献   

16.
ObjectivesTo document the diuretic effect of different oral doses of spironolactone (SP) in healthy dogs.BackgroundSP is currently mentioned as a diuretic agent in the dog. However, the recommended doses were empirically defined and their corresponding diuretic effect has never been documented in dogs.Animals, materials and methodsEight adult Beagle dogs were used for two separate 2 * 2 cross-over designs. In the first cross-over, 4 dogs received SP orally for 8 days at 1 and 2 mg/kg per day. In the second cross-over the 4 other dogs received SP similarly, but at 4 and 8 mg/kg per day. Dogs were weighed on the first and last day of each period. Plasma SP and canrenone (the main active metabolite of SP) were assayed by high performance liquid chromatography (HPLC). Daily water consumption, urine weight, urine specific gravity, and urine excretion of sodium and potassium were measured during the SP treatment.ResultsTwo hours after SP administration, SP was metabolized into canrenone. A significant 14 and 22% decrease in urine potassium excretion was observed at 1 and 2 mg/kg, respectively, but not at the two other dose levels. Daily water consumption, urine weight, urine specific gravity, and urine excretion of sodium were not significantly altered by the SP treatment regardless of dose.ConclusionsRepeated oral administration of SP at 1, 2, 4 or 8 mg/kg for 8 days had no effect on water and sodium diuresis in healthy dogs.  相似文献   

17.

Introduction

Diuretic failure is a potential life-ending event but is unpredictable and poorly understood. The objectives of this study were to evaluate pharmacodynamic markers of furosemide-induced diuresis and to investigate mechanisms of diuretic braking in dogs receiving constant rate infusion (CRI) of furosemide.

Animals

Six healthy male dogs.

Methods

Raw data and stored samples from one arm of a previously published study were further analyzed to mechanistically investigate causes of diuretic braking in these dogs. Urine volume was recorded hourly during a 5-h furosemide CRI. Urine and blood samples were collected hourly to measure serum and urine electrolytes, urine aldosterone, and plasma and urine furosemide. Serum electrolyte fractional excretion was calculated. Urine sodium concentration was indexed to urine potassium (uNa:uK) and urine furosemide (uNa:uFur) concentrations, plasma furosemide concentration was indexed to urine furosemide concentration (pFur:uFur), and urine aldosterone was indexed to urine creatinine (UAldo:C). Temporal change and the relationship to urine volume were evaluated for these measured and calculated variables.

Results

Urine volume was significantly correlated with urine electrolyte amounts and with uNa:uK. The ratio of pFur:uFur decreased during the infusion, whereas furosemide excretion was unchanged.

Conclusions

There was a strong relationship between urine volume and absolute urine electrolyte excretion. Urine volume was strongly correlated to uNa:uK, giving it potential as a spot indicator of urine production during diuresis. The decrease in uNa:uK over time during the infusion is consistent with mineralocorticoid modification of urinary electrolyte excretion, supporting renin–angiotensin–aldosterone activation as a cause of diuretic braking in this model.  相似文献   

18.
Nursing sickness in mink is thought to be precipitated by inadequate salt intake, whether this is due to inadequate salt levels in the diet or inadequate total dietary intake. To test this hypothesis, lactating females raising large litters were given 2 daily intramuscular injections of the loop diuretic furosemide (Lasix, 4 + 4 mg/kg/day) for 2.5 d during the normal weaning period 6 wk after parturition or served as untreated controls. Following the same protocol, barren mink (i.e. unsuccessfully mated females) were treated similarly. Dams were carefully inspected for clinical signs of nursing sickness during and after the treatment. Urinary osmolality and concentrations of sodium, potassium, chloride, creatinine and carbamide (urea) were measured prior to treatment (day 1) and on day 3, immediately before and 4 h after the final diuretic treatment. Plasma concentrations of aldosterone and cortisol were determined by radioimmunassay 4 h after the last injection with furosemide on day 3. Biochemical changes in urine (a low osmolality, low concentrations of carbamide and creatinine, and extremely low sodium concentrations) and in plasma (aldosteronism) similar to those found in nursing sickness were elicited in the nursing dams. Nevertheless, none of the dams developed overt clinical signs of nursing sickness. It is concluded that the biochemical signs of volume and salt depletion associated with nursing sickness are sequelae rather than etiological factors of this disorder.  相似文献   

19.
A 10-year-old, intact male, cocker spaniel was presented with hypothermia, without shivering, and progressive stupor leading to coma. Myxedema coma, potentially precipitated by diuretic therapy, was tentatively diagnosed and treatment initiated, but progressive respiratory depression led to the decision to euthanize. Postmortem findings supported the diagnosis of myxedema coma.  相似文献   

20.
A method is described for precise investigation of diuresis and saluresis in cats, using trained animals in a special diuresis apparatus. Furosemide given intramuscularly (IM) to cats at the dose level of 10 mg/kg produced slight untoward reactions of short duration. Therefore, this dose lies at the upper limit of tolerance. Saluretic and diuretic effect of 5 different doses of furosemide was investigated in 4 cats and 20 dogs. A dose-dependent increase in diuresis was achieved in cats given doses of furosemide ranging from 1.25 to 10 mg/kg. In the dog, the range of effectiveness was broader. In both species, there was a parallel increase in the excretion of sodium and chloride ions. The excretion of potassium ions in the cat remained unaffected, whereas in the dog, there was a dose-dependent increase in potassium ion excretion, which became especially distinct when large doses were given. A direct comparison of total saluretic and diuretic values in the dog and cat after IM administration of furosemide was not possible, since the calculated straight lines had different slopes, and their points of intersection lay outside the scope of this study. A difference can be assumed to exist between dog and cat in the mode of action of diuresis and saluresis after administration of furosemide.  相似文献   

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