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Changes in urea clearance after a single dose of diuretics during water diuresis.

The action of various diuretics on the excretion fraction of urea (Curea/Ccr) was studied in 91 healthy volunteers under conditions of maintained maximal water diuresis. On the basis of previous data on transtubular transport or urea it should be expected that with an increase in the excretion fraction of water (V/Ccr) under the given experimental conditions we should find an increase in Curea/Ccr. After administration of polythiazide, which has a predominantly distal localisation of action in the nephron, Curea/Ccr did not change. After administration of chlorothiazide, furosemide and after i.v. administration of ethacrynic acid there was a marked increase in V/Ccr, ranging from 5.4 to 18%. Despite this there was no significant increase in Curea/Ccr. After i.v. administration of acetazolamide or oral administration of ethacrynic acid Curea/Ccr even showed a statistically significant decrease. These findings suggest that a decrease in proximal tubular reabsorption of water after administration of diuretics during maximal water diuresis is not a decisive factor for the renal excretion of urea. The data suggest that the diuretics affected the permeability of the distal segment of the nephron for urea in the sense of an increase of tubular reabsorption.

Acetazolamide↗

[Treatment of resistant forms of cardiac insufficiency with a combination of diuretics].

The possibility of treating resistant forms of cardiac insufficiency by a combination of furosemide and brinaldix was studied. The efficacy of the diuretics was appraised with reference to diurnal diuresis, sodium-potassium- and chloruresis on the days of taking the diuretics. In making investigations the method of dispersion analysis (permutation trial test) was used. The final results show that the proposed combination (80 mg of furosemide and 40 mg of brinaldix) is effective and warranted in dealing with patients resistant to many diuretics including furosemide. The action of this combination continues for a long time in the presence of signs of cardiac incompetence and is not accompanied by the development of a marked hypokalemia.

Chlorine↗

[Inhibitory activity of Dianthus superbus L. and 11 kinds of diuretic Traditional Chinese medicines for urogenital Chlamydia trachomatis in vitro].

OBJECTIVE: To detect the susceptibility of urogenital chlamydia trachomatis(CT) to 12 kinds of diuretic traditional Chinese medicines. METHODS: The inhibitory activity of these medicines for CT was detected by microculture technique of McCoy cell in vitro. RESULTS: All the 12 kinds of diuretic traditional Chinese medicines had inhibitory activities for urogenital CT, with minimal inhibitory concentrations (MICs) from 0.122 mg.ml-1 to 62.5 mg.ml-1. The activities of Dianthus superbus L., Poria cocos(Shcw.) Woft, Polyporus umbellatus and Artemissia capillaris were stronger. The number and volume of CT inclusions reduced gradually and disappeared finally with the rise of concentration. CONCLUSION: All the 12 kinds of diuretic traditional Chinese medicines possess some inhibitory activity for urogenital CT.

Artemisia↗

The effect of loop of Henle diuretics on the tubuloglomerular feedback mechanism.

Increases in the delivery of solute to the loop of Henle result in increased reabsorption, vasoconstriction of the afferent arteriole, and a reduction in the glomerular filtration. Although the details of this tubuloglomerular feedback (TGF) mechanism are not completely worked out, it appears certain that alterations in reabsorption by the loop of Henle are critical to its operation. In the following study, we assessed the effect of several different loop of Henle diuretics on the response of the TGF mechanism. The function of TGF was monitored by measuring the stop-flow pressure (SFP) in the early proximal tubule in response to alterations in perfusion rate through the loop of Henle. All drugs were given directly into the loop of Henle in a concentration of 10(-4) M. With control solutions, SFP fell in a sigmoidal fashion over a perfusion range of 5 to 45 nl/min. When furosemide was added to the perfusate at a dose of 10(-4) M, SFP did not change. Bumetanide had an effect similar to furosemide, but muzolimine failed to inhibit the reduction in SFP over the perfusion range. Three experimental compounds were tested. All three cause diuresis when administered orally to animals. MK447 had no effect on SFP, but its metabolite, MK447-SO4, had an effect similar to furosemide. Another compound with modest diuretic effects, ICI 207,828, actually increased the response in SFP. Two distal diuretics, hydrochlorothiazide and amiloride, had no effect on SFP. The response of SFP to all these compounds correlated with its measured effect on loop reabsorption of sodium. Furosemide, bumetanide and MK447-SO4 significantly reduced sodium reabsorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Diuretics, the most critical therapy in heart failure, yet often neglected in the literature.

Dietary sodium restriction and diuretics are basic requirements in the treatment of CHF. The reduction in pulmonary venous congestion following the use of diuretics leads to a rapid improvement in dyspnea, promotes natriuresis without direct positive inotropic effects, and does not reflexively activate the neuroendocrine system. The recent literature has been replete with reports on the treatment of HF. However, very little has been said about the importance and the methods of use of diuretics in HF. Treatment of HF cannot succeed without regard for the role of the sodium ion in HF. There are nearly 5 million cases of HF in the United States. More than 500,000 new cases are diagnosed each year. Hospital discharges and deaths due to HF have increased more than 100% in the past 2 decades with a 5-year mortality rate close to 50%. Since the leading cause of HF in Western countries is ischemic heart disease, aggressive therapy to halt progression of coronary atherosclerosis can have a major impact on controlling and often curing HF.

Diet, Sodium-Restricted↗

Diuretics in therapy of epilepsy; their use for the potentiation of anticonvulsant drugs.

Animal experiments having indicated a nearly twofold increase in anticonvulsant protection with the use of diuretics which increase blood-brain barrier permeability, the principle was applied to treatment of humans with epilepsy. The addition of diuretics to anticonvulsant medication permitted a decrease of previously toxic dosages in ten epileptics, followed for six months, without lessening (and in some cases improving) the control of seizures. In three cases excessive diuresis and gastric distress necessitated discontinuance or decrease in dosage of the diuretic used.

Animals↗

Which anti-hypertensive to add to a beta-blocker: ACE inhibitor or diuretic?

Thirty-eight patients already treated with atenolol 50 mg once daily were randomly assigned to treatment with either hydrochlorothiazide (12.5-25 mg once daily) or lisinopril (10-20 mg once daily) for 8 weeks in a double-blind crossover study. Eight weeks' treatment with the combination of ACE inhibitor and beta-blocker or the diuretic and beta-blocker produced falls in blood pressure (lying: -8.4 +/- 15.4/ -7.3 +/- 80 mmHg and -6.1 +/- 15.3/ -5.2 +/- 8.8 mmHg [mean +/- SD] for lisinopril and hydrochlorothiazide respectively; standing: -10.2 +/- 14.2/8.2 +/- 9.2 mmHg and -6.8 +/- 14/ -6.3 +/- 10.3 mmHg for lisinopril and hydrochlorothiazide respectively) which were not statistically significantly different. Heart rate was significantly increased on the combination of beta-blocker and diuretic (lying: +4.3 +/- 10.7; standing: +3.2 +/- 10.0 beats/min) compared with a fall on beta-blocker+ACE inhibitor (lying; -0.5 +/- 7.6; standing: -1.5 +/- 7.4). Both therapeutic regimens were equally well tolerated. These results suggest that where patients fail to respond to monotherapy with a beta-blocker the addition of an ACE inhibitor may be as effective as the more traditional option of diuretic therapy.

Adolescent↗

The effect of diuretics and vasopressin on the osmotic permeability of the frog urinary bladder.

1. Large concentrations (in mM) of ethacrynic acid (0.1), furosemide (1.0), theophylline (5.0) and osmotic diuretics (100.0) sharply increased the flux of water along an osmotic gradient through the frog urinary bladder wall. Spironolactone (0.1), and hydrochlorothiazide (5.0) showed only a weak action on osmotic permeability. MercusalR, clopamide and triamterene did not affect water transport. 2. The presence of 0.2--1.0 mU/ml vasopressin (ADH) after pretreatment with a diuretic did not result in summation of the effects of both drugs used. 0.01--0.1 mM ethacrynic acid and 0.01 mM MercusalR significantly decreased the reaction to ADH. 1.0 mM furosemide, 0.1 mM spironolactone, 0.01 mM clopamide and 0.8 mM acetazolamide did not change the reaction to ADH. A reduction in the cellular response to ADH and a decrease in the osmotic permeability of the tubular wall may be responsible in part for the diuretic action of ethacrynic acid and MercusalR.

Animals↗

How should diuretic-refractory, volume-overloaded heart failure patients be managed?

Hospitalization is often required for patients with decompensated heart failure, usually with volume overload. Intravenous diuretics are recommended to optimize volume status; however, the management of patients refractory to diuretic therapy is not addressed in American Heart Association/American College of Cardiology, European Society of Cardiology or Heart Failure Society of America guidelines. This review focuses the invasive/interventional cardiologist on the rationale for greater involvement in the care of patients admitted to the hospital with decompensated volume overload, in particular when such patients are diuretic refractory.

Blood Volume↗

Protective effect of loop diuretics, piretanide and frusemide, against sodium metabisulphite-induced bronchoconstriction in asthma.

We determined whether the loop diuretic, piretanide, had a similar inhibitory action against sodium metabisulphite (MBS)-induced bronchoconstriction in asthmatic subjects as frusemide and, if so, its duration of action. In the first study, we compared the effect of inhaled placebo, piretanide (24 mg), or frusemide (40 mg), on the provocative concentration of MBS needed to cause a 20% fall in baseline forced expiratory volume in one second (FEV1) (PC20MBS) in 12 mild asthmatic subjects before, immediately after, and at 1.5, 3, 6, and 24 h, after inhalation. Both piretanide and frusemide induced a significant diuresis lasting at least 24 h. Frusemide caused a mean 3.8 fold (95% confidence interval: 2.3-6.3 fold), piretanide a 2.5 fold (1.8-3.4 fold) and placebo a 1.7 fold (1.5-1.9 fold) increase in PC20MBS. The effects of frusemide and piretanide were significantly greater than that of placebo. At later time points, tachyphylaxis to the bronchoconstrictor effects of MBS was observed during the placebo limb. In the second study, we measured PC20MBS at 90 min after inhalation of either placebo, piretanide (24 mg), or frusemide (40 mg). No significant difference in PC20MBS was observed. We conclude that piretanide in addition to frusemide significantly inhibits MBS-induced bronchoconstriction and that this action is short-lived over less than 90 min. Frusemide was more potent in inhibiting MBS-induced bronchoconstriction despite causing a smaller diuretic effect than piretanide. The basic mechanism of action of the loop diuretics in the airways remains unclear.

Administration, Inhalation↗

[Molecular pharmacology in diuretics].

Recently, much knowledge of the molecular mechanism of diuretic actions has been accumulated. Molecular cloning of carbonic anhydrase revealed a difference in isozymes and the localization of each isozymes was also identified. Carbonic anhydrase VI, located in brush border of the proximal tubules, is inhibited by acetazolamide. Loop diuretics, furosemide, bumetanide, piretanide and ethacrynic acid, inhibit Na(+)-K(+)-Cl(-)-cotransport system in the thick ascending limb of the Henle's loop. The histochemical localization and biological characterization were investigated by using [3H]-bumetanide. Loop diuretics cotransport protein and inhibit Na+ and Cl- reabsorption. Spironolactone inhibits the binding of aldosterone and cytosol mineralocorticoid receptor in the cortical connecting tubule competitively.

Carbonic Anhydrase Inhibitors↗

[Revival of antihypertensive therapy: use of thiazide diuretics].

In the international and the Hungarian guidelines, the diuretics in the first line of the treatment of hypertension. Their sometimes false judgment is based on the side effects, because of the over dosage of the applied medication. According to finished studies, efficiency of thiazides is usually the same as that of their competitors in influencing of the cardiovascular morbidity and mortality. Thiazides have to be given in the first line an antihypertensive treatment to the patients, especially if they are old, or have a great risk for a cardiovascular complication (stroke, coronary heart disease, heart failure, left ventricular hypertrophy). In the case of natrium-retention (diabetes, obesity, nephropathy), the treatment without diuretics is not effective. Thiazides make stronger the effects especially of ACE-inhibitors, angiotensin receptor blockers, and beta receptor blockers. The newer diuretics--with fewer side effects--have very likely extrarenal way of effects, so their long time application seems very favourable.

Adrenergic beta-Antagonists↗

[Azosemide--a loop diuretic with protracted effect].

Azosemide, a novel loop diuretic that has been available for the past few years, acts qualitatively like thiazide, viz by prolonging the diuretic effect with, however, only a slight delay in the onset of diuresis, in combination with the quantitative effect of previous loop diuretics, i.e. large excretion volumes. On the basis of experience gained to date, specific indications will presumably be cardiac and renal edema and ascites, also as long-term treatment. Provided that no NaCl or volume deficiency presents, side effects are insignificant.

Diuretics↗

Effects of chronic and in utero treatment with diuretics on mouse exocrine cells studied by X-ray microanalysis.

In an attempt to develop an animal model for the disease cystic fibrosis, mice were chronically treated with diuretics. In addition, pregnant mice were treated with diuretics and the effect of this treatment in utero on the newborn mice was studied. Pancreas and submandibular gland acinar cells were investigated by X-ray microanalysis and transmission electron microscopy. Long-term treatment with furosemide (up to 13 months) caused transient changes in the elemental content of the pancreatic acinar cells: a decrease in chloride and sulfur, and an increase in phosphorus, potassium and magnesium. All changes normalized with prolonged treatment. Some morphological changes were found in the zymogen granules. Treatment with amiloride or furosemide in utero caused a decrease in cellular sodium and chloride levels, indicative of inhibition of transepithelial ion and fluid transport. Also treatment of adult animals for two months with amiloride caused lower intracellular sodium and chloride levels. In adult animals only minor effects of diuretic treatment on submandibular gland acinar cells were noted. In utero treatment with amiloride caused an increase in sodium and chloride content indicative of cell damage.

Amiloride↗

[Acute renal failure caused by treatment with diuretics and ACE inhibitors in the absence of renal artery stenosis].

The Authors describe a clinical case of a patient affected by arterial hypertension of severe degree (IV grade OMS) that during therapy with ACE inhibitors and diuretics developed acute renal failure that reversed after stopping treatment. The clinical course was quite similar to acute renal failure induced by ACE inhibitors and diuretics in patient with bilateral renal artery stenosis. In interpreting the pathogenesis, the Authors suppose, beside a reductions of effective plasma flow, the coexistence of hyalinosis of renal arterioles. They underline the necessity of monitoring renal function at least in the first weeks of therapy when a treatment with ACE inhibitors and diuretics is started especially in patients with hypertension of high degree and/or reduced renal function.

Acute Kidney Injury↗

Diuretic and analgesic effects of the methanol extract of Phoenix sylvestris root.

The analgesic and diuretic activities of the methanol extract of Phoenix sylvestris root on Swiss albino mice were observed. The extract showed significant (p<0.001) analgesic activity by reduction of percent inhibition of writhing induced by acetic acid (0.5% v/v) in 20.07% and 32.57% at a dose level of 150 mg/kg and 300-mg/kg body weights respectively. The methanol extract also showed diuretic effect at 1st hour of the study at 300-mg/kg and 2nd and 4th hour of the study at 150-mg/kg-body weight on swiss albino mice. The onset of diuretic effect was faster at a dose of 300-mg/kg body weights than 150 mg/kg body weight. The obtained results may give a clue for extensive phytochemical investigation of the plant for the development of herbal medicine.

Analgesics↗

A pathophysiological interpretation of unresponsiveness to spironolactone in a stepped-care approach to the diuretic treatment of ascites in nonazotemic cirrhotic patients.

It has been hypothesized that the magnitude of proximal sodium reabsorption affects the response to aldosterone antagonists in nonazotemic cirrhotic patients with ascites. To verify this hypothesis, we evaluated intrarenal sodium handling by lithium clearance in 51 nonazotemic ascitic cirrhotic patients and in 23 controls who were maintained on the same low-sodium diet (80 mmol/day). Seven of 51 cirrhotic patients underwent spontaneous diuresis, whereas 44 required diuretic treatment. Treatment was started with spironolactone at a dose of 150 mg once daily. The dose was increased to 300 mg and then to 500 mg once daily if no response ensued. Cirrhotic patients who did not experience ascites mobilization with 500 mg spironolactone were then treated with a combined diuretic regimen that included spironolactone at a fixed dose (500 mg once daily) and furosemide at an initial dose of 50 mg once daily. The dose was increased to 100, 150 and 200 mg once daily if no response was noticed. Response to diuretic treatment was defined as body weight loss greater than 700 gm every 3 days until ascites became clinically undetectable. Nonresponders (43%) to spironolactone showed lower sodium fractional excretion (0.34% +/- 0.28% vs. 0.80% +/- 0.50%; p less than 0.001) because of a lower fractional sodium delivery to the distal tubule (18.2% +/- 5.8% vs. 23.4% +/- 7.2%; p less than 0.025) than responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Diltiazem compared with metoprolol as add-on-therapies to diuretics in hypertension. Swedish Diltiazem-Metoprolol Multicentre Study Group.

In a randomized, double-blind, parallel group study, diltiazem was compared with metoprolol as add-on therapy to diuretic treatment in 115 patients with hypertension. Following a placebo and diuretic period of four weeks, patients were randomized to either slow release diltiazem 90 mg twice daily or metoprolol 100 mg once daily using a double dummy technique. If after four weeks a target supine diastolic blood pressure (DBP) less than or equal to 90 mmHg pressure was not reached, the doses of diltiazem and metoprolol were doubled. Supine inclusion systolic/diastolic blood pressures (SBP/DBP) at randomization were 158 +/- 13 (mean +/- SD)/102 +/- 5 mmHg in the diltiazem group and 158 +/- 17/101 +/- 6 mmHg in the metoprolol group. Active therapy significantly lowered SBP and DBP in both groups by 7-10%. Heart rate was significantly lowered in both groups, although the effect of metoprolol was more pronounced. Response rates (supine DBP less than or equal to 90 mmHg and/or decreased by greater than or equal to 10%) were 43% on diltiazem 90 mg twice daily and 52% on metoprolol 100 mg once daily, increasing to 82% and 62%, respectively, after dose escalations. No serious side effects were seen, but three patients, two on diltiazem and one on metoprolol, were withdrawn from the study due to severe headache, nausea and bradycardia respectively. of mild to moderate adverse reactions, tiredness was most frequent, occurring in 14.5% and 15.8% on active diltiazem and metoprolol therapy, respectively. We conclude that both diltiazem and metoprolol lower BP when added to diuretics in hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗