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PubMed1984

N2-(4-Substituted-2,6-dichlorophenyl)-N1,N1-dimethylformamidines as antihypertensive and diuretic agents.

The synthesis of a series of N2-[4-[(arylmethyl)amino]-2, 6-dichlorophenyl]-N1,N1-dimethylformamidines that caused marked blood pressure lowering and/or diuresis in spontaneously hypertensive rats (SHR) is reported. Diuretic activity was not always associated with acute antihypertensive activity. Central nervous system effects, most notably sedation, were observed. Compound 9d, which lowered arterial blood pressure 37 mmHg in SHR when dosed at 100 mg/kg, was further evaluated in chronic hypertensive dogs because of apparent minimal CNS effects. A reduction in arterial blood pressure of 32 mmHg at 1.0 mg/kg during a 6-h postdosing interval was observed. This response was unrelated to alpha- or beta-adrenergic blockade, angiotensin I antagonism, or neuronal or ganglionic blockade. CNS effects were also observed.

Amidines↗
PubMed1975

[Use of aldactone-saltucine for patients with chronic circulatory insufficiency].

In 50 patients with congestive heart failure a compound diuretic drug aldactone--saltucine was used. Diuresis, urine excretion of sodium and potassium, rate of glomerular filtration and tubular reabsorption of water, as shown by endogenous creatinin, were measured in all patients. In 13 patients the study was conducted dynamically in 8 three-hour portions of urine during 24 hours. In 6 patients the drug was administred in combination with furosemid. In 11 patients the effect of several days of therapy with aldactone-saltucine upon the urine excretion of electrolytes and their plasma level was studied. The effect of the compound drug was evaluated separately in patients with IIA, IIB and III stage of circulatory insufficiency. Aldactone-saltucine was shown to execute a distinct diuretic and natriuretic effect that lasts for 24 hours after a single dose. The drug has also a clear potassium-preserving action that manifests itself in a low level of potassium excretion with urine and an elevation of a potassium plasma level. A combination of aldactone-saltucine with furosemid considerably increases diuresis and natriuresis, without any signifcant increase in potassiuresis, which permits to use these drugs in the severest cases of congestive heart failure.

Adult↗
PubMed2002

Evaluating routine diuretics after coronary surgery: a prospective randomized controlled trial.

BACKGROUND: Routine diuretic administration after cardiopulmonary bypass is common despite the lack of evidence for its benefit. We performed a prospective study to evaluate if diuretics assist in weight loss or alter clinical outcome. METHODS: Seventy-nine patients undergoing primary elective coronary bypass surgery were randomized to either diuretic (fusemide and amiloride) or placebo (lactose) postoperatively until preoperative weight was achieved or for 5 days in total. Proportions were compared with chi2 or Fisher's exact test. RESULTS: Forty patients were randomized to diuretics and 39 to placebo. By day 5, 97% of patients (37 of 38) still in the diuretic arm, and 74% of patients (29 of 39) in the placebo arm, achieved preoperative weight (p = 0.02). There were no differences in clinical outcomes. CONCLUSIONS: Routine diuretics promote an earlier diuresis but no clinical benefits are apparent in low risk patients with normal renal function. Clinicians should reconsider routine diuretic prescription in this setting.

Aged↗
PubMed2002

Diuretic Doppler ultrasonography in chronic unilateral partial ureteric obstruction in dogs.

OBJECTIVE: To compare the effects of diuresis induced by a loop diuretic (frusemide), an osmotic diuretic (mannitol) and a high-osmolar radio-contrast medium (sodium iothalamate) on the intrarenal resistive index (RI) in dogs with chronic unilateral partial ureteric obstruction (UPUO). MATERIALS AND METHODS: The split renal clearance and intrarenal RI were estimated in 11 dogs with chronic UPUO. Doppler ultrasonography measurements of the interlobar arteries were obtained before and 10 min after the intravenous infusion of 1 mg/kg frusemide, 1 g/kg mannitol or 20 mL 60% sodium iothalamate. The same experimental protocol was repeated with another drug at 1-week intervals. RESULTS: There was a significant difference between the intrarenal RI of obstructed and unobstructed kidneys in the chronic phase of UPUO. While mannitol and sodium iothalamate significantly increased the RI in both kidneys, differences in RI between the kidneys decreased after infusing the two drugs. However, while frusemide insignificantly increased the RI in the obstructed kidney, it decreased the RI in unobstructed one. Consequently, the difference in RI between the kidneys increased significantly after administering frusemide. There were no significant differences in urinary volume after administering each of the drugs. CONCLUSIONS: As there were no significant differences in the diuretic effects of the drugs, frusemide may have additional effects on the RI of unobstructed kidneys other than diuresis. Frusemide increased the difference between the intrarenal RI of the kidneys and therefore may improve the detection of unilateral urinary obstruction in humans.

Animals↗
PubMed1965

TREATMENT OF CONGESTIVE HEART FAILURE WITH TRIAMTERENE.

Triamterene, a newer oral diuretic, was administered to nine hospitalized patients with congestive heart failure for an average of 15 days, and to 22 ambulatory patients for a period of three to 11 months. The daily dosage of triamterene ranged from 50 to 250 mg., but usually 100-200 mg. was administered daily in two divided doses, with or without the addition of 50 mg. of hydrochlorothiazide daily.Triamterene is a safe and effective diuretic at doses of 100-200 mg. daily and no drug tolerance develops with long-term therapy. However, when used alone, it is not as effective as hydrochlorothiazide, but in combination with the latter drug the resultant diuresis is unsurpassed by any other oral diuretic therapy that we have used to date.Triamterene itself does not produce kaliuresis and it blocks thiazide-induced kaliuresis. Serum uric acid levels may rise slightly, but no clinical gout was seen in this study.

Blood↗
PubMed1981

Perfusion technology in the hypothyroid patient.

Cardiopulmonary bypass may, by necessity, have to be performed in patients who are frankly hypothyroid. In treating five such patients, all of whom required coronary revascularization, it was noted that fluid balance during perfusion was considerably different than that in the normal population. In order to attempt to evaluate this difference, ten consecutive euthyroid patients having revascularization and the five hypothyroid patients were compared to correlate all fluid absorbed and excreted with the duration of bypass, the serum sodium, and subsequent weight gain. Fluid intake, urine output, and retained fluid were significantly elevated in the hypothyroid as compared to the euthyroid group, while serum sodium following operation was not significantly different. While there are considerable data indicating that hypothyroidism is associated with abnormal salt and water excretion, there is no information concerning the alterations which occur during cardiopulmonary bypass. The present study indicates that hypothyroidism is associated with significant diuresis (without administration of exogenous diuretic agents during cardiopulmonary bypass). The proposed explanation for this diuresis rests with the assumption that with cardiopulmonary bypass and appropriate fluid administration, the contracted blood volume in hypothyroid patients expands acutely and a diuresis results.

Angina Pectoris↗
PubMedDate not supplied

Diuretic therapy in congestive heart failure.

Diuretics are a mainstay of therapy in patients with congestive heart failure. A small number of patients can achieve adequate diuresis with a thiazide diuretic alone, but most require a loop diuretic. Some patients with severe disease require combinations of diuretics. Most patients with congestive heart failure manifest resistance to diuretics by having a diminished natriuresis compared with healthy counterparts. This diminished response even to potent diuretics means that dietary sodium may exceed sodium excretion, resulting in patient decompensation. The pharmacokinetics and pharmacodynamics of loop diuretics have been characterized in patients with congestive heart failure, thereby allowing rational therapeutic strategies in terms of what type of doses should be administered, how often, and when to use diuretic combinations. The purpose of this review is to show how understanding pharmacokinetics and pharmacodynamics results in logical diuretic use. (c)2000 by CHF, Inc.

Journal Article↗
PubMed1982

What are the metabolic complications of diuretic treatment?

Severe volume depletion from diuresis can produce potentially life-threatening hypotension, coronary and cerebral insufficiency, and significant renal impairment. Appropriate precautions include initiating diuretics at low doses and monitoring patients closely. Metabolic alkalosis, another frequent side effect of diuretic therapy, can usually be diagnosed by near absence of chloride in the urine. Corrective agents used include potassium chloride and sodium chloride.

Aged↗
PubMed2002

Diuretic effect of sodium artesunate in patients with malaria.

Previously, we described a direct inhibitory effect of sodium artesunate on sodium chloride transport in the thick ascending limb of Henle's loop, indicating that artesunate acts as a diuretic agent. Here we present 2 cases of falciparum malaria treated with 4 intravenous 60-mg doses of sodium artesunate. Neither diuretics nor vasoactive drugs were administered. A rise in diuresis (6 L/24 hours) was accompanied by an increase in natriuresis, and both declined at the end of the treatment. This diuretic effect has not been reported previously in patients and may modify the course of renal failure and respiratory distress syndrome, both of which complicate severe malaria.

Adolescent↗
PubMed1976

The rational use of diuretics in the treatment of arterial hypertension.

The development of modern pharmacologic diuretic agents has revolutionized the therapy of arterial hypertension. The diuretics currently available are easily administered orally, are effective in the presence of alkalosis or acidosis, are non-toxic and have a low incidence of side effects which are readily circumvented or treated. Loop diuretics such as furosemide have the capacity to be effective in patients with diminished renal function or clinical situations that have a powerful stimulus to sodium retention. In clinical circumstances when renal potassium loss is to be prevented such as in patients receiving digitalis, the addition of a potassium-sparing diuretic to either a thiazide or furosemide will achieve the clinical goal of providing an effective diuresis while inhibiting potassium excretion. The mechanism of antihypertensive activity of the diuretic agents appears to be the reduction of extracellular fluid volumes and plasma volumes. Hence, the clinical dictum that to be effective as an antihypertensive agent, diuretics should be administered in diuretic doses. Besides being the cornerstone of initial antihypertensive therapy, diuretics also play an important role in antihypertensive therapy of patients with moderate to severe hypertension who are receiving potent antihypertensive drugs of the vasodilator or sympatholytic class of compounds. Indeed, one of the most important steps in the successful therapy of these patients receiving multiple drugs, is the re-assessment of the diuretic agent. The sodium retention and consequent fluid volume expansion associated with the administration of these potent antihypertensive agents may often cause these patients to develop apparent drug resistance since the thiazide diuretics are not potent enough to counteract the powerful stimulus to sodium retention caused by these antihypertensive agents. The re-evaluation of the diuretic agent at this point will usually necessitate the substitution of furosemide for thiazide or the doubling of the dose of the present loop diuretic. A working knowledge of the physiology of urine formation and the sites of action of currently available diuretic agents will enable the clinician to tailor the diuretic agent to the clinical circumstances of an individual patient and allow the clinician to rationally select a diuretic for the treatment of arterial hypertension.

Antihypertensive Agents↗
PubMed1985

Clinical pharmacology of loop diuretics: a comparative study.

The authors performed two studies to clarify the characteristics, analogies and differences of three loop diuretics (furosemide, bumetanide and piretanide) aiming at more precise indications for their clinical use. In the first study, they compared bumetanide and piretanide by the method of compensated diuresis; in the second, they tested the three loop diuretics' efficacy in refractory ascites. The authors demonstrated that with the three substances analogous results were obtained when administered at equivalent doses and that only intensive diuresis was able to resolve refractory ascites.

Adult↗
PubMedDate not supplied

Furosemide compounds enhance urinary excretion of active kallikrein independently of their effects on urinary electrolyte excretion.

The chemical and diuretic effects of furosemide on the excretion and activation of urinary prokallikrein were investigated in rats by treatment with furosemide compounds with a range of diuretic activity or amiloride hydrochloride or the vehicle. Diuresis occurred with furosemide and benzyl furosemide, but not with isofurosemide, amiloride hydrochloride, or the vehicle. The urinary excretion rate of active kallikrein was significantly elevated above controls throughout the 72 h of treatment with all of the drugs tested, regardless of the level of diuresis or the rate of urinary electrolyte excretion. In contrast, the urinary excretion rate of total kallikrein (prokallikrein + active kallikrein) was unchanged in all groups. These data indicate that furosemide derivatives increase the activation, but not the excretion, of urinary prokallikrein and that these effects are unrelated to the chemical structure or diuretic activity of the compounds or to overall changes in urinary electrolyte excretion rates.

Animals↗
PubMed1995

Haemodynamic, diuretic and hormonal responses to prostaglandin E1 infusion in halothane anaesthetized dogs: comparison among epidural lidocaine, epidural fentanyl and epidural saline.

Deliberate hypotension decreases blood loss and transfusion but it may be accompanied by adverse effects due either to the hypotensive agents themselves or to haemodynamic alterations. Prostaglandin E1 (PGE1) has the advantage of a diuretic effect coupled with systemic hypotension. To elucidate the mechanisms by which PGE1 induces diuresis we compared the haemodynamic, diuretic and hormonal responses to PGE1 infusion simultaneously with epidural lidocaine (EP-L n = 7), epidural fentanyl (EP-F n = 8) or epidural saline (CONT n = 7) in halothane anaesthetized mongrel dogs. All groups developed a decrease in mean arterial pressure during PGE1 infusion (from 105 +/- 24 to 77 +/- 18 mmHg in EP-L; 106 +/- 19 to 79 +/- 13 mmHg in the EP-F; and 129 +/- 14 to 106 +/- 18 mmHg in the CONT groups (mean +/- SD)) (P < 0.05). In the EP-F and CONT groups urinary output increased during PGE1 infusion (from 4.31 +/- 1.89 to 6.15 +/- 2.03 ml.min-1 and 2.71 +/- 1.23 to 4.48 +/- 1.66 ml.min-1 (P < 0.05), respectively) and was accompanied by increases in renal blood flow (from 87.0 +/- 40.7 to 111.0 +/- 42.8 ml.min-1 and from 121.6 +/- 46.6 to 158.4 +/- 64.9 ml.min-1 (P < 0.05), respectively) and in fractional excretion of sodium (FENa) (from 4.78 +/- 3.88 to 7.63 +/- 5.20% in CONT group).(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1998

[The dobutamine-dopamine combination versus amrinone in congestive heart failure with a marked edematogenic sign complicated by functional kidney failure. A comparison between 2 different models of inotropic stimulation and diuresis potentiation].

BACKGROUND: We evaluated the diuretic output in patients with decompensated chronic heart failure (CHF), previously treated by i.v. infusion with dobutamine and dopamine (dob-dop) or with amrinone (amr). Our target was to identify the possible discrepancies in urinary output perhaps linked to the different type of inotropic stimulation in the two subsets. METHODS: Adjunctive therapy with dob-dop or amr was chosen because the administration of diuretics only, without cardiac support, as tested in previous hospitalizations, had been demonstrated to produce unfavourable results, mainly expressed by finding of a low output syndrome in 50% of cases or more. The administration of i.v. infusion was maintained during 17 hours (1000 min approximatively), and included infusion in separate pumps of the two amines, dobutamine at dose of 5 micrograms/kg/min and dopamine at dose of 2.8 micrograms/kg/min or, alternatively, i.v. infusion of amr, administered at dose of 7 micrograms/kg/min. Infusion volumes were similar in the two subsets. The two subsets were homogeneous relatively to renal impairment, i.e. to the parameters (urinary Na, U/P creatinine, U/P urea, urinary osmolality) we fixed as markers idoneous to demonstrate the occurrence of organic renal damage (acute tubular necrosis). RESULTS: The diuresis was recovered in all 24 patients, and the urine volume resulted more pronounced in the subset attributed to the dob-dop at both the 8th and the 17th hour readings. We found no harmful alterations in HR and AP, whereas renal function parameters have been shown to enhance in both the dob-dop and amr arms. The diuretic effectiveness of the SIEV obtained by catecholamine implementation exercised a synergistic, favourable effect on diuresis, renal flow, glomerular filtration rate, and sodium post-proximal delivery. Amr resulted less effective then dob-dop simultaneous administration relatively to the diuretic effect. No remarkable differences were found in the two subsets as regards the heart rate, whereas a decrease in arterial pressure was found after amr. A persistent shift towards a condition of chronic renal failure, was identified in 4/24 patients, the two groups despite of the prolonged treatment at optimized doses: no remarkable side effects were reported. CONCLUSIONS: Thus, the selective effect upon renal hemodynamics, as exercised by dob-dop infusion low doses of dop, together with the enhanced renal output due to dob, has been shown to be more effective than amr influence: thus, the catecholamine therapeutical approach has been demonstrated to possess the best effectiveness in excitation of diuresis, among the CHF oliguric patients.

Aged↗
PubMed2004

Continuous recording of excretory water loss from Musca domestica using a flow-through humidity meter: hormonal control of diuresis.

Water loss from adult male houseflies was continuously recorded using a flow-through humidity meter, which enabled losses to be apportioned between the sum of cuticular and respiratory transpiration, salivation and excretion. Transpiration accounted for >95% of water lost from sham-injected flies, compared with excretion (3.0%) and salivation (2.4%). In contrast, excretion accounted for 40% of water lost from flies injected with > or =3 microl of saline, whereas salivary losses were unchanged. Saline injections (1-5 microl) expanded the abdomen in the dorsal-ventral plane, and this expansion was positively correlated with the magnitude of the ensuing diuresis, suggesting the signal for diuretic hormone release originates from stretch receptors in abdominal tergal-sternal muscles. The effects of decapitation, severing the ventral nerve cord within the neck or ligaturing the neck, showed the head was needed to initiate and maintain diuresis, but was neither the source of diuretic hormone nor did it control the discharge of urine from the anus. These findings indicate the head is part of the neural-endocrine pathway between abdominal stretch receptors and sites for diuretic hormone release from the thoracic-abdominal ganglion mass. Evidence is presented for Musdo-K having a hormonal role in the control of diuresis, although other neuropeptides may also be implicated.

Animals↗
PubMed1991

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↗