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PubMed1980

Combined treatment of severe intractable hypertension with captopril and diuretic.

The converting-enzyme inhibitor, captopril, in a dose of 450 mg daily, was given together with a diuretic to eleven patients with severe hypertension unresponsive to previous therapy. Sustained control of blood pressure was achieved. Plasma angiotensin II and aldosterone fell significantly, whereas plasma active and total renin, and blood-angiotensin-I concentrations increased. Adverse effects included temporary taste disturbance, tachycardia, nephrotic syndrome, and possible drug-induced Guillain-Barré neuropathy. The combination of captopril and diuretic is thus very effective in controlling refractory hypertension. However, because of the frequency and severity of side-effects it should probably be used only in patients whose blood pressure has previously been uncontrolled by other means.

Blood Pressure↗
PubMed1981

Effects of magnesium infusions in diuretic induced hyponatraemia.

Eight hyponatraemic patients with severe congestive heart failure, long-term diuretic treatment, oedema, and increasing resistance to diuretic treatment, were studied with skeletal muscle biopsies and serum electrolytes before and after magnesium infusions. The infusions resulted in an increasing serum sodium level, a decrease in muscle sodium and chloride, and an increase in muscle potassium. The effect was probably mediated through the magnesium effect on membrane ATPase.

Aged↗
PubMed1989

Long-term use of thiazide diuretics and risk of hip fracture.

To assess whether long-term thiazide use is associated with a decreased risk of hip fracture, a nested case-control study was done in the Canadian province of Saskatchewan between 1984 and 1985 among residents who were 65 years of age or older and who were not receiving other drugs thought to affect bone mass. There were 905 hip fractures identified from hospital discharge records and 5137 population controls matched for age, sex, and calendar year. Drug use was ascertained from computerised pharmacy records. Risk of hip fracture decreased significantly with increasing duration of current thiazide use: relative risk (95% confidence interval) of 1.2 (0.9-1.5) for less than 2 years use, 0.8 (0.7-1.0) for use of 2-5 years, and 0.5 (0.3-0.7) for 6 or more years. In contrast, there was no such trend for use of other antihypertensive-diuretic drugs (relative risk 0.9 [0.6-1.3] for use of 6 or more years). This protective effect was not altered by age, sex, nursing home residence, previous hospital admission, or use of other antihypertensive-diuretic drugs or psychotropic drugs. Medical record review for a sample of 235 cases suggested this finding was not due to confounding by body mass, ambulatory status, functional status, or dementia. These results support the hypothesis that thiazides protect against osteoporosis in elderly people.

Aged↗
PubMed1993

Advantages of the new loop diuretic torasemide over furosemide in patients with cirrhosis and ascites. A randomized, double blind cross-over trial.

Torasemide is a new loop diuretic with a longer half-life and longer action than furosemide in healthy subjects. In order to evaluate the pharmacodynamic effects, single oral doses of furosemide (80 mg) and torasemide (20 mg), which were equipotent in healthy subjects, were given to 14 patients with cirrhosis and ascites. Before the study patients underwent an equilibration period of 4 days without diuretics. The drugs were alternated following a randomized double-blind cross-over design after a wash-out period of at least 2 days. Urine was collected at defined intervals for 24 h after drug administration and blood samples were taken before, 6 h and 24 h after medication. Torasemide induced greater cumulative 24 h diuresis (2863 +/- 343 vs. 2111 +/- 184 ml, p < 0.01) than furosemide. Torasemide did not differ from furosemide for cumulative 0-6 h sodium excretion (96 +/- 17 vs. 92 +/- 23 mmol sodium) but caused a more pronounced cumulative 6-24 h natriuresis (38 +/- 11 vs. 17 +/- 4 mmol, p < 0.05). Five patients exhibited a weak response to furosemide (0-36 mmol sodium/24 h, median 24 mmol; 690-1460 ml urinary volume/24 h, median 1325 ml). These patients showed significantly higher natriuresis and diuresis following torasemide (26-136 mmol sodium/24 h, median 78 mmol, p < 0.05; 1670-3610 ml urinary volume/24 h, median 2200 ml, p < 0.05). Twenty-four hours after administration of both drugs there were no significant changes in hemodynamic, renal or hormonal parameters. No adverse effects were noted with either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2002

Occurrence of insect kinins in the flesh fly, stable fly and horn fly-mass spectrometric identification from single nerves and diuretic activity.

MALDI-TOF mass spectrometric analysis of single lateral abdominal nerves (LANs) demonstrate the presence of the insect kinin Musdo-K in the housefly Musca domestica, and identify heretofore unknown insect kinins in two other Dipteran species as Musdo-K in the stable fly Stomoxys calcitrans and horn fly Haematobia irritans. The insect kinin native to the flesh fly Neobellieria bullata is identified as Drome-K. Musdo-K and Drome-K are identical save for the conservative substitution of Ser for Thr in position 2. The sequences of the insect kinins are, therefore, remarkably conserved throughout Dipterans. The in vitro Malpighian tubule fluid secretion activity of Musdo-K in the stable fly is similar to that in the housefly, whereas that of Drome-K is 30-fold more potent in the flesh fly than in the fruit fly. Given the structural identities of the kinins and CRF-like diuretic hormones of these Dipteran species, the housefly can serve as a model insect for the study of diuretic peptides and their functions in the stable fly and horn fly, both livestock pests.

Amino Acid Sequence↗
PubMed1999

Isolation, characterization and biological activity of a diuretic myokinin neuropeptide from the housefly, Musca domestica.

A competitive ELISA employing a polyclonal antiserum raised against leucokinin-I was used to isolate and purify a myokinin (muscakinin) from 1.05 kg of adult houseflies (Musca domestica). Following solid-phase purification, seven HPLC column steps were used to purify 4.8 nmol of leucokinin-immunoreactive material. Sequence analysis and mass spectrometry were consistent with the structure Asn-Thr-Val-Val-Leu-Gly Lys-Lys-Gln-Arg-Phe-His-Ser-Trp-Gly NH2. This peptide was synthesized and co-eluted with the natural peptide on three different HPLC columns. The activities of natural and synthetic muscakinin were identical, with both producing a 4-5 fold increase in fluid secretion by housefly Malpighian tubules at nanomolar concentrations. The presence of a pair of basic residues (Lys-Lys) suggested muscakinin might be processed further, with the peptide pGlu-Arg-Phe-His-Ser-Trp-Gly NH2 being produced by conversion of an N-terminal glutamine to pyroglutamic acid. However, this analog was 1000-fold less active than the intact peptide, comparable to the activity of AK-V which shares the same C-terminal pentapeptide sequence. The diuretic activity of muscakinin is more than double that of a previously identified CRF-related diuretic peptide (Musca-DP) from the housefly, and the two peptides act synergistically in stimulating fluid secretion. Muscakinin also increased the frequency and amplitude of contractions by housefly hindgut which might further contribute to the excretory process.

Amino Acid Sequence↗
PubMed2000

Synthesis and diuretic activity of bicyclic fused heterocycles containing oxime-O-sulfonic acid moiety.

In order to investigate the origin of the loop-type diuretic activity of M17055 (1), several variants (3-9) were designed and synthesized by modifying the quinolinone skeleton, and their diuretic activities were compared with the lead 1 and furosemide in dogs. It was found that the negative charge distribution pattern afforded by the dispositional arrangement of the 4-oxime-O-sulfonic acid and 1-N-acyl carbonyl moiety attached to the tetrahydropyridine ring system is inevitable for the development of the activity, which strongly supports the previously proposed model for the active site of the Na(+)-K(+)-2Cl(-) cotransporter. Also reported is the first synthesis of the dihydrothieno[3,2-b]pyridine-7(4H)-one ring system required in the synthesis of compound 9.

Animals↗
PubMed1985

Diuretics and calcium metabolism.

In this review the normal renal tubular handling of calcium is briefly described. A detailed examination follows of the sites and modes of action of furosemide and thiazide diuretics on renal calcium handling and overall calcium metabolism. The clinical applications of these effects are also considered. Finally, the use of diuretics with different tubular sites of action on calcium transport as probes to study disorders of calcium excretion is discussed.

Absorption↗
PubMed1998

Effects of spironolactone on exercise capacity and neurohormonal factors in patients with heart failure treated with loop diuretics and angiotensin-converting enzyme inhibitor.

1. Treatment with spironolactone is reported to be useful when combined with loop diuretics and an angiotensin-converting enzyme (ACE) inhibitor in severe congestive heart failure (CHF). However, the effects of the addition of spironolactone on exercise capacity and neurohormonal variables have not been demonstrated. This study determined the effects of additive spironolactone on exercise capacity and neurohormonal factors in patients with mild CHF. 2. Oxygen uptake (VO2), plasma norepinephrine (NE), renin activity (PRA), angiotensin II (AII), aldosterone (ALD), and atrial natriuretic peptide (ANP) were measured at rest and after peak exercise in nine patients with CHF (six idiopathic and three ischemic cardiomyopathy; New York Heart Association (NYHA) classes II and III) who were already taking furosemide (mean 29 +/- 5 mg/day) and enalapril (mean 4.7 +/- 0.8 mg/day). Studies were repeated after 16 weeks of treatment with additive single daily dose of 25 mg of spironolactone. In four of nine patients, the exercise test was repeated after a 4-weeks washout of spironolactone. 3. Treatment with spironolactone caused natriuresis, decreased cardiothoracic ratio in chest X-ray (before vs. after treatment: 53.7 +/- 1.2 vs. 50.7 +/- 1.4%, P < 0.01), and improved NYHA functional class. Peak VO2 (17.1 +/- 1.6 vs. 17.5 +/- 2.2 ml/min/kg, NS) and heart rate and blood pressure responses to exercise were not altered. Resting NE (215 +/- 41 vs. 492 +/- 85 pg/ml, P < 0.01) and resting PRA (8.2 +/- 2.3 vs. 16.2 +/- 4.1 ng/ml/hr, P < 0.01) as well as peak NE (1618 +/- 313 vs. 2712 +/- 374 pg/ml, P < 0.01) and peak PRA (12.8 +/- 3.2 vs. 28.1 +/- 11.8 ng/ml/hr, P = 0.17) were augmented after additive spironolactone. ALD and AII were insignificantly increased, and ANP was insignificantly decreased at peak exercise after spironolactone treatment. Spironolactone washout was associated with a trend of the neurohormones to return toward pretreatment values. 4. In conclusion, chronic additive treatment with spironolactone was associated with neurohormonal activation both at rest and during exercise without changing the exercise capacity of patients with mild CHF who were already on loop diuretics and ACE inhibitor therapy.

Adult↗
PubMed1997

Changes in body water compartments with diuretic therapy in infants with chronic lung disease.

The effects of diuretic therapy on body water compartments were studied in preterm infants with chronic lung disease. Gestational age of the infants ranged from 24 to 28 weeks, while the median postnatal age at the time of study was 40 days. Infants were randomized to receive furosemide (1.0 mg/kg/day) alone (n = 5) or combined with metolazone (0.2 mg/kg/day, n = 7) for 4 consecutive days. Treatment in both groups produced a significant decrease (P < 0.05) in extracellular water (ECW) without changes in plasma volume, total body water or body weight. The decrease in ECW with furosemide (503 +/- 28 to 446 +/- 19 ml/kg initial body weight) was of similar magnitude to that seen with combined furosemide plus metolazone (522 +/- 30 to 454 +/- 15 ml/kg initial body weight). Water and electrolyte intakes were similar in both groups and unchanged over the course of the study. These findings suggest that in infants with chronic lung disease, diuretic therapy induces intercompartmental shifts in body water, ultimately decreasing interstitial water while preserving PV. Only combined treatment with furosemide plus metolazone produced a significant increase in urine output, confirming the increased efficacy of combination therapy in inducing diuresis.

Body Water↗
PubMed1989

Comprehensive screening procedure for diuretics in urine by high-performance liquid chromatography.

A rapid and reliable screening procedure using high-performance liquid chromatography for the detection of 23 diuretics (belonging to five different pharmacological groups) in urine has been developed. Two aliquots of 2-ml urine samples were extracted separately under acidic and basic conditions. The acidic and basic extracts were pooled, evaporated to dryness and reconstituted in methanol. The methanolic extract was injected onto a Hewlett-Packard Hypersil ODS C18 (5 microns) column (column I) and a Hewlett-Packard LiChrosorb RP-18 (5 microns) column (column II; an alternative column). The same gradient mobile phase was used for both columns. A diode array ultraviolet detector was set to monitor the signal to the integrator (Chem Station) at 230 and 275 nm. Recovery studies of the 23 diuretics were performed under acidic and basic conditions. The overall lower limits for detection on column I using both extraction procedures ranged from 0.5 to 1.5 micrograms/ml of urine (average 1.0 micrograms/ml). Amiloride, ethacrynic acid and probenecid could not be detected below 5 micrograms/ml of urine. No interference from the biological matrix was apparent. Amiloride could be detected in urine 4 h after oral administration of 15 mg of amiloride to a healthy volunteer, when the sample was extracted under alkaline conditions. The suitability of the screening method for the analysis of urine samples was tested by studying the variation with time of chlorthalidone, furosemide, probenecid, acetazolamide, quinethazone, spironolactone, bendroflumethiazide, bumetanide, triameterene and hydrochlorothiazide concentrations in the urine of normal human volunteers after minimum single or multiple (probenecid) doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMed2001

Screening, confirmation and quantification of diuretics in urine for doping control analysis by high-performance liquid chromatography-atmospheric pressure ionisation tandem mass spectrometry.

A sensitive, selective, robust and fast method to identify 32 diuretics and masking agents in urine is described. The analytical procedure is reduced to a single XAD extraction step for sample preparation, followed by reversed-phase liquid chromatography in combination with atmospheric pressure ionisation/tandem mass spectrometry. This technique is, after minor modifications, suitable for screening analyses and confirmation of identity as well as quantitation of diuretics. Considerations relating to the stability and metabolism of the compounds are given if relevant for routine screening analyses.

Atmospheric Pressure↗
PubMed2000

Experimental diuretic effects of Rosmarinus officinalis and Centaurium erythraea.

Herbal remedies are widely used in Moroccan pharmacopoeia. We assessed the diuretic effect of two medicinal plants: Rosmarinus officinalis L., Labiatae, and Centaurium erythraea L., Gentianaceae, both reputed for the treatment of urinary ailments. To determine the action of these herbs on urinary volume (UV) and the excretion of sodium (U(Na)V), potassium (U(K)V), and chloride (U(Cl)V), the aqueous extracts of both plants were administered daily to Wistar rats for 1 week. The concentration of electrolytes and urea in plasma and creatinine clearance were also investigated. Daily oral administration of the aqueous extracts of R. officinalis and C. erythraea at the dose of 10 ml/kg of 8 or 16% extract in distilled water significantly enhanced diuresis in rats compared to the control group from the fifth day of treatment. For R. officinalis at the dose of 8% the peak of urinary excretion of sodium, potassium and chloride was reached after 6 days of treatment (P<0.001). The aqueous extract of of R. officinalis at the dose of 16% did not significantly affect the excretion of water and electrolytes over a similar period but slight increases in urinary excretion of sodium and chloride on the seventh day and of potassium on the sixth day (P<0.05) were observed. No increase was recorded for 24 h urinary excretion of Na+, K+ and Cl- during the first 4 days of treatment for the groups treated with C. erythraea at the doses of 8 and 16% whereas their effects on the same parameters were highly significant thereafter. No change was observed in plasma electrolytes and urea in any group, except for a decrease in sodium and chloride concentration in the group treated with 16% of R. officinalis. A decrease in creatinine clearance was demonstrated after treatment with 8% of R. officinalis and C. erythraea. Our findings demonstrate a diuretic effect of aqueous extracts of R. officinalis L. and C. erythraea L. with the most effective dose for water and electrolyte excretion being 8% for both plants.

Animals↗
PubMed2000

Acute diuretic, natriuretic and hypotensive effects of a continuous perfusion of aqueous extract of Urtica dioica in the rat.

This study was performed on anaesthetized male Wistar rats that received a continuous intravenous perfusion during 1.25 h of an aqueous extract of aerial parts of Urtica dioica L. (Urticaceae) at a low dose of 4 mg/kg/h or at a high dose of 24 mg/kg/h, or furosemide (control diuretic) at a dose of 2 mg/kg/h. As compared with a control period in each rat, the arterial blood pressure was reduced proportionally to the dose of the perfusion of the plant extract (15 and 38%, P<0.001, respectively). These effects were accompanied by a correlative increase of diuresis (11 and 84%, P<0. 001, respectively) and natriuresis (28 and 143%, P<0.001, respectively). In the rats perfused by furosemide, the arterial blood pressure was reduced by 28% (P<0.001). The diuresis and natriuresis were also increased proportionally in this case (85 and 155%, P<0.001, respectively). Nevertheless, the hypotensive action of U. dioica was reversible during the recovery periods in about 1 h with the lower dose of the plant extract and furosemide, while the effect of the higher dose was persistent, indicating a possible toxic effect. In conclusion, the results demonstrate an acute hypotensive action of U. dioica that indicates a direct effect on the cardiovascular system. Moreover, diuretic and natriuretic effects were also observed, suggesting an action on the renal function. Finally, the plant extract seems to have a toxic effect at the higher dose.

Analysis of Variance↗
PubMed2001

Chronic diuretic effect of the water extract of Spergularia purpurea in normal rats.

The purpose of this study was to examine the chronic diuretic effect of the water extract of the whole plant of Spergularia purpurea (SP) at different doses (100, 200 and 400 mg/kg) in normal rats. Daily oral administration of the water extract was tested for 4 weeks. Urinary water and electrolytes excretion were determined weekly. Oral administration of the water extract at different doses produced a significant and dose-dependent diuresis and increase in electrolytes excretion. The highest dose (400 mg/kg) of the water extract of SP enhanced urine output from 7.15 +/- 0.42 ml/24 h at the start to 23.01 +/- 0.75 ml/24 h after 4 weeks (p < 0.001). It also produced significant increase in urinary excretion of Na+ (P < 0.01), K+ (P < 0.01) and Cl(-) (P < 0.01). Chronic treatment with SP decreased significantly urine osmolality (P < 0.01 vs. control), while a slight increase in glomerular filtration rate was also observed (P < 0.05) for both doses of water extract (100 and 400 mg/kg). It is concluded that the water extract of whole plant of SP has a significant diuretic effect in rats.

Animals↗
PubMed2002

Diuretic effect and mechanism of action of parsley.

This work provides substantial evidence for the advocated diuretic effect of parsley in folk medicine and determines the mechanism of action of the herb. Rats offered an aqueous parsley seed extract to drink, eliminated a significantly larger volume of urine per 24 h as compared to when they were drinking water. These findings were supported by the results of other experiments using an in situ kidney perfusion technique which demonstrated also a significant increase in urine flow rate with parsley seed extract. This effect was still apparent in presence of amiloride, furosemide and in the absence of sodium, but not in the absence of potassium, suggesting that the diuretic effect of the herb is mediated through an increase in K+ retention in the lumen. Parsley extract, was shown on the other hand, to reduce the activity of the Na+-K+ ATPase in both cortex and medulla homogenates. Such an inhibition would decrease apical cellular Na+ reabsorption, lower K+ secretion, increase K+ concentration in the intercellular space and consequently would inhibit passive K+ influx across the tight junctions. The mechanism of action of parsley seems to be mediated through an inhibition of the Na+-K+ pump that would lead to a reduction in Na+ and K+ reabsorption leading thus to an osmotic water flow into the lumen, and diuresis.

Animals↗
PubMed2003

Diuretic use, progressive heart failure, and death in patients in the Studies Of Left Ventricular Dysfunction (SOLVD).

OBJECTIVES: We sought to determine whether non-potassium-sparing diuretics (PSDs) in the absence of a PSD may result in progressive heart failure (HF). BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors incompletely suppress ACE activity in HF patients. Furthermore, non-PSDs are activators of aldosterone secretion. We reasoned that non-PSDs, in the absence of a PSD, might result in progressive HF. METHODS: In the 6,797 patients in the Studies Of Left Ventricular Dysfunction (SOLVD), we compared the risk of hospitalization for, or death from, HF between those taking a PSD and those who were not, adjusting for known covariates. RESULTS: The risk of hospitalization from worsening HF in those taking a PSD relative to those taking only a non-PSD was 0.74 (95% confidence interval [CI] 0.55 to 0.99; p = 0.047). The relative risk for cardiovascular death was 0.74 (95% CI 0.59 to 0.93; p = 0.011), for death from all causes 0.73 (95% CI 0.59 to 0.90; p = 0.004), and for hospitalization for, or death from, HF 0.75 (95% CI 0.58 to 0.97; p = 0.030). Compared with patients not taking any diuretic, the risk of hospitalization or death due to worsening HF in patients taking non-PSDs alone was significantly increased (risk ratio [RR] = 1.31, 95% CI 1.09 to 1.57; p = 0.0004); this was not observed in patients taking PSDs with or without a non-PSD (RR = 0.99, 95% CI 0.76 to 1.30; p = 0.95). CONCLUSIONS: The use of PSDs in HF patients is associated with a reduced risk of death from, or hospitalization for, progressive HF or all-cause or cardiovascular death, compared with patients taking only a non-PSD.

Aged↗
PubMed2001

The effects on knowledge of the systematic education of patients with joint diseases treated with NSAIDs and diuretics.

In a randomised, controlled trial, patients with joint diseases and concomitant treatment with NSAIDs and diuretics received systematic education. The intervention group was given information by a self-conducted, interactive Kodak Photo-CD program in addition to personal drug information and non-commercial drug leaflets. Awareness of drug interactions and encouragement of self-adjustment of treatment was focused on. Control patients received conventional information. Three months after randomisation, knowledge was tested by means of a questionnaire. At 3 months there was a significant difference in attained score between the intervention group and the control group. Greater knowledge was achieved, especially on drug interaction, in the intervention group. In conclusion, less than 1 h of systematic education significantly improved patients' knowledge on essential issues of concomitant treatment with NSAIDs and diuretics. Knowledge of effects, side-effects and interactions of drugs is essential for self-adjustment of treatment. The method employed, which is standardised and produces a reproducible quantity of education, might be applicable to several other medical conditions.

Adult↗