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PubMedDate not supplied

Hypokalaemia in the elderly: is it always diuretic-induced?

Serum potassium was measured within 24 hours in 156 patients (48 male, 108 female) with an average age of 81.9 years admitted to the unit with acute illness. Of the 156 patients, 88 (56.4%) were taking diuretics (none was on ACE inhibitors); 20 patients (12.8%) were also on digoxin therapy. In all, 24 patients (16%) had hypokalaemia and 3 (2%) hyperkalaemia. Hypokalaemia was seen in patients associated with acute illness. There was no significant difference between the diuretic and non-diuretic groups. Monitoring of serum potassium is not routinely indicated to detect hypokalaemia in patients on diuretic therapy except in those with severe hepatic or renal impairment or those on digoxin.

Aged↗
PubMedDate not supplied

Prevention of hypokalemia caused by diuretics.

Hypokalemia induced by the use of diuretics is common. Those at risk include the elderly, women, patients with edematous states, and patients in whom higher doses and/or the more potent agents are used. Prevention should include a low-salt diet rich in potassium, magnesium, and chloride (either through foods enriched with these elements or through potassium chloride supplements) and use of low doses of short-acting diuretics in the treatment of mild to moderate hypertension. The subgroup of hypertensive patients in whom hypokalemia develops despite these recommendations may benefit from a change to the potassium-sparing diuretic spironolactone or substitution of diuretics with alternative first-line drugs.

Benzothiadiazines↗
PubMedDate not supplied

ICI 206,970: a novel eukalemic diuretic with calcium channel blocking activity.

ICI 206,970, an aminomethylphenol pyrazine derivative, produced diuretic and saluretic effects, but caused only minimal alterations in kaliuresis in dogs and rats after oral and parenteral administration. ICI 206,970, unlike HCTZ, increased diuretic activity in a more clearly defined dose-related manner, and did not reach the plateau level even up to a dose of 100 mg/kg p.o. The diuretic and natriuretic response is believed to be a combination of a direct effect on tubule function and changes in GFR, particularly at higher doses. Based upon studies in in vitro amphibian models for mimicking mammalian nephron, ICI 206,970 appeared to possess a furosemide-like activity in toad cornea and amiloride-like activity in toad bladder. It is concluded that ICI 206,970 is a potent eukalemic diuretic with the potential of multiple sites of renal action.

Animals↗
PubMed1993

Diuretic and renal protective effects of 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902), a novel adenosine A1-receptor antagonist, via pertussis toxin insensitive mechanism.

KW-3902 [8-(noradamantan-3-yl)-1,3-dipropylxanthine] is a novel potent and selective adenosine A1-receptor antagonist. In anesthetized rats, KW-3902 (0.1 and 1 mg/kg p.o.) antagonized the 5'-N-ethylcarboxamidoadenosine (NECA) induced bradycardic response, which is thought to be mediated via adenosine A1-receptors. However, the hypotensive response to NECA, which is predominantly due to adenosine A2-receptor activation, was not affected by KW-3902. Diuretic and renal protective effects of KW-3902 were investigated in normal and pertussis toxin (IAP; 10 micrograms/kg i.v.)-treated rats. KW-3902 (0.001-1 mg/kg p.o.) caused significant increases of urine volume and sodium excretion with little change of potassium excretion in saline-loaded normal rats. In anesthetized normal rats, KW-3902 (0.01 and 0.1 mg/kg i.v.) caused significant diuresis and natriuresis with no change in renal plasma flow and glomerular filtration rate. These findings suggest that KW-3902 caused the diuretic effect not by the change in the renal hemodynamics, but by the inhibition of water and sodium reabsorption in tubular sites. KW-3902 (0.01-1 mg/kg p.o.) significantly attenuated increases of serum creatinine and urea nitrogen and renal tubular damage in glycerol-induced acute renal failure rats. Neither diuretic nor renal protective effects of KW-3902 were affected by pretreatment of rats with IAP, which totally abolished the bradycardic response to NECA. These results are compatible with the hypothesis that diuretic and renal protective effects by adenosine A1-receptor blockade are mediated via IAP-insensitive mechanism.

Absorption↗
PubMed1993

[Progress in management for heart failure: diuretics].

In congestive heart failure (CHF), a variety of compensatory mechanisms such as activation of sympathetic nervous system, renin-angiotensin system and vasopressin, facilitate water and sodium retention and increase circulating blood volume, which primarily improve systemic perfusion. However, hypervolemia sometimes induces pulmonary edema and afterload elevation, resulting in a further decrease in cardiac output. Diuretics are administered in patients with CHF to cut this vicious cycle by reducing blood volume. Evaluation of hemodynamic states is important in patients with severe CHF, since an excessive reduction in preload could critically decrease cardiac output. Among conventional diuretics, loop diuretics is the most potent and widely used for management of CHF. Inhibition of such compensatory mechanisms such as angiotensin-converting enzyme inhibitors and atrial natriuretic peptide-related agents is shown to exert natriuretic and desirable hemodynamic effects in CHF and is among candidates for future diuretics.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

[The value of diuretics in monotherapy of hypertension].

AIM: To represent the usefulness of thiazide diuretics as monotherapy of primary hypertension. MAIN POINTS: Moderate doses of thiazide diuretics can produce a reduction in blood pressure equal to that of beta blockers, calcium antagonists and ACE inhibitors, and achieve an equally high response rate. The advantages and disadvantages of the specific action profile of these diuretics are described. Discussions about the reduction in cardiovascular mortality is represented and practical conclusions drawn. The specific indications for monotherapy with thiazide diuretics include systolic, diastolic and isolated systolic hypertension in the elderly hypertensive, and hypertension in NYHA III and IV cardiac insufficiency. Suggestions for their use in practice are given.

Antihypertensive Agents↗
PubMed1995

Utility of technetium-99m-MAG3 diuretic renography in the neonatal period.

UNLABELLED: Diuretic renography performed in the neonatal period has been reported to be unreliable in diagnosing obstruction. METHODS: The scans of 27 neonates (age up to 28 days; mean 17 days) with a total of 53 renal units were reviewed; a renal unit being defined as comprising a kidney and its ureter. All were referred following perinatal ultrasound diagnosis of hydronephrosis or hydroureteronephrosis. The neonates had standard diuretic renography using MAG3 with a frusemide dose of 1 mg/kg followed by another image obtained after gravity-assisted drainage. RESULTS: There were 17 normal undilated renal units showing excellent diuretic responses with clearance half-times of 0.6-7.7 min. Eighteen renal units were diagnosed as having pelvi-ureteric junction (PUJ) obstruction, with surgical confirmation in all. Eight were diagnosed as unobstructed and of these seven were confirmed nonobstructed by serial imaging using ultrasound and MAG3, but one subsequently had pyeloplasty performed for PUJ obstruction. One unit was indeterminate for PUJ obstruction but had good clearance with gravity-assisted drainage and was shown to be unobstructed on repeat studies. Of nine units diagnosed as having vesico-ureteric junction (VUJ) obstruction, eight had surgical confirmation and one remains of uncertain final diagnosis. Co-existing VUJ obstruction could not be diagnosed in two units with PUJ obstruction because of insufficient radiotracer drainage through the tight stenosis into the ureter. CONCLUSION: An adequate diuretic response is present in the neonatal period using MAG3 and this allows for reliable diagnosis of obstruction. An unobstructed or indeterminate result necessitates follow-up imaging to ensure obstruction does not develop. Co-existing VUJ obstruction may be missed in a scan showing PUJ obstruction.

Diuretics↗
PubMed1995

[Predictive analysis of the response to treatment with diuretics of patients with liver cirrhosis and ascites].

Our aim was to develop and validate a prognostic model to predict the evolution of cirrhotic patients admitted to the hospital because of ascites and treated with diuretics. Two hundred and two patients were evaluated. After collection of clinical and laboratory data, a prognosis of the response to diuretics was given by one of us. After univariate analysis, 37 parameters were used to construct a database. A new prognosis was obtained for each patient comparing his/her data with the database, with the help of a computer and using Bayes' theorem. Gender: female, poor general status, disturbed consciousness, increased serum glucose, increased BUN, low prothrombin time, increased bilirubin, leucocytosis, thrombopenia and low urine sodium were associated with a poor response to diuretics. Sensitivity and specificity of clinical and computer prognosis were similar. Computer prognosis allowed the classification of patients in groups of risk which showed a different evolution and improved the accuracy of the clinical prognosis. We conclude that the objective analysis of clinical and laboratory data is useful to improve the accuracy of the prediction of the evolution in cirrhotic patients with ascites treated with diuretics.

Ascites↗
PubMed1996

Gender effect on diuretic response to hydrochlorothiazide and furosemide.

Gender has been shown to elicit differences in drug disposition and response to therapeutic agents. We measured the diuretic response to oral hydrochlorothiazide, oral and intravenous furosemide in 6 male and 6 female normal volunteers. After fasting overnight, each subject received single doses of the individual diuretics or no treatment on 4 separate days. Total urine output was collected over the next 24 hours for volume measurement and determination of sodium and potassium concentrations. There was no statistically significant difference found between male and female subjects with respect to urine flow rate, sodium, and potassium excretion rates among the treatments. However, when natriuretic response was adjusted for mg/kg of the intravenous furosemide dose received, male subjects had a higher peak sodium excretion rate than the female subjects. Results of this study reveal a gender-related difference on the natriuretic response to diuretics. Further studies are necessary to identify if this gender-related difference is caused by differences in drug metabolism, disposition, or intrinsic diuretic responsiveness at the site of action.

Administration, Oral↗
PubMed1996

[Value of diuretics in hypertension].

Diuretics still remain a cornerstone in the treatment of hypertension. Adverse effects such as disorders of the carbohydrate and lipid metabolism as well as development of hypokalemia or hypomagnesemia are obviously directly correlated to the administered dosage. Therefore, there is increasing agreement for low-dose drug therapy. In contrast to hydrochlorothiazide treatment, metabolic disorders are less commonly encountered with indapamide therapy. A pronounced diuretic efficacy is linked to the combined use of diuretics which act on different segments of the nephron (for example administration of a loop diuretic together with a thiazide). In chronic renal failure indapamide appears to be superior to hydrochlorothiazide considering preservation of renal function. In contrast to thiazides, indapamide is the therapy of choice in patients with diabetes.

Antihypertensive Agents↗
PubMed1996

[Etiology and treatment of diuretic resistance].

Basically the cause of the resistance to diuretics can be found out. Essential is a detailed knowledge of the physiology and pathophysiology of volume regulation as well as renal water and electrolyte excretion. To get diagnostic and therapeutic access to diuretic resistance main efforts have to be put into the work up of current diagnostics and therapy of the main disease (heart failure, liver failure, nephrotic syndrome, and renal failure) as well as the symptomatic, drug related volume regulation (exact balancing of fluid intake and excretion with and without diuretics) in these severely ill patients. Has the underlying cause for resistance to diuretic medication been found, therapy is generally easy and effective. It might be unsuccessful in patients with severe impairment of renal function. Then the only way may be extracorporeal fluid removal.

Antihypertensive Agents↗
PubMed1997

Studies on the phototoxic effects of oral antidiabetics and diuretics.

A number of sulphonamide derived oral antidiabetics (chlorpropamide, glibenclamide, glipizide, gliquidone, glymidine, tolazamide and tolbutamide) and diuretics (bemetizide, bendroflumethiazide, benzylhydrochlorothaizide, bumetanide, butizide, chlortalidone, furosemide, hydrochlorothiazide, hydroflumethiazide, indapamide, piretanide, polythiazide, trichlormethiazide and xipamide) were investigated for phototoxicity in a cell culture model. Cell death dependent on UVA fluence and test substance concentration was observed in the presence of the oral antidiabetics glibenclamide and gliquidone, as well as the diuretics bemetizide, bendroflumethiazide, benzylhydroxhlorothiazide, bumetanide, butizide, hydrochlorothiazide, hydroflumethiazide, piretanide, polythiazide and trichlormethiazide. Bendroflumethiazide was phototoxic at 5 x 10(-5) mol/l and higher concentrations, bemetizide, benzylhydrochlorothiazide, bumetanide and hydroflumethiazide were phototoxic at 2.5 x 10(-4) mol/l and higher concentrations, and the oral antidiabetics glibenclamide and gliquidone as well as the diuretics butizide, hydrochlorothiazide, piretanide, polythiazide and trichlormethiazide were phototoxic at 5 x 10(-4) mol/l and higher concentrations. The oral antidiabetics chlorpropamide, glipizide, glymidine, tolazamide and tolbutamide as well as the diuretics chlortalidone, furosemide, indapamide and xipamide did not induce phototoxicity in this assay.

Carcinoma in Situ↗
PubMed1976

A comparative diuretic and tissue distribution study of bumetanide and furosemide in the dog.

Intravenous dose-response data obtained from renal clearance studies in anesthetized dogs indicated that bumetanide was approximately 30-fold more potent than furosemide in enhancing sodium excretion. After the administration of 0.01 mg/kg of bumetanide or 1.0 mg/kg of furosemide, the relationship between i.v. diuretic activity and tissue distribution was evaluated. In dog renal clearance experiments, bumetanide and furosemide significantly enhanced urine flow, sodium and potassium excretion. Inulin clearance as an estimate of glomerular filtration rate was not altered by either drug, but sodium reabsorption was decreased with bumetanide (13%) and furosemide (12%). At these diuretic doses, both compounds were bound to dog plasma protein to about the same extent (86-91%), although total plasma levels were 100-fold higher for furosemide. Within 1/2 hour after the i.v. administration of 14C-bumetanide or 14C-furosemide, 86 to 99% of the 14C in urine, plasma, kidney, and liver appeared as unchanged drug. One minute after maximal diuresis bumetanide was found to have a higher affinity (3-fold) for kidney compared to furosemide. These data offer a possible explanation for the i.v. diuretic potency difference between these two compounds. Furthermore, the lack of significant difference in plasma protein binding and the absence of urinary metabolites of either drug suggest that other factors may also contribute to the marked differences in diuretic activity between bumetanide and furosemide.

Animals↗
PubMed1998

The effects of thiazide diuretics on bone mineral metabolism.

Thiazide diuretics cause changes in calcium metabolism. Clinically, these changes include a decreased excretion of calcium, and in some instances, this results in a corresponding increase in bone mineral. The study of mineral metabolism in bone is difficult because of the slow turnover rate of bone. For this reason, the rat fracture model was used to study bone mineral metabolism in animals given thiazide diuretics. Fifty rats were divided into four groups: group 1 received a fracture of the right tibia and thiazide diuretics, group 2 received thiazide and no fracture, group 3 received no drugs and a fracture, and group 4 received no drugs and no fracture. At the end of 35 days postinjury, all animals were sacrificed. Biochemical and biomechanical results were analyzed, and revealed that animals that received thiazide diuretics and a fracture had the highest bone mineral content.

Animals↗
PubMed1998

Felodipine extended release versus conventional diuretic therapy for the treatment of systolic hypertension in elderly patients. The National Trial Group.

OBJECTIVE: To compare 8 weeks of monotherapy using either felodipine extended release (ER) or a conventional diuretic therapy, triamterene/hydrochlorothiazide (HCTZ), in elderly patients with systolic hypertension. DESIGN: Prospective, randomized, single-blind screening, double-blind treatment, parallel group comparison. SETTING: Twenty-nine general and family practice sites across Canada. PARTICIPANTS: Men and post-menopausal women aged 60 to 85 years, with mild to moderate primary systolic hypertension (systolic blood pressure > 160 mm Hg or blood pressure > 140/ > 90 mm Hg). INTERVENTIONS: Daily doses of either felodipine ER (2.5 mg) or triamterene/HCTZ (25/12.5 mg) for 8 weeks. After the first 4 weeks, the patients who responded to the initial dosage (a reduction in systolic blood pressure of at least 15 mm Hg) or whose blood pressure was controlled on the dosage (systolic blood pressure < 140 mm Hg) continued to take the low dose. Among the others, the daily doses were doubled for the final 4 weeks. OUTCOME MEASURES: Systolic blood pressure before beginning treatment and at the end of the study, as well as adverse events and results of heart rate measurement, clinical chemistry tests, electrocardiograms and physical examinations before and after therapy. RESULTS: Sufficient data for analysis were obtained from 216 patients (86 men and 130 women). Mean seated blood pressure was reduced significantly in both the felodipine group (from 168/91 to 151/84 mm Hg) and the diuretic group (from 168/92 to 147/84 mm Hg). The difference in mean reductions in systolic blood pressure between the groups was 2.2 mm Hg (with a 95% confidence interval of-1.7 to 6.0 mm Hg), which was not significant. Clinical chemistry measurements taken before treatment and at the end of the study showed that more patients in the diuretic group developed abnormal values for blood urea nitrogen, uric acid and creatinine. Other changes were unremarkable. The incidence of adverse events was similar in both groups, but more patients in the felodipine group (9) than in the diuretic group (3) discontinued treatment owing to an adverse event. CONCLUSIONS: Felodipine ER (2.5 to 5 mg daily) is as effective in reducing systolic blood pressure as triamterene/HCTZ (25/12.5 mg to 50/25 mg daily). More patients discontinued felodipine treatment than triamterene/HCTZ treatment owing to adverse events. However, patients receiving triamterene/HCTZ tended to have abnormal levels in clinical chemistry tests; these should be monitored.

Aged↗
PubMed1998

[Diuretics in the treatment of hypertension].

Diuretics belong into the group of basic antihypertensive drugs. A number of clinical trials provided evidence that long-term administration of diuretics leads not only to effective control of hypertension but has at the same time a favourable impact on cardiovascular morbidity and mortality. Along with beta-blockers diuretics are recommended as drugs of first choice in patients with arterial hypertension. The author presents a brief account of different groups of diuretics incl. their indications.

Diuretics↗
PubMed1998

CVT-124, a novel adenosine A1 receptor antagonist with unique diuretic activity.

Administration of the selective adenosine A1 receptor antagonist, CVT-124, to conscious chronically instrumented rats resulted in significant increases in urine flow rate and sodium excretion without affecting potassium excretion or renal hemodynamics. Its maximum effect was twice that of hydrochlorothiazide which was associated with a significant kaliuresis. The diuretic effect of CVT-124 was less than that observed with furosemide; however, furosemide administration was associated with a large increase in potassium excretion as well as a reduction in glomerular filtration rate. When given at equinatriuretic doses, CVT-124 enhanced the diuretic and natriuretic activity of furosemide without further increasing potassium excretion. In contrast, the combination of hydrochlorothiazide and furosemide resulted in a 3-fold increase in potassium excretion. These data suggest that CVT-124 possesses unique diuretic activity and, as such, it represents a potential new therapeutic in fluid retaining disorders. In addition, its unique mechanism of action suggests that CVT-124 would be effective in otherwise diuretic-resistant patients.

Animals↗
PubMed1998

[Diuretic resistance: mechanisms and therapeutic possibilities].

The diuretics, with the exception of spironolactone, act on the luminal (or apical) surface of the tubular cells of different segments of the nephron. In order to act, they must be secreted into the tubular lumen. This transfer of the drug to its site of action may be blocked by decreased renal blood flow, the saturation of the systems of tubular transport or fixation to the albumin present in the primary urine. All these pharmacokinetic abnormalities (observed in renal failure or the nephrotic syndrome) lead to diuretic resistance. Increasing the dosage, the repetition, intravenous administration, even as an infusion, are possible solutions. Resistance may be observed in the absence of pharmacokinetic abnormalities: in these cases, there is an abnormal response of the tubular cells to otherwise effective diuretic concentrations, or the activation of homeostatic mechanisms leading to sodium retention and preventing negativisation of the salt and water balance. These situations are often associated in cardiac failure or cirrhosis with oedema. Increasing the dosage is not a logical solution, but increasing the frequency of administration may be helpful. The importance of secondary hyperaldosteronism in cirrhotic oedema makes spironolactone the treatment of choice. In all cases, the addition of two mechanisms of inhibition of tubular reabsorption of sodium at different sites in the nephron often results in an effective diuresis: usually, this implies the addition of a thiazide (e.g. hydrochlorothiazide) to an initial prescription of a loop diuretic.

Diuretics↗