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PubMed1986

Intracellular cations and diuretic therapy following acute myocardial infarction.

In a controlled, prospective, randomized study of the effects of diuretic therapy on serum, lymphocyte, and erythrocyte potassium, magnesium, and calcium concentrations, 155 patients were followed up for six months after experiencing acute myocardial infarction. Of these, 48 patients received furosemide and potassium; 37 patients received hydrochlorothiazide and amiloride hydrochloride; and 70 patients did not require diuretics. Lymphocyte and erythrocyte cation concentrations were all statistically significantly lower in the furosemide-treated patients when compared with the patients in the nondiuretic-therapy group or the hydrochlorothiazide-amiloride-treated group, with no change in serum levels. Since the combination of low intracellular potassium and magnesium concentrations in patients with recent myocardial infarction may be of importance in the cause of arrhythmias, we suggest that potassium- (and magnesium-) sparing diuretics be used in the treatment of patients, when necessary, unless their diuretic needs cannot be met by such agents.

Amiloride↗
PubMed1987

Comparative cardiovascular effects of loop-acting, thiazide-type and potassium-sparing diuretics in spontaneously hypertensive rats.

Studies were carried out in conscious, chronically-cannulated, spontaneously hypertensive (SH) rats to determine the comparative cardiovascular actions of a series of diuretic compounds. The effects of three oral doses of hydrochlorothiazide, trichlormethiazide, chlorthalidone, metolazone, spironolactone, triamterene, amiloride, furosemide, ethacrynic acid, MK-447, hydrochlorothiazide + amiloride, and MK-447 + amiloride on blood pressure and heart rate were monitored continuously for four hr and again 24 hr post-dose. Thiazides, thiazide derivatives and antikaliuretic diuretics exerted little or no antihypertensive effects, while the loop-acting diuretics (except ethacrynic acid) and combinations markedly reduced blood pressure. Antihypertensive responses to furosemide, MK-447 and the diuretic combinations were associated with either stable heart rate or paradoxical bradycardia, but not compensatory tachycardia. Heart rate remained relatively unaltered by individual doses of the remaining compounds.

Animals↗
PubMed1978

[Experiences with a new hypouricemic diuretic (tienilic acid): comparison with hydrochlorothiazide].

A new hypouricemic diuretic (tienilic acid) was compared with hydrochlorothiazide in a double-blind study in 8 patients with mild essential hypertension. After a two-week placebo period the patients received either 250 mg tienilic acid or 50 mg hydrochlorothiazide in a single daily dose for 3 weeks. After a second placebo period of 2 weeks the patients received, in a crossover design, either tienilic acid or hydrochlorothiazide for a further 3 weeks. The reduction of blood pressure and of body weight was similar for both drugs. When treatment was started diuresis and natriuresis increased with tienilic acid and with hydrochlorothiazide. Whereas serum sodium levels showed only minor variations, serum potassium levels fell with both diuretics and urinary potassium excretion increased. Urinary calcium excretion decreased and serum calcium levels slightly increased under both treatments. Both diuretics induced similar increases of plasma renin activity, plasma aldosterone concentration and aldosterone-18-glucuronide excretion. Blood urea nitrogen and, to a lesser extent, serum creatinine levels were raised slightly under both drug regimens. Whereas the serum uric acid level rose and remained elevated for the duration of hydrochlorothiazide treatment, it fell significantly and remained lowered during treatment with tienilic acid. Uric acid clearance was about twice as high with tienilic acid as with hydrochlorothiazide. Tienilic acid therefore appears to be a therapeutic alternative to thiazides and other hyperuricemic diuretics in hypertensive patients in whom hyperuricemia should be avoided or corrected.

Adult↗
PubMed1986

Thiazide diuretics inhibit chloride absorption by rabbit distal colon.

In order to investigate the cellular mechanisms of action of thiazide diuretics, the effect of diuretic and nondiuretic thiazide compounds on Cl- absorption across rabbit distal colon was assessed in tissues mounted in Ussing chambers. This epithelium absorbs Cl- via an active electroneutral transport process. Net 36Cl- absorption across short-circuited tissues was decreased 53, 36 and 20% after addition of 10(-4) M trichlormethiazide, bendroflumethiazide or hydrochlorothiazide, respectively, to the mucosal bathing solution. This inhibitory effect was a result of a decrease in the mucosa-to-serosa unidirectional Cl- flux (P less than .02). Neither the serosa-to-mucosa Cl- flux nor Isc was affected by the thiazides. Thiazide diuretics may exert their effect on Cl- transport across rabbit distal colon through inhibition of a Cl(-)-HCO-3 exchange mechanism. The nondiuretic thiazide, diazoxide, had no effect on Cl- transport. The similarity between the diuretic potency of these compounds and their potency as inhibitors of Cl- absorption by rabbit colon suggests that the thiazides have a similar mechanism of action in renal epithelia.

Animals↗
PubMed1986

Digitalis and diuretics: still the standard therapy?

Although digitalis preparations are effective in controlling the ventricular rate in atrial fibrillation and certain other supraventricular tachyarrhythmias, with consequent haemodynamic benefit, there is increasing controversy about significant sustained inotropic efficacy in patients in sinus rhythm. Digoxin toxicity is a serious hazard and subtherapeutic dosing a deception and waste of resources; blood levels are the key to optimum dosing. A considered withdrawal of the drug and reintroduction if haemodynamic deterioration ensues is probably the only way of proving in an individual patient if the drug is really worth using long-term. Diuretics have had a major place in management of cardiac failure, correcting the fluid overload. However there are a number of troublesome metabolic and other consequences, and excessive diuresis can be dangerous. Vasodilator therapy has recently had a major impact on management of more severe forms of cardiac failure, usually with coadministration of diuretics, but the predominant pattern of drug use in milder heart failure is to rely primarily or even exclusively on diuretics. Rational use of drugs in cardiac failure would be greatly facilitated by availability of simple non-invasive techniques to measure cardiac function and filling pressures. Until this becomes possible it will be difficult to alter the traditional pattern of long-term use of digoxin and diuretics whenever there have been symptoms attributable to heart failure.

Digitalis Glycosides↗
PubMed1985

Inhibition of human red blood cell Na+, K+-cotransport by various "high ceiling" diuretics.

The rank order of diuretic efficacy of furosemide analogs, e.g. bumetanide and piretanide, in humans is reflected better by their ability to inhibit Na+, K+-cotransport in human red blood cells than by their natriuretic activity in rats. High ceiling diuretics which are structurally unrelated to sulfamoyl diuretics, e.g. muzolimine, tizolemide, MK 447, may be similarly effective in rat and man, but by acting via other mechanisms cannot be detected by use of the Na+, K+-cotransport system. On the other hand, a possible conversion of such compounds to metabolites active in the cotransport system cannot be ruled out. In contrast to ethacrynic acid, the weak inhibitory activity of muzolimine on the Na+, K+-cotransport was not potentiated by cysteine. These results suggest that the diuretic activity of muzolimine is not caused by inhibition of Na+, K+-cotransport.

Adult↗
PubMed1985

Renal failure with potassium-sparing diuretics.

In one year 19 patients aged 73 SD 8 yr were referred with renal failure (plasma creatinine 0.14-0.52 mmol/l; urea 7.9-39.5 mmol/l; potassium 2.9-6.1 mmol/l, who were taking amiloride/hydrochlorothiazide (ten), amiloride alone (one) or triamterene/hydrochlorothiazide (eight). Six patients were taking other diuretics. Sixteen patients were being treated for hypertension and three for fluid retention; five hypertensive patients were also taking non-steroidal anti-inflammatory drugs (NSAID). Four patients were hypokalaemic, three were volume-depleted. All potassium-sparing diuretics and NSAID were stopped (four required another diuretic). Six-100 days later renal function was improved in 17 patients, unchanged in one and one patient had died of uraemia. Blood pressure was satisfactory on no therapy in 11 patients and two normotensive patients were oedema-free. In elderly patients with renal impairment potassium-sparing diuretics may cause renal failure, sometimes secondary to hypovolaemia, and NSAID may potentiate the effect.

Acute Kidney Injury↗
PubMed1985

Influence of muzolimine and other diuretics on human red cell Na+, K+-cotransport.

It is known that the diuretic activity of so-called loop diuretics is characterized by the ability of such compounds to inhibit the Na+, K+-cotransport system of the cell membrane. A good correlation has been demonstrated of the inhibitory activity of several furosemide- and ethacrynic acid-related compounds with their natriuretic activity in man. It was the aim of the study to examine, wether muzolimine has Na+, K+-cotransport inhibitory activity, and if so, if this occurs in a dose range which might be relevant for its natriuretic activity. For reasons of comparison, several other diuretics with high ceiling activity were studied. Cotransport inhibitory activities were compared with natriuretic activities in rats. Na+, K+-cotransport was measured by determination of furosemide-sensitive, ouabain-insensitive Na+-extrusion from Na+-loaded human red blood cells. Whereas the natriuretic activity of muzolimine is equal to that of furosemide in rats and superior in man, its cotransport inhibitory activity is merely 1/13 of that of furosemide. Additionally, only 50% inhibition is reached. The inhibitory activity of muzolimine, in contrast to ethacrynic acid, is not enhanced in the presence of equimolar cysteine. Muzolimine therefore appears to act via other mechanisms than furosemide-like diuretics. However, it cannot be excluded that muzolimine might act by an active metabolite.

Adult↗
PubMed1985

[Hypotensive and diuretic effect of heparin in patients with glomerulonephritis].

The hypotensive and diuretic properties of heparin were evaluated in 95 patients with different clinical and morphological varieties of chronic glomerulonephritis (CGN). The arterial blood pressure dropped in all the patients treated with heparin. The maximal effect was attained toward the end of heparin treatment (by the 35th-50th day). In patients with hypertonic and mixed nephritis associated with renal failure, (the glomerular filtration rate under 35 ml/min), the BP lowering induced by heparin was accompanied by the deterioration of renal function. The diuretic and natriuretic effects were recorded in 81 out of the 95 patients. The maximal values of diuresis and sodium excretion were detected on the 14th-16th day of the treatment during the use of the maximal doses of heparin. It was established that heparin-induced inhibition of aldosterone synthesis plays the key role in the genesis of the diuretic, natriuretic and hypotensive action of the drug. It is concluded that diuretic and hypotensive properties of heparin can be made use of in the treatment of nephrological patients.

Adolescent↗
PubMed1985

Pharmacological properties of the new potent diuretic torasemide in rats and dogs.

Torasemide, a pyridine-3-sulfonylurea derivative, has potent diuretic activity in rats and dogs. In both species urinary volume and electrolyte excretion increased linearly with the logarithm of the dose, thus resembling the profile of a high ceiling diuretic. The minimum effective dose by oral route was 0.2 mg/kg in the rat and less that 0.1 mg/kg in the dog. Maximal effect was obtained with about 10 mg/kg. Experiments by oral and i.v. routes in the rat indicated that torasemide was equally potent by both oral and parenteral administration. In both rats and dogs, urinary excretions induced by torasemide were similar to those obtained with furosemide. However, for the same natriuretic effect, potassium losses with torasemide were significantly less than with furosemide. On a weight basis, torasemide was 9-40 times more potent than furosemide in the rat and about 10 times in the dog. After oral administration the diuretic effects of torasemide started within 20 min and lasted approximately 2 h in the rat and more than 8 h in the dog. The activity of torasemide was not decreased after a repeated daily oral dose of 10 mg/kg for 15 days in the rat. Torasemide at a daily oral dose of 5 mg/kg for 12 days effectively reduced the arterial blood pressure in desoxycortone induced hypertension in the rat. Besides the diuretic and antihypertensive effects no other significant pharmacological effects were observed with torasemide in the different in vitro and in vivo experiments. Torasemide was practically fully absorbed by the gastrointestinal tract, its bioavailability by oral route ranged from 80 to 100%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1977

[Comparative studies on the diuretic activities of Etozolin and a reference compound in normal volunteers (author's transl)].

The novel diuretic (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)-acetic acid ethylester (Etozolin; Elkapin) has been investigated against a benzothiazide (Vs) and placebo on 8 volunteers. Etozolin and Vs show a dose dependent diuretic effect: 400 mg etozolin being equipotent to 75 mg Vs and 1200 mg etozolin being 2.8 times more effective than 75 mg Vs. Both substances show maximum effect 2 to 4 h after application, no differences from placebo being demonstrable 10 h after administration. There were no significant differences in potassium excretion between etozolin, Vs and placebo, etozolin and Vs causing, however, a significant excretion of sodium and chloride in contrast to placebo. Etozolin seems to act like a diuretic of the sulfonamide-type in respect to the profile of daily urinary output whereas resembling the loop-diuretic type in respect to urinary volume elimination.

Adolescent↗
PubMed1979

[Diuretic agents in urine extracts: clearance studies, tubular glucose absorption and blood pressure].

We previously described diuretic agents of human urine. The extracts cause a significant decrease in sodium and plasma albumin concentration in the medulla of the kidney. In the present study further investigations were performed to detect the site of action of these fractions. In the bio-assay of sodium depleted rats urine extracts of hydrated, healthy human volunteers cause a significant increase in water and sodium excretion. In a dose of 100 micrograms/kg b.w. the rise in water elimination exceeds that of sodium excretion. Compared with control the glomerular filtration rate (inulin clearance), the renal plasma flow (PAH-clearance), and the systemic blood pressure (Statham element) are not affected. There is no change in the tubular glucose absorption of glucose loaded rats. In contrast to the glucose induced increase of the renal water elimination the diuretic potency of the urine extracts is only modest. The data provide further evidence of the existence of a diuretic factor in human urine extracts. The results show that the diuretic activity is not caused by an enhanced glomerular filtration rate or by an augmented renal plasma flow. However, an effect on the renal medullary hemodynamics, that is not detected by the PAH-clearance, could play an important role.

Absorption↗
PubMed1984

Acute effects of high ceiling diuretics on pancreatic blood flow and function.

The possibility that a decrease in extracellular volume, induced by diuretics, would cause a decrease in pancreatic blood flow which, in turn, might compromise pancreatic function was examined. Employing fasted anesthetized mongrel dogs, the acute effects of furosemide, a typical high ceiling diuretic, on pancreatic blood flow and plasma levels of insulin and glucose were examined. Furosemide was found to induce a decline in pancreatic blood flow which was similar in all regions of the pancreas and the decrease was antagonized when extracellular volume depletion was prevented by infusing saline at the same rate as urine flow. The decrease in blood flow was significantly correlated with cumulative volume loss. Plasma levels of insulin and glucose were, however, not significantly altered during the studies. To increase the likelihood of determining significant decreases in plasma levels of insulin, acute studies were repeated in dogs in which plasma levels of insulin were increased by a continuous infusion of glucose. Both furosemide and the structurally unrelated high ceiling diuretic, ethacrynic acid, caused a decrease in pancreatic blood flow which was similar in all regions of the pancreas. The cumulative volume loss observed with administration of either furosemide or ethacrynic acid was significantly correlated with the level of pancreatic blood flow observed. Plasma levels of insulin and glucose were not significantly altered. It can be concluded that high ceiling diuretic drugs such as furosemide and ethacrynic acid do produce a loss in volume which is correlated with a decrease in pancreatic blood flow, but decreases in pancreatic blood flow alone do not appear to be sufficient to produce overt changes in pancreatic function in acute studies.

Animals↗
PubMed1984

[Effect of diuretics on the humoral system of kidney prostaglandins in hypertension patients].

Sixty-four patients with stage IIB essential hypertension were examined for the urinary excretion of prostaglandins E2 and F2 alpha, natriuresis and diuresis in the control period and then on the 3rd, and the 12th-14th day of the treatment with diuretics (furosemid, hypotiazid, oxodolin, brinaldix). All diuretics were found to alter the urinary PG excretion, with the degree of their effect depending on the type of the drug, the route and duration of its administration. Furosemid, to a greater degree than other diuretics, increased the urinary excretion of PGE2 thus bringing down the PGF2 alpha/PGE2 ratio, brinaldix increased PGF2 alpha excretion whereas hypotiazid, in cases of its prolonged employment, reduced the excretion of both PGs, the PGF2 alpha decrease being more prominent. PGE2 contributed to a decrease in BP and to the development of natriuresis. The physiological effect of PGF2 alpha depended on the status of the water-electrolyte balance in the body: in patients with IIB stage essential hypertension it facilitated the development of natriuresis and BP decrease. When following the administration of the diuretics the balance of sodium and water in the body lowered, PGF2 alpha caused the retention of sodium and water in the body and did not affect the BP.

Adult↗
PubMed1983

Different blood pressure responses to diuretic treatment in normotensive subjects with and without a family history of hypertension.

The possibility that the familial background for hypertension may influence the blood pressure response to diuretic treatment was evaluated in 14 normotensive subjects with negative and 14 normotensive subjects with positive family history of hypertension. Under control conditions, blood pressure, heart rate, body weight, urinary sodium and potassium, plasma sodium, potassium, creatinine, norepinephrine, epinephrine, renin and aldosterone levels did not differ between the two study groups. Each subject received chlorthalidone, 100 mg/day, or indapamide, 2.5 mg/day for eight weeks. Compared with control values, blood pressure was decreased during diuretic treatment in subjects with positive (P less than 0.05), but not in those with negative family history for hypertension. Diuretic-induced decreases in plasma potassium (P less than 0.005), increases in plasma renin activity and aldosterone (P less than 0.005), and a tendency towards higher plasma norepinephrine levels were not different between the two study groups. These findings suggest that the familial background of hypertension may, at least in part, determine the blood pressure response to diuretic treatment.

Adult↗
PubMed1984

Drug interactions with diuretics.

Interactions between diuretics and other substances may have beneficial or adverse consequences. Co-prescription of diuretics with antihypertensive agents, potassium, magnesium or acid salts, probenecid, quinidine, anticoagulants, lithium, cardiac glycosides or other diuretics can result in both beneficial and adverse interactions. Laxatives, oral antidiabetic agents, non-steroidal anti-inflammatory drugs, adenylate cyclase activators, mineralocorticoids, hypolipidaemic agents, neuromuscular blockers, chloral hydrate, carbenoxolone, drugs likely to produce the syndrome of inappropriate secretion of antidiuretic hormone and some antibiotics may be involved in adverse interactions with diuretics.

Aminoglycosides↗
PubMed1984

Diuretic effect of ITA 529.

The diuretic and saluretic activity of ITA 529 (Ethyl-beta-[(5-tert-butyl-3-chloro-2-hydroxy)benzylamino]crotonate++ +) in rat, rabbit and monkey is described in this study. In rat, the diuretic ED50 of ITA 529 was 1.23 mg/kg p.o. and its ED100 1.69 mg/kg p.o. The diuretic ED50 of furosemide was 18.48 mg/kg p.o. and its ED100 22.38 mg/kg p.o. Their effect lasted approximately 3 hours. In monkey, the diuretic ED50 of ITA 529 was 2.29 mg/kg p.o. and its ED100 6.54 mg/kg p.o. while for furosemide its ED50 was 2.44 mg/kg p.o. and its ED100 5.72 mg/kg p.o. In rabbit the ED50 of ITA 529 was 1.83 mg/kg p.o. and its ED100 3.37 mg/kg p.o. For furosemide, its ED50 was 2.25 mg/kg p.o. and its ED100 7.13 mg/kg p.o. The natriuretic activity of ITA 529 was reduced by indomethacin.

Amines↗
PubMed1984

Potassium and diuretic-induced ventricular arrhythmias in ambulatory hypertensive patients.

We studied 17 hypertensive men to determine the relationship of diuretic-induced hypokalemia to ventricular ectopic activity ( VEA ). Blood values and 24-hour ambulatory ECG monitoring were done at baseline, after diuretic and after serum potassium normalization. Two subgroups of patients were identified: group A patients were older (63.0 vs. 53.8 years) and had clinical evidence of organic heart disease compared to group B. Group A had increased frequency and complexity of VEA with diuretic which reverted to baseline after potassium normalization. Group B had no changes. Serum and intra-red blood cell potassium decrements were equal in both groups. We conclude that clinical in addition to laboratory observation should be used to identify those hypertensive patients most susceptible to diuretic-induced VEA and their serum potassium level should be normalized in order to minimize this complication.

Adult↗