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At least 19 recordsLinked to original sources
PubMed1980

Quantitative gas chromatographic determination of two oxidized metabolites of the diuretic mefruside in human urine, plasma and red blood cells.

A gas chromatographic method is reported for the quantitative analysis of two metabolites of mefruside, viz., 5-oxo-mefruside (mefruside lactone) and its hydroxy-carboxylic acid analogue in human body fluids. Use was made of extractive methylation as the derivatization technique, and quantitation was achieved, with a suitable internal standard, by means of a nitrogen-sensitive detector. Because the two metabolites are linked chemically through a lactone-open acid equilibrium, interconversion prior to their separation had to be avoided. A pH partitioning study was performed to find optimal separation conditions. The lactone could be extracted quantitatively at pH 7.4, without any trace of co-extracted hydroxy acid. The latter was extracted either at pH 2 directly (in the case of plasma and urine), or after conversion to the lactone at pH 7.4 (in the case of red cells or whole blood). Concentrations down to 25 ng per sample of both compounds could be analysed with a standard deviation of 5%. The two metabolites of mefruside equilibrated instantaneously between red cells and plasma in vitro. At 37 degrees, the red cell/plasma concentration ratio was 20 for the lactone, but only 0.1 for the open acid compound. 5-Oxo-mefruside was able to displace mefruside from its red blood cell binding sites in vitro.

Carboxylic Acids↗
PubMed1987

Effects of diltiazem alone and combined with mefruside on cardiovascular response at rest and during exercise, carbohydrate metabolism and serum lipoproteins in patients with systemic hypertension.

The antihypertensive effects of the calcium antagonist diltiazem, both alone and combined with the diuretic mefruside, were assessed over 14 months in 36 patients with essential hypertension. Patients received 180 or 270 mg/day; those with inadequate response were given 270 mg/day plus mefruside, 20 mg/day. Both monotherapy and combination therapy significantly reduced blood pressure (BP) at rest and during exercise. However, adding mefruside did not significantly decrease BP below that achieved with diltiazem alone. After 14 months of therapy, the percentage of responders (patients with at least 10% reduction in diastolic BP at rest) was 64% for all patients, 100% (by definition) for those receiving diltiazem alone and 47% for those receiving the combination. Diltiazem decreased heart rate by 6% (4 beats/min at rest) (p less than 0.05). Combined therapy with mefruside did not further reduce heart rate. There were few adverse effects and no undesirable metabolic effects with either monotherapy or combined therapy. Plasma renin activity, aldosterone levels, carbohydrate metabolism, serum lipoprotein levels and routine laboratory test results were unchanged in both groups at the end of the study. Thus, diltiazem is an effective antihypertensive agent and apparently the combination of diltiazem and mefruside does not potentiate the antihypertensive effect of diltiazem alone during long-term therapy.

Adult↗
PubMed1995

Nitrendipine and mefruside in elderly hypertensives: effects on blood pressure, cardiac output, cerebral blood flow and metabolic parameters.

In this multicentre, randomised, double-blind, cross-over study, we evaluated and compared the effects of nitrendipine (a calcium entry blocker of the dihydropyridine group) and mefruside (a diuretic) on BP, cardiac output, cerebral blood flow and metabolic parameters in 22 elderly hypertensives. Eight weeks of treatment with nitrendipine (27.3 mg daily) and mefruside (30.7 mg daily) significantly reduced BP values to almost the same extent. Heart rate, cardiac output (n = 14), cerebral blood flow (n = 20), renin activity and aldosterone remained unchanged during nitrendipine and mefruside treatment. Nitrendipine did not alter any metabolic parameter (electrolytes, lipid values and blood glucose); in patients treated with mefruside serum potassium fell by 0.4 mmol/l (P < 0.001). Minor adverse events were reported in both treatment groups, mostly due to vasodilation. We conclude that both drugs possess potent and comparable haemodynamic and anti-hypertensive properties. They reduce BP by reducing total peripheral vascular resistance with maintained autoregulation of cerebral blood flow. The metabolic disturbances induced by mefruside seem to be less pronounced than that observed with other thiazide diuretics.

Aged↗
PubMed1980

An evaluation of debrisoquine and mefruside in the treatment of hypertension in African and Indian patients.

A double-blind, crossover trial was carried out in 20 hypertensive patients (9 African and 11 Indian) to compare the effectiveness and tolerance of treatment with debrisoquin, mefruside, and a fixed-dose combination of the two drugs with placebo. Patients were treated initially with placebo for 2 weeks before being crossed-over to treatment for 4 weeks with each of the other regimens. Maximum daily dosages of the active drugs were 20 mg debrisoquin and 25 mg mefruside. Satisfactory hypotensive control, i.e. diastolic blood pressure less than or equal to 90 mmHg, was not achieved in any of the treatment periods. The best hypotensive response was obtained in African patients on mefruside. The combination of debrisoquin and mefruside did not produce the expected synergistic response. Few side-effects were reported. The failure of an adequate hypotensive response to debrisoquin in African and Indian patients could be due to a genetic difference in the hydroxylation of debrisoquin.

Adult↗
PubMed1977

[Correlations between blood pressure, blood volume and plasma renin during therapy with diuretics in essential hypertension. Comparison between the mineralocorticoid antagonist spironolactone and the "loop" diuretic mefruside].

35 patients with benign essential hypertension were treated for 6 weeks with high doses of the mineralocorticoid-antagonist spironolactone (400 mg/day), or with the "loop-diuretic" mefruside (mean maximal dose 110 mg/day). Spironolactone caused greater reductions in blood pressure and blood volume and a more marked increase in plasma renin activity (PRA) than mefruside (p less than 0.05). It appears possible that he weaker antihypertensive effect of mefruside may relate partly to its lesser influence on circulatory volume. With both diuretics, mean decreases in blood pressure were greater in patients with low pre-therapeutic PRA than in patients with normal or high PRA. However, the diuretic-induced changes in blood pressure did not correlate with the associated variations in blood volume or PRA. Thus, the increased blood pressure sensitivity to diuretics in patients with low-renin essential hypertension did not appear to be volume or renin-dependent. Under normal conditions, the maintenance of a constant blood pressure during volume depletion may partly depend on compensatory activation of the sympathetic nervous system. Moreover, patients with low-renin essential hypertension have been found to have decreased adrenergic activity. It seems possible, therefore, that the marked blood pressure sensitivity to diuretic treatment in such patients may be the result of an impaired compensatory sympathetic response to sodium and volume depletion. Analysis of the literature suggests that the diuretic furosemide, a structural relative of mefruside, may also have less blood pressure lowering efficacy in patients with essential hypertension than the distally-acting thiazides, chlorthalidone or spironolactone. Consideration of possible differences in the blood pressure reducing potential of certain diuretics thus appears to be necessary in planning the pharmacotherapy of essential hypertension.

Blood Pressure↗
PubMedDate not supplied

Simultaneous determination of the binary mixture of nifedipine and mefruside using derivate spectroscopy, capillary gas-liquid chromatography and high performance liquid chromatography.

Accurate, precise first-derivative ultraviolet spectrophotometric, gas-liquid and high performance liquid chromatographic methods for the determination of nifedipine and mefruside in tablet dosage form were described. The first-derivative method depends on measurements of the derivative amplitudes by peak-to-base and zero-crossing techniques, at 390 and 282 nm, for the determination of nifedipine and mefruside, respectively. Calibration graphs were linear (r = 0.9999) ranging from 8-40 and 20-60 micrograms ml-1 for nifedipine and mefruside, respectively, in presence of one another. The gas-liquid chromatographic method (GLC) was based on using cross-linked methylsilicone gum capillary column with flame ionization detector for the determination of nifedipine and mefruside in the binary mixture. The high performance liquid chromatographic (HPLC) method was based on using a reverse-phase column with a mobile phase of methanol-water (55-45, pH = 4.5) with UV detection at 260 nm. The three methods showed good linearity, precision and reproducibility. The proposed methods were successfully applied to the determination of both drugs in pharmaceutical tablets.

Chromatography, Gas↗
PubMed1984

Comparison of nifedipine (retard formulation) and mefruside in the treatment of mild to moderate hypertension--a prospective randomized double-blind crossover study in general practice.

Twenty-two patients under general practice care, suffering mild to moderate hypertension and receiving no active treatment had three baseline blood pressure measurements taken during a single blind 4-week placebo run-in period. One patient was secondarily excluded at this stage because of a placebo response and one patient dropped out for personal reasons. The remaining 20 patients were randomized to receive either nifedipine 20 mg twice a day or mefruside 25 mg once a day in a classical two-period crossover design with 8-week treatment periods separated by a 4-week single-blind placebo washout. During 8 weeks nifedipine therapy the mean supine blood pressure was reduced from 173 (s.d. = 15.4)/107(s.d. = 6.4) mmHg to 150(s.d. = 16.7)/93(s.d. = 10.8) mmHg whereas the corresponding reduction for mefruside was from 174(s.d. = 15.9)/107(s.d. = 9.4) mmHg to 153(s.d. = 19.1)/94(s.d. = 9.7) mmHg. Neither drug affected postural changes in blood pressure. Standing blood pressure measurements under 8 weeks nifedipine therapy fell from 172(s.d. = 12.3)/103(s.d. = 5.6) mmHg to 150(s.d. = 17.9)/94(s.d. = 10.0) mmHg with corresponding changes for mefruside being 174(s.d. = 14.7)/106(s.d. = 9.0) mmHg to 150(s.d. = 20.2)/95(s.d. = 9.4) mmHg. Since blood pressures returned to within 4% of baseline values by the end of the placebo washout period it can be inferred that each therapy was a significant (P less than 0.05 for all blood pressure variables) antihypertensive treatment in its own right.

Clinical Trials as Topic↗
PubMed1987

Effect of nifedipine and mefruside on renal function and platelet function in hypertensive patients.

A study was carried out in 16 patients with moderately severe hypertension to investigate the effects of nifedipine, given alone or combined with a diuretic, on blood pressure and on renal and platelet function. After 4 weeks on placebo, patients were randomized to receive treatment for 6 weeks with either 20 mg, nifedipine twice daily or 25 mg mefruside once daily on a double-blind, double-dummy basis. All patients then received treatment for a further 6 weeks with a combination of the two drugs in the same dosage as before. The results of blood pressure measurements and laboratory investigations during the three phases of the study showed that significantly better blood pressure control was achieved with nifedipine alone than with mefruside alone. Mefruside had an additional hypotensive effect when added to nifedipine. There was no significant change in the renal blood flow or glomerular filtration rate, with a satisfactory control of blood pressure. There was also no detectable change in platelet aggregation with increasing concentrations of ADP and ristocetin. An adaptive mechanism could be responsible for the apparent lack of change compared with single dose studies.

Blood Pressure↗
PubMedDate not supplied

Effect of equivalent antihypertensive doses of mefruside and cyclopenthiazide on serum electrolytes, uric acid and glucose tolerance in hypertensive patients.

1. A comparative cross-over trial of mefruside and cyclopenthiazide, each drug being given for 6 weeks, was conducted on thirty hypertensive patients with diabetes mellitus or impaired glucose tolerance. Other antihypertensive therapy, any antidiabetic therapy and potassium supplementation were kept constant throughout the trial. Dosages of mefruside and cyclopenthiazide were adjusted to give approximately equal blood pressure levels in the two drug periods. 2. There was no significant difference in the following parameters studied during the sixth week of each of the two periods of drug therapy: serum electrolytes, total CO2, chloride, urea, amylase, haemoglobin, erythrocyte sedimentation rate, platelet and white blood cell counts, lying and standing blood pressure and pulse rate, weight, fasting and 2-h glucose and insulin levels and five-value glucose and insulin curve areas, fasting calcium and phosphate. 3. Serum creatinine and uric acid showed a small but significant fall during mefruside therapy.

Aged↗
PubMed1979

Blood pressure reduction and vascular adaptation. A study on long-term effects of treatment with mefruside or atenolol.

Systemic BP reduction, calf blood flow and vascular resistance in the calf were determined in forty-two previously untreated patients with mild to moderate essential hypertension (WHO I-WHO II) before and after 6 weeks, 6 months and 18 months of BP-lowering treatment with mefruside (25 mg daily) or atenolol (100--400 mg daily). Blood flow was determined with venous occlusion plethysmography using a mercury-in-rubber strain gauge technique in the supine patient. Auscultatory BP was measured on the right arm simultaneously with the flow determinations and resistance was calculated from the flow and pressure. BP was reduced significantly and to the same extent by the two drugs. In the atenolol group a rise in resting resistance and a corresponding fall in resting blood flow was seen initially. These changes were entirely normalized during continued treatment for 18 months. In the mefruside group no significant haemodynamic changes during treatment were observed at rest apart from the BP fall. None of the drugs reduced resistance at "maximal" vasodilatation, indicating that no regress of the hypertensive structural changes of the calf blood vessels had taken place.

Adult↗
PubMed1971

Clinical trial of mefruside, a new diuretic.

A controlled clinical trial of a new diuretic-mefruside-is reported, in which it was compared with frusemide in 15 normal subjects and 15 patients with fluid retention. It was found to be an effective diuretic which, in the patients, produced a significantly greater excretion of water and electrolytes than an equal dose of frusemide. Its smooth prolonged action, maximal in the first 12 hours, made it of particular value for maintenance therapy. In a short-term trial on a further 15 hypertensive patients mefruside was shown to have a useful hypotensive action. The drug was well tolerated with minimal side effects.

Adult↗
PubMed1977

[Hyperreninism without hyperaldosteronism in diuretic abuse: a report of a case with identification of mefruside and ethacrynic acid in urine (author's transl)].

A 46-year-old nurse had been hospitalized 16 times during the preceding five years because of episodes of excessive hypokalaemia. On admission to hospital there was hypokalaemia, polyuria, excessive plasma renin activity but no increased aldosterone secretion rate. Diuretic abuse was confirmed by gas-chromatography and mass spectrometry of mefruside and ethacrynic acid in the patient's urine. Apart from other interesting aspects of this case there was the demonstration of hyperreninism without hyperaldo-steronism. The stimulating effect of renin on aldosterone secretion was obviously lower than the inhibiting effect of hypokalaemia. The general term "renin-angiotensin-aldosterone system" is, therefore, misleading because it mentions only one pathway of aldosterone regulation. The combination of hypokalaemia, polyuria, hyperreninism without hyperaldosteronism is apparently the principal but not widely recognised feature of diuretic abuse.

Aldosterone↗
PubMed1977

Haemodynamic effects of four months' mefruside therapy in hypertensive patients.

The haemodynamic changes after 4 months' mefruside therapy in 13 patients with essential hypertension have been studied. Intraarterial BP was significantly reduced both at rest supine and during standardized leg exercise in sitting position. The reduction was caused mainly by a decrease in cardiac output in about half of the patients and mainly by a decrease in total peripheral vascular resistance in the remainder. Thus, for the total material there was no significant change in either cardiac output or total peripheral vascular resistance. At rest, however, there was a significant decrease in storke volume (p less than 0.05) and an increase in heart rate (p less than 0.05). On changing from supine to sitting position, the average systolic and diastolic pressures increased before and decreased after therapy, the differences being significant. The results indicate that the hypotensive effect of long-term saluretic therapy is accomplished by a decrease in cardiac output and/or peripheral vascular resistance, with large interindividual variations.

Adult↗
PubMed1988

Effect of nifedipine and mefruside on renal reserve in hypertensive patients.

Changes in glomerular filtration rate and effective renal plasma flow following a protein meal were measured in seven patients with essential hypertension on no treatment and after 6 weeks' treatment with nifedipine and mefruside. Glomerular filtration rate and effective renal plasma flow increased significantly following a protein meal in patients on no treatment (P less than 0.01 and P less than 0.05 respectively). The response to a protein meal was lost following antihypertensive treatment (P less than 0.5 and P less than 0.1 respectively). Although there was some increase in the fasting values of glomerular filtration rate and effective renal plasma flow this was less pronounced and more difficult to demonstrate when only fasting values were compared. We propose that the loss of response to a protein meal is due to recruitment of renal reserve function and that protein meal challenge is a sensitive test for detecting changes in renal function.

Adult↗
PubMed1987

A double-blind, placebo-controlled, crossover trial to investigate the additive hypotensive effect of a diuretic (mefruside) to that produced by nifedipine.

Several reports suggest that when diuretics are added to nifedipine (N), they do not exert any additional hypotensive effect to that produced by N alone. We present the first double-blind, crossover trial to investigate this interaction. Twenty-four black patients with moderate to severe essential hypertension entered the trial. After an initial "open" 4 weeks of therapy with N slow release (SR) 20 mg. b.i.d., those 17 patients whose blood pressures (BP) were not controlled (greater than 160 mm Hg systolic and/or greater than 90 mm Hg diastolic) were randomly allocated (double-blind) to 4 weeks treatment with N SR 20 mg. b.i.d., plus either mefruside 1 q.d. (a thiazide-like diuretic) or matching placebo. Patients then crossed over for a second 4 week treatment period. Blood pressures were measured at 2 weekly intervals under the same conditions using Hawksley random zero sphgymomanometers by one of two standardized observers after patients had been lying for 5 min and standing for 2 min. Analysis (taking account of period effect) of the mean results for the 16 patients completing the trial confirms that, contrary to what previous uncontrolled data suggest, lying and standing systolic and diastolic BPs are significantly lower (8.5/4.5 mm Hg: 2p less than 0.01 and 7.9/5.0 mm Hg: 2p less than 0.05, respectively) with nifedipine plus diuretic than with nifedipine plus placebo.

Adult↗
PubMed1979

[Gas liquid chromatographic analysis for quantitative determination of mefruside and oxomefruside in blood plasma (author's transl)].

A specific and sensitive GLC-analytical method was developed for the determination of mefruside, its lactone and hydroxy acid metabolites in blood plasma. It requires the derivatization of the isolated compounds with dimethyl-formamide dimethylacetal and the quantization of the derivatives using a phosphorus nitrogen detector. The method has a sensitivity limit of 2 ng mefruside/ml, 10 ng lactone/ml and 10 ng hydroxy acid/ml, respectively, using 1 ml of blood plasma per assay. It was applied to the determination of plasma levels in a dog following a single oral dose of 10 mg mefruside/kg.

Animals↗
PubMed1984

Effects of acebutolol combined with mefruside on total-body and serum potassium in essential hypertensive patients.

Fifteen essentially hypertensive patients were treated with a fixed combination of the beta-adrenoceptor antagonist acebutolol and the diuretic substance mefruside for 6 weeks. The systolic and diastolic blood pressure as well as the heart rate were significantly reduced. Before and after the treatment period, total-body and serum potassium were examined. Both parameters were not significantly changed. Diuretic therapy causes hypokalemia by increased potassium excretion in the distal tubulus, whereas beta-adrenoceptor antagonists could compensate this effect by a mechanism which is not yet clarified.

Acebutolol↗
PubMed1980

Effects of mefruside treatment in hypertension.

Fifty-two middle-aged patients with essential hypertension were treated for five months with 25 mg mefruside as the only antihypertensive drug. Blood pressure, heart rate, fasting blood glucose, cholesterol, triglycerides, uric acid, electrolytes and weight were controlled regularly before and during treatment. Blood pressure normalized in 43 cases (82.7%). The decrease was more marked in the females and their maximal response appeared later. No significant changes were seen in cholesterol and triglycerides. Serum uric acid levels increased significantly in both sexes (p < 0.001) but no patient developed gout. A significant decrease (p < 0.001) in serum potassium was seen; only one male, with heredity for diabetes mellitus, showed a decreased glucose tolerance.

Aged↗