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At least 19 recordsLinked to original sources
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

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↗
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↗
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↗
PubMed1977

Haemodynamic effects of saluretic treatment and beta-receptor blockade in patients with essential hypertension.

The long-term haemodynamic effects of treatment with mefruside alone or in combination with alprenolol have been studied in nine patients with essential hypertension. After four months of mefruside therapy alone there was a significant decrease in intraarterial BP both at rest and during standardized leg exercise. Cardiac output and calculated total peripheral vascular resistance (TPVR) showed only minor mean decreases which were not statistically significant. Stroke volume tended to decrease and heart rate to increase. After another four months' treatment with addition of alprenolol there was a further significant decrease in intraarterial BP, related mainly to a further mean decrease in cardiac output which was not statistically significant. Heart rate decreased significantly, stroke volume was not significantly changed. Compared with the pretreatment levels, combination therapy induced a substantial decrease in intraarterial BP and a significant decrease in cardiac output both at rest in supine position and during standardized leg exercise. TPVR decreased slightly both at rest and during exercise but the change was not statistically significant. The results suggest that the decrease in BP after combined therapy with mefruside and alprenolol is mainly related to a decrease in cardiac output, the changes in TPVR being not significant. The additive hypotensive effect of alprenolol seems to be related in part to blocking of the increase in sympathetic activity that was found after treatment with mefruside alone.

Adult↗
PubMed1975

[Dose-effect comparison of antihypertensive combinations with and without alpha-methyldopa].

In an open clinical trial, 30 compensated cardiac patients with essential hypertension were selected and randomly distributed. Treatment was given by means of two combinations of active agents, one containing 0.15 mg reserpine, 15 mg mefruside and 150 mg inositol nicotinate and the other 0.10 mg reserpine, 10 mg mefruside and 125 mg alpha-methyldopa. A randomized control group of 30 patients with essential hypertension received 0.15 mg reserpine, 15 mg mefruside and 150 mg isositol nicotinate exclusively over the same treatment period. By substituting only 125 mg alpha-methyldopa for 150 mg inositol nicotinate, the reserpine-mefruside portion can be reduced by one third while still obtaining the same antihypertensive effect.

Aged↗
PubMed1990

Influence of co-dergocrine mesilate/nifedipine compared to mefruside/nifedipine on circadian blood pressure in patients with essential hypertension.

This randomised, parallel group study was designed to compare the efficacy of nifedipine (40 mg once daily) combined with either the dopamine agonist, co-dergocrine mesilate (4 mg once daily) or the diuretic mefruside (25 mg once daily) in 40 patients with essential arterial hypertension and a diastolic blood pressure greater than 105 mmHg. Circadian blood pressure and heart rate were measured over 24 h every 15 min from 6 a.m. to 6 p.m. and every 30 min from 6 p.m. to 6 a.m. with an automatic, portable instrument (ICR 5300, Squibb) before and after a three-week treatment period. At the end of the three-week treatment period the mean value of all 24 h blood pressure measurements reflected highly significant decreases (2P less than 0.001), from 148/92 +/- 16/12 before treatment to 131/83 +/- 12/12 mmHg after treatment in the co-dergocrine mesilate/nifedipine group and from 145/92 +/- 16/10 before treatment to 129/84 +/- 10/6 mmHg after treatment in the mefruside/nifedipine group. Blood pressure reduction was still significant in both groups during the early morning hours at the end of the dosage interval. The efficacies of nifedipine combined with co-dergocrine mesilate or mefruside were comparable but side-effects were rated as more severe in the mefruside group. Therefore, the combination co-dergocrine mesilate/nifedipine may be preferable to the combination mefruside/nifedipine.

Adult↗
PubMed1977

Effect of saluretic therapy on muscle content of water and electrolytes in relation to hemodynamic variables.

Muscle content of water and electrolytes (needle biopsy), intraarterial BP and cardiac output (dye dilution technique) were measured in 12 patients with essential hypertension before and after 4 months of mefruside therapy (25 mg/day). Before therapy there were no significant differences in muscle tissue electrolyte and water content compared with normotensive subjects. No correlation was found between central hemodynamic variables and the electrolyte and water content of muscle tissue either before or after therapy. After 4 months of mefruside therapy, muscle tissue water showed a mean decrease which was not significant. Serum potassium and muscle potassium content decreased significantly but there was no significant change in intracellular potassium concentration. Intracellular sodium concentration increased significantly, while muscle sodium content showed a mean increase which was not statistically significant. The change in intracellular sodium concentration showed a significant negative correlation with the decrease in mean arterial BP. The change in total cellular water content showed a significant negative correlation to the changes in total peripheral vascular resistance. Saluretic therapy seems to induce counterregulatory mechanisms that interfere with the hypotensive effect.

Adult↗
PubMed1977

Carotid baroreceptor function in hypertensive patients.

Carotid baroreceptor function has been studied in twenty-five patients with essential hypertension and in ten normotensive control subjects of corresponding age. The carotid baroreceptors were stimulated by increasing the transmural pressure over the carotid arteries by the application of negative pressure in a box enclosing the neck. Stimulation elicited significant decreases in intra-arterial blood pressure, heart rate and cardiac index in both hypertensive and normotensive subjects. Both groups also showed a significant decrease in stroke index and a significant increase in total peripheral vascular resistance index. The response to carotid sinus stimulation did not differ significantly between the two groups. In fourteen of the hypertensive subjects, carotid baroreceptor function was studied after 4 months of saluretic therapy, mefruside, and in nine of these patients after additional treatment with a beta-receptor blocking drug, alprenolol, for another 4 months. Both mefruside and alprenolol induced a significant decrease in mean arterial blood pressure but the response to the carotid baroreceptor stimulation was not significantly altered. The findings indicate that the carotid baroreceptor is re-set to the actual blood pressure level, with little or no change in gain in hypertensive subjects both without and during hypotensive therapy.

Adult↗
PubMed1977

Sex hormone binding globulin binding capacity, testosterone, 5alpha-dihydrotestosterone, oestradiol and prolactin in plasma of patients with prostatic carcinoma under various types of hormonal treatment.

Sex hormone binding globulin (SHBG) binding capacity, the concentrations of testosterone (T), of 5alpha-dihydrotestosterone (DHT), of oestradiol-17beta (Oe2), of oestrone (Oe1), of prolactin (hPr) and the percentual specific binding of T to SHBG (%TB) were measured in plasma of patients suffering from prostatic carcinoma and of a control group of similar age. No significant differences in any of the investigated parameters were found between the control group and the carcinoma patients before treatment although 15% of the latter showed distinctly elevated hPr values. Treatment of carcinoma patients with 1) Antiandrogen (cyproterone acetate, Androcur) resulted in a significant decrease of T, Oe2 and SHBG. The DHT/T-ratio increased. n=5. 2) Orchidectomy caused an even more pronounced fall in T, DHT, Oe1 and Oe2 blood levels. SHBG was not altered. DHT/T-ratio increased. n=32. 3) Cyproterone acetate after orchidectomy led to elevated hPr values. n=5. 4) Oestrogen (diethylstiboestrol-diphosphate, Honvan) after orchidectomy increased SHBG and hPr. n=6. 5) Corticosteroid (Prednisone, Decortin) after orchidectomy decreased T and SHBG below the levels found after orchidectomy alone. n=5. 6) Diureticum (Mefruside, Baycaron) (n=5) or 7) a placebo (n=7) did not alter any of the parameters measured. 8) Treatment with HCG (Primogonyl) of patients suffering from oligozoospermia resulted in a significant increase of T, DHT and Oe2. SHBG was not altered. DHT/T-ratio decreased. n=7.

Chorionic Gonadotropin↗
PubMed1991

[Therapy of mild to moderate hypertension. Efficacy and tolerance of Amlodipine in comparison with the combination nifedipine/mefruside].

Earlier clinical trials demonstrated the anti-hypertensive effect of amlodipine, a new calcium channel blocker of the dihydropyridine type. In the present comparative study, we investigated the anti-hypertensive effect of amlodipine in comparison with a combination of nifedipine and mefruside. In both groups, the anti-hypertensive effect was comparable. Normalization of the supine diastolic blood pressure was observed in 72.3% of patients treated with amlodipine and in 66.6% of those patients in the combination group. Both drugs were generally well tolerated, with a somewhat higher incidence of side effects being observed in the combination group. The study shows that amlodipine monotherapy in mild-to-moderate hypertension is equally as effective as combination therapy with nifedipine/mefruside, with amlodipine being superior in terms of tolerability.

Adult↗