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.

Marked hypokalemic rhabdomyolysis with myoglobinuria due to diuretic treatment.

A 74-year-old male was admitted to hospital with acute rhabdomyolysis and myoglobinuria due to hypokalemia. The hypokalemia resulted from diuretic treatment. He had no family history of myopathy, and no diarrhea and vomiting. The neurological examination revealed painful quadriplegia. The blood pressure was 160/74 mm Hg. Laboratory examination showed hypokalemic and hypochloremic metabolic alkalosis (serum K 1.5 mEq/l, serum Cl 89 mEq/l, base excess + 20.9, HCO3- 44.9 mmol/l, pH 7.563) and marked elevations of serum CPK, LDH, GOT, GPT and myoglobin. Endocrinological and renal functions were normal. Muscle biopsy revealed marked necrosis with remarkable phagocytosis and vacuolar degeneration. The cessation of diuretics and intravenous infusion of potassium chloride resulted in a marked improvement in clinical and laboratory findings. The diuretics-induced hypokalemic myopathy is rare in the literature.

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.

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.