Familial hypomagnesemia--hypercalciuria and pseudotumor cerebri.

Approximately 30 patients with familial hypomagnesemia-hypercalciuria have been reported. We describe an 8-year-old girl with cardinal findings of familial hypomagnesemia-hypercalciuria (hypomagnesemia, hypermagnesiuria, hypercalciuria, renal insufficiency, hyperuricemia, elevated serum parathormone, hyposthenuria and nephrocalcinosis), who received combination therapy consisting of magnesium salts, thiazide diuretic and potassium supplementation. At the 4-year follow-up investigation under this treatment, the patient was found to have cerebral pseudotumor (increased intracranial pressure with normal or small ventricles on neuroimaging, no evidence of an intracranial mass and normal cerebrospinal fluid composition) with papilledema and visual field defects. Thiazide therapy was terminated and the cerebral pseudotumor disappeared. The authors hypothesize that cerebral pseudotumor in this patient was related to severe hypocalcemia, as a consequence of profound hypomagnesemia induced by protracted thiazide treatment. To our knowledge, this is the first report of a child with familial hypomagnesemia-hypercalciuria who developed pseudotumor cerebri after thiazide therapy.

Long-term diuretic therapy in patients with chronic renal failure.

Ten patients with chronic renal failure from different genesis (serum creatinine levels 150-200 mumol/l), were evaluated from the aspect of the effect of the diuretic therapy. The effects of furosemide (FUR) and polythiazide (POL) were assessed after 3-month application. The mean values of the estimated parameters before treatment, after 3-month administration of FUR as a monotherapy and after the next 3 months simultaneously used (FUR + POL), presented a stable increase of the diuresis, without statistically significant changes of the global renal function, and triglyceride disorders. On the contrary, the improvement of calciuria through combined using of furosemide and polythiazide is statistically and clinically significant.

Thiazide induced hypotension: the role of plasma volume reduction and the urinary kallikrein system.

The hypotensive response the thiazide diuretics was studied in 15 males with moderate essential hypertension and correlated with serial changes in plasma volume, weight, plasma renin activity, urinary aldosterone, and urinary kallikrein, both total and activity. A greater than 10 mmHg fall in mean arterial pressure after four weeks of treatment defined the responders to therapy (n = 10) while all others were considered non-responders (n = 5). In responders, the fall in mean arterial pressure was accompanied by sustained reduction in plasma volume and weight. No sustained fall in plasma volume was noted in non-responders. Plasma renin activity and urinary aldosterone excretion increased in responders but not in non-responders. Urinary kallikrein, both total and active, increased in the responders but remained unchanged in the non-responders. The results are consistent with the hypothesis that a sustained reduction in plasma volume is necessary for the maintenance of a hypotensive response to thiazides. Stimulation of the renal kallikrein-kinin system may be necessary to balance the antinatriuretic and pressor effects of the renin-angiotensin-aldosterone system. If unopposed, this system would return plasma volume and blood pressure to pretreatment levels.

Effects of prazosin and propranolol on serum lipids in patients with essential hypertension.

The effects of prazosin and propranolol on total serum cholesterol concentration, low-density lipoprotein and high-density lipoprotein cholesterol fractions, and serum triglyceride concentration were compared in a crossover study in 29 patients with mild to moderate essential hypertension. All patients received polythiazide at a constant dose throughout control and drug treatment periods. Comparable blood pressure reduction was achieved with prazosin (9.3 +/- 7.1 mg per day) and propranolol (183.6 +/- 154.5 mg per day). Prazosin administration was associated with a significant reduction in the concentrations of total serum cholesterol (-5.5 percent), triglyceride (-20.0 percent), and low-density lipoprotein cholesterol (-10.1 percent). High-density lipoprotein cholesterol concentration increased (+8.0 percent) as did the ratio high-density lipoprotein: total cholesterol (+14.1 percent). No significant changes in any of the serum lipid fractions were observed during propranolol administration.

Comparative effects of propranolol and prazosin upon serum lipids in thiazide- treated hypertensive patients.

Earlier reported thiazide-induced changes in serum lipid concentrations were confirmed with increased triglyceride and total cholesterol levels. However, lipoprotein cholesterol ratios were unchanged. Propranolol caused further increases in triglyceride and very low-density lipoprotein cholesterol, and lowered high-density lipoprotein cholesterol and the high-density lipoprotein:total cholesterol ratio. With the addition of prazosin to the polythiazide regimen, there was a significant increase in serum high-density lipoprotein cholesterol when compared with the placebo.

Prazosin as initial antihypertensive therapy: correlates of sympathetic function.

Abnormal sympathetic function has been proposed as a factor in the development of essential hypertension. If this is the case, prazosin hydrochloride, which works by a selective, peripheral, antisympathetic effect--postsynaptic alpha blockade--may have an advantage over other antihypertensive agents. In this study, blood pressure response and measures of sympathetic and baroreflex function were followed in 13 hypertensive patients. Prazosin alone significantly reduced standing and sitting diastolic blood pressures without affecting pulse rates, plasma catecholamines or baroreflex slopes in all patients. The addition of a thiazide diuretic in persons who did not achieve goal blood pressure on prazosin alone was generally successful in reducing blood pressure to desired levels, and increased both plasma renin activity and aldosterone concentrations. No significant relation was apparent between specific characteristics of sympathetic function and response to prazosin as initial therapy, although patients responding tended to have initially higher plasma norepinephrine concentrations.

Comparison of blood pressure, plasma lipid and cardiac performance responses to prazosin versus propranolol in thiazide-treated hypertensive patients.

Twenty-seven patients with uncontrolled hypertension (diastolic blood pressure greater than or equal to 95 mm Hg) receiving thiazide diuretics were treated with the addition of either propranolol (n = 10) or prazosin (n = 17). Nine patients were successfully controlled with propranolol and 12 with prazosin. Six patients required both study drugs for optimal blood pressure control, 5 of whom had received prazosin as the initial study drug. Changes in serum lipid components and cardiac performances with the addition of the study drugs were monitored. A decrease in total cholesterol and an increase in high-density lipoprotein (HDL) cholesterol were seen when prazosin was added, and an increase in total cholesterol and a decrease in HDL cholesterol occurred after the addition of propranolol. Although in this small group of patients these changes did not reach statistical significance, they were similar to changes described in other studies in which these drugs were used as monotherapy for hypertension. The only lipid change of statistical significance was a small increase in the serum triglyceride concentration in patients receiving propranolol. The findings for total cholesterol and its fractions suggest that the effects of the study drugs may not be additive to those of thiazides and that thiazides had already effected a maximal lipid response. Both agents in combination with a thiazide diuretic were equally effective in decreasing diastolic blood pressure to the goal of less than or equal to 85 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

A double-blind study of trimazosin and methyldopa in hypertensive patients receiving polythiazide.

Data are presented on 22 hypertensive patients in an 18-week, double-blind comparison of trimazosin and methyldopa during which treatment with polythiazide was continued. Maximum daily doses of trimazosin and methyldopa were 800 and 2000 mg, respectively. Eight of nine patients receiving trimazosin and 8 of 12 receiving methyldopa had excellent or good overall responses. (One trimazosin patient was not evaluated for overall response.) Quantitative criteria of blood pressure response indicated that trimazosin was as effective as methyldopa. There were no clinically significant changes in results of Holter monitor recordings, ECGs, chest x-ray films, cardiopulmonary tests, or ophthalmoscopy. There were no abnormalities in laboratory tests of trimazosin patients. One patient receiving methyldopa had a positive Coombs' test. Significant side effects developed in two methyldopa patients-syncope in one patient and postural hypotension in the other. No significant side effects occurred in the patients taking trimazosin.

Double-blind comparison of trimazosin and propranolol in essential hypertension.

This report describes a double-blind, parallel, comparative study of trimazosin (+/- polythiazide) and propranolol (+/- polythiazide) in 130 patients with essential hypertension. Both treatment regimens were shown to be effective in achieving statistically significant sustained reduction in blood pressure. Propranolol alone was somewhat more effective, at the doses selected, than trimazosin alone, but the hypertension of nonresponders in each treatment group was effectively controlled by the addition of low doses of polythiazide. Trimazosin had no effect on heart rate, whereas propranolol significantly lowered resting heart rates, which was occasionally troublesome. Side effects were less frequent in the trimazosin-treated group. Trimazosin lowered serum creatinine and blood urea nitrogen, an effect significantly different from that of propranolol. There was also a tendency for serum uric acid to rise in patients receiving propranolol and fall in those receiving trimazosin; polythiazide significantly raised uric acid levels. The effects of trimazosin and propranolol on the lipid profile were small, but the difference between the increase in the high-density lipoprotein-cholesterol fraction in trimazosin-treated patients and the decrease in propranolol-treated patients was significant and thought to be of interest.

Effect of trimazosin on serum lipid profiles in hypertensive patients.

Abnormalities in the serum lipid profile correlate strongly with the presence and severity of atherosclerosis. Increases in serum lipids and a reduction in high-density lipoprotein (HDL) cholesterol have been demonstrated following treatment with some beta blockers and diuretics, either alone or in combination. A new alpha-1-adrenoceptor antagonist, trimazosin, was studied to determine its effects on serum lipids. Ninety-six hypertensive patients were randomly assigned in double-blind fashion to trimazosin or placebo for 8 weeks. Trimazosin was associated with a significant reduction (p less than or equal to 0.01) in total cholesterol when compared with the placebo group. This effect was seen in all patients regardless of whether or not they were taking a diuretic concomitantly. In addition, a 9-month, double-blind parallel comparison was made of trimazosin and propranolol. Trimazosin was found to be superior to propranolol in its effect on HDL cholesterol and the HDL/total cholesterol ratio. These studies have demonstrated that, in contrast to placebo and propranolol, trimazosin lowers total serum cholesterol without undesirable effects on other serum lipid fractions. When polythiazide is given concomitantly, it diminishes the favorable effects of trimazosin and accentuates the opposite, adverse effects of propranolol.

Cardiac muscle mass during vasodilation therapy of hypertension.

M-mode echocardiography has become a valuable tool in the evaluation of changes in left ventricular muscle mass during antihypertensive therapy. We evaluated the effects of treatment with the vasodilator trimazosin, alone and in combination with the diuretic polythiazide, on cardiac muscle mass in hypertensive subjects. Trimazosin alone was given to 11 subjects for 18 mo, and average supine blood pressure fell from 154/100 to 146/89 mm Hg. Heart rate and body weight did not change during therapy. Initially, a slight decrease (approximately 6%) was observed in left ventricular muscle mass, but left ventricular transverse dimension and left ventricular muscle mass returned to control levels during the last 6 mo of the 18-mo study. The combination of trimazosin and polythiazide was given to nine subjects and decreased blood pressure from 152/102 to 138/92 mm Hg. Heart rate increased and body weight decreased slightly. No changes in left ventricular muscle mass were observed during combination therapy. It is possible that increases in activity of the sympathetic nervous system during therapy with trimazosin alone, and the observed increase in renin activity during treatment with trimazosin and polythiazide, might have offset the effects of the reduction in blood pressure on left ventricular muscle mass.

Prazosin and clonidine for moderately severe hypertension.

In a single-blind comparative study of the cases of 30 moderately hypertensive patients, clonidine hydrochloride and prazosin hydrochloride had similar effectiveness in lowering blood pressure. Neither agent had significant effects on the renin-aldosterone axis. Addition of polythiazide to prazosin and chlorthalidone to clonidine notably increased the antihypertensive effect of both drugs. Serum cholesterol levels were observed to decrease when prazosin and clonidine were given and to rise when the diuretics were added to the regimen. The patients treated with clonidine were troubled by side effects, particularly drowsiness and dry mouth. Prazosin was better tolerated, with side effects tending to diminish with time. The "first-dose" effect was seen in two patients given prazosin, but it did not limit treatment. Both diuretics induced notable hypokalemia.

A study of the use of prazosin in hypertensive patients in Korea.

1. The effects of prazosin administered alone or in combination were studied in thirty patients between August 1974 and March 1975. 2. All patients had previously received treatment for hypertension with other agents, for from 2 months to 10 years. All thirty patients had refractory hypertension which had not responded satisfactorily to other treatment. 3. Patients were treated initially with prazosin; polythiazide, or polythiazide plus tolamolol, were added when necessary. 4. A satisfactory blood pressure response to prazosin alone, or prazosin in dual or triple combination therapy, occurred in all thirty patients. 5. Prazosin was well tolerated.