Step II treatment with labetalol for essential hypertension.

Labetalol, a new alpha- and beta-adrenergic blocking agent, was administered to 57 patients with essential hypertension whose standing diastolic blood pressure was 105 to 120 mm Hg after three and four weeks of placebo therapy and greater than 90 mm Hg after three to four weeks of therapy with hydrochlorothiazide, 25 mg twice a day. Patients were then randomly assigned on a double-blind basis to receive either labetalol, 100 mg twice a day, or placebo combined with hydrochlorothiazide. Thereafter, the dose of labetalol was titrated weekly in both groups to a maximum of 400 mg twice a day to achieve a standing diastolic blood pressure of less than 90 mm Hg that was also decreased from the hydrochlorothiazide baseline by 10 mm Hg or more (therapeutic goal). Labetalol was abruptly discontinued after four weeks of treatment and patients were given hydrochlorothiazide alone for two additional weeks. After one week of labetalol therapy, 100 mg twice a day (added to hydrochlorothiazide), there was a significantly greater reduction in supine systolic/diastolic blood pressure (6/5 mm Hg, p less than 0.04/less than 0.03) and standing blood pressure (9/7 mm Hg, p less than 0.01/less than 0.01) than with placebo therapy (3/0.5 and 3/1 mm Hg, respectively). The blood pressure reduction in the labetalol-treated group was associated with a 4 and 5 beats per minute reduction in the supine and standing heart rates, respectively. The median labetalol dose required to achieve the standing diastolic blood pressure goal was 400 mg twice a day. After four weeks of labetalol treatment, the mean reduction in blood pressure from the hydrochlorothiazide baseline was 12/13 mm Hg (p less than 0.01/0.01) in the standing position and 8/8 mm Hg (p less than 0.01/0.01) in the supine position. These blood pressure reductions were accompanied by a mean reduction in heart rate of 7 beats per minute. The most frequently reported complaints other than thiazide-induced nocturia included dizziness, fatigue, nausea, rash, and/or pruritus. Most of these complaints were reported at a similar incidence while patients were receiving placebo or hydrochlorothiazide alone as when receiving labetalol with hydrochlorothiazide. After abrupt withdrawal of labetalol, no evidence of rebound hypertension was observed. Labetalol is a safe and effective step II drug when added to hydrochlorothiazide for the treatment of patients with moderate to moderately severe hypertension.

Effects of low-calcium diet on urine calcium excretion, parathyroid function and serum 1,25(OH)2D3 levels in patients with idiopathic hypercalciuria and in normal subjects.

We have used a low-calcium diet providing only 2 mg/kg (body weight) per 24 hours of calcium to distinguish between "renal" and "absorptive" idiopathic hypercalciuria. Sixteen of 27 hypercalciuric subjects excreted calcium in excess of intake during days seven, eight and nine of he diet, suggesting some element of renal hypercalciuria; however, all patients had low or normal serum PTH and urine cAMP levels. In general, fasting urine calcium was elevated in these 16 subjects and normal in the remaining 11, who conserved calcium more normally. SErum 1,25(OH)2D3 levels were the same in patients and normal subjects, even though PTH levels of the patients were below those of he normal subjects. Urine magnesium excretion and phosphorus excretion were both increased in the patients who excreted calcium in excess of intake. Our findings suggest that renal and absorptive hypercalciuria may not be distinct entities but rather the two extremes of a continuum of behavior. A uniform elevation of intestinal calcium absorption and a variable defect of renal calcium reabsorption could explain our results far better than the hypothesis of distinct absorptive and renal forms of hypercalciuria.