Alpha-adrenoceptor blockade by labetalol during long-term dosing.

The hypotensive effect of short-term labetalol, the alpha- and beta-adrenoceptor blocker, is greater in subjects in the orthostatic position, possibly because of the alpha-adrenoceptor blockade. During prolonged use the orthostatic blood pressure fall disappears. To verify whether or not this is due to reduction in alpha-blocking activity, phenylephrine-induced increase in blood pressure was studied in six subjects with mild essential hypertension before and after 3 and 6 days and 1 and 6 mo of continuous treatment with 200 mg labetalol three times a day by mouth. At the same intervals, isoproterenol-induced tachycardia was followed to assess beta-blockade. After 3 days on labetalol, the log dose-response curve of phenylephrine-induced increase in blood pressure shifted to the right and the dose of agonist required to elicit a 20% increase in systolic pressure was 1.7 times that before treatment. There was a progressive decline in the dose of agonist that induced the same increase in pressure so that after 6 mo of continuous labetalol it was the same as control. In contrast, the amount of isoproterenol needed to induce a 20% increase in heart rate was two to three times that before labetalol and did not change throughout 6 mo of therapy. These data indicate a decline in the alpha-adrenoceptor-blocking effect of oral labetalol without concomitant change in the degree of beta-adrenoceptor blockade. This might account for the disappearance of orthostatic hypotension early in the course of treatment and for some decrease in the antihypertensive efficacy of labetalol.

Comparison of sotalol and propranolol in mild to moderate essential hypertension.

The controlled, open, cross-over study reported in this article demonstrates that sotalol and propranolol administered twice daily to 20 patients provide an equally satisfactory control of moderately elevated blood-pressure for 24 hours. The average daily dose of sotalol and propranolol required to achieve this effect was 200 +/- 95 mg and 154 +/- 90 mg respectively. No important side-effects were observed.

[Use of labetalol in the treatment of hypertensive crises]. / Uso del labetalolo nel trattamento delle crisi ipertensive.

Labetalol, a combined alpha and beta adrenoceptor blocking drug, has been shown to be effective in the treatment of hypertensive crises when given intravenously. It also offers the advantage that treatment can be continued with the oral preparation. The purpose of our study was to evaluate if the administration of an intravenous bolus followed by an iv infusion and subsequently by the oral preparation might increase the efficacy of the drug without reducing its tolerance. Thirteen patients with severe essential hypertension and one with pheochromocytoma were treated during one or more hypertensive crises with Labetalol, 100 mg bolus i.v. injection in two minutes, followed by an intravenous infusion (2-4 mg/min for 60-90 minutes) and, one hour after the end of the infusion, by the oral preparation (200 mg t.i.d.). In 11 subjects with essential hypertension and in the patient with pheochromocytoma a 30% fall in systolic and diastolic blood pressure [from 240 +/- 10/155 +/- 6 mmHg (mean +/- 1 s.e.m.), to 162 +/- 8/111 +/- 6, p less than 0.01] was achieved within five minutes from the beginning of the treatment. Blood pressure remained well controlled thereafter, throughout the infusion period and during the first 24 hours of the oral administration. Heart rate fell simultaneously with the fall in blood pressure. Only in one patient blood pressure was not adequately controlled despite of the bolus and of an infusion at the rate of 4 mg/min for 20 minutes. In another case the fall in pressure caused near-fainting and the infusion was therefore not started. No other side effects were encountered except for transient orthostatic hypotension. We conclude that the administration of a bolus plus infusion of Labetalol is more effective than single or repeated boluses or graded infusions and it is equally well tolerated.

Intravenous labetalol in severe hypertension.

1 Labetalol was administered by intravenous infusion or by the combination of intravenous bolus injection plus infusion to 15 patients with severe essential hypertension and to one with phaeochromocytoma. 2 With the infusion alone the reduction of arterial pressure was slow to develop and limited in degree, but with the combination of the bolus injection plus the infusion the reduction in pressure was more prompt, more pronounced and longer lasting. Apart from an uncomplicated syncopal attack in one patient, no serious side--effects were encountered. 3 Subsequent treatment with oral labetalol usually required the addition of a diuretic to control the blood pressure probably due to sodium and fluid retention during treatment with labetalol alone.