Ketanserin and prazosin: a comparison of antihypertensive and biochemical effects.

A randomized crossover trial was conducted in 15 patients with essential hypertension to compare the actions of prazosin, a specific alpha 1-adrenoceptor blocker, and ketanserin, an antagonist at alpha 1-adrenergic and serotonin receptors. After placebo dosing for 2 weeks, active drug was given double-blind in two 4-week phases. Satisfactory control of supine blood pressure was obtained in nine of the 12 subjects who completed the prazosin phase and 11 of the 15 subjects who completed the ketanserin phase. Whether comparison was based on supine, erect, postexercise, or ambulatory values, the blood pressure responses to prazosin (2 or 4 mg/day) and ketanserin (40 or 80 mg/day) were closely similar. Neither of the drugs significantly altered supine or erect pulse rates, body weight, serum triglyceride concentrations, plasma renin activity, or urinary aldosterone excretion, and their side effect profiles were similar. The serum cholesterol concentration was lowered by prazosin but was not affected by ketanserin. However, no other features were observed that distinguished the clinical effects of ketanserin from those of prazosin.

Use of an intravenous sodium load in screening for primary hyperaldosteronism.

A sodium loading test was performed in 35 patients presenting with hypertension and hypokalemia. In 14 of these patients, intravenous administration of 0.9% saline (2 l in 4 h) on two consecutive days caused urinary aldosterone excretion to fall to values within the range for normal volunteers. The other 21 patients, in whom urinary aldosterone excretion did not decline following two days of saline loading, or in whom pronounced hypokalemia after the first day of loading precluded further saline infusion, were designated as having primary aldosteronism. Seventeen of this group underwent surgery and discrete adrenal adenomas were found in 16. When serum potassium concentration, plasma renin activity or the relationships of serum potassium to concurrent urinary potassium excretion or of urinary aldosterone excretion to plasma renin activity were used as alternative diagnostic criteria for primary aldosteronism, overlapping of the two groups occurred. It is concluded that measurement of urinary aldosterone excretion after intravenous sodium loading is a useful test in the test in the identification of primary aldosteronism due to aldosterone-producing adenoma. In this series the saline loading test was more specific in diagnosis than criteria based on serum and urinary potassium, plasma renin activity or unsuppressed aldosterone excretion.

On the combination of alpha- and beta-adrenoceptor blockade in hypertension.

A randomized double-blind crossover trial was conducted in 20 patients with moderate to severe hypertension to compare the efficacy of labetalol, which combines alpha- and beta-adrenoceptor blocking properties, with that of metoprolol alone or in combination with prazosin. After placebo for 1 wk, active medication was given in two 6-wk phases. During one phase, metoprolol (100 to 400 mg/day) was given with prazosin (2 to 4 mg/day) as an option in the last 3 wk, whereas during the other phase, labetalol (200 to 1000 mg/day) was given alone. Satisfactory control of supine blood pressure was obtained in 10 patients with metoprolol and in another four patients after the addition of prazosin. During the labetalol phase, blood pressure control was achieved in 11 of 19 patients tested. Gastrointestinal disturbances, nasal congestion, impotence, failure to ejaculate, scalp tingling, and headache were more prevalent in the labetalol phase than in the other. In four cases these occurred in patients who did not require prazosin. Supine, erect, and exercise pulse rates were reduced by both metoprolol with or without prazosin and by labetalol; the effects were less in the labetalol phase. These differences could arise from an action of labetalol on cardiac presynaptic alpha-adrenoceptors. Adjunctive use of prazosin in nonresponders to metoprolol increases the response rate and avoids unnecessary deployment of alpha-adrenoceptor blockade in patients whose blood pressure can be controlled by beta-blockade alone.

Prediction of response to antihypertensive therapy with prazosin.

Blood-pressure responses and changes in plasma drug concentration were studied in 11 hypertensive patients after an initial oral dose of 2 mg of prazosin. Subsequently, blood pressure was monitored during long-term treatment with prazosin. The prazosin reactivity index, a value derived during the first-dose study, appeared to predict the long-term antihypertensive effect of prazosin alone or prazosin combined with bendrofluazide.