Effect of indoramin, labetalol and alinidine on sympathetic function in normal man.

The effects of single oral doses of indoramin (mean dose 58 mg), abetalol (mean dose 150 mg), alinidine 80 mg and placebo on arterial pressure and heart rate in the supine and standing positions were studied in six normal volunteers. Doses were chosen to give equivalent reductions of arterial pressure in the standing position. Observations were made before and at 2 and 4 h after drug administration. Plasma noradrenaline (NA) was measured at each time interval in the supine position, and after 4 min of standing. Plasma renin activity (PRA) was measured at each time interval after 30 min in the standing position. In the supine position, alinidine produced a significant reduction of systolic arterial pressure from 124.0 +/- 3.0 mm Hg to 104.3 +/- 4.1 mm Hg at 2 h (P less than 0.01) and to 101.7 +/- 2.2 mm Hg at 4 h (P less than 0.01). Diastolic pressure was reduced from 74.7 +/- 2.6 mm Hg to 57.0 +/- 4.6 mm Hg at 4 h (P less than 0.01). Arterial pressure was unchanged after indoramin or labetalol administration. In the supine position, heart rate was unchanged after indoramin, and small reductions were observed after labetalol and alinidine. Indoramin produced a significant increase in plasma NA. A small increase of plasma NA was observed after labetalol, and a small decrease after alinidine. In the standing position, the three active drugs reduced systolic arterial pressure to a similar extent (indoramin, -26.7 mm Hg at 4 h after drug administration; labetalol, -21.3 mm Hg at 2 h; alinidine, -21.7 mm Hg at 4 h).(ABSTRACT TRUNCATED AT 250 WORDS)     

A double-blind randomized cross-over study of the efficacy and tolerability of nifedipine and nitrendipine in the treatment of mild to moderate hypertension.

1. In order to examine whether nitrendipine was superior to slow release nifedipine as monotherapy in the treatment of mild to moderate essential hypertension, the two agents were administered to 22 patients in a double-blind randomized cross-over study, incorporating low and titrated dose regimes. 2. Six patients failed to complete the study because of vasodilator side-effects such as headache, flushing and ankle swelling. Three were taking nitrendipine and three took nifedipine and all withdrawals occurred at the introduction of the drug. 3. Both agents reduced blood pressure in the 16 patients who completed the study, and neither agent was superior to the other; mean blood pressure after the placebo phase was 177 +/- 5.5/100 +/- 2.6 mm Hg supine and 175 +/- 5.3/113 +/- 2.4 mm Hg standing. At the end of therapy with nifedipine pressures were 160 +/- 4.0/91 +/- 3.0 mm Hg supine and 158 +/- 4.6/103 +/- 2.7 mm Hg standing. After 8 weeks treatment with nitrendipine blood pressures were 162 +/- 4.4/90 +/- 2.9 mm Hg supine and 161 +/- 6.2/104 +/- 2.7 mm Hg standing. Comparisons of these attained blood pressures on both agents showed no statistically significant differences. 4. Nitrendipine did not appear to be effective on a once daily basis.     

Antihypertensive effect of carteolol in thiazide-treated hypertensive subjects

The antihypertensive effect of carteolol, a new potent nonselective beta-adrenergic antagonist, was investigated in a double-blind, parallel study of 35 patients with mild-to-moderate, essential hypertension whose blood pressures were not adequately controlled with a diuretic. Patients were randomly assigned to receive placebo, carteolol 5 mg, or carteolol 20 mg once a day in addition to hydrochlorothiazide 50 mg for six weeks. Thirty-four patients completed the study: 11 patients received placebo (group 1), 12 patients received carteolol 5 mg (group 2), and 11 patients received carteolol 20 mg (group 3). After six weeks of treatment, the two groups that received carteolol had significant reductions in systolic (SBP) and diastolic (DBP) blood pressure from baseline in both the supine and standing positions. In group 2, mean SBP decreases for supine and standing positions were 11 +/- 2.1 and 11 +/- 1.9 mm Hg, respectively (P less than .01) and 8 +/- 1.2 and 9 +/- 1.3 mm Hg, respectively, for DBP (P less than .01); whereas in group 3, values were 8 +/- 2.8 and 12 +/- 3.0 mm Hg for SBP, in 5 +/- 1.9 and 9 +/- 3.1 mm Hg, respectively, for DBP (P less than .01). The hypotensive effect was associated with slight but significant decreases in heart rate (P less than .01 in group 2 and P less than .05 in group 3). Reductions in SBP and DBP with the 20-mg dose were not significantly different from those with the 5-mg dose.2+ moderate hypertension.     

Comparison of equal-weight oral dosages of verapamil hydrochloride and diltiazem hydrochloride in patients with mild to moderate hypertension

The clinical efficacy, safety, and tolerability of oral verapamil and diltiazem, at total daily dosages of equal weight, were evaluated in a placebo-controlled, double-blind crossover study. Thirty-six ambulatory patients with chronic, stable, mild to moderate hypertension (supine diastolic blood pressure of 94-116 mm Hg) received a dosage of either verapamil or diltiazem 80 mg t.i.d. as the hydrochloride salt for one week after an antihypertensive-drug washout period. Each then received 120 mg of the same drug t.i.d. for one week. After another two-week washout period, the patients were crossed over to the other drug. Each patient had a 12-lead electrocardiogram and measurement of supine and standing blood pressure weekly. In the 32 patients completing the study, low-dose verapamil reduced supine diastolic blood pressure (DBP) from a mean of 101.5 +/- 5.2 to 95.3 +/- 9.5 mm Hg; high dose verapamil reduced DBP to 90.9 +/- 7.4 mm Hg. Standing DBP was reduced to a similar degree. Diltiazem showed an almost identical effect: Supine DBP was reduced from a mean of 101.7 +/- 5.3 to 94.0 +/- 10.1 mm Hg with the low dose and to 91.0 +/- 8.6 mm Hg with the high dose, with similar effects on standing DBP. The high dose of both drugs significantly increased the QTc interval, and both doses of diltiazem significantly increased the PR interval compared with baseline. Both drugs exhibited consistent efficacy with minimal adverse effects. The electrophysiologic safety profile of verapamil was superior to that of diltiazem.     

An acute dose-response pharmacodynamic evaluation of orally administered isradipine (PN-200-110) in hypertensive patients

This study was conducted to assess acute oral dose-responses of four dose levels (2.5, 5, 10, 20 mg) of isradipine, a new calcium channel blocking agent of the 1,4-dihydropyridine group. Sixteen patients with mild essential hypertension were investigated using a randomized, four-way cross-over, double-blind, placebo-controlled design. After a 2-week washout period, all patients were admitted to a research unit where they entered a 3-day placebo equilibration, followed by 9 days of double-blind single doses of isradipine. Drug administration was randomized, and baseline blood pressure values obtained preceding active medication doses were fairly constant. Dose-related reductions in supine and in standing blood pressures were obtained. The mean peak supine blood pressure decrements to doses of 2.5, 5, 10, and 20 mg were 17/16, 25/19, 35/22, and 37/25 mm Hg, respectively. Pulse rates increased slightly. Similar responses were obtained with patients in the erect position. Peak hypotensive responses occurred within 3 hours after dosing. The duration of effect persisted as long as 21 hours, particularly after the 10- and 20-mg doses (15/9 and 17/12 mm Hg mean supine blood pressure decrements, respectively).     

Oral clonidine for rapid control of accelerated hypertension

Thirty emergency-room patients, 15 men and 15 women, from 27 to 64 years old with diastolic blood pressures (DBP) greater than 115 mm Hg, were admitted to an open-label, oral loading trial of clonidine. At this time, their supine mean arterial pressures (MAP) averaged 150 +/- 2 mm Hg. An initial clonidine dose of 0.1 to 0.2 mg was to be followed every hour by another 0.1 mg until the DBP had been lowered to a level allowing treatment to be continued on an ambulatory basis or until a total of 0.5 mg had been given. A satisfactory response--defined as a reduction of the supine DBP to 105 mm Hg or lower if the baseline was between 115 and 135 mm Hg, or reduction of a baseline DBP greater than 135 mm Hg by at least 30 mm Hg--was achieved in all but one of the patients in an average of 118 minutes; the mean dose required was 0.26 mg. The mean reduction from the baseline MAP was 23.1 +/- 0.9%. Drug-related adverse experiences comprised drowsiness and dry mouth in 13 patients. Thereafter, 28 of the patients were chronically treated with clonidine for an average of 73 days. In 24 patients treated for at least 80 days, the daily clonidine dose averaged 0.375 mg. All the patients required concurrent diuretic therapy. A satisfactory response (as defined above) to this maintenance treatment was shown by 85% of the patients, and full blood-pressure control (supine DBP less than 95 mm Hg) was attained in 78%.(ABSTRACT TRUNCATED AT 250 WORDS)     

A double-blind, parallel, comparative evaluation of amlodipine vs. captopril in the monotherapeutic treatment of mild and moderate essential hypertension

A double-blind, parallel, comparative study of the antihypertensive efficacy and safety of once-daily oral doses of amlodipine (5-10 mg/day) vs. twice-daily oral doses of captopril (25-50 mg twice daily) in adult patients with mild or moderate essential hypertension (supine diastolic blood pressure of 95-115 mm Hg) was undertaken in two hospital centers. Interim analysis of data from 40 patients shows that amlodipine and captopril both significantly (p < 0.05) reduced blood pressure compared with baseline. Nineteen of 21 (90.5%) amlodipine-treated patients and 15 of 19 (78.9%) captopril-treated patients had their diastolic blood pressure "normalized" (< 90 mm Hg) with mean final doses of 8.2 and 76.7 mg/day, respectively. At the final visit, there were no statistically significant differences between the two treatment groups in either mean supine or standing blood pressure. Minor nonsignificant changes in standing heart rate were observed in both treatment groups. Seven of the 21 amlodipine-treated patients and 3 of the 19 captopril-treated patients reported adverse experiences. No patients in either treatment group discontinued due to adverse events; one patient in the amlodipine group required a dose reduction. These interim data indicate that the overall efficacy and safety profiles of these two drugs are comparable.     

Controlled trial of nifedipine and bendroflumethiazide in hypertension

In a double-blind study 30 patients with mild or moderate (World Health Organization classification I or II) hypertension were treated with either nifedipine, 20 mg twice a day, or bendroflumethiazide, 2.5 mg (+0.57 g KCl) twice a day for 24 weeks. All patients were then given a combination of half the initial dosage of both drugs for an additional period of 6 weeks. Nifedipine caused a significant reduction of both supine and standing blood pressures (16/10 and 11/5 mm Hg, respectively). Bendroflumethiazide also reduced both recumbent and standing blood pressures significantly (15/10 and 11/10 mm Hg, respectively). Combined treatment with nifedipine and bendroflumethiazide caused a further reduction of both supine and standing blood pressures. The total reduction compared with placebo was 23/12 mm Hg (p less than 0.001) and 17/11 mm Hg (p less than 0.001), respectively. There was no significant correlation between antihypertensive effect and age of patient.     

Atenolol, methyldopa, and chlorthalidone in moderate hypertension.

Combined treatment with low doses of different drugs is widely used for moderate hypertension. The effects of atenolol and methyldopa at two dose levels and in combination at the lower doses were studied in patients with moderate hypertension on continuous treatment with moderate hypertension on continuous treatment with chlorthalidone. The mean reduction in standing blood pressures obtained with atenolol 150 and 300 mg/day was about 27/17 mm Hg and with methyldopa 750 and 1500 mg/day about 28/14 mm Hg. Combined treatment with atenolol 150 mg/day and methyldopa 750 mg/day for four weeks resulted in a reduction of 38/25 mm Hg. No difference was observed between the two doses of methyldopa. The lower dose of atenolol was better than the lower dose of methyldopa in reducing lying and standing diastolic blood pressures. These findings show that in patients on continuous treatment with chlorthalidone the addition of atenolol alone or methyldopa alone or of atenolol and methyldopa in combination is effective in the treatment of moderate hypertension.     

Amlodipine in hypertension: its effects on platelet aggregation and dynamic exercise

The antihypertensive efficacy and safety of once-daily amlodipine (5-10 mg) were studied in patients with essential hypertension. The study also included an assessment of the effects of single doses of amlodipine on platelet aggregation. Ten patients received amlodipine (mean daily dose of 7 mg) for 12 weeks in an open chronic study preceded by a 4-week placebo run-in period. Amlodipine significantly reduced the mean dorsal supine (-31/-20 mm Hg), sitting (-34/-23 mm Hg), standing (-34/ -23 mm Hg), and postexercise (-30/-20 mm Hg) blood pressures (BPs) at the end of 12 weeks of treatment compared with the placebo run-in period (p < 0.005), with no significant change in heart rate. At the end of a 4-week placebo washout phase following the chronic study, nine of the patients received an acute single 10-mg dose of amlodipine. Exercise testing before and 6 h after dosing showed that an acute 10 mg dose of amlodipine reduced BP without modifying the physiologic response to dynamic exercise. Amlodipine significantly reduced the degree of platelet aggregation in these patients (p < 0.005) induced by either collagen or ADP. This study demonstrated that amlodipine once daily was an effective antihypertensive agent and significantly inhibited platelet aggregation.     

Effect of temazepam on blood pressure regulation in healthy elderly subjects.

1. Blood pressure regulation was studied in 12 healthy elderly subjects after double-blind randomised administration of placebo, 15 mg and 30 mg temazepam at 10.00 h and 22.00 h. 2. Supine and standing heart rate and blood pressure were measured after daytime administration and supine measurements were obtained during sleep. 3. Temazepam caused a fall in systolic blood pressure and an increase in heart rate after morning administration. These changes were greater in the standing position and were dose-dependent; for standing blood pressure and heart rate 1 h after administration there was a 7 mm Hg fall and 6 beats min-1 increase after 15 mg temazepam and a 10 mm Hg fall and 8 beats min-1 increase after 30 mg temazepam. Temazepam magnified the fall in systolic blood pressure and increase in heart rate that occurred with standing. Temazepam enhanced the fall in systolic blood pressure that occurred during sleep (mean +/- s.d.; placebo: -23 +/- 10 mm Hg, 15 mg temazepam: -31 +/- 13 mm Hg, 30 mg temazepam: -36 +/- 14 mm Hg). 4. These changes in blood pressure regulation caused by temazepam may have clinical importance in some elderly individuals.     

Effect of labetalol on limb haemodynamics in patients following coronary artery bypass graft surgery.

Labetalol is a competitive inhibitor of alpha- and beta-adrenergic receptors and has an antihypertensive action. To determine limb haemodynamic effects, we measured calf blood flow and venous capacitance by venous occlusion plethysmography before and after oral labetalol in 10 patients 3-7 days following coronary bypass surgery. Vascular resistance was calculated as the ratio of mean arterial pressure to arterial flow. The peak effect of labetalol was taken as the point of maximum blood pressure decline, and this interval was selected for evaluation of the limb haemodynamic response. Ninety to 120 min after administration of 100-200 mg of labetalol the mean blood pressure fell from 88 +/- 3 to 79 +/- 3 mm Hg; (P less than 0.005). The mean arterial blood flow registered 5.1 +/- 1.0 ml 100 ml-1 limb tissue min-1 which was not significantly different from the control value of 4.4 +/- 0.8 ml 100 ml-1 limb tissue min-1. The calculated index of limb vascular resistance was not affected by labetalol administration, averaging 37 +/- 12 mm Hg 100-1 ml limb tissue min-1 before labetalol and 30 +/- 11 mm Hg ml-1 100 ml limb tissue min-1 at the time of peak hypotensive effect. There was a slight but statistically significant increment in limb venous volume to 1.9 +/- 0.3 from 1.5 +/- 0.3 ml 100 ml-1 limb tissue (P less than 0.025). Placebo administration produced no consistent changes in blood pressure, arterial blood flow, vascular resistance or venous capacitance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antihypertensive effects of a new sustained-release formulation of nifedipine

The blood pressure response to a new sustained-release formulation of nifedipine was evaluated in an 8-week, double-blind, placebo-controlled study. Twenty-nine patients with mild essential hypertension were randomized to receive placebo (N = 9), 30 mg nifedipine (N = 10), or 60 mg nifedipine (N = 10). During treatment, 30-mg and 60-mg doses of nifedipine administered once daily decreased office blood pressures from 137/98 +/- 8/2 mm Hg and 141/98 +/- 15/2 mm Hg at baseline, respectively, to 126/89 +/- 9/7 mm Hg and 126/86 +/- 6/7 mm Hg (P less than .005). Noninvasive automatic ambulatory blood pressure monitoring demonstrated a marginally significant (P less than .10) reduction in the mean 24-hour blood pressure of 2/6 +/- 8/8 mm Hg and 5/6 +/- 9/9 mm Hg for patients taking 30 mg and 60 mg nifedipine once daily, respectively. Diastolic blood pressure load (the percentage of ambulatory diastolic blood pressure readings greater than 90 mm Hg) during 24 hours was decreased by 41% and 35%, with 30 mg and 60 mg nifedipine administered once daily, respectively. No significant dose response to nifedipine at these dose levels was observed. Although the once-daily formulation of nifedipine achieved effective control of office blood pressure, similar control was not observed in awake and 24-hour periods in all patients.     

Effect of UK-52,046, an alpha 1-adrenoceptor antagonist, on baroreflex function in man.

1. In a placebo controlled study (six healthy male subjects), the effects of UK-52,046 (0.4 microgram kg-1 i.v.) and prazosin (0.25 mg i.v.) on baroreflex function were compared, at doses which produced antagonism to phenylephrine, but which had no effect on supine blood pressure. 2. Baroreflex function [delta R-R interval ms mm Hg-1 change in SBP] was assessed following increases in systolic blood pressure (SBP) with phenylephrine and during the Valsalva manoeuvre. 3. At these doses neither UK-52,046 nor prazosin had an effect on supine SBP or heart rate; however following prazosin, standing SBPs at 5 s (69.7 +/- 7.6 mm Hg) and at 3 min (65.5 +/- 11.7 mm Hg) were less than the respective pre-treatment (P less than 0.05) values (96.0 +/- 2.9, 110.3 +/- 6.2 mm Hg) and placebo (82.7 +/- 5.6, 98.7 +/- 11.1 mm Hg). UK-52,046 had no significant effects on standing SBP at 5 s or 3 min. At 5 s, pre- and post-treatment R-R intervals (584 +/- 26, 541 +/- 27 ms respectively) were not significantly different with prazosin, but at 3 min the post-treatment R-R interval following prazosin (519 +/- 17 ms) was less (P less than 0.05) than the pre-treatment value (658 +/- 36 ms). 4. UK-52,046 had no effect on baroreflex sensitivity (12.7 +/- 1.3 ms mm Hg-1) compared with placebo (17.9 +/- 2.7 ms mm Hg-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of enalapril and metoprolol as initial therapy for mild to moderate hypertension

The safety and efficacy of step-one therapy with enalapril, a new angiotensin-converting enzyme inhibitor, and metoprolol were compared in a double-blind, multicenter study involving 150 patients who had mild to moderate essential hypertension. After a four-week period of placebo run-in, therapy was initiated with twice-daily administration of either 5 mg of enalapril (N = 75) or 50 mg of metoprolol (N = 75). Patients who did not achieve a supine diastolic blood pressure of less than 90 mm Hg after six weeks of enalapril (maximum dose = 40 mg/d) or metoprolol (maximum dose = 400 mg/d) had hydrochlorothiazide 50 mg/d added to their treatment regimen for an additional six weeks. Both treatments produced significant (P less than .001) mean reductions in supine and standing blood pressures after 2, 4, 6, 8, 10, and 12 weeks of active therapy. Maximum reductions from baseline values of supine blood pressure in enalapril-treated (-25/-16 mm Hg) and metoprolol-treated (-21/-15 mm Hg) patients were observed after 12 weeks of single- or double-drug therapy. Approximately two-thirds of the patients responded to single-drug therapy; when hydrochlorothiazide was added, response rates increased to 88% of the patients treated with enalapril and 80% of the patients treated with metoprolol. Enalapril produced a consistently greater reduction in systolic blood pressure. Blacks had a significantly smaller mean blood pressure response to both enalapril and metoprolol than did nonblacks. Metoprolol patients had significant mean pulse rate reductions; enalapril patients had no significant change. Four enalapril-treated and six metoprolol-treated patients discontinued treatment because of side effects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ketanserin in essential hypertension: use as monotherapy and in combination with a diuretic or beta-adrenoceptor antagonist.

1. The antihypertensive efficacy and tolerability of twice-daily treatment with the 5-hydroxytryptamine antagonist ketanserin were examined in a double-blind, placebo-controlled trial of 7 weeks duration in 56 hypertensive patients. Twenty were untreated, 20 were already taking bendrofluazide 5 mg daily, and 16 were already taking atenolol 100 mg daily. Randomisation was stratified to compare ketanserin with placebo as monotherapy (n = 20), when added to bendrofluazide (n = 20), and when added to atenolol (n = 16). 2. The antihypertensive effect of ketanserin in all patients completing the study (mean daily dose 71 mg) was 10/6 mm Hg supine (P less than 0.01/P less than 0.01) and 6/6 mm Hg standing (NS/P less than 0.01) when blood pressure was measured 2 h after the morning dose. Responses were similar in patients taking ketanserin as monotherapy, in addition to bendrofluazide, and in addition to atenolol, with reductions in mean arterial pressure of 4.6, 7.4 and 8.9 mm Hg respectively. 3. Ketanserin had no antihypertensive effect when measured 14 h after the last dose. The rise in blood pressure between 2 and 14 h after dosing was 11/4 mm Hg supine (P less than 0.01/NS) and 8/5 mm Hg standing (P less than 0.05/P less than 0.05). 4. The antihypertensive response to ketanserin was positively related to initial blood pressure and, independent of this, to age. It was not related to plasma concentrations of ketanserin or ketanserinol. 5. Five of 28 patients taking ketanserin discontinued treatment because of side-effects, compared with one of 28 patients taking placebo.(ABSTRACT TRUNCATED AT 250 WORDS)     

A double-blind, randomized, placebo-controlled comparison of the metabolic effects of low-dose hydrochlorothiazide and indapamide

To compare the metabolic effects of indapamide (I) and hydrochlorothiazide (HCTZ) at equivalent hypotensive doses, 11 hypertensive patients (5 male, 8 black, aged 56 +/- 8 yr--mean +/- SEM) having serum uric acid concentrations greater than 8.0 mg/dL while receiving previous therapy with thiazides, received 28-day courses of placebo, indapamide (2.5 mg/d), and HCTZ (25 mg/d) in randomized, double-blind, double-crossover design. Supine and standing blood pressures, weight, pulse rates and sera were obtained after each 28 day period. Blood pressures and weights were lowered (P less than .001 and 0.01, respectively) equally by the diuretics: supine blood pressures fell from 168 +/- 4/104 +/- 2 (placebo) to 153 +/- 4/93 +/- 2 (HCTZ) and 155 +/- 4/94 +/- 2 mm Hg (I); standing blood pressures (after 2 minutes upright) also decreased: 171 +/- 5/104 +/- 2 (placebo) to 156 +/- 5/93 +/- 2 (HCTZ) and 157 +/- 4/94 +/- 2 mm Hg (I). There was a statistically significant difference (P less than .05) across treatments by analysis of variance in both uric acid and potassium concentrations: serum urate (in mg/dL) was lowest with placebo (7.1 +/- 0.3), and rose to 8.3 +/- 0.2 with HCTZ (P less than .001 compared with placebo by paired t test), and 8.1 +/- 0.2 with I (P less than .005 vs. placebo). The urate concentration with I was significantly lower than that with HCTZ (P less than .02), but the magnitude of the difference was small (0.2 mg/dL).(ABSTRACT TRUNCATED AT 250 WORDS)     

Double-blind study of dilevalol and captopril, both in combination with hydrochlorothiazide, in patients with moderate to severe hypertension.

Sixty-one patients (41 men, 20 women) aged 29-73 years, with moderate to severe hypertension, were enrolled in a multicentre study to compare the efficacy, safety, and tolerability of dilevalol (D) and captopril (C). At the end of the baseline period, supine diastolic blood pressure (SuDBP) was 105-140 mm Hg on hydrochlorothiazide (HCTZ) 25 mg once daily and placebo t.i.d. Patients were randomly assigned to D + HCTZ (n = 29) or C + HCTZ (n = 32) and entered phase II titration of D (100-800 mg b.i.d.) or C (12.5 mg b.i.d. to 50 mg t.i.d.). If SuDBP was greater than 99 mm Hg, hydralazine was added (25 mg once daily to 50 mg b.i.d.). If SuDBP was less than or equal to 99 mm Hg, patients entered phase III, a 3-month maintenance period. Demographic profiles were not significantly different between the two groups. Baseline supine BP (mean +/- SEM) was similar in the two groups (D + HCTZ: 182 +/- 3/112 +/- 1; C + HCTZ: 179 +/- 4/113 +/- 1 mm Hg), as was baseline standing BP (D + HCTZ: 175 +/- 3/114 +/- 2; C +/- HCTZ: 173 +/- 4/113 +/- 1 mm Hg). At the end of phase II, there were no significant differences between treatments with respect to the changes in BP from baseline.(ABSTRACT TRUNCATED AT 250 WORDS)     

The pharmacokinetics of doxazosin in patients with hypertension and renal impairment.

1. The pharmacokinetics of doxazosin, following a single oral dose (1 mg) and chronic oral dosing (doubling doses up to a maximum of 16 mg day-1), were studied in 18 patients with mild to moderate hypertension and stable renal function varying from normal to severely impaired. In addition, the effect of chronic administration of doxazosin on renal haemodynamics was evaluated. 2. Significant accumulation of doxazosin occurred with chronic dosing, but comparison of dose-adjusted AUC after single and chronic dosing suggested that there was no change in clearance or bioavailability during chronic administration. 3. There was no significant relationship between plasma elimination half-life or the AUC for doxazosin and the degree of renal impairment. 4. Symptomatic postural hypotension occurred in six patients following the initial dose of 1 mg doxazosin. Systolic and diastolic blood pressure measured 24 h after the previous dose were significantly reduced during chronic administration of doxazosin by a mean of 12/6 mm Hg supine and 10/7 mm Hg on standing. 5. During chronic administration of doxazosin, there was a significant reduction of 13% in glomerular filtration rate compared with pre-treatment, but no change in effective renal plasma flow.     

Felodipine vs hydralazine: a controlled trial as third line therapy in hypertension. Cooperative Study Group.

In a placebo-controlled, double-blind, randomized, parallel group study one hundred and one patients with supine diastolic blood pressure greater than or equal to 100 mm Hg phase V, despite treatment with atenolol 100 mg plus chlorthalidone 25 mg once daily also received either felodipine 5-20 mg twice daily or hydralazine 25-100 mg twice daily for 6 weeks. Felodipine achieved a lower supine blood pressure (mean +/- s.d. 177/108 +/- 29/8-138/82 +/- 19/8 mm Hg) than hydralazine (174/109 +/- 25/8-149/92 +/- 26/11 mm Hg), (P less than 0.05/P less than 0.001). Felodipine also lowered supine diastolic blood pressure to less than 90 mm Hg more often than hydralazine (42 vs 22 patients, P less than 0.001). The incidence of unwanted effects was similar in both groups. The felodipine treated patients experienced more ankle swelling and flushing than those in the hydralazine group who experienced more headache and minor gastro-intestinal upset.