Oral labetalol in hypertensive urgencies

The response to incremental doses of oral labetalol in 16 patients with hypertensive urgencies is presented. After inadequate blood pressure control with 20 mg of intravenous furosemide, each patient received a 300 mg oral dose of labetalol. Subsequent oral doses of labetalol, 100 mg, were administered at 2-hour intervals, if the diastolic blood pressure remained greater than 100 mm Hg. The maximum dose of labetalol per patient was 500 mg. Five patients required only the initial 300 mg dose of labetalol. Two patients required further therapy for satisfactory blood pressure control. Mean arterial pressure fell from 156 +/- 12 mm Hg to 123 +/- 14 mm Hg.     

Antihypertensive effects of parenteral nicardipine alone and in combination with captopril

We studied the safety and efficacy of intravenous nicardipine alone and in combination with oral captopril. Sixteen patients with essential hypertension received a single oral dose of captopril, 50 mg, to be certain that excessive hypotension would not occur. Nicardipine was given intravenously as a 2 mg bolus, followed by an infusion at a rate designed to lower the supine diastolic blood pressure at least 10 mm Hg; then oral captopril, 50 mg, or placebo was given. The next week, nicardipine was again infused, but the alternate oral treatment was given. Intravenous nicardipine reduced blood pressure from 156 +/- 15/101 +/- 5 mm Hg (mean arterial blood pressure 120 +/- 6 mm Hg) to 140 +/- 11/88 +/- 4 mm Hg (mean arterial blood pressure 105 +/- 5 mm Hg). When captopril was added to nicardipine, the mean arterial blood pressure fell an additional 8 mm Hg but the heart rate did not increase. The combination of angiotensin-converting enzyme inhibition and calcium channel blockage produces additive antihypertensive effects without additional reflex tachycardia.     

Cerebral blood flow during the acute therapy of severe hypertension with oral clonidine

A major risk associated with the acute treatment of severe hypertension is a reduction in cerebral blood flow (CBF) with ischemic injury to the central nervous system. The authors studied CBF before and after the acute treatment of severe hypertension (diastolic blood pressure greater than 115 mm Hg) with clonidine in 13 patients. One patient did not reach goal blood pressure (diastolic blood pressure 105 mm Hg or a decrease by 30 mm Hg) after clonidine alone. In the remaining 12 patients, oral clonidine reduced supine blood pressure from 201.7 +/- 5.0/126.3 +/- 2.1 mm Hg to 149.4 +/- 5.3/96.8 +/- 1.7 mm Hg over an average time period of 85 +/- 7 minutes. Although mean CBF for the group did not change (72.6 +/- 4.2 v 73.7 +/- 3.5 mL/100 mg/min), a significant (greater than 10%) change occurred in 9 of the 12 patients (5 increases and 4 reductions). The magnitude and direction of the change were dependent upon initial CBF (r = -0.65, P less than .05); patients with low pretreatment CBF experienced an increase, whereas those with high initial flow exhibited a decrease. No significant adverse effects were observed. These data confirm previous reports that clonidine is effective in the acute treatment of severe hypertension and demonstrate that its effects on CBF are determined by the pretreatment levels of flow.     

Plasma levels of enalaprilat in chronic therapy of heart failure: relationship to adverse events

Angiotensin-converting enzyme (ACE) inhibitors are established as first-line therapy in chronic heart failure (CHF). However, little is known about the dosage-plasma-level relationship of ACE inhibitors in CHF and its relation to drug-induced adverse effects. We investigated 45 patients (age 55 +/- 10 years) with stable CHF who presented with a maintenance dosage of enalapril of either 5 mg b.i.d. (E10, n = 16), 10 mg b.i.d. (E20, n = 18), or 20 mg b.i.d. (E40, n = 11). This dosage was changed three times to treat all patients with lower, higher, and, finally, the initial dosage for 4 weeks each. Patients were examined clinically, by questionnaire, and by spiroergometry. In addition, neurohormones (atrial and brain natriuretic peptide and norepinephrine), enalaprilat trough levels, and serum potassium and creatinine were measured. Enalaprilat trough levels differed significantly between the three groups at study entry but also varied markedly within each group. In addition to the dose of enalapril, serum creatinine, severity of CHF, basal metabolic rate, and body weight significantly influenced enalaprilat trough levels (R2 =.84, p <.001). Within-patient comparisons revealed that serum creatinine (107 +/- 26 versus 102 +/- 20 micromol/liter) and potassium (3.8 +/- 0.4 versus 3.7 +/- 0. 3mmol/liter) were higher, cough was more common (scored on a scale of 0-8: 1.7 +/- 2.1 versus 1.4 +/- 1.8), and blood pressure was lower (systolic, 112 +/- 14 versus 117 +/- 13 mm Hg; diastolic, 66 +/- 9 versus 69 +/- 11 mm Hg) on the highest than on the lowest enalaprilat trough level (all p <.05). Highly variable enalaprilat trough levels and the fact that adverse effects were more common on high enalaprilat trough levels provide a rationale for individually adjusting ACE-inhibitor dose in case of adverse effects.     

Combined action of enalapril or timolol with hydrochlorothiazide plus amiloride in hypertension

59 mild to moderate hypertensives were treated for four weeks with 50 mg hydrochlorothiazide plus 5 mg of amiloride, then concomitantly with these diuretics with either enalapril (10-20 mg) or timolol (10-20 mg) in two parallel treatment groups for an additional 12 weeks in an open study. Addition of these drugs lowered the blood pressure by 25 +/- 3/16 +/- 2 mm Hg and 15 +/- 3/14 +/- 1 mm Hg, respectively. The difference of the reduction of the systolic blood pressure between enalapril and timolol group at the end of the combined treatment was statistically significant (p less than 0.01). The mean serum potassium was elevated by 0.3 mmol/l after addition of enalapril to the diuretic treatment, but none of the patients developed hyperkalaemia. No adverse effects on other routine laboratory values were observed. Both drug combinations can be considered efficient, well tolerated and safe in the treatment of mild to moderate hypertension.     

The effects of benazepril, a new angiotensin-converting enzyme inhibitor, in mild to moderate essential hypertension: a multicenter study

Benazepril hydrochloride is a new angiotensin-converting enzyme inhibitor. In a multicenter study, 206 patients with mild to moderate hypertension were randomized to receive benazepril at a dose of 2, 5, 10, or 20 mg, hydrochlorothiazide, 25 mg, or placebo once daily for 4 weeks. The 20 mg dosage of benazepril lowered blood pressure to a degree equal to that of 25 mg hydrochlorothiazide: -12.2/7.7 mm Hg and -13.4/-7.5 mm Hg, respectively. Hydrochlorothiazide proved to be more effective in black subjects. At lower dosage levels of benazepril (2, 5, and 10 mg), blood pressure reduction was not significantly different from that with placebo. In those patients who failed to achieve goal diastolic blood pressure of less than 90 mm Hg with monotherapy after 4 weeks, the addition of open-label hydrochlorothiazide (25 mg/day) to benazepril, hydrochlorothiazide, or placebo produced a substantial additional decrease in blood pressure over a 2-week period. No definite adverse effects on hematologic measurements, serum biochemistry test results, or urinalyses were noted. Subjective adverse experiences were common in all groups but except in three or possibly four instances were not considered causally related to the study drug.     

Effects of caffeine on baroreflex activity in humans

The effects of caffeine or placebo on blood pressure, heart rate, and baroreflex activation (elicited by phenylephrine) were studied on young normotensive volunteers after a 7-day caffeine-free period. Subjects received oral doses of either 250 mg caffeine (n = 6) or placebo (n = 4), and hemodynamic changes were studied at 0, 30, 60, 120, and 180 minutes after drug administration. Thirty minutes after the caffeine dose, blood pressure had risen from 127 +/- 8/57 +/- 4 mm Hg to 136 +/- 3/68 +/- 5 mm Hg, heart rate was unchanged, and the baroreflex slope had decreased from 31 +/- 7 msec/mm Hg to 11.6 +/- 2 msec/mm Hg. Baroreflex sensitivity remained inhibited for the rest of the single-dose experimental period. In contrast, no significant changes were observed after either long-term caffeine ingestion in the same group or in the placebo group during the single- or multiple-dose study. These findings indicate that single but not multiple caffeine administration inhibits baroreflex activation in normotensive volunteers and this could contribute to the acute hemodynamic effects of caffeine.     

Individual variability in the blood pressure response to intravenous phenylpropanolamine: a pharmacokinetic and pharmacodynamic investigation

The intersubject variability in blood pressure response to 0.44 mg/kg intravenous phenylpropanolamine (d,l-norephedrine) was studied in 10 normal subjects. A phenylpropanolamine or placebo infusion was administered over 45 minutes on separate days according to a double-blind, balanced protocol. Blood pressure increased by 24 +/- 13/16 +/- 7 mm Hg (systolic/diastolic, mean +/- SD) after the phenylpropanolamine infusion and was statistically different from the placebo infusion response (7 +/- 5/8 +/- 3 mm Hg). Phenylpropanolamine infusions were terminated early in two subjects (hyperresponders) after 0.31 and 0.23 mg/kg because of excessive increases in blood pressure (52/30 and 34/21 mm Hg, respectively). The hyperresponders had the lowest peak serum phenylpropanolamine concentrations. These data suggest that considerable intersubject variability exists in the blood pressure response to intravenous phenylpropanolamine. A pharmacokinetic basis for the variability in response to racemic phenylpropanolamine was not observed. A relationship did not exist within the group between blood pressure effect and serum concentration but did exist within each subject. Therefore phenylpropanolamine's blood pressure effect in an individual cannot be predicted solely from a serum concentration of racemic drug.     

Nicardipine and hydrochlorothiazide in essential hypertension

Nicardipine is an investigational dihydropyridine calcium channel blocking agent. One hundred fifty-one patients with hypertension received either 30 mg nicardipine t.i.d. or 25 mg hydrochlorothiazide b.i.d. in a double-blind, randomized, multicenter trial. After 4 weeks of therapy and at the end of the dosing interval, nicardipine reduced arterial pressure by 10/6 mm Hg and 12/6 mm Hg in the supine and standing positions, respectively (all p less than 0.01). In the hydrochlorothiazide group, the reductions were 12/6 mm Hg and 14/6 mm Hg, respectively (all p less than 0.01). The maximum reduction in blood pressure of 16/14 mm Hg supine and 20/15 mm Hg standing occurred within 1 hour after administration of nicardipine. The mean reduction in the hydrochlorothiazide group after 1 hour was 14/11 mm Hg supine and 16/12 mm Hg standing. Neither drug affected autonomic reflexes associated with maximum exercise. Nicardipine increased urinary sodium excretion during the 4-hour period after the first dose. Adverse effects of nicardipine were primarily extensions of its vasodilator effect and included flushing, headache, and edema.     

Effect of cianopramine, a tricyclic antidepressant, on platelet serotonin uptake and peripheral adrenergic function

Cianopramine, a new tricyclic antidepressant, is a potent inhibitor of neuronal serotonin (5-HT) uptake in animals. We studied the effect of cianopramine on 5-HT uptake (ex vivo) in platelets and on peripheral neuronal adrenergic function in catecholamine pressure response tests in normal subjects. The inhibition of 14C-labeled 5-HT uptake into platelets was 57% +/- 12% 2 hr after 0.5 mg (after 24 hr: 27% +/- 13%), 59% +/- 10% 2 hr after 1 mg (24 hr: 41% +/- 13%), and 80% +/- 2% 2 hr after 2 mg cianopramine (24 hr: 52% +/- 10%). Systolic blood pressure response to intravenous tyramine and norepinephrine was unchanged after 2 mg cianopramine. The phenylephrine dose required for an increase of 40 mm Hg in systolic blood pressure was 67 +/- 25 micrograms/min before cianopramine and 86 +/- 32 micrograms/min 2 hr after 2 mg cianopramine, which suggests weak alpha-receptor antagonism of cianopramine. Our results in man are consistent with potent, specific 5-HT uptake inhibition by cianopramine without a clinically relevant effect on peripheral neuronal norepinephrine reuptake.     

Labetalol infusion in hypertensive emergencies

The antihypertensive effects of labetalol infusion (2 mg/min; maximal dose 150 mg) were evaluated in 22 subjects requiring rapid lowering of blood pressure because of severe hypertension, a hypertensive crisis after surgery, or before angiographic examination. Overall systolic and diastolic blood pressures were reduced from 201 +/- 4 to 164 +/- 4 mm Hg and from 123 +/- 3 to 107 +/- 3 mm Hg, respectively. By the end of the infusion, diastolic blood pressure in 16 (73%) subjects was lowered to less than or equal to 110 mm Hg. No adverse effects were encountered, but one subject had a transitory hypotensive episode that did not require treatment. Intravenous labetalol appears effective and well tolerated in the control of blood pressure in hypertensive emergencies.     

Local forearm vasodilation with intra-arterial administration of enalaprilat in humans.

To determine whether converting enzyme inhibitors could produce peripheral vasodilation through a local mechanism, we infused enalaprilat, 2 micrograms/min/dl forearm volume (FAV), into the brachial artery of normal subjects and measured changes in forearm blood flow (FBF) with strain-gauge plethysmography. Enalaprilat produced a peak increase in FBF of 2.82 +/- 0.54 ml/min/dl FAV (78% increase) at 1 minute (p less than 0.01 versus vehicle) and an increase of 1.11 +/- 0.28 ml/min/dl FAV at 4 minutes (p less than 0.05 versus vehicle). Blood pressure and plasma renin activity measured at the completion of infusion did not change. Intravenous enalaprilat infusion at the same dose in seven additional normal subjects did not increase FBF. Pretreatment of seven subjects with 75 mg oral indomethacin attenuated the peak response to enalaprilat (4.13 +/- 1.52 versus 0.58 +/- 0.32 ml/min/dl; p less than 0.05). We conclude that intra-arterial enalaprilat produces an increase in FBF in normal subjects. This peripheral vasodilation is caused by a local effect independent of circulating renin-angiotensin system inhibition. This response is attenuated by indomethacin, suggesting that prostaglandins contribute to the vasodilator response.     

Acute effects of nitric oxide synthase inhibition on systemic, hepatic, and renal hemodynamics in patients with cirrhosis and ascites.

BACKGROUND: Nitric oxide synthase (NOS) inhibition has been demonstrated to correct systemic vasodilation and renal hypoperfusion in studies of patients with cirrhosis. In patients with decompensated cirrhosis, NOS blockade increases arterial pressure, but the acute effects on hepatic and renal hemodynamics are not known. METHODS: We examined the acute systemic, hepatic, and renal hemodynamic effects of N(G)-monomethyl-L-arginine (L-NMMA) in 10 patients with decompensated cirrhosis. After baseline measurements, 3 mg/kg L-NMMA was administered as an IV bolus. At 20 minutes, if mean arterial pressure did not increase by at least 10 mm Hg above the baseline value, a second injection of 6 mg/kg was administered. RESULTS: In 5 of 10 patients, the second injection of L-NMMA 6mg/kg was necessary to achieve at least a 10 mm Hg increase in mean arterial pressure. Acute NOS inhibition increased systemic vascular resistance and decreased cardiac output, without causing changes in the hepatic venous pressure gradient. Hepatic blood flow decreased, but the indocyanine green intrinsic clearance and extraction remained unchanged. Plasma renin activity (from 9.5 +/- 2.9 to 6.7 +/- 1.6 ng/ml/h) and urinary prostaglandin E2 (from 299 +/- 40 to 112 +/- 36 pg/ml) significantly decreased. No significant changes in glomerular filtration rate, renal plasma flow, and natriuresis occurred, however. CONCLUSIONS: Acute L-NMMA infusion in patients with decompensated cirrhosis reduced hepatic blood flow and decreased plasma renin activity and urinary prostaglandin E2, without causing significant changes in renal hemodynamics.     

Effects of indenolol on blood pressure, lower limb blood flow, adrenergic reflexes, and plasma renin activity

The antihypertensive effects of indenolol, a new not-cardioselective beta-blocking agent, were evaluated in patients with WHO grades I and II essential hypertension (range 160/95 to 200/115 mm Hg) in a double-blind, placebo-controlled study after acute (12 patients) and 2-week treatment (seven patients). Indenolol (30 to 120 mg) reduced blood pressure in a dose-dependent fashion. Maximum reduction was 26 mm Hg for systolic and 17 mm Hg for diastolic pressure. Hypotensive activity commenced within 10 minutes, peaked in 60 minutes, and persisted for about 7 hours. Lower limb vascular resistance (strain-gauge plethysmography) was significantly lowered, thus suggesting an intrinsic sympathomimetic activity. Heart rate was progressively reduced at 30 and 60 mg without any additional effect at 120 mg. Indenolol did not alter adrenergic reflexes (standing, cold application, and hand-grip) and did not induce any side effect. In conclusion, indenolol possesses an antihypertensive activity associated with reduction of vascular resistance.     

Treatment of mild and moderate hypertension with enalapril (multicenter study of enap and enap N in Ukraine)

AIM: Assessment of efficiency and safety of enalapril (enap) and its combination with hydrochlorotiaside (enap-N). MATERIALS AND METHODS: 127 patients with mild and moderate blood hypertension entered an open non-comparative multicenter trial. 60 of them received enap (group 1), 67--enap N (group 2). Group 1 patients were given enap for 2 weeks in a dose 10 mg/day. If this dose was not adequate to normalize blood pressure, it was raised to 20-40 mg/day. Patients of group 2 received enap-N one tablet a day for 3 weeks. If the pressure persisted higher than 140/90 mm Hg, the treatment was continued for 3 weeks more in a dose of 2 tablets a day. RESULTS: Blood pressure lowered under 140/90 mm Hg in 40 patients of group 1 (66.7%). Systolic pressure dropped by 10 mm Hg minimum and diastolic by 5 mm minimum in 18 group 1 patients (30%). Enap-N reduced blood pressure under 140-90 mm Hg in 44 of 67 patients (65.7%). Systolic and diastolic pressure dropped, respectively, in 23(34.3%) patients. CONCLUSION: Enap and enap-N tablets were found highly effective and well tolerated. Side effects were caused by lowering of blood pressure.     

Low-dose combination treatment for hypertension versus single-drug treatment-bisoprolol/hydrochlorothiazide versus amlodipine, enalapril, and placebo: combined analysis of comparative studies

To assess the efficacy and safety of 2.5, 5, and 10 mg bisoprolol/6. 25 mg hydrochlorothiazide (HCTZ), 2.5, 5, and 10 mg amlodipine; and 5, 10, 20, and 40 mg enalapril in subjects (n = 541) with a sitting diastolic blood pressure of 95 to 114 mm Hg, data from two comparative studies were pooled. All drugs were titrated to a diastolic blood pressure 90 mm Hg or less. Both studies were double-blind, randomized, parallel dose escalation trials with similar designs and included three active treatments. The second study also had a placebo group. The mean change from baseline of systolic and diastolic blood pressure for placebo (n = 79) was -0. 1/-2.2 mm Hg; amlodipine (n = 154), -12.4/-10.3 mm Hg; enalapril (n = 155), -9.4/-8.2 mm Hg; and bisoprolol/HCTZ (n = 155), -14.0/-12.0. Overall efficacy analyses documented a statistically significant decrease in sitting diastolic blood pressure for bisoprolol/6.25 mg HCTZ compared with placebo, amlodipine, and enalapril. There was a significant reduction in sitting systolic blood pressure for bisoprolol/6.25 mg HCTZ compared with placebo and enalapril but not amlodipine. Also, there was a significant decrease in sitting heart rate for bisoprolol/6.25 mg HCTZ (-6.2 beats/min) compared with placebo (+0.1 beats/min), amlodipine (+1.2 beats/min), and enalapril (+0.5 beats/min). The control rate (diastolic blood pressure < or = 90 mm Hg) for bisoprolol/6.25 mg HCTZ (66.5%) was significantly better than for placebo (21.8%) and enalapril (47.1%) but not amlodipine (58.4%). Of those patients achieving and maintaining control, 49% of the bisoprolol/6.25 mg HCTZ subjects were on the lowest two doses compared with 30% of the amlodipine and 26% of the enalapril subjects. Percentages of patients reporting at least one drug-related adverse event through week 12 were 27%, 24%, 28%, and 25% for placebo, bisoprolol/6.25 mg HCTZ, amlodipine, and enalapril (not significant). Lower doses of two drugs in fixed combination can provide as good or better blood pressure control compared with higher doses of a single drug with similar tolerability and safety.     

Evaluation of isradipine (PN 200-110) in mild to moderate hypertension

The efficacy and safety of isradipine (PN 200-110), a new dihydropyridine calcium antagonist, was evaluated in 87 hypertensive patients in a placebo-controlled, double-blind, randomized multicenter trial. After a 3-week single-blind washout phase, isradipine (or matching placebo) was administered for 4 weeks, beginning at 2.5 mg b.i.d. with increments of 2.5 mg b.i.d. at weekly intervals if supine diastolic blood pressure remained greater than or equal to 90 mm Hg. At the end of 1 week average supine blood pressure in the isradipine group (n = 45) fell from a baseline of 156 +/- 13/104 +/- 4 mm Hg to 146 +/- 14/97 +/- 7 mm Hg. By week 4 blood pressure was reduced by 19/14 mm Hg compared with 4/5 mm Hg in the placebo group (P less than 0.001 between groups). Supine and standing pulse rates were slightly increased initially with isradipine therapy but returned to baseline with increasing isradipine doses. Blood pressure responses at week 4 were good or excellent (supine diastolic less than or equal to 90 mm Hg or greater than or equal to 10 mm Hg decrease from baseline) in 87% of isradipine-treated patients and in 26% of placebo-treated patients. Headache, edema, abdominal discomfort, and constipation occurred slightly more frequently in isradipine-treated patients than in placebo-treated control subjects. The results indicate that isradipine, administered as monotherapy in doses of 2.5 to 10 mg b.i.d., is safe and effective in patients with mild to moderate essential hypertension.     

Comparative study of spirapril (quadropril) and amlodipine efficacy. Results of randomized trial in patients with mild to moderate arterial hypertension

AIM: To compare in the non-blind randomised parallel study the efficiency of quadropril and amlodipine in the treatment of mild to moderate arterial hypertension. MATERIAL AND METHODS: A total of 80 patients (57.6 +/- 1.0 years) were included in this study. The patients were randomised in two groups, 40 patients each. Patients of group 1 received monotherapy with quadropril, while those of group 2 were treated with amlodipine. The treatment duration was 8 weeks in both groups. Quadropril was given in a fixed dose of 6 mg once daily. The initial dose of amlodipine was 5 mg/day. In case of insufficient effect the dose was elevated to 10 mg/day. The efficacy was evaluated by changes in blood pressure (BP) measured at rest. Moreover, in 50 randomly chosen patients 24-h monitoring of BP was performed at the start and end of the treatment. RESULTS: In the quadropril group baseline systolic BP reached 158.6 +/- 2.1 mm Hg, diastolic BP--101.8 +/- 0.8 mm Hg, heart rate was 74.3 +/- 1.6 beats/min. In the amlodipine group baseline systolic BP was 159.9 +/- 2.4 mm Hg, diastolic BP--101.8 +/- 1.0 mm Hg, heart rate was 71.3 +/- 1.0 beats/min. Systolic BP decreased at the end of quadropril therapy to 138.5 +/- 2.2 mm Hg, diastolic BP to 88.1 +/- 1.4 mm Hg. No significant change of the heart rate was observed. Under 5 mg of amlodipine systolic BP decreased to 137.9 +/- 2.5 mm Hg and diastolic BP to 87.1 +/- 1.6 mm Hg. Heart rate increased to 73.3 +/- 2.2 beats/min. Under therapy with 10 mg amlodipine systolic BP decreased to 145.9 +/- 3.8 mm Hg, diastolic BP to 89.7 +/- 3.4 mm Hg. Heart rate increased to 77.3 +/- 4.0 beats/min (p < 0.01). The hypotensive effect of quadropril remained stable while the effect of amlodipine decreased by the 8th week of therapy (p < 0.01). Side effects were observed significantly more often in the amlodipine group, then in the quadropril group. The main quadropril side effect was cough. Side effects observed in the amlodipine group were edemas, tachycardia, weakness. CONCLUSION: Both quadropril and amlodipine demonstrated a comparable antihypertensive effect although in 11 of 40 patients in the amlodipine group a dose increase was necessary and tolerability of quadropril was better.     

Comparison of intravenous dilevalol with placebo in moderate hypertension

Dilevalol, an agent that combines nonselective beta-blocking and beta 2-mediated vasodilating properties, was compared with placebo in 16 subjects with moderate hypertension in a double-blind crossover study. Dilevalol or a placebo was administered intravenously in bolus injections of 25, 50, and 50 mg at 15-minute intervals. Fifteen minutes after a cumulative dose of 125 mg, the blood pressure was lowered by 11/9 mm Hg, compared with 2/1 mm Hg after placebo (p less than 0.01 between groups for systolic and diastolic blood pressure), an effect that persisted for at least 105 minutes. Standing systolic blood pressure was also lowered in dilevalol-treated patients without orthostatic symptoms. No significant effects on heart rate were noted. Fifteen minutes after the last dose of dilevalol, plasma norepinephrine levels increased from a baseline of 200 +/- 24 to 495 +/- 44 pg/ml (p less than 0.01), compared with a nonsignificant rise from 262 +/- 21 to 306 +/- 28 pg/ml with placebo vehicle. Dilevalol also increased alpha-human atrial natriuretic factor by 5.4 pg/ml, compared with 0.5 pg/ml after placebo (p less than 0.01 between groups). Plasma renin activity and plasma epinephrine, aldosterone, and cyclic guanosine monophosphate levels were unchanged by dilevalol. There were no significant adverse effects with dilevalol administration. Compared with placebo, dilevalol given intravenously appears to be safe and effective antihypertensive treatment.     

Blood pressure control in patients with mild to moderate essential hypertension switched from nifedipine gastrointestinal therapeutic system (GITS) 30 mg to nifedipine GITS 20 mg

BACKGROUND: Nifedipine gastrointestinal therapeutic system (GITS) is a once-daily formulation of nifedipine that provides sustained plasma nifedipine concentrations throughout the 24-hour dosing interval. OBJECTIVE: This study was undertaken to determine if adult patients with mild to moderate essential hypertension whose blood pressure had been controlled for > or = 3 months with nifedipine GITS 30 mg could be successfully switched to a 20-mg daily dose with continued antihypertensive efficacy. METHODS: This was a randomized, double-blind, parallel-group study. Patients entered a 1-week run-in period during which they continued to receive their usual antihypertensive medication, including nifedipine GITS 30 mg. After baseline assessment, patients entered a 6-week treatment period during which they were randomly assigned to receive nifedipine GITS 30 or 20 mg. Men and women were eligible to participate if they were > or = 55 years of age, had received a diagnosis of mild to moderate essential hypertension (sitting diastolic blood pressure [DBP] 95-114 mm Hg), and had exhibited good blood pressure control (sitting DBP < or = 90 mm Hg) while taking nifedipine GITS 30 mg once daily for > or = 3 months. Systolic blood pressure (SBP), DBP, and heart rate were recorded at baseline and after 1, 3, and 6 weeks of treatment. Adverse events were reported by patients. The responder rate was defined as the percentage of patients whose sitting DBP was < 95 mm Hg at the final study assessment. Results were based on the intent-to-treat analyses, which included data for all patients who received > or = 1 dose and had 1 postbaseline blood pressure assessment. Statistical significance was set at P < 0.05. RESULTS: Seventy-five patients entered the 1-week run-in period; 71 patients (94.7%) were randomized to treatment. Twenty-four patients received nifedipine GITS 30 mg for 43.0 +/- 3.3 days, and 47 patients received nifedipine GITS 20 mg for 42.5 +/- 6.7 days. Both groups exhibited a sustained decrease in blood pressure throughout the study; minor variations were not statistically significant. End-point SBP and DBP for the 30- and 20-mg groups were 135.5 +/- 9.8/81.7 +/- 5.4 mm Hg and 138.6 +/- 11.8/82.9 +/- 7.6 mm Hg, respectively. Changes from baseline in end-point SBP and DBP did not differ significantly between groups. At the end of treatment, goal DBP (< 95 mm Hg) was achieved by 24 of 24 patients (100%) receiving the 30-mg dose and 45 of 47 patients (95.7%) receiving the 20-mg dose. Blood pressure control (sitting DBP < 90 mm Hg) was achieved by 21 of 24 (87.5%) patients in the 30-mg group and 35 of 47 (74.5%) patients in the 20-mg group. The most commonly reported adverse event was headache; 2 patients discontinued the study because of adverse events. Overall, 9 of 24 patients (37.5%) in the 30-mg group and 14 of 47 patients (29.8%) in the 20-mg group experienced > or = 1 treatment-related adverse event. CONCLUSIONS: Patients whose mild to moderate essential hypertension is controlled with nifedipine GITS 30 mg once daily may be able to switch to 20 mg once daily with continued antihypertensive efficacy. In addition to safety and economic advantages, such a switch may be a reasonable alternative in patients with lower body weight or as an adjunct to existing antihypertensive therapy.