Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical assessment of a novel antihypertensive drug combination was undertaken in a group of essential hypertensive patients (n = 20). The effects of several doses of clonidine and its association with prazosin on blood pressure (BP), systolic time intervals (STI), and electrocardiogram (ECG) were investigated. Clonidine monotherapy induced a good BP control at 60%. BP was controlled in those patients in which prazosin was combined with clonidine (87.7%). LVETc was reduced by 0.3, 0.6, and 0.9 mg clonidine daily (p less than 0.05). PEPc was increased by only 0.9 mg, and it was diminished after its combination with 20 mg prazosin daily (p less than 0.05). PEP/LVET index was significantly increased by a higher dose of clonidine (p less than 0.05). ECG intervals did not change with the exception of PR, which was prolonged by 0.9 mg clonidine daily (p less than 0.05). Dry mouth, sedation, constipation, and drowsiness were the main side effects observed during the investigation. These results suggest an alternative treatment of essential hypertension, with a novel clinical application of drugs such as clonidine and prazosin, which have pharmacologic action via different alpha-adrenergic mechanisms.
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PMID:Clonidine and prazosin in the treatment of hypertensive outpatients--a preliminary study. 664 91

This study analysed the effects of both seven and 30 days of treatment with clonidine on heart rate, blood pressure (BP), plasma norepinephrine (NE) levels and dopamine-beta-hydroxylase (DBH) activity at rest and after standing in seven patients with essential hypertension. The patients and 10 age-matched normotensive control subjects were evaluated under medication-free baseline conditions; the hypertensive patients were then given clonidine 0.1 mg twice daily. Baseline plasma NE and DBH levels were similar between the groups. Seven and 30 days of clonidine therapy reduced blood pressure (p less than 0.001) and NE concentrations (p less than 0.05) significantly. Clonidine did not effect the percent increase in NE induced by standing and was not associated with orthostatic hypotension. The blood pressure lowering effects of clonidine appear related to the centrally mediated and/or direct suppression of peripheral noradrenergic activity, indicating the utility of clonidine in cases of hypertension were the sympathetic nervous system (SNS) is hyperactive. Clonidine may also prove especially useful in cases where the initial pharmacotherapy (such as a diuretic) causes activation of the SNS.
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PMID:Effect of clonidine on sympathetic nervous system activity in patients with essential hypertension. 667 10

Clonidine was given orally as monotherapy in increasing daily doses from 3.1 to 25.7 micrograms/kg to patients with essential hypertension (n = 6). When a steady state concentration in plasma was reached at each dose level, the blood pressure (BP) and heart rate were measured during a dosage interval. Effect time-plasma concentration data were submitted to nonlinear regression analysis, which showed that the observed BP effects could be dissociated into depressor and pressor components. A window for the anti-hypertensive effect was established. At a plasma clonidine concentration of 0.65 +/- 0.07 ng/ml 50% of the maximal depressor effect was found, and it was only separated by a factor of 2 from the half maximal pure pressor concentration in plasma. No relationship between the change in heart rate and the plasma clonidine was observed. The findings strengthen the importance of close monitoring of clonidine therapy.
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PMID:Relationship between the cardiovascular effects and steady-state kinetics of clonidine in hypertension. Demonstration of a therapeutic window in man. 673 92

To determine whether the alpha-adrenergic antagonist phenoxybenzamine would alter cardiovascular or plasma catecholamine response to the alpha-adrenergic agonist clonidine, six patients with pheochromocytomas and eight with labile hypertension were studied. Clonidine, 0.3 mg, was given with and without 48 hr pretreatment with 30 mg/day phenoxybenzamine. The response to 10 mg diazepam was also observed in seven of the subjects who had labile hypertension. In the hypertensive patients, clonidine alone induced a fall in supine blood pressure from 137 +/- 21/91 +/- 14 to 109 +/- 18/76 +/- 17 mm Hg and, with phenoxybenzamine, clonidine reduced blood pressure from 141 +/- 22/89 +/- 10 to 107 +/- 21/72 +/- 11 mm Hg. Plasma norepinephrine fell from 179 +/- 60 to 107 +/- 79 pg/ml without phenoxybenzamine and from 229 +/- 159 to 95 +/- 46 pg/ml with phenoxybenzamine in hypertensive subjects. Responses with phenoxybenzamine did not differ from those without phenoxybenzamine and diazepam induced no cardiovascular or plasma catecholamine changes. Clonidine did not lower plasma catecholamines in patients with a pheochromocytoma in the presence or in the absence of phenoxybenzamine. Blood pressure tended to decline after clonidine in pheochromocytoma patients not taking phenoxybenzamine, but it was not reduced by clonidine when these patients were taking phenoxybenzamine. Phenoxybenzamine does not inhibit reduction in blood pressure and plasma catecholamines induced by clonidine in patients with essential hypertension or interfere with the clonidine suppression test in patients with pheochromocytomas.
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PMID:Effect of phenoxybenzamine on cardiovascular and plasma catecholamine responses to clonidine. 682 28

Two studies of the responses to clonidine as the sole antihypertensive drug in the treatment of mild-to-moderate hypertension are reported. In the first, 11 patients with mild hypertension were treated with 0.1 mg clonidine twice daily for eight weeks. Those patients with "low renin" hypertension (n = 7) were noted to show an increase in plasma renin activity; the patients with "normal renin" hypertension (n = 4) tended to show a decrease. Both groups had a similar decrease in blood pressure. The changes in renin activity correlated significantly (p less than 0.01) with the small changes in endogenous creatinine clearance (r = 0.84). In the second study, 16 patients with mild-to-moderate essential hypertension were treated for three months with 0.2 mg clonidine three times daily. Blood pressure decreased from 167 +/- 4/105 +/- 2 to 140 +/- 3/90 +/- 2 mm Hg (p less than 0.01). Blood pressure changes correlated with decreases in plasma catecholamines (r = 0.61, p less than 0.001) and heart rate (r = 0.78, p less than 0.001). No significant changes in cardiac output, blood volume, renal blood flow, or glomerular filtration rate were noted. Clonidine is an effective and safe therapy when used as the sole medication in treating mild-to-moderate hypertension.
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PMID:Hormonal and hemodynamic effects of short- and long-term clonidine therapy in patients with mild-to-moderate hypertension. 682 31

Forty-eight elderly patients with uncomplicated mild essential hypertension entered two drug regimens. In group 1, clonidine monotherapy (n = 15), clonidine was titrated to achieve goal blood pressure (less than 90 mm Hg diastolic) in dosages of 0.05 mg twice daily to 0.2 mg three times daily. Blood pressure decreased without major side effects (p less than 0.001). Three patients required small doses of diuretic after six months of clonidine monotherapy. In group 2, step-care therapy (n = 33), clonidine was added to chlorthalidone, 25 mg daily, for three weeks. Eight patients achieved the goal blood pressure with chlorthalidone, 25 required clonidine (0.1 mg to 0.3 mg twice daily) to achieve blood pressure control. Side effects of clonidine did not require discontinuation of therapy. Retrospective analysis of up to 2 1/2 years of clonidine plus diuretic (n = 51) showed a similar blood pressure reduction. Clonidine can be used effectively with or without a diuretic in the elderly hypertensive.
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PMID:Clonidine in the elderly hypertensive. Monotherapy and therapy with a diuretic. 682 40

Eight patients with essential hypertension, WHO grade I-III, were studied under standardized conditions in a metabolic ward, before and after 8-20 weeks of treatment with clonidine in a maintenance dose of 300-600 micrograms/24 h. Before clonidine, plasma noradrenaline concentration (PNA), plasma adrenaline concentration (PA), plasma renin activity (PRA) and plasma aldosterone concentration (PAC) increased in response to standing and submaximal exercise for 20 min. PNA was positively correlated to pulse rate in the supine position (R = 0.74, p 0.05) and the increase in PNA to the increase in pulse rate during exercise (min 10, R=0.73, p less than 0.05; min 15, R = 0.79, p less than 0.05; min 20, R = 0.74, p less than 0.05). No other significant correlations were found between PNA, PA, PRA and PAC on the one hand and blood pressure (BP) and pulse rate on the other. Clonidine reduced BP, pulse rate, PNA and PRA under all conditions studied. PA was reduced in the upright position and in connection with exercise. PAC was reduced during clonidine after exercise but otherwise unaltered. The clonidine-induced decrease in PNA was positively correlated to the decrease in diastolic BP both in the supine (R = 0.76, p less than 0.05) and in the upright (R = 0.80, p less than 0.05) position. thus, long-term clonidine treatment lowered the BP and pulse rate, at least partly by reducing sympathetic activity via a central mechanism. However, clonidine did not block the sympathetic reflex mechanisms engaged in the maintenance of BP in the upright position. During clonidine, the adrenaline values were lower than before treatment in the supine and in the upright position and also following exercise, indicating that clonidine exerts an inhibitory effect on the sympatho-adreno-medullary system.
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PMID:Prolonged clonidine treatment: catecholamines, renin activity and aldosterone following exercise in hypertensives. 701 96

Sixteen patients with uncomplicated essential hypertension were treated with 0.2 mg of clonidine three times daily as the sole antihypertensive drug. Blood pressure decreased from 167 +/- 4/105 +/- 2 to 139 +/- 3/89 +/- 2 mm Hg (mean +/- standard error of the mean) after 1 week (p less than 0.001) and remained at 140 +/- 3/90 +/- 2 mm Hg after 3 months of therapy. There were no significant changes in cardiac output, blood volume, renal blood flow or glomerular filtration rate during clonidine therapy. Clonidine significantly decreased plasma catecholamines and there was a linear correlation between the change in blood pressure and decreases in plasma catecholamine concentration (r = 0.61, p less than 0.001). There was also a significant correlation between the decreases in heart rate and blood pressure (r = 0.78, p less than 0.001). It is concluded that clonidine can be used effectively and safely as the sole agent in the treatment of mild to moderate hypertension.
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PMID:Clonidine, a centrally acting sympathetic inhibitor, as monotherapy for mild to moderate hypertension. 703 69

Two sets of studies were performed in 13 patients with proved adrenal pheochromocytoma to test the hypothesis that the sympathetic nervous system (SNS) is active and might contribute to the hypertensive state. Similar studies were performed in 15 additional patients considered to have essential hypertension. In the first set, 13 patients with pheochromocytoma were subjected to head-up tilt to assess the activity of the SNS. This maneuver decreased diastolic blood pressure in only two; heart rate increased appropriately in all except one. Changes in plasma norepinephrine (NE) were variable and did not correlate with changes in blood pressure (BP) and heart rate (HR). In the second set, 10 patients with pheochromocytoma were given a single oral dose of clonidine (0.3 mg) to evaluate what role, if any, the SNS might contribute to the hypertensive state. Fifteen patients with essential hypertension were studied similarly for comparison. Clonidine produced significant decreases in BP and HR but left plasma renin activity unchanged in both groups. In essential hypertension, the cardiovascular responses were accompanied by significant reductions in plasma NE. By contrast, plasma NE was unchanged in patients with pheochromocytoma, despite similar reductions in BP and HR. These results suggest that the sympathetic reflexes are intact in pheochromocytoma, and that much of the hypertension associated with these tumors may be related to increased sympathetic activity.
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PMID:Blood pressure regulation in pheochromocytoma. 704 Feb 38

1 Clonidine kinetics were studied in 21 patients with essential hypertension. All received two bolus i.v. injections in the mean dose range of (0.78--3.36 micrograms kg-1) and one single oral dose (mean dose 1.7--2.3 micrograms kg-1) on separate occasions. The kinetics were also studied in some of these patients after multiple therapeutic oral dose (mean dose 1.1 or 1.9 micrograms kg-1) twice daily during a dosage interval after 6--12 months monotherapy with clonidine. The multiple oral dosage was based on the therapeutic response. 2 With increasing i.v. doses the rate constants (alpha, beta) decreased and the plasma clearance was reduced by 74% (9.94--2.61 ml min-1 kg-1) indicating dose-dependent kinetics. The volume of distribution (Vd beta) did not change with dose in contrast to the volume of the plasma compartment (Vc) which was increased at the highest doses. 3 The single oral dose kinetics agreed with the i.v. kinetics at comparable dose. The bioavailability was 90%. 4 During multiple oral dosing the elimination rate constants decreased compared to the single dose. The plasma clearance increased (7.18 ml min-1 kg-1) compared to the corresponding single dose (4.17 ml min-1 kg-1). The latter change was probably caused by the decrease in bioavailability to about 65%. 5 The pharmacodynamic properties of the drug could explain the changes in pharmacokinetics with increased dose and during multiple doses.
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PMID:Clonidine kinetics in man--evidence for dose dependency and changed pharmacokinetics during chronic therapy. 733 29


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