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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

4,260 patients were included in an open surveillance study simultaneously with the introduction of doxazosin for treatment of essential hypertension in Norway. The main aim of the study was to systematically collect information on side effects and events in patients being treated with a new drug. The effect on blood pressure, heart rate and lipids was also recorded. The study lasted for one year. 21 deaths were reported. 53% of the patients reported side effects and/or events. The frequency of side effects was particularly high during the first month of treatment. No new types of side effects were found. The initial higher frequency of reported side effects referred to all organ systems, and was also of the same magnitude in the different systems. A relation was found between certain cardiac side effects and/or events and cessation of previous medication upon starting treatment with doxazosin. The study shows that certain safety precautions should be observed in patients with coronary heart disease and heart failure. In three patients, doxazosin should be used only in combination with more specific treatment. Special caution should be observed when changing the specific basic treatment. Doxazosin had a very favourable antihypertensive effect. A drop in cholesterol and triglycerides was observed, as expected. The HDL-cholesterol value declined, which was unexpected. The results are difficult to interpret, owing to lack of a control group. On the other hand, the study shows how high blood pressure is being treated with drugs in ordinary practice. The authors discuss the methodology of surveillance studies.
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PMID:[Doxazosin (Carduran)--a research survey]. 790 29

In a previous open study on the metabolic effects of doxazosin in patients with essential hypertension, subgroup analysis indicated that subjects with an accumulation of risk factors for coronary heart disease (high VLDL triglycerides, low HDL cholesterol and high fasting blood glucose) seemed to benefit most from the metabolic actions of doxazosin treatment. Those results formed the basis of this double-blind, parallel-group study undertaken to elucidate the metabolic effects of 6 months of doxazosin and enalapril treatment in patients with both essential hypertension and hypertriglyceridemia. Insulin sensitivity was measured with the euglycemic hyperinsulinemic clamp method. Hemodynamic evaluation included measurements of office and ambulatory blood pressure and ultrasonic measurements of femoral artery blood flow. Both drugs significantly reduced both office BP and 24-h ambulatory BP. Office systolic BP was significantly better reduced by enalapril. Doxazosin, in contrast to enalapril, significantly increased insulin sensitivity (by 21%, P = .02). It also reduced serum-triglycerides (by 23%, P = .01), VLDL triglycerides (by 30%, P = .008) and VLDL cholesterol (by 24%, P = .02). This lipid-lowering effect of doxazosin was accompanied by an increase in both plasma lipoprotein lipase activity and the elimination rate of an intravenous fat emulsion load. Neither treatment significantly increased femoral artery blood flow. It is speculated that without measurably increasing blood flow in conduit vessels such as the femoral artery, doxazosin, by capillary recruitment, may prolong the transit time for the blood over the muscle bed, which could explain the increased glucose disposal and increased lipoprotein lipase activity.
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PMID:Metabolic effects of doxazosin and enalapril in hypertriglyceridemic, hypertensive men. Relationship to changes in skeletal muscle blood flow. 872 35

This single-blind study assessed the role of the sympathetic nervous system in primary hypertensives, at rest and during stress, and examined blood pressure responses to an alpha 1-blocker, doxazosin. Twenty patients were selected who had a sitting diastolic blood pressure 95 to 115 mm Hg at the end of the placebo period. Doxazosin was given in doses of 1 mg per day initially, then increased weekly to 2, 4, 8, and 16 mg, until goal blood pressure or maximum dose was reached or side effects limited further increase. Their determined dose of doxazosin was held constant for 16 weeks of the maintenance period. Mental and isometric stress tests were performed at the end of placebo and at the first and last months of maintenance. Diastolic blood pressures were related to baseline plasma norepinephrine, r = 0.61, P < .01. The dose of doxazosin administered was 8.4 +/- 4.1 mg. After 4 months of therapy, doxazosin lowered blood pressure from 147 +/- 16/99 +/- 3 to 135 +/- 5/87 +/- 8 sitting, and from 146 +/- 14/99 +/- 6 to 130 +/- 14/86 +/- 7 standing, respectively. Heart rates were not changed. The reduction of standing systolic blood pressure was related to baseline norepinephrine in the 12 patients who reached goal blood pressure, r = 0.57, P < .05. During mental and isometric stress tests, the percentage changes of blood pressures were related to their baseline plasma norepinephrine. Doxazosin reduced the percentage increments of blood pressure during mental stress 12.2 +/- 5.7/11.8 +/- 4.3% versus 5.7 +/- 1.0/8.1 +/- 7.4%, P < .01/.05. Doxazosin also blunted the diastolic blood pressure response to isometric exercise from 18.3 +/- 12.2% to 9.3 +/- 11.0%, P < .05. Neurogenic factors participate in the elevation of blood pressure in some patients with primary hypertension. The alpha-blocker doxazosin was effective in 60% of the hypertensive patients--it controlled blood pressure during laboratory stress, suggesting particular value in reduction of blood pressure during ambient stress of everyday living.
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PMID:Neural mechanisms in primary hypertension. Efficacy of alpha-blockade with doxazosin during stress. 883 6

Hemorheological factors play an important role in the pathogenesis of different cardiovascular diseases. The hemorheological and hemodynamic parameters in essential hypertension and their possible modification by antihypertensive treatment were examined in the following two studies. In the first study the fundus appearance and hemorheological parameters (plasma and whole blood viscosity (WBV), fibrinogen level) of 33 hypertensive patients (mean age: 55 years) were examined. The fundus appearance showed retinopathy in all the cases between stages I-III. All the measured hemorheological parameters of the examined patients were in the pathological range (WBV at 90 s(-1): 5.18 mPa s) and were significantly (p < 0.01) higher than in healthy controls (WBV at 90 s(-1): 4.18 mPa s). The hemorheological factors showed a parallel deterioration with the fundus appearance, namely their values were significantly (p < 0.01) higher in patients with a fundus appearance stage III (WBV at 90 s(-1): 6.02 mPa s) than stage I (WBV at 90 s(-1): 4.51 mPa s). These results show that there is a correlation between hemorheological parameters and fundus appearance in hypertensives, and this suggests that hemorheological factors may play a role in the development of hypertensive retinopathy. In the second study the hemorheological and hemodynamical effects of Doxazosin, a selective alpha-1-adrenoreceptor blocker agent, was examined in twenty patients (mean age: 54 years) with essential hypertension. Hemorheologic (hematocrit, fibrinogen, plasma and whole blood viscosity) and hemodynamic (cardiac output and index, total peripheral resistance) parameters and plasma lipids were determined. The measurements were carried out before the beginning of the treatment, after 1 week and after 12 weeks treatment periods. Besides significant reduction of blood pressure and total peripheral resistance (p < 0.001), a decrease in cholesterol (p < 0.001) and triglycerides (p < 0.01) levels and a beneficial effect on hemorheological parameters was detected. Fibrinogen and plasma viscosity decreased significantly (p < 0.01). Hematocrit value was also lower after one week (p < 0.001), then an increase could be seen. Whole blood viscosity showed similar changes as hematocrit, but the degree of its final increase was slighter, which was supported by the significantly lower value of corrected blood viscosity (p < 0.05). All these findings indicate that hemorheological factors may play a role in the pathogenesis and in the development of organ damages in hypertension.
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PMID:Hemorheological and hemodynamic parameters in patients with essential hypertension and their modification by alpha-1 inhibitor drug treatment. 1071 45

Patients with peripheral vascular disease or diabetes mellitus tend to have elevated circulating levels of naturally occurring platelet agonists like serotonin (5 hydroxytryptamine; 5-HT). This bioamine can induce platelet shape change (PSC) an early phase of platelet activation, which is essentially aspirin resistant. In addition, 5-HT exerts other harmful effects (eg stimulating vascular smooth muscle proliferation and inducing vasoconstriction in atheromatous coronary vessels). The aim of this study was to determine whether doxazosin inhibits 5-HT-induced PSC. Doxazosin is a long acting alpha(1)-adrenoceptor antagonist, used in the treatment of essential hypertension and/or benign prostatic hyperplasia (BPH). Platelet rich plasma (PRP) was prepared from healthy volunteers (n = 8; five males and three females with a median age of 32 years, range: 26-57). Agonists (5-HT, 0.06-0.5; ADP, 0.1-0.2 micromol/l or U46619, a TXA(2)analogue, 0.025-0.05 micromol/l) were added to PRP and aliquots were removed at specific time points for median platelet volume (MPV) measurement (using a high-resolution channelyser). The MPV was used as an indicator of PSC. PRP was also incubated with doxazosin (final concentration: 0.33 microM, a concentration similar to therapeutic plasma levels) prior to the addition of each of the above-mentioned agonists. Doxazosin significantly inhibited (P = 0.007 and P = 0.008, at 30 sec and 60 sec, respectively) the 5-HT-induced increase in MPV. Doxazosin did not significantly inhibit ADP- or U46619-induced PSC. The inhibitory effect of doxazosin seems to be specific to platelet 5-HT(2) receptors, since there was no effect on ADP- or U46619-induced PSC. This inhibition of platelet activation may be an additional, clinically relevant, advantage. Future in vivo studies should consider assessing the effect of doxazosin on 5-HT-induced platelet activation.
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PMID:Doxazosin, an alpha1-adrenoceptor antagonist, inhibits serotonin-induced shape change in human platelets. 1131 6

Essential hypertension is associated with impairment of both endothelial function and insulin action, and this has provided rationale for the use of antihypertensive agents that are at least neutral, if not beneficial, in these areas. This study examines the effect of the alpha-adrenergic blocker, doxazosin, on endothelial function and insulin action. Sixteen patients with essential hypertension were recruited with 13 (3 men/10 women; median age, 55 years; range, 38 to 65 years) completing the study. A double-blind, placebo-controlled crossover study design was used. After a 6-week placebo run-in, there were two 12-week treatment periods of either placebo or doxazosin, separated by a 6-week wash out period. Subjects were studied at the end of each treatment period with endothelial function assessed by forearm plethysmography and insulin action by the hyperinsulinemic clamp technique. Blood pressure was significantly lowered by doxazosin (doxazosin 144 +/-3/86 +/- 2 mm Hg; placebo 159 +/- 3/96 +/- 1 mm Hg, P <.005 for both systolic and diastolic pressure; mean +/- SEM). Baseline forearm blood flow (FBF) was unchanged (doxazosin 4.9 +/- 0.9; placebo 4.0 +/- 0.7 mL x 100 mL(-1) x min(-1), P >.05), however, FBF responses (area under dose response curve, percentage change in infused:control arm ratio) to acetylcholine (endothelium-dependent vasodilation) were improved by doxazosin (doxazosin 58.6 +/- 11.7 standard units [SU]; placebo 22.1 +/- 7.0 SU, P =.03) with responses to sodium nitroprusside (endothelium-independent vasodilation) unchanged (doxazosin 40.3 +/- 5.5 SU; placebo 46.3 +/- 8.1 SU, P >.05). Exogenous glucose infusion rates to maintain euglycemia during hyperinsulinemia were not significantly different (doxazosin 30.4 +/- 0.9; placebo 32.3 +/- 1.0 micromol x kg(-1) min(-1), P >.05). Suppression of postabsorptive endogenous glucose production by insulin was also unchanged by treatment (doxazosin 65.6% +/- 7.5% suppression; placebo 68.3% +/- 11.2% suppression, P >.05). Doxazosin has a neutral effect on both peripheral and hepatic insulin action, but improves endothelium-dependent vasodilation. These results indicate that doxazosin can be used safely in patients with insulin resistance, while its positive effect on endothelial function may lessen the subsequent incidence of atherosclerosis.
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PMID:Effect of the alpha-adrenergic blocker, doxazosin, on endothelial function and insulin action. 1450 21

Wave intensity analysis is a method of studying intravascular flow wave propagation, calculated as the product of the rate of change in pressure (d P/ t) and the rate of change in velocity (d U/d t). The typical pattern of wave intensity seen during the cardiac cycle has two dominant peaks. The larger first peak (FP) occurs during early systole when a forward traveling compression wave is generated by the left ventricle. The second smaller peak (SP) follows a period of relatively little net wave production during mid-systole. Wave reflection is seen as a small backward-traveling compression wave occurring just after the first peak of wave intensity (NP). In this study, we investigated the usefulness of parameters from the wave intensity for estimating the efficacy of the Alpha-1 blocker, doxazosin, to reduce blood pressure, by the reduction of peripheral vascular resistance. We examined 20 patients with essential hypertension. Patients were included if their diastolic blood pressure was >95 mmHg on at least three separate visits to the clinic. The study consisted of a 2-week baseline phase followed by a 2-4-week dose-adjusted phase with doxazosin. Treatment began with 1 mg/day doxazosin, and the dose was doubled fortnightly until the diastolic blood pressure was <90 mmHg. Blood-pressure measurements and side effects were recorded at intervals of 2 weeks. Before and after 4 weeks of stable treatment with doxazosin, a comprehensive clinical evaluation was given. Doxazosin reduced systolic and diastolic blood pressure. Both FP and SP increased and NP decreased. DeltaMBP (change in mean blood pressure) correlated well with NP before and after the antihypertensive therapy. The efficacy of doxazosin was confirmed by the decreased reflection wave of aortic flow from wave intensity analysis. Thus, patients with a significant reflection wave may be good candidates for antihypertensive treatment by a vasodilator, such as doxazosin.
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PMID:Clinical application of wave intensity for the treatment of essential hypertension. 1468 50

Previous studies have shown that a single nighttime dose of standard doxazosin, an alpha-adrenergic antagonist, reduces blood pressure (BP) throughout the 24 h. We investigated the administration-time-dependent effects of the new doxazosin gastrointestinal therapeutic system (GITS) formulation. We studied 91 subjects (49 men and 42 women), 56.7+/-11.2 (mean+/-SD) yrs of age with grade 1-2 essential hypertension; 39 patients had been previously untreated, and the remaining 52 had been treated with two antihypertensive medications with inadequate control of their hypertension. The subjects of the two groups, the monotherapy and polytherapy groups, respectively, were randomly assigned to receive the single daily dose of doxazosin GITS (4 mg/day) either upon awakening or at bedtime. BP was measured by ambulatory monitoring every 20 min during the day and every 30 min at night for 48 consecutive hours just before and after 3 months of treatment. After 3 months of doxazosin GITS therapy upon awakening, there was a small and nonstatistically significant reduction in BP (1.8 and 3.2mm Hg in the 24 h mean of systolic and diastolic BP in monotherapy; 2.2 and 1.9mm Hg in polytherapy), mainly because of absence of any effect on nocturnal BP. The 24 h mean BP reduction was larger and statistically significant (6.9 and 5.9 mm for systolic and diastolic BP, respectively, in monotherapy; 5.3 and 4.5 mm Hg in polytherapy) when doxazosin GITS was scheduled at bedtime. This BP-lowering effect was similar during both the day and nighttime hours. Doxazosin GITS ingested daily on awakening failed to provide full 24h therapeutic coverage. Bedtime dosing with doxazosin GITS, however, significantly reduced BP throughout the 24h both when used as a monotherapy and when used in combination with other antihypertensive pharmacotherapy. Knowledge of the chronopharmacology of doxazosin GITS is key to optimizing the efficiency of its BP-lowering effect, and this must be taken into consideration when prescribing this medication to patients.
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PMID:Administration-time-dependent effects of doxazosin GITS on ambulatory blood pressure of hypertensive subjects. 1533 47

High morning blood pressure is related to target organ damage and future cardiovascular events. Chronobiologic therapies focusing on the early morning period may be an important strategy for antihypertensive therapy. The aim of this study was to clarify the add-on effects of bedtime dosing of the alpha(1)-adrenergic receptor antagonist doxazosin on morning blood pressure in patients with essential hypertension who were under long-acting calcium channel blocker amlodipine monotherapy. The add-on effects of doxazosin at the maximum dose of 6 mg at bedtime on home blood pressure and left ventricular geometry for 1 year were investigated in 49 subjects (37 men and 12 women, aged 57.5+/-9.1 years) with morning hypertension who had been treated with amlodipine alone for more than 1 year. Doxazosin induced a significant decrease in morning blood pressure (145.6+/-5.6/91.5+/-5.4 to 132.4+/-3.7/83.6+/-5.6 mmHg, p<or=0.001/<0.001) without a change of evening blood pressure (128.9+/-5.1/79.8+/-5.1 to 127.7+/-6.0/78.8+/-6.2 mmHg, p=0.056/0.051). Left ventricular mass index (LVMI; 124.8+/-19.8 to 95.6+/-15.7 g/m(2), p<0.001), relative wall thickness (0.457+/-0.061 to 0.405+/-0.047, p<0.001) and homeostasis model assessment of the insulin resistance index (HOMA-IR; 2.62+/-1.43 to 1.33+/-0.75, p<0.001) were decreased after doxazosin therapy. A stepwise multivariate regression analysis revealed that the changes in morning systolic blood pressure (adjusted r(2)=34.9%, p<0.001) and HOMA-IR (adjusted r(2)=4.5%, p=0.046) were significant contributory factors to the change in LVMI after doxazosin therapy. These results suggest that bedtime dosing of doxazosin is useful for the control of morning blood pressure and regression of left ventricular hypertrophy.
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PMID:Add-on effect of bedtime dosing of the alpha(1)-adrenergic receptor antagonist doxazosin on morning hypertension and left ventricular hypertrophy in patients undergoing long-term amlodipine monotherapy. 1825 May 47


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