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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The physicochemical properties, pharmacology, pharmacokinetics, cardiovascular and metabolic effects, adverse effects, dosage, and administration of doxazosin are described, and comparative clinical studies of doxazosin therapy in patients with mild to moderate hypertension are reviewed. Doxazosin mesylate, an alpha 1-adrenoceptor antagonist, is rapidly absorbed after oral administration and undergoes extensive hepatic metabolism. The drug decreases blood pressure by reducing peripheral resistance. Maximum hypotensive effects occur four to eight hours after the dose. Doxazosin favorably affects serum lipids by increasing concentrations of high-density lipoprotein (HDL) cholesterol, increasing the HDL:total cholesterol ratio, and decreasing concentrations of low-density lipoprotein cholesterol, total cholesterol, and triglycerides. In comparative clinical trials, doxazosin lowered standing and supine systolic and diastolic blood pressures as effectively as other alpha-adrenoceptor antagonists, beta-adrenoceptor antagonists, diuretics, angiotensin-converting-enzyme inhibitors, and calcium-channel-blocking agents. The most frequently reported adverse effects are dizziness, headache, nausea, lethargy, and fatigue. Doxazosin may be used either alone or in combination with a beta-adrenoceptor inhibitor or a diuretic. Orthostatic hypotension after the first dose occurs infrequently and may be minimized by initiating therapy at a dosage of 1 mg/day. The dosage may be increased at two-week intervals as needed, and blood pressure should be closely monitored. Doxazosin has blood-pressure-lowering effects comparable to those of other alpha 1-adrenoceptor inhibitors and to those of antihypertensives in other drug classes.
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PMID:Doxazosin: a new alpha 1-adrenergic antagonist. 134 55

Doxazosin, an alpha 1-adrenergic inhibitor, has been shown to decrease hypertension and plasma lipids, especially total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), thus reducing certain risk factors associated with increased incidence of cardiovascular disease. One preliminary report indicated that the decrease in LDL-C in hypercholesterolemic hamsters treated with doxazosin was associated with a reduction in fatty streak formation. However, since the effects of doxazosin on plasma lipids, aortic fatty streak development, or the relationship between the two have not been studied in a dose-dependent manner, these effects were further investigated over varying doses of doxazosin (0, 1, 5, 10, and 20 mg/kg body wt/day) during a 10-week period. Doxazosin administration was associated with a dose-dependent decrease in LDL-C of 2%, 29%, 52%, and 60%, whereas the degree of fatty streak formation was reduced 11%, 45%, 76%, and 92% compared with controls, with the first statistically significant decrease for both parameters at the 10 mg/kg dose. Significant correlations between LDL-C concentrations and fatty streak area suggest that doxazosin altered aortic lipid infiltration primarily by its effect on plasma lipids. However, the 20 mg/kg dose of doxazosin significantly decreased lesion area compared with the 10 mg/kg dose without a further effect on plasma lipid concentrations. Three animals at these higher doses demonstrated no stainable lipid inclusions while maintaining plasma lipid values similar to their cohorts. These exceptions to the lipid-lesion relationship raise the possibility of additional effects of doxazosin, which may occur independent of or in concert with lipoprotein cholesterol lowering, on lesion formation.
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PMID:Dose-related effects of doxazosin on plasma lipids and aortic fatty streak formation in the hypercholesterolemic hamster model. 135 67

Doxazosin, an alpha-adrenergic antagonist with potentially favourable effects on lipid status was evaluated in 25 otherwise healthy general practice patients with mild to moderate hypertension. A mean dose of 5.7 mg produced a significant fall in lying and standing systolic and diastolic blood pressure over an 11 week period as well as an 8% increase in HDL cholesterol and a 7.5% decrease in the total cholesterol/HDL cholesterol ratio. Following this, the doxazosin dose was halved and pindolol, a beta-blocker with intrinsic sympathomimetic activity, was added (mean dose 7.8 mg) to maintain blood pressure control. At the completion of 11 weeks of combined alpha- and beta-blockade, HDL cholesterol and triglyceride levels were found to be unaltered when compared to pretreatment; however there was a small but significant fall in total cholesterol. This study demonstrates that this combination of alpha- and beta-blocking antihypertensive therapy can produce potentially favourable blood lipid changes.
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PMID:Combined effect of doxazosin and pindolol on blood pressure control and lipid concentrations in patients with essential hypertension selected from general practice. Hunter Hypertension Research Group. 135 27

A reduced venous compliance and/or inadequate venoconstriction could impair hemodynamics during hemodialysis. Therefore, compliance and reactivity of the peripheral venous system were assessed in hemodialysis patients and controls using strain gauge plethysmography. Reactivity of the venous system towards an efferent sympathetic stimulus was assessed using a cold pressor test. Results showed that venous compliance was reduced in hypertensive hemodialysis patients compared to normotensive dialysis patients (P = 0.013) and normotensive controls (P = 0.004). After one dosage with a directly acting venodilator (nitroglycerin 5 mg s.l.) and 3 days of treatment with an alpha 1-sympathicolytic agent (Doxazosin 2 mg), venous compliance remained unaltered in hypertensive dialysis patients. During the cold pressor test, the blood pressure response, rise in noradrenaline levels and decline in venous compliance were normal in hemodialysis patients. However, their response to the Valsalva manoeuver was significantly impaired (P = 0.011) compared to healthy controls. We conclude that hypertension, not renal failure, causes the reduction of peripheral venous compliance in hemodialysis patients, for which structural factors might be responsible. Despite the existence of autonomous neuropathy, the reaction of the peripheral venous system towards an efferent sympathetic stimulus is intact in hemodialysis patients.
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PMID:Compliance and reactivity of the peripheral venous system in chronic intermittent hemodialysis. 135 48

Twenty-two patients with diabetes and hypertension were treated with Doxazosin. An acceptable fall in blood pressure was found with 1 mg. in 50% of patients and 2-8 mgs. in 50%. An increase in HDL cholesterol and a fall in LDL cholesterol levels which reached statistical significance was observed. A small but significant increase in HBA1 levels occurred in the 50% of patients on the higher Doxazosin dose.
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PMID:Doxazosin in the management of hypertensive diabetes--a cautionary note (?). 138 16

The effect of doxazosin, an alpha 1-adrenoceptor blocking drug, on blood pressure, sensitivity to insulin and serum lipids has been evaluated in 14 hypertensive, non-insulin dependent diabetic patients. The dose was titrated individually upwards from 1 mg until the diastolic blood pressure was below 90 mm Hg, side-effects precluded further dosage increase or the maximum daily dose of 16 mg was achieved. After 12 weeks of treatment (mean doxazosin dose 5.6 +/- 5.1 mg daily), the supine and standing diastolic blood pressure of the patients had declined by about 7 mm Hg, whereas their systolic blood pressure and heart rate were not significantly changed. The metabolic clearance rate of glucose increased from 2.35 to 3.37 ml.min-1.kg-1 during treatment, suggesting improved sensitivity to insulin. Fasting plasma glucose was 11.9 mmol.l-1 before and 10.9 mmol.l-1 after doxazosin therapy (NS). Serum electrolytes and lipids did not change significantly but serum uric acid decreased from 305 to 281 mumol.l-1. Doxazosin may be a useful alternative for the treatment of hypertension in NIDDM patients.
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PMID:Effect of doxazosin on insulin sensitivity in hypertensive non-insulin dependent diabetic patients. 145 14

The antihypertensive efficacy and safety of doxazosin (once daily) and prazosin (twice daily) were compared in patients with mild or moderate essential hypertension (diastolic blood pressure [DBP] 95 to 114 mm Hg) not adequately controlled by diuretics and beta-blockers. Doxazosin produced significantly greater mean reductions in standing (p = 0.01) and supine (p = 0.04) DBP than did prazosin; there were no significant between-group differences in either mean systolic blood pressure or heart rate. The overall mean daily doses for efficacy-evaluable patients were 4.7 mg of doxazosin and 6.7 mg of prazosin. Sixteen patients (84.2%) treated with doxazosin and 13 patients (56.5%) treated with prazosin were considered therapeutic successes (decrease in standing DBP greater than or equal to 10 mm Hg or to less than or equal to 90 mm Hg with greater than or equal to 5 mm Hg reduction from baseline). Of the 19 efficacy-evaluable patients treated with doxazosin, 15 (78.9%) showed improvement in the severity category of hypertension; an improvement in severity was reported in 14 patients (60.9%) treated with prazosin. Doxazosin produced a more favorable effect on serum lipid levels than did prazosin, although no statistically significant within- or between-group differences were observed. Most side effects experienced with either doxazosin or prazosin were mild or moderate and were tolerated or disappeared with continued treatment. The overall evaluation of toleration was excellent or good for 18 (90%) doxazosin- and 21 (91%) prazosin-treated patients. Clinical efficacy was rated as excellent or good for 16 patients (80%) treated with doxazosin and 15 patients (68%) treated with prazosin.
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PMID:A double-blind comparative study of doxazosin and prazosin when administered with beta-blockers or diuretics. 167 Jul 44

The goal of antihypertensive treatment must be not only the reduction of high blood pressure, but also the effective management of elevated cholesterol levels and other risk factors of coronary heart disease (CHD). In controlled clinical trials, doxazosin has been shown to have antihypertensive efficacy comparable with other classes of antihypertensive agents and to lower the levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides while increasing the levels of high-density lipoprotein cholesterol. Doxazosin appears to inhibit the development of CHD on two fronts. First, doxazosin binds to the alpha 1-adrenoreceptor and inhibits the receptor-mediated responses to epinephrine and norepinephrine. Second, doxazosin has direct and indirect effects on lipid metabolism by increasing LDL receptor activity, decreasing intracellular LDL synthesis, reducing the synthesis and secretion of very low-density lipoprotein cholesterol, and stimulating lipoprotein lipase activity. Doxazosin may also inhibit platelet aggregation. Long-term studies will determine how these actions translate into reductions in the morbidity and mortality rates of CHD. First-year results from the Treatment of Mild Hypertension Study (TOMHS) have demonstrated expected reductions in blood pressure for all antihypertensive agents studied. The lipid changes have varied with the type of antihypertensive treatment and have been favorable for doxazosin.
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PMID:Effects of doxazosin on serum lipids: a review of the clinical data and molecular basis for altered lipid metabolism. 182 47

In practice, some of the major problems for the physician who treats hypertension are patients who are resistant to treatment or who have other complicating risk syndromes. Therefore the overall efficacy of an antihypertensive agent must include an assessment of effect in patients with serious ancillary problems. In this article, doxazosin is reviewed for its efficacy in the treatment of severe essential hypertension and specific complications or conditions of mild or moderate essential hypertension, namely, left ventricular hypertrophy, hyperlipidemia, noninsulin-dependent diabetes mellitus, renal insufficiency, pheochromocytoma, chronic obstructive pulmonary disease, peripheral vascular disease, and smoking. Doxazosin is particularly efficacious in many specific subgroups of patients with hypertension, and the results of relevant studies are discussed.
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PMID:Efficacy of doxazosin in specific hypertensive patient groups. 182 52

This study investigated the safety and efficacy of doxazosin treatment in a large population of patients (n = 336) with essential hypertension and assessed the effect of doxazosin on the serum lipid profile and the calculated risk of developing coronary heart disease. Patients were assigned to two groups: those with a baseline diastolic blood pressure greater than or equal to 95 mm Hg (group 1) and those with a baseline diastolic blood pressure less than 95 mm Hg (group 2) that was controlled by previous antihypertensive therapy. Doxazosin treatment (monotherapy in 76.2% of patients) significantly (p less than 0.05) reduced the blood pressure of patients in group 1 (-23/-17 mm Hg) after 10 weeks and maintained the control of blood pressure for patients in group 2. Heart rate was essentially unchanged in both groups. Mean final daily doses of 3.6 and 3.2 mg were achieved in groups 1 and 2, respectively. Treatment with doxazosin improved the severity category of hypertension for 88.4% of patients in group 1; 87.3% of patients were considered a therapy success. Doxazosin had a favorable effect on the serum lipid profile in both groups of patients. The majority of lipid changes achieved statistical significance and resulted in a significant 27% decrease in the calculated risk of developing coronary heart disease. Doxazosin was well tolerated; only 24.1% of patients had side effects that were related or possibly related to treatment. In nine (2.7%) patients the dose of doxazosin was reduced and 26 (7.7%) patients withdrew from doxazosin therapy because of side effects.
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PMID:Clinical experience with doxazosin in general medical practice in New Zealand. 182 55


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