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)

The sympathetic nervous system plays a major role in the pathogenesis of essential hypertension and is mediated by the alpha and beta receptors. The alpha receptor is divided into two types, alpha 1 and alpha 2, based on response to epinephrine and norepinephrine. alpha 1-Adrenergic receptors have a high affinity for drugs such as prazosin, doxazosin, and terazosin, which act to reduce blood pressure by selective blockade of the receptor. These agents provide a rational approach to the treatment of hypertension by correcting elevated total peripheral resistance, the fundamental hemodynamic abnormality in essential hypertension. In contrast, early alpha-adrenergic receptor blockers nonselectively blocked both alpha 1 and alpha 2 receptors and were unsuitable as antihypertensive agents because they induced tachycardia and patients developed a tolerance to them rapidly. alpha 1-Adrenergic blockers also have beneficial effects on plasma lipoproteins, tending to decrease levels of triglycerides and cholesterol and increase levels of high-density lipoprotein (HDL) cholesterol and the HDL cholesterol/total cholesterol ratio. beta-Adrenergic blockers, such as propranolol and atenolol, have been shown to have an adverse effect on the lipid profile by tending to increase levels of triglycerides and decrease HDL cholesterol. A number of mechanisms contribute to these effects, in particular, adrenergic modulation of lipoprotein lipase and the triglyceride secretion rate. Doxazosin has been shown to increase the activity of LDL receptors, which may be partly responsible for its beneficial effect on plasma lipids and lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha-adrenergic blockers: mechanism of action, blood pressure control, and effects of lipoprotein metabolism. 198 Feb 36

Doxazosin (mean dose 11 mg) given once daily in combination with 100 mg atenolol (n = 44) was compared with placebo and atenolol (n = 43) in a double-blind, multicenter study in patients with mild to moderate essential hypertension. In the atenolol/doxazosin-treated group, standing blood pressure significantly decreased by 17.0/12.3 mm Hg compared to 6.2/6.7 mm Hg in the atenolol/placebo group whereas supine blood pressure decreased by 13.2/9.8 mm Hg and 9.2/6.0 mm Hg, respectively in the two groups. Serum lipids did not change significantly in either group. The majority of side-effects reported were mild and transient. This study confirms that doxazosin may be safely combined with a beta-blocker. Doxazosin proved to be well tolerated and effective in patients with blood pressure refractory to atenolol alone.
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PMID:Doxazosin in combination with atenolol in essential hypertension: a double-blind placebo-controlled multicentre trial. 214 9

Hypertension is often associated to other risk factors, such as abnormal lipid and carbohydrate metabolism, which should be considered for the choice of antihypertensive drug treatment. Doxazosin is a postsynaptic alpha-1 adrenoceptor blocker suitable for once a day treatment regime. It seems to induce fewer side effects than older drugs of the same class and it may improve lipid and carbohydrate profile, thereby reducing the risk of coronary artery disease. To verify its effects on blood pressure, serum lipids and glucose tolerance, doxazosin (1-8 mg od) was given for 8 weeks to 32 patients suffering from essential hypertension, of whom 16 had fasting serum cholesterol higher than 6 mmol/l and/or fasting serum triglycerides higher than 1.9 mmol/l. Sitting and standing blood pressure were significantly reduced (from 163 +/- 18/101 +/- 6 mmHg to 147 +/- 19/94 +/- 8, p less than 0.001 and from 162 +/- 18/107 +/- 9 to 145 +/- 18/95 +/- 8, p less than 0.001, respectively) at a mean daily dose of 5 mg. Normotension or a good hypotensive response was achieved in 60% of the patients. The daily dose which turned out to be effective in 50% of the patients was 7 mg. The drug treatment was well tolerated and orthostatic hypotension was never observed either on starting treatment or on increasing dosage. Blood lipids and glucose tolerance were not significantly affected. Doxazosin is therefore an effective antihypertensive agent suitable for use in patients with essential hypertension alone or combined with hyperlipidemia.
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PMID:[Doxazosin for the treatment of arterial hypertension]. 215 71

A single dose of doxazosin, a long-acting postsynaptic alpha 1-adrenoceptor antagonist, was administered to seven patients with essential hypertension. Following administration of a single dose, all the patients except one who was forced to be discharged from the hospital for work, continuously received doxazosin once daily (o.d.) for evaluation of its consecutive dosing effect. The antihypertensive effect, pharmacokinetics, and effects on the plasma renin activity (PRA) of doxazosin were investigated. Following a 2-mg single dose of doxazosin, the systolic blood pressure (SBP) decreased significantly up to 12 h, whereas consecutive dosing produced a significant decrease in the SBP up to 24 h and a significant decrease in the mean blood pressure up to 24 h as compared with placebo. The pharmacokinetic parameters of doxazosin in both single- and consecutive-dose study were 18.9 and 25.8 ng/ml in Cmax, 11.1 and 12.9 h in half life (t1/2), and 182.0 and 273.0 ng h/ml in area under the curve (AUC)24(0), respectively. No significant changes were observed in PRA and plasma concentration of catecholamines. Neither were there any observable changes in endogenous creatinine clearance and in the urinary excretion rates of Na, K, and Cl. Doxazosin was well tolerated by all patients, and no untoward effects were observed. Doxazosin effectively reduces blood pressure and, because of its long t1/2 and minimal effects on PRA catecholamines, and electrolytes, seems to be a useful antihypertensive agent in patients with essential hypertension.
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PMID:Antihypertensive effects and pharmacokinetics of single and consecutive administration of doxazosin in patients with mild to moderate essential hypertension. 244 Nov 60

The effects of once-daily therapy with doxazosin (1 to 8 mg/day) on exercise capacity, left ventricular performance and hemodynamics (radionuclide ventriculography) were compared with those of atenolol (50 to 100 mg/day) and placebo in a randomized, double-blind crossover trial in 16 patients (9 men) with mild hypertension. Both medications controlled blood pressure (BP) to a similar degree (mean BP was 150 +/- 12, 137 +/- 17 and 141 +/- 14 mm Hg for placebo, atenolol and doxazosin, respectively) but by different mechanisms. Changes during maximal semierect bicycle exercise were similar to those seen at rest. Doxazosin decreased total peripheral resistance and maintained cardiac output, whereas atenolol decreased cardiac output. Exercise capacity (136 +/- 56 watts with placebo) was maintained by doxazosin (135 +/- 56 watts) but decreased with atenolol (122 +/- 55 watts). Compared with atenolol, doxazosin slightly increased the left ventricular ejection fraction at rest and during exercise. The significance of this study is in the choice of a first-line antihypertensive agent. Both are once-a-day medications that control BP. However, doxazosin does so by improving the abnormal physiology of essential hypertension and, consequently, does not adversely affect exercise performance.
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PMID:Comparison of doxazosin and atenolol in mild hypertension, and effects on exercise capacity, hemodynamics and left ventricular function. 252 29

We have studied the contribution of neurohumoral and structural factors to pressor responsiveness and peripheral resistance in mild/moderate hypertension. Pressor responses to intravenous infusions of phenylephrine (an alpha1 agonist) and angiotensin II were studied in groups of patients with essential hypertension before and after treatment, for 6 weeks with either nifedipine (20 mg bid), enalapril (20 mg daily) or doxazosin (2 mg daily). All drugs lowered blood pressure to a similar extent. Pressor responsiveness to both phenylephrine and angiotensin II showed wide intersubject variation when expressed as the dose of agonist required to raise mean arterial pressure by 20 mmHg (PD20). A group of age-matched normotensive controls showed a similar PD20 for phenylephrine to hypertensives. Angiotensin 11 sensitivity was greater in hypertensives. Drug treatment had different effects in hypertensive patients. Doxazosin, an alpha blocker, reduced the responsiveness to phenylephrine but had no effect on responses to angiotensin II. Nifedipine attenuated responses to both agonists while treatment with enalapril increased responsiveness to both phenylephrine and angiotensin II. We have not found evidence of systematic differences in alpha 1 receptor responses in hypertensives and different "vasodilator" drugs can lower blood pressure with widely different effects on adrenergic and non-adrenergic vascular responses.
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PMID:Pressor responsiveness in essential hypertension and the effects of treatment with an alpha blocker, calcium antagonist or ACE inhibitor. 256

Control of high blood pressure has failed to reduce the risk of atherosclerotic coronary heart disease (CHD). Hypercholesterolemia, which is common among hypertensive patients, cigarette smoking, and hypertension are the major risk factors for CHD. To minimize CHD risk, elevated blood pressure and atherogenic lipid levels should be lowered, but various antihypertensive agents appear to adversely affect lipid levels, actually precluding the CHD risk reduction expected from blood pressure control. Doxazosin, a once-daily, long-acting, alpha 1-adrenergic inhibitor, not only is effective therapy for essential hypertension but also has a favorable impact on lipids. During controlled studies of doxazosin's antihypertensive efficacy, the following blood lipid levels were measured: total cholesterol, total triglycerides, high-density lipoprotein (HDL) cholesterol (including HDL2 and HDL3), low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein cholesterol, and apoproteins (apos) AI and B. Results showed total cholesterol (-0.8 to -8.9 percent), total triglycerides (-5.0 to -17.4 percent), and LDL (-9.0 to -16.9 percent) were reduced. The positive prognostic indicators, HDL (+0.7 to +13.0 percent) and HDL:total cholesterol ratio (+3.1 to +26.3 percent), were increased. Apo B decreased, but apo AI remained unchanged. In these hypertension studies, doxazosin has favorably reduced two major CHD risk factors. As part of a new, long-term, controlled, multicenter trial, the prospective benefits of these risk factor reductions on CHD morbidity and mortality will be quantified for doxazosin and other antihypertensive agents.
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PMID:Review of the effects of doxazosin, a new selective alpha 1-adrenergic inhibitor, on lipoproteins in patients with essential hypertension. 256 25

Hypertension and hypercholesterolemia are 2 major risk factors for atherosclerotic coronary artery disease (CAD). Elevations of both blood pressure and serum cholesterol levels should be reduced to control CAD risk. Doxazosin is a once-daily, long-acting, selective alpha 1-adrenergic inhibitor that is effective for the treatment of essential hypertension. During controlled studies of doxazosin's antihypertensive efficacy, 3 serum lipid parameters were measured; total cholesterol, total triglyceride and high density lipoprotein (HDL) cholesterol. In 10- to 12-week placebo-controlled studies, 142 doxazosin-treated patients were compared with 155 placebo-controlled subjects. Doxazosin patients had an increase of 8.9% in the HDL/total cholesterol ratio (p less than 0.05), whereas total cholesterol, HDL cholesterol and triglyceride levels were not significantly different between the 2 study groups. During a 52-week comparison of doxazosin versus atenolol, doxazosin treatment was associated with a significant decrease in total triglyceride levels (5%; p less than 0.001) and increases in HDL cholesterol levels (3.9%; p less than 0.01) and HDL/total cholesterol ratio (5.4%; p less than 0.0001). Doxazosin is an effective antihypertensive agent that has a favorable impact on serum lipid levels, thereby promoting a beneficial effect on 2 major CAD risk factors.
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PMID:Plasma lipid lowering effects of doxazosin, a new selective alpha1 adrenergic inhibitor for systemic hypertension. 288 53

The long-term safety, efficacy and effect on serum lipid profile of doxazosin, a new alpha 1-adrenoceptor inhibitor administered once daily, were compared with those of prazosin, administered twice daily, in 104 patients with essential hypertension treated for 1 year. Doxazosin produced clinically significant decreases in standing and supine blood pressures over a period of 1 year. These decreases were similar to those produced after an initial period of 12 weeks of double-blind therapy. The reductions in blood pressure produced by doxazosin were greater than those produced by prazosin. Minor and clinically nonsignificant changes in heart rate were observed with both drugs. The favorable changes from baseline in plasma lipid concentrations observed after 12 weeks of double-blind therapy were maintained throughout the 1-year open study. These were average increases in the mean high density lipoprotein cholesterol concentration and the derived high density lipoprotein/total cholesterol ratio, and average decreases in total cholesterol and total triglyceride concentrations. The incidence of side effects reported was similar for doxazosin and prazosin. Most were rated as being mild or moderate in severity and were tolerated or disappeared with continued therapy. Results of laboratory tests, electrocardiograms, ophthalmoscopy and body weight measurements revealed only minor changes from baseline, and none was judged to be of clinical significance. These findings demonstrate that doxazosin is a safe and effective antihypertensive agent suitable for once-daily dosing, and has favorable effects on the serum lipid profile.
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PMID:An open one-year comparison of doxazosin and prazosin for mild to moderate essential hypertension. 288 55

The efficacy and safety of doxazosin (mean dosage 6.9 mg, range 1 to 16) in the treatment of essential hypertension were compared in a double-blind study with those of hydrochlorothiazide (HCTZ) (mean dosage, 84.6 mg, range 25 to 100) in 104 hypertensive patients treated once daily for 6 months. Thirty-five patients were also assessed for comparative effects of the 2 agents on serum lipid parameters. Doxazosin produced potentially favorable changes from baseline in the concentrations of serum lipid fractions (total triglycerides, total cholesterol, high density lipoprotein [HDL] cholesterol and the derived HDL/total cholesterol ratio) compared with HCTZ. The decreases in total triglyceride and total cholesterol concentrations and an increase in the HDL/total cholesterol ratio were significantly different (p less than 0.006) from the opposite changes observed with HCTZ. Clinically relevant decreases from baseline in supine and standing blood pressures at 24 hours after administration did not significantly differ between the 2 agents. The incidence and severity of side effects were similar for both drugs. Three patients receiving doxazosin and 6 receiving HCTZ were withdrawn due to drug-related clinical side effects including 2 patients receiving HCTZ who were withdrawn because of laboratory test abnormalities. Eight HCTZ- and 1 doxazosin-treated patients developed hypokalemia and 6 HCTZ-treated patients developed hyperuricemia. These findings indicate that doxazosin and HCTZ provide comparable antihypertensive efficacy after 6 months of treatment using a once-daily regimen, but doxazosin produces a beneficial effect on the serum lipid profile as well as fewer biochemical aberrations.
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PMID:Comparative effects of doxazosin and hydrochlorothiazide on serum lipids and blood pressure in essential hypertension. 288 61


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