Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Doxazosin, as a mono-therapy, was studied in 28 patients with mild to severe hypertension over a period of 8 weeks. After a wash-out period of 2 weeks, doxazosin was started at a dose of 1 mg daily and increased gradually until the diastolic blood pressure fell to below 90 mm Hg or a maximum dose of 16 mg daily was reduced. Forty-three percent of the patients had good response with diastolic blood pressure falling to normal (< 90 mm Hg) or by more than 10 mm Hg whilst 68% of the patients had a reduction of greater than 5 mm Hg. Doxazosin reduced blood pressure without significant increase in heart rate and was, overall, well tolerated producing mild side effects not requiring withdrawal, or reduction in dosage of the drug in 6 cases. The effect of doxazosin on lipids showed a trend towards reduction of total cholesterol and increase in HDL, but these data need confirmation in a longer study in a larger population sample.
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PMID:Open trial of doxazosin in hypertensive Africans: dose finding, efficacy and safety studies. 911 55

Hypertension, hypercholesterolemia, atherosclerosis, and coronary heart disease are associated with abnormal endothelium-dependent, nitric oxide-mediated vasorelaxation. In rats, hypercholesterolemia in combination with deficiencies of vitamin E and selenium results in increased endogenous lipid oxidation and endothelial dysfunction. Two hydroxymetabolites of doxazosin, an alpha 1-adrenergic blocking antihypertensive agent, inhibit human lipid oxidation in vitro in a dose-dependent fashion. The present studies were performed to determine the effect of in vivo treatment with doxazosin on endothelial dysfunction in hypercholesterolemic/ antioxidant-deficient rats. Dahl rats were fed 1) a standard diet, 2) a high cholesterol (4%) diet, or 3) a high cholesterol, vitamin E- and selenium-deficient diet. A subgroup of animals in each group were administered doxazosin (3.5 mg/100 g/day) for 16 weeks. In the aortas, vascular relaxations induced by acetylcholine were significantly decreased (P < .05) in high cholesterol/antioxidant-deficient rats compared with normal and high cholesterol animals. Doxazosin treatment prevented the impairment in endothelium-dependent vascular relaxation in the high cholesterol/antioxidant-deficient group. Vasorelaxation in response to the exogenous nitric oxide donor diethylamine nanoate, which was significantly impaired (P < .05) in aortas from high cholesterol/antioxidant-deficient animals compared with normal and high cholesterol animals, was normalized in aortas from high cholesterol/ antioxidant-deficient animals that had received doxazosin. The antioxidant effect of doxazosin may have therapeutic implications in diseases associated with endothelial dysfunction linked to products of lipid oxidation.
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PMID:Effect of doxazosin on endothelial dysfunction in hypercholesterolemic/antioxidant-deficient rats. 939 45

The incidence of benign prostatic hyperplasia (BPH) is increasing, and an estimated one quarter of men older than 60 years have both BPH and hypertension. Medical management of BPH is now an effective alternative to surgery, and primary care physicians are treating more patients for this condition. Alpha-adrenergic blockers reduce the tone of prostatic smooth muscle, and doxazosin, a selective alpha-1 adrenergic blocker, is effective and well tolerated in the treatment of BPH. Doxazosin can be given in a convenient once-daily dose, and its efficacy is maintained in the long term. Patients with BPH who are already being treated for hypertension with doxazosin need no alteration in their dosage regimen, and doxazosin can be used as a single agent to treat both conditions. Selective alpha-adrenergic blockers are likely to be used increasingly by primary care physicians in the treatment of BPH.
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PMID:Doxazosin for benign prostatic hyperplasia in primary care. 944 39

The long-term efficacy and safety of once-daily treatment with doxazosin or atenolol were compared in a 5-year study in patients with mild-to-moderate hypertension. The study consisted of a 1-year, multicenter, double-blind, parallel-group phase, followed by a 4-year, open-label extension phase. Of the 228 patients enrolled, 100 patients (54/111 doxazosin and 46/117 atenolol) completed the 5-year study. Both treatments were similarly efficacious in controlling blood pressure. As assessed by the Framingham risk equation, which incorporates lipid parameter values, patients receiving doxazosin had significantly less chance of developing coronary heart disease (CHD) within 10 years compared with those patients receiving atenolol (p < 0.05). Doxazosin significantly (p=0.0005) reduced the mean CHD risk from baseline to final visit by 12.3%; whereas, atenolol produced essentially no change in mean risk (0.2% increase). In patients receiving doxazosin, statistically significant (p < 0.05) increases from baseline were observed in serum concentrations of high-density lipoprotein (HDL) cholesterol and the HDL/total cholesterol ratio during the first 2 and 3 years of treatment, respectively. In contrast, significant (p < 0.05) percent reductions from baseline in both these lipid parameters were seen in atenolol-treated patients during most of the 5-year trial. Between-group differences were statistically significant (p < 0.01) at all time points. Decreases in total cholesterol were similar between the two treatment groups. Triglycerides, however, significantly increased with atenolol treatment (p < 0.0001 vs baseline) while remaining essentially unchanged with doxazosin treatment. The safety profiles of doxazosin and atenolol were comparable. Thus, while demonstrating similar antihypertensive efficacy and safety during this 5-year study, once-daily treatment with doxazosin produced a significantly greater beneficial effect on both 10-year CHD risk and serum lipid parameters compared with atenolol.
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PMID:A 5-year comparison of doxazosin and atenolol in patients with mild-to-moderate hypertension: effects on blood pressure, serum lipids, and coronary heart disease risk. 955 76

Doxazosin (Cardura-Pfizer) is a alpha 1-adrenoreceptor antagonist. This drug significantly decreases the blood pressure in subjects with hypertension. Despite decreasing blood pressure, doxazosin has a beneficial effect on many disorders observed in subjects with diabetes mellitus. Doxazosin 1) improves the regulation of lipids disturbances, 2) improves tissue sensitivity to insulin, 3) decreases the frequency of sexual disorders. In this situation Doxazosin is a good choice in the treatment of hypertension in diabetic subjects, in subjects with hypertension and hypercholesterolemia, with left ventricular hypertrophy, in old male subjects with hypertension and benign prostatic hypertrophy.
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PMID:[Use of doxazosin (Cardura-Pfizer), alpha 1-adrenoreceptor antagonist, in treatment of hypertension in patients with diabetes]. 968 27

alpha-Adrenergic blockers are potential alternative antihypertensive agents for diabetic patients. Data on their relative efficacy and their effect on kidney function and albuminuria are very limited however. 76 patients with diabetes type 2, hypertension (>/=140/90 mm Hg) and albuminuria (>/=30 mg/24 h) were randomized into three groups to receive cilazapril (2.5-10 mg), doxazosin (2-8 mg) or both. Patients of the first and second groups received a single agent for 4 months, the agents were then crossed for an additional period of 4 months followed by the addition of hydrochlorothiazide (25 mg) for a third 4-month period. Blood pressure was monitored monthly, creatinine clearance and HbA1c were measured before and at the end of each treatment period. Patients of the third group received reduced doses of cilazapril and doxazosin for 4 months. Hydrochlorothiazide was then added for the subsequent 4 months. There was a significant decline in blood pressure values during the first period in all groups. Cilazapril: systolic blood pressure (SBP) 160 +/- 6 to 149 +/- 5 mm Hg; diastolic blood pressure (DBP): 101 +/- 3 to 94 +/- 3 mm Hg (p = 0.001). Albuminuria declined from 350 +/- 105 to 205 +/- 96 mg/24 h (p = 0.001), creatinine clearance (CrCl) was unchanged. Doxazosin: SBP: 160 +/- 7 to 151 +/- 6 mm Hg; DBP: 97 +/- 4 to 90 +/- 4 mm Hg (p = 0.001). Albuminuria 373 +/- 121 to 322 +/- 107 mg/24 h (p = 0.065) and CrCl 87 +/- 7 to 91 +/- 6 ml/min. The combination of both agents at half doses was equipotent or superior to either drug alone. Cross-over of cilazapril and doxazosin reproduced the hypotensive effect and reversed the antialbuminuric effect. The addition of hydrochlorothiazide resulted in a further decline of 6-14 mm Hg in SBP and 3-11 mm Hg in DPB.
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PMID:Effect of an alpha-adrenergic blocker, and ACE inhibitor and hydrochlorothiazide on blood pressure and on renal function in type 2 diabetic patients with hypertension and albuminuria. A randomized cross-over study. 973 16

This review analyses the expanding role of alpha adrenoceptor blockers in the treatment of BPH and examines the rationale for their use. The safety and efficacy of currently available alpha adrenoceptor blockers is reviewed, with emphasis on the most extensively studied agent, doxazosin. Like other alpha adrenoceptor blockers, doxazosin improves both symptoms of BPH and urinary flow rates by a statistically significant effect compared with placebo. Doxazosin also significantly reduces blood pressure in the 30% of BPH sufferers who also have hypertension; furthermore, there is a beneficial effect on lipid metabolism, which may translate into a reduced risk of coronary heart disease. It is concluded that existing alpha adrenoceptor blockers constitute a valuable adjunct to other BPH therapies, and further refinement of alpha adrenoceptor selectivity based on the alpha-1A subtype in the near future promises even better targeted alpha blockade.
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PMID:Expanding role of alpha adrenoceptor blockade in the treatment of benign prostatic hyperplasia. 989 77

The alpha 1-blocker doxazosin is a well-established therapy for hypertension and benign prostatic hyperplasia; however, in its standard form, a multiple-step titration regimen is usually required. The new gastrointestinal therapeutic system (GITS) formulation of doxazosin greatly minimizes the need for titration by changing drug-delivery rate and the pharmaco-kinetic profile. To demonstrate this in hypertensive patients, we assessed the effects of doxazosin GITS 4 or 8 mg once daily versus doxazosin standard 1-8 mg once daily, and placebo, in an integrated analysis of two multicenter, double-blind, randomized, parallel-group trials. Each trial included a 2-week washout period and 12 weeks of therapy. One study compared doxazosin GITS, doxazosin standard, and placebo in 392 patients with mild hypertension [blood pressure (BP) 95-105/ < or = 180 mm Hg]; the other study compared doxazosin GITS with doxazosin standard in 315 patients with mild-to-moderate hypertension (BP 95-115/ < or = 220 mm Hg). The primary outcome measure was the proportion of responders (sitting diastolic BP < 90 mm Hg or 10-mm Hg decrease from baseline 24 h after the dose) at the final visit for the per-protocol population. Mean baseline BP and heart rate were well matched in each group. Approximately 64% of patients with doxazosin GITS (198 of 309 patients) and 68% with doxazosin standard (207 of 304 patients) achieved goal BP response at the final visit versus 36% with placebo (25 of 70 patients; p < 0.05). The majority with doxazosin GITS (60%) remained at the initial 4-mg starting dose. Doxazosin GITS was as effective as doxazosin standard, and both were more effective than placebo in controlling BP in mild-to-moderate hypertension. Doxazosin GITS was well tolerated, and fewer patients with the GITS formulation discontinued therapy because of side effects compared with doxazosin standard or placebo. Syncope was not reported with doxazosin GITS. Whereas the efficacy of doxazosin GITS at 4 or 8 mg is equivalent to that of the standard regimen in this combined analysis, the GITS formulation appears to eliminate the need for titration in most patients.
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PMID:Effects of doxazosin in the gastrointestinal therapeutic system formulation versus doxazosin standard and placebo in mild-to-moderate hypertension. Doxazosin Investigators' Study Group. 1022 68

As men age, the incidence of both benign prostatic hyperplasia (BPH) and hypertension increases. Concomitant occurrence of these conditions also increases with age, and the 2 are frequently encountered together in primary care practice. In addition, many patients with hypertension require >1 antihypertensive agent to adequately control blood pressure. In a multicenter, community-based, 8-week, uncontrolled, open-label study, we evaluated doxazosin, a selective alpha1-adrenergic-receptor antagonist, in 491 patients with concomitant symptomatic BPH (American Urological Association [AUA] symptom score > or =12) and hypertension, some previously untreated and some with inadequately controlled hypertension (systolic blood pressure 120-179 mm Hg or diastolic blood pressure [DBP] 80-109 mm Hg) despite taking 1 or 2 antihypertensive agents. Patients were allocated to 1 of 4 groups at baseline according to their diastolic blood pressure (control was considered DBP <90 mm Hg) and whether they had received antihypertensive medication before the study. Thus the 4 groups were treated/well-controlled, treated/poorly controlled, untreated/hypertensive, and untreated/normotensive. In all patient groups, doxazosin therapy significantly improved AUA total symptom and bothersomeness scores and BPH-specific indices of health status and interference with activities (P<0.001). Significant improvements in BPH symptoms were observed with doxazosin, regardless of whether initial symptoms were moderate or severe (P<0.001). Clinically important blood pressure lowering occurred only in the patient groups in which blood pressure had been elevated at baseline. Patients whose blood pressure was poorly controlled at baseline, either without or with treatment (predominantly with angiotensin-converting enzyme inhibitors or calcium channel blockers), achieved adequate blood pressure control (reduction to <140/90 mm Hg) with the addition of doxazosin. Similar improvements in blood pressure and BPH symptoms were seen in both older (> or =65 years) and younger (45 to 64 years) patients, and doxazosin was well tolerated by both groups. The most frequent treatment-related adverse event was dizziness (13.0% of patients); however, patients classified the dizziness as mild in approximately 75% of reports, and severe dizziness was reported by only 2 patients (0.4%). Doxazosin is an effective antihypertensive agent when used in combination with agents from other antihypertensive classes in patients with poorly controlled hypertension and BPH, and is also successful as monotherapy for controlling both BPH and hypertension in patients with mild to moderate hypertension.
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PMID:A multicenter, community-based study of doxazosin in the treatment of concomitant hypertension and symptomatic benign prostatic hyperplasia: the Hypertension and BPH Intervention Trial (HABIT). 1056 69

Doxazosin, an effective treatment for mild-to-moderate hypertension and benign prostatic hyperplasia, in its standard formulation requires a multiple-step titration regimen to minimize the potential for first-dose effects. A new controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin was developed to enhance the pharmacokinetic profile, significantly reducing serum peak-to-trough ratios, thereby minimizing the need for titration. We assessed the efficacy and tolerability of doxazosin GITS compared with doxazosin standard and placebo in a prospective, randomized, double-blind, parallel-group, dose-titration, multicenter study of 392 patients with mild hypertension (blood pressure [BP] < or = 180/95-105 mmHg). Patients were randomized to doxazosin GITS, doxazosin standard, or placebo in 2:2:1 manner. The primary outcome measure was the proportion of patients in the per-protocol analysis (PPA) who achieved goal BP response (sitting BP < or = 90 mmg or 10 mmHg decrease from baseline at 24 h postdose at the final evaluable visit). Goal BP response in the intention-to-treat (ITT) population and prespecified BP and/or heart rate changes in the PPA and/or ITT population were also analyzed. Tolerability was assessed throughout the study. Doxazosin GITS and doxazosin standard produced comparable goal BP responses superior to that of placebo, with 92 of 156 patients (59.0%) on doxazosin GITS and 86 of 152 patients (56.6%) on doxazosin standard in the PPA population achieving goal BP response 24 hours postdose on the final visit, compared with 25 of 70 patients (35.7%) on placebo. Both active treatments produced mean significant BP reductions compared with baseline and placebo (p < 0.001). The most commonly reported side effects were headache, dizziness, and asthenia. No syncope was reported in the doxazosin GITS group; two cases were observed in the doxazosin standard group and one case in the placebo group. Doxazosin GITS was well tolerated and as effective as doxazosin standard in patients with mild hypertension, producing well-tolerated, comparable BP reductions with minimal need for titration. Both active treatments were clinically and statistically superior to placebo.
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PMID:Doxazosin GITS compared with doxazosin standard and placebo in patients with mild hypertension. 1059 97


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