Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 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

This study was designed to assess the efficacy and tolerance of doxazosin in patients with mild, moderate, or severe essential hypertension in a general practice setting. Ninety-six adults of a mean age of 55 1/2 years took part in the 14-week study, consisting of a placebo phase (2 weeks), a dose-adjustment phase with doxazosin (8 weeks), and a maintenance phase (4 weeks). Doxazosin, at a final mean daily dose of 3.4 mg, produced a significant (p less than 0.05) reduction in blood pressure at all points of measurement during the study. The mean change in sitting blood pressure at the end of treatment was -15.4/-15.8 mm Hg. Of the 85 patients who could be categorized as a success or failure, 78 (92%) were considered a therapeutic success; 78 (89%) of the 88 efficacy-evaluable patients demonstrated an improvement in the severity category of their hypertension. Treatment with doxazosin produced a reduction in serum cholesterol (-3.1%) and triglyceride (-3.8%) levels, although these changes did not attain statistical significance. The calculated probability of developing coronary heart disease in 10 years (according to the Framingham equation) was significantly (p less than 0.001) reduced by 22%, from 16.7 chances per 100 (baseline) to 14.3 chances per 100 (final visit). Twenty-six patients (27.1%) reported side effects that were possibly related to treatment, the most prevalent of which were vertigo (7.3%) and headache (6.3%). In four (4.2%) patients the dose of doxazosin was reduced and two (2.1%) were withdrawn prematurely. The investigator's assessments of tolerance was reduced and two (2.1%) were considered to be excellent or good in 85 (88%) patients.
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PMID:A multicenter study of doxazosin in the treatment of essential hypertension in France. 182 57

Doxazosin is a new quinazoline derivative that, like prazosin, has selectivity for alpha 1-receptors. A three-way crossover, randomized, open study in 18 patients with essential hypertension was conducted to investigate the clinical pharmacokinetics of 2, 4, and 8 mg doxazosin at steady state. The pharmacokinetics of the initial 2 mg dose was also studied. Doxazosin showed linear pharmacokinetics. Increases in doses from 2 to 8 mg (steady state) produced proportional increases in doxazosin serum levels (maximum plasma drug concentration [Cmax] minimum plasma drug concentration [C min], and O-24-hour area under the curve [AUC(p-24)], whereas half-life (t1/2) (19.4, 18.7, and 19.7 hours, respectively), volume of distribution (3.4, 3.4, and 3.6 L/kg, respectively), clearance from serum (2.2, 2.2, and 2.1 ml/min/kg, respectively), and degree of protein binding (1.2%, 1.0%, and 1.0% unbound, respectively) were dose independent. Similar t1/2 and time to reach peak concentration (tmax) were obtained with 2 mg initial dose and 2 mg steady state. alpha 1-Acid glycoprotein levels were unchanged during doxazosin treatment. Doxazosin lowered supine and standing systolic and diastolic blood pressure. The blood pressure reduction was associated with an increase in heart rate. Peak hypotensive and tachycardic effects occurred 5.7 +/- 0.1 hours after administration, whereas Cmax was achieved at 2.4 +/- 0.7 hours (tmax). Greater decreases in systolic blood pressure and increases in heart rate were seen in standing than in supine position. The reduction in standing systolic and diastolic blood pressure with 8 mg was greater than with 2 mg (P less than 0.05); however, the increases in heart rate were not different. Dizziness, headaches, and dry mouth were the most frequent side effects. This study indicates that doxazosin shows linear pharmacokinetics between 2 and 8 mg and that because of its long t1/2, once-a-day administration should be adequate for the treatment of hypertension.
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PMID:Clinical pharmacology of doxazosin in patients with essential hypertension. 295 Oct 51

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

The purpose of this paper is to review the role of doxazosin, a long-acting alpha(1)-blocker, as a component of combination therapy for patients with stage 1 and stage 2 hypertension and for patients with concomitant hypertension and hyperlipidemia or glucose intolerance. Recent studies that evaluated doxazosin as combination therapy in the treatment of patients with inadequately controlled hypertension and patients with concomitant hypertension and other disorders were reviewed. Data extraction was based on the tolerability and efficacy data of doxazosin in patients with hypertension. Compared with placebo, doxazosin combination therapy leads to significant improvements in sitting and standing blood pressure. Doxazosin is well tolerated, with only minor adverse effects (e.g., headache, dizziness) as the most commonly reported treatment-related complications. The studies described demonstrate that doxazosin is effective as combination therapy for patients with stage 1 and stage 2 hypertension. The positive effects of doxazosin on serum lipids make combination therapy with doxazosin an attractive treatment option for patients who have concomitant hyperlipidemia or glucose intolerance.
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PMID:Doxazosin as combination therapy for patients with stage 1 and stage 2 hypertension. 1277 63