Effects Of Doxazosin Research Articles

Effectiveness of Doxazosin in Treatment of Distal Ureteral Stones in Children

We evaluated the effectiveness of doxazosin in children with distal ureteral stones in terms of stone expulsion rates and time to expulsion. A total of 39 patients 2 to 14 years old with lower ureteral stones smaller than 10 mm were enrolled and randomly divided into 2 groups. Group 1 consisted of 20 controls receiving ibuprofen for pain and group 2 consisted of 19 patients receiving doxazosin. Doxazosin dose was approximately 0.03 mg/kg daily. All patients were evaluated with x-ray, ultrasound or spiral computerized tomography. Stone expulsion rates and time to expulsion between the groups were compared. Mean followup was 19 days. Effects of doxazosin were also evaluated by comparing subgroups with stones smaller than 5 mm and 5 to 10 mm. Results were also evaluated with special emphasis on gender and age. Expulsion was observed in 14 patients (70%) in group 1 and 16 (84%) in group 2 (p >0.05). Mean expulsion times for groups 1 and 2 were 6.1 and 5.9 days, respectively (p >0.05). Although fewer pain episodes were observed in the treatment group, this finding could not be evaluated objectively. None of the patients experienced any adverse effects. Administration of 0.03 mg/kg doxazosin daily in children to treat distal ureteral stones up to 10 mm is not superior to analgesic alone. This result is not affected by gender, stone size or patient age. However, additional randomized controlled studies, especially including larger stone volumes, and different doses of doxazosin and other alpha-blockers, might highlight the usefulness of alpha-blockers for ureteral stones in children.

The Role of α1-Adrenoceptor and Arachidonate Pathways in Increased Tone of Demucosalized Bladder Tissue

We investigated the role of the alpha1-adrenoceptor system, and cyclooxygenase and lipoxygenase pathways in increased contractile reactivity of demucosalized bladder tissues. A total of 20 male Sprague-Dawley rats were used. From each bladder 2 tissue strips were prepared. One strip was demucosalized, while the other was kept intact. Isometric tension studies were done at baseline tone with contractile responses assessed to 120 mM potassium, electrical field stimulation (1 to 40 Hz) and carbachol (10(-9) to 10(-4) M). Relaxation responses to electrical field stimulation, isoproterenol (10(-9) to 10(-4) M), papaverine (10(-4) M) and sodium nitroprusside (10(-4) M) were recorded in carbachol precontracted strips. The effects of doxazosin, the cyclooxygenase inhibitor indomethacin and the lipoxygenase inhibitor REV5901 (each 3 x 10(-5) M) on these responses were investigated. Carbachol and electrical field stimulation induced significantly greater contractions in demucosalized strips. All contractile responses were significantly decreased in the presence of doxazosin, indomethacin and REV5901 in intact and demucosalized tissues. Indomethacin augmented the effect of doxazosin on demucosalized tissue contractions compared to results obtained with doxazosin alone. In carbachol precontracted tissues relaxation responses to isoproterenol and electrical field stimulation were significantly lower in demucosalized tissues. These responses were significantly decreased with doxazosin or indomethacin independent of mucosa. Bladder mucosa is a determinant of rat bladder tissue contractility. Doxazosin, and cyclooxygenase and lipoxygenase pathways significantly affect rat bladder tissue contractility independent of mucosa. However, the effect of doxazosin is significantly amplified by cyclooxygenase inhibition in the absence of bladder mucosa. These findings may have important clinical implications regarding the single and combined use of doxazosin with cyclooxygenase inhibitors.

Effect of doxazosin on the left ventricular structure and function in morning hypertensive patients: the Japan Morning Surge 1 study

Doxazosin is reported to increase the incidence of congestive heart failure. The benefits of doxazosin, for controlling morning blood pressure as well as its effect on the left ventricular structure and function, are herein examined. In this study, 223 morning hypertensive patients were randomized into either the doxazosin group, with a once-daily bedtime dose of doxazosin, or the control group, who continued their current medication. Atenolol was added to the doxazosin group when needed. The effect of doxazosin was evaluated by measurement of echocardiographic parameters and B-type natriuretic peptide. The left ventricular wall thickness decreased, but the left ventricular diastolic diameter in the doxazosin group increased from the baseline. The changes in the left ventricular mass index were similar between the groups, whereas the relative wall thickness in the doxazosin group decreased more than that in the control group. The left ventricular diastolic function could deteriorate in the doxazosin group. In the doxazosin group, an increase in the left ventricular diameter was only seen in the patient who did not take diuretics throughout the study. The office and home blood pressure in the doxazosin group decreased more than that in the control group, whereas the B-type natriuretic peptide increased in the doxazosin group. Three cases of congestive heart failure were observed in the doxazosin group, but none in the control group. Although a bedtime dose of doxazosin can significantly lower the blood pressure, it can also increase left ventricular diameter, thus increasing the risk of congestive heart failure. However, the prior use of diuretics can prevent the unfavorable effects of doxazosin on the left ventricular structure.

Doxazosin in the current treatment of hypertension

Background: Evidence from various studies has shown that even a very small reduction in the blood pressure explains the majority of benefits in cardiovascular outcomes. Although doxazosin is a relatively old drug, it is a very effective add-on therapeutic agent. It has been used in a variety of clinical trials, including different groups of hypertensive patients such as diabetics, the elderly, patients with benign prostatic hyperplasia or hypercholesterolaemia, the obese or Afro-Americans and in combination with all major groups of antihypertensive drugs such as: calcium channel antagonists, diuretics, β-adrenoreceptor antagonists, angiotensin-converting enzyme inhibitors and angiotensin-2 receptor blockers. Objective: The purpose of this article is to review the role of doxazosin in the current treatment of hypertension. Methods: English-language reports published in 1986 – 2007 were retrieved. Data extraction was based on articles reporting at least 15 or more patients treated with combination of doxazosin with other antihypertensive drugs. Results/conclusions: In these studies doxazosin in either standard or extended-release formulation was added as a second- or third-line agent. The two formulations of doxazosin, although chemically identical, appear to differ in some other effects. A large proportion of patients demonstrated a favourable blood pressure response with relatively few treatment-associated side effects showing that this drug appears to be a valuable add-on antihypertensive treatment option. Doxazosin reduces blood pressure and additionally influences other risk factors of coronary heart disease. However, it should be clearly stated that the clinical role of ‘beyond blood pressure’ effects of doxazosin are largely undetermined.

Long Term Effectiveness of Doxazosin in Men with Lower Urinary Tract Symptoms Suggesting of Benign Prostatic Hyperplasia

Purpose: The aim of this study was to evaluate the efficacy of doxazosin over 6 years in men with benign prostatic hyperplasia (BPH). Materials and Methods: This retrospective study enrolled 33 patients with symptomatic BPH who were prescribed an alpha-blocker from January 1999 to December 2000. We evaluated the changes of International Prostate Symptom Score (IPSS), maximal flow rate (Qmax), quality of life (QoL) and residual urine volume (RUV) between before and after 6-year of treatment. Results: The percentages of improvement were 40.2% in total IPSS, 40.6% in obstructive symptom, 39.4% in irritative symptom, 44.7% in QoL, 124.8% in Qmax, 33.5% in RUV (p<0.05). Three patients (9.1%) experienced acute urinary retention and BPH-related surgery was performed in 6 patients (18.2%). Conclusions: Our study revealed that long-term treatment over 6 years with alpha-blocker resulted in significant improvements in the IPSS, QoL, Qmax and RUV. (Korean J Urol 2008;49:1003-1006) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

The Effect of Doxazosin, Finasteride and Combination Therapy on Nocturia in Men With Benign Prostatic Hyperplasia

We evaluated the effectiveness of single or combination drug therapy on nocturia in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. A total of 3,047 men with lower urinary tract symptoms/benign prostatic hyperplasia enrolled in the Medical Therapy of Prostatic Symptoms trial were randomly assigned to receive doxazosin alone, finasteride alone, combination therapy or placebo. Treatment effectiveness was assessed according to intent to treat by mean reduction in self-reported nightly nocturia at 1 and 4 years. A subgroup analysis by age (younger than 70 vs 70 years old or older) was also performed. Of the men 2,583 reported 1 or more episodes of nocturia and finished 12 or more months of the trial. Mean nocturia was similar in all groups at baseline. Mean nocturia was reduced at 1 year by 0.35, 0.40, 0.54 and 0.58 in the placebo, finasteride, doxazosin and combination groups, respectively. Reductions with doxazosin and combination therapy were statistically greater than with placebo (p <0.05). At 4 years nocturia was also significantly reduced in patients treated with doxazosin and combination therapy (p <0.05 vs placebo). In men older than 70 years (495) all drugs significantly reduced nocturia at 1 year (finasteride 0.29, doxazosin 0.46 and combination 0.42) compared to placebo (0.11, p <0.05). Doxazosin and combination therapy reduced nocturia more than placebo, but the net benefit of active drug compared to placebo was often modest with a net difference of less than 0.20 fewer nightly nocturia episodes at 1 and 4 years. Findings in men 70 years old or older were similar, with an even smaller effect observed for finasteride.

1549: The Effect of Doxazosin, Finasteride, and Combination Therapy on Nocturia in Men with Benign Prostatic Hyperplasia

1549: The Effect of Doxazosin, Finasteride, and Combination Therapy on Nocturia in Men with Benign Prostatic Hyperplasia

Effect of Doxazosin With and Without Rho-Kinase Inhibitor on Human Corpus Cavernosum Smooth Muscle in the Presence of Bladder Outlet Obstruction

We investigated the relationship of adrenergic responses in corpus cavernosum tissues in the presence of BOO using the alpha1-adrenergic receptor antagonist doxazosin (Pfizer, New York, New York) and the rho-kinase inhibitor Y-27632 (Calbiochem, San Diego, California). CCSM tissue was obtained from patients who underwent penile prosthesis implantation. Patients were divided into 2 groups according to the presence of BOO. The submaximal (EC80) concentration of phenylephrine (Sigma Chemical Co., St. Louis, Missouri) was calculated by evaluating adrenergic activity responses with cumulatively applied phenylephrine. After achieving a stable contraction plateau test compounds were put in an organ bath. The relaxant potencies of doxazosin and Y-27632 were expressed as the percent of inhibition of the contraction plateau induced EC80 concentration of phenylephrine. Relaxation responses in the 2 groups were compared. At the highest dose of increasing concentrations phenylephrine generated 70% more contraction response in the BOO positive group than in the BOO negative group. Doxazosin and Y-27632 caused concentration dependent relaxation in CCSM precontracted by phenylephrine. With doxazosin significantly higher relaxation responses were attained in the BOO positive group in terms of log IC50 and the maximal relaxation response (p = 0.0353 and 0.0003, respectively). Maximum relaxation responses following Y-27632 administration were significantly higher in the BOO positive group. The contractility of human corpus cavernosum is increased in the presence of BOO. Doxazosin and Y-27632 generate effective CCSM relaxation in the presence of BOO. Doxazosin and Y-27632 may be the alternatives for the treatment of erectile dysfunction associated with BPH.

Effect of Doxazosin on C-Reactive Protein Plasma Levels and on Nitric Oxide in Patients With Hypertension

Inflammation has been hypothesized to play a role in the development of hypertension. The high-sensitivity C-reactive protein (hs-CRP) is a well-studied marker of systemic inflammation that has a predictive power with regard to the development of hypertension. This study was designed to test the hypothesis that hs-CRP plasma levels are altered in hypertension. Moreover, the study was to assess whether chronic antihypertensive treatment with doxazosin would normalize hs-CRP and nitrites/nitrates. We measured plasma levels of hs-CRP and nitrites/nitrates in 44 normotensive subjects and in 44 patients with hypertension before and after doxazosin therapy for 4 months. hs-CRP plasma levels were significantly higher (P < 0.007) in untreated hypertensive group compared to controls. Significant decrease was observed for hs-CRP (P < 0.05) in hypertensive patients after antihypertensive treatment. Nitrites/nitrates were significantly lower (P < 0.0001) in the untreated hypertensive group compared to controls. A significant increase was observed for nitrites/nitrates (P < 0.05) in hypertensive patients after antihypertensive treatment. These results suggest that doxazosin treatment exerts anti-inflammatory effects in addition to its antihypertensive properties in hypertensive patients.

Is Nocturia Equally Common Among Men and Women? A Population Based Study in Finland

We assessed the prevalence of nocturia and its association with sociodemographic factors. Information was collected with a questionnaire mailed to a random sample of 6,000 subjects 18 to 79 years old, identified from the Finnish Population Register Centre. Nocturia was defined as 1 or more, or 2 or more voids per night. Information was collected using the DAN-PSS questionnaire with an additional question from the AUA-SI questionnaire. Age standardized prevalence was calculated using the European standard population. Logistic regression was used for multivariate analysis. Of the 6,000 subjects 62.4% responded and 97.9% of the participants provided information on all nocturia questions. The age standardized prevalence of nocturia (1 or more voids per night) was 37% (95% CI 34%-40%) among men and 43% (95% CI 40%-46%) among women. With criterion of 2 or more voids per night prevalence was 12% (95% CI 10%-14%) for men and 13% (95% CI 11%-14%) for women. Women 18 to 49 years old had more nocturia than men. At 50 to 59 years old half of men and women reported nocturia. In older age groups nocturia was more frequent among men than women. The prevalence of nocturia increased at a constant rate with age. It increased twice as rapidly in men as among women (increase in OR 7.3% [95% CI 6.5%-8.2%] and 3.5% [95% CI 2.9%-4.1%] per year among men and women, respectively). The age standardized prevalence of nocturia (1 or more voids per night) was approximately 40% for both genders. In men the prevalence of nocturia increases more rapidly with age than in women. Nocturia is more common among women at a younger age but the differences disappear by middle age. In the elderly nocturia is more frequent among men.

Effect of Doxazosin on Oxidative Stress Related Proteins in Essential Hypertensive Patients

The role of oxidative stress in the pathophysiology of hypertension has stimulated the investigation of strategies to reduce oxidative stress via antioxidant defenses. Using a molecular biology approach, we report, in essential hypertensive patients, the effect of doxazosin treatment on the mononuclear cell gene and protein expression of two major elements in the oxidative stress and vascular remodeling-related pathways: p22phox and PAI-1. Ten essential hypertensive patients were treated with Doxazosin (4 mg/day) for two weeks (EH + D) and compared with ten untreated hypertensive patients (EH) and ten normotensive subjects (C). In EH p22phox and PAI-1 mRNA and protein level was increased compared with C. In EH + D, doxazosin reduced p22phox and PAI-1 gene and protein expression, which was similar to that of C. These results demonstrate for doxazosin an inhibitory effect on oxidative stress related proteins at gene and protein level, which confirms at molecular level a powerful antioxidant potential for this agent that could translate, in the long term, into a powerful antiatherosclerotic effect.

Tu-P10:454 Comparative effects of doxazosin and guanabenz on vascular inflammation and collagen metabolism in patients with morning hypertension

Tu-P10:454 Comparative effects of doxazosin and guanabenz on vascular inflammation and collagen metabolism in patients with morning hypertension

395 The effect of doxazosin on nocturnal orthopnea and left ventricular dysfunction in patients with congestive heart failure

395 The effect of doxazosin on nocturnal orthopnea and left ventricular dysfunction in patients with congestive heart failure

Maspin sensitizes prostate cancer cells to doxazosin-induced apoptosis.

Maspin is a mammary serine protease inhibitor or serpin with tumor suppressive and antiangiogenic activity that inhibits tumor motility, invasion and metastasis, at least by its actions on cell membrane and extracellular matrix (ECM) proteins. Previous studies documented that the quinazoline-derived alpha1-adrenoceptor antagonist doxazosin affects the attachment and migration of prostate cancer cells. In this study, we investigated the effect of maspin overexpression on the apoptotic/antiadhesion response of prostate cancer cells to doxazosin. The response of maspin-overexpressing clones of human prostate cancer cells DU-145 to doxazosin was evaluated by determining cell viability, apoptosis and cell proliferation on the basis of the trypan blue exclusion assay/methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, Hoechst staining and caspase-3 activation, and [(3)H]thymidine incorporation assay. Vascular endothelial growth factor (VEGF), transforming growth factor betaRII (TGFbetaRII), Smad4 (a TGFbeta intracellular effector) and bax expression was evaluated at the mRNA and protein level using reverse transcriptase-polymerase chain reaction and Western blotting, respectively. The effect of doxazosin on cell attachment of maspin-expressing prostate cancer cells was evaluated on collagen- and fibronectin-coated plates. Cell migration was assessed using the wounding assay. In response to tumor necrosis factor-related apoptosis-inducing ligand, DU-145-maspin expressing cells undergo apoptosis, via poly(ADP-ribose) polymerasecleavage and caspase-3 activation. DU-145-maspin cells exhibited higher sensitivity to doxazosin and an earlier temporal activation of caspase-3. The number of apoptotic cells detected in response to doxazosin was significantly higher compared to the neo control (P<0.0001). Doxazosin resulted in dramatic downregulation of the 189 isoform of VEGF in maspin transfectants, while a fivefold induction of Smad4 mRNA expression was detected in those cells after 24 h of treatment. Maspin overexpression in prostate cancer cells resulted in an increased ability to attach to ECM-coated plates, and doxazosin treatment considerably antagonized this effect by decreasing the attachment potential to collagen and fibronectin. The present study supports the ability of maspin to enhance the apoptotic threshold of prostate cancer cells to the quinazoline-based alpha1-adrenoceptor antagonist doxazosin. These findings may have therapeutic significance in the development of antiangiogenic targeting by doxazosin and derivative agents for advanced prostate cancer.

Effects of Doxazosin and Irbesartan on Blood Pressure and Metabolic Control in Patients with Type 2 Diabetes and Hypertension

The objective of this trial was to compare the metabolic effects of long-term treatment with doxazosin to those of irbesartan in patients with type 2 diabetes and hypertension. We evaluated 96 hypertensive diabetic patients who were randomized to 12 months of double-blind treatment with doxazosin 4 mg/d or irbesartan 300 mg/d. At the end of the study, systolic and diastolic blood pressure (SBP and DBP) were significantly reduced from 152 to 140 mm Hg and from 97 to 87 mm Hg, respectively, with doxazosin (P < 0.01). SBP and DBP were reduced from 150 to 134 mm Hg and from 94 to 83 mm Hg, respectively, with irbesartan (P < 0.01). Irbesartan had significantly better antihypertensive efficacy than doxazosin (P < 0.05). Doxazosin had the greatest effect on glucose metabolism and lipid parameters, with significant (P </= 0.05) reductions observed at study end compared with baseline in glycosylated hemoglobin, fasting plasma glucose, fasting plasma insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and Homeostasis Model Assessment Index. In conclusion, both doxazosin and irbesartan reduced BP during long-term treatment, but not to recommended levels, and doxazosin had the more beneficial effect on glucose metabolism and lipid profile.

THE COMPARISON AND EFFICACY OF 3 DIFFERENT α1-ADRENERGIC BLOCKERS FOR DISTAL URETERAL STONES

alpha1-Adrenergic blockers have recently been shown to increase the rate of spontaneous passage of distal ureteral stones. We compared efficacy of 3 different alpha1-adrenergic blockers for this purpose. A total of 114 patients between 18 and 65 years old who had lower ureteral stones were included in the study. Patients were randomly divided into 4 groups. Group 1 consisted of 28 patients and acted as the control group. Group 2 comprised 29 patients who received tamsulosin, group 3 was 28 patients receiving terazosin and group 4 was 29 patients receiving doxazosin. These agents were given for up to a month and hydration was also recommended simultaneously. Every week patients were controlled with x-rays of the kidneys, ureters, bladder and urinary ultrasonography. Meanwhile the number of pain episodes, analgesic dosage and the number of days for spontaneous passage of the calculi through the ureter were also recorded. There were no differences between the groups with respect to age, weight, height, sex and stone size. The calculi passed through the ureter spontaneously in 15 patients in group 1 (53.57%), in 23 patients in group 2 (79.31%), in 22 patients in group 3 (78.57%), and in 22 patients in group 4 (75.86%). In groups 2 to 4 the number of pain episodes, expulsion time and analgesic dosage were found to be lower compared with those in group 1. alpha1-Adrenergic blockers increase the frequency of spontaneous passage of the distal ureteral calculi. All 3 agents tested were equally efficacious.

Comparative effects of doxazosin and guanabenz on vascular inflammation and collagen metabolism in patients with morning hypertension

Comparative effects of doxazosin and guanabenz on vascular inflammation and collagen metabolism in patients with morning hypertension

Effects of Doxazosin on Cardiovascular Risk Factors and Nervous Function in Diabetic Hypertensives

Effects of Doxazosin on Cardiovascular Risk Factors and Nervous Function in Diabetic Hypertensives

Induction of anoikis by doxazosin in prostate cancer cells is associated with activation of caspase-3 and a reduction of focal adhesion kinase.

The quinazoline family of alpha1-blockers (prazosin, doxazosin, and terazosin) induce apoptosis of prostate cells through an alpha1-adrenoceptor-independent mechanism. The objective of this study was to gain insight into the non-adrenergic, apoptotic mechanism of action of doxazosin in the prostate and the induction of anoikis by doxazosin. Primary cultures of benign prostate stromal and epithelial cells and the LNCaP (androgen sensitive) and PC-3 (androgen insensitive) prostate carcinoma cell lines were treated with doxazosin (0-50 microM). The effects of doxazosin on cell morphology, caspase-3 activity, and the expression levels of focal adhesion kinase (FAK) and integrin-linked kinase (ILK) were examined. Doxazosin induced changes in morphology consistent with anoikis in both benign and cancerous prostatic cells and increased caspase-3 activity. The effects were similar comparing benign cells (which express alpha1-adrenoceptors) and cancer cells (which do not express alpha1-adrenoceptors), but were more robust in benign cells. Norepinephrine had no effect on doxazosin-induced cell morphology or caspase-3 activity. Treatment of PC-3 cells with doxazosin significantly reduced the protein levels of FAK but did not significantly affect the levels of ILK. These findings suggest that doxazosin induces apoptosis and anoikis of prostate cancer cells by a mechanism of action that is alpha1-adrenoceptor independent. The apoptosis of cancer cells induced by doxazosin counteracts cell proliferation and may have the potential of retarding or reversing prostate cancer cell growth.

1194: The Long Term Effects of Doxazosin, Finasteride, and the Combination on Sexual Function in Men Participating in the MTOPS Study

1194: The Long Term Effects of Doxazosin, Finasteride, and the Combination on Sexual Function in Men Participating in the MTOPS Study