Doxazosin Group Research Articles

Effect of different alpha-receptor antagonists on metabolic parameters: a head-to-head comparison.

Although it is known that alpha-adrenergic receptor antagonists have positive effects on metabolic parameters such as glucose metabolism, lipid profile, and insulin sensitivity, it is unclear whether this is a class effect. Tamsulosin is reported to have adverse effects on glucose metabolism and insulin resistance, and this may be because of its lack of glycolysis-enhancing effect compared with other alpha-adrenergic receptor antagonists with glycolysis-enhancing effects such as doxazosin, terazosin, and alfuzosin. The aim of this study was to compare the effect of tamsulosin on metabolic parameters with another alpha-1 adrenergic receptor antagonist, doxazosin. In this prospective, observational, controlled, 12-week clinical study, a total of 60 male patients aged ≥ 40years who were first started on tamsulosin (n = 30; 0.4mg/day, oral; mean age, 59.20 ± 8.97years) or doxazosin (n = 30; 4 or 8mg/day, oral; mean age, 58.50 ± 8.93years) for benign prostatic hyperplasia (BPH) or lower urinary tract symptoms (LUTS) were enrolled. The groups were compared according to the changes in anthropometric and biochemical parameters (glycemia, lipid profile, and insulin sensitivity) at the end of treatment. In intragroup analyses, systolic blood pressure, diastolic blood pressure, total cholesterol, and HbA1c levels decreased significantly in the doxazosin group compared with baseline (p < 0.05 for all), while no significant change was observed in the tamsulosin group. In comparisons between groups, systolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol levels showed a significant decrease in the doxazosin group compared with the tamsulosin group (percent change: - 6.68 ± 13.08 vs. 0.53 ± 11.02, p = 0.025; - 3.63 ± 9.56 vs. 4.02 ± 10.86, p = 0.005; and - 5.62 ± 18.18 vs. 5.24 ± 15.42, p = 0.015, respectively). Although these results do not support previous findings that tamsulosin has adverse effects on metabolic parameters, they suggest that doxazosin treatment may be a reason for preference in patients with BPH or LUTS accompanied by metabolic disorder.

Prophylactic doxazosin reduces urinary retention and promotes recovery after total joint arthroplasty: A randomized controlled trial.

Background: Postoperative urinary retention (POUR) is a common and disruptive complication following total joint arthroplasty (TJA). The aim of this study is to investigate whether doxazosin can decrease the incidence of POUR and promote recovery under the setting of modern enhanced recovery after TJA. Methods: In this randomized placebo-controlled trial, patients over 35years of age undergoing primary unilateral TJA were recruited. Patients received doxazosin (4mg once) or placebo 2h before surgery. The primary outcome of interest was the development of POUR, which was diagnosed when patients with a urine volume over 400ml or overflow incontinence. Postoperative recovery was assessed in terms of hospital length of stay after surgery, daily ambulation distance, visual analogue scale (VAS) pain score and opioid consumption. Results: A total of 170 male patients were equally randomized into Doxazosin group (mean age 54.2 ± 13.7years, range 36-88years) and Placebo group (mean age 54.6 ± 13.9years, range 38-81years). The POUR rate was significant lower in Doxazosin group (17.6%) than in Placebo group (36.5%) (p = .006). The mean LOS in the Doxazosin group was 3.1 ± 1.1days compared to 3.6 ± 1.7days in the Placebo group (p = .030). Doxazosin group had a longer daily mobilization distance than Placebo group on postoperative day 1 (26.8 ± 11.1 vs. 22.8 ± 9.7; p = .015). Postoperative pain assessed by VAS score and opioid usage was comparable between two groups. Conclusion: Our results support the routine use of prophylactic doxazosin in male patients to decrease POUR rate and promote postoperative recovery under the setting of modern enhanced recovery after TJA.

Comparison of Preoperative Alpha-blockade for Resection of Paraganglioma and Pheochromocytoma

ObjectivePhenoxybenzamine (nonselective, noncompetitive alpha-blocker) is the preferred drug for preoperative treatment of pheochromocytoma, but doxazosin (selective, competitive alpha-blocker) may be equally effective. We compared the efficacy of doxazosin vs phenoxybenzamine. MethodsWe conducted a prospective study of patients undergoing pheochromocytoma or paraganglioma resection by randomizing pretreatment with phenoxybenzamine or doxazosin at a single tertiary referral center. The high cost of phenoxybenzamine led to high crossover to doxazosin. Randomization was halted, and a consecutive historical cohort of phenoxybenzamine patients was included for a case-control study design. The efficacy of alpha-blockade was assessed with preinduction infusion of incremental doses of phenylephrine. The primary outcomes were mortality, cardiovascular complications, and intensive care unit admission. The secondary outcomes were hemodynamic instability index (proportion of operation outside of hemodynamic goals), adequacy of blockade by the phenylephrine titration test, and drug costs. ResultsTwenty-four patients were prospectively enrolled (doxazosin, n = 20; phenoxybenzamine, n = 4), and 15 historical patients treated with phenoxybenzamine were added (total phenoxybenzamine, n = 19). No major cardiovascular complications occurred in either group. The phenylephrine dose-response curves showed less blood pressure rise in the phenoxybenzamine than in the doxazosin group (linear regression coefficient = 0.008 vs 0.018, P = .01), suggesting better alpha-blockade in the phenoxybenzamine group. The median hemodynamic instability index was 14% vs 13% in the phenoxybenzamine and doxazosin groups, respectively (P = .56). The median highest daily cost of phenoxybenzamine was $442.20 compared to $5.06 for doxazosin. ConclusionPhenoxybenzamine may blunt intraoperative hypertension better than doxazosin, but this difference did not translate to fewer cardiovascular complications and is offset by a considerably increased cost.

EFFICACY OF DOXAZOSIN VERSUS TAMSULOSIN IN LOWER URETERIC STONE EXPULSION IN ADULT POPULATION OF DISTRICT DERA ISMAIL KHAN, PAKISTAN

Background: Urolithiasis is the third common disease of the urinary tract after UTIs and pathological diseases of the prostate. The objective of this study was to compare the efficacy of doxazosin versus tamsulosin in lower ureteric stone expulsion in adult population of District Dera Ismail Khan, Pakistan.Materials Methods: This non-randomized control trial was conducted in the Department of Urology, Gomal Medical College, Dera Ismail Khan, Pakistan from February 2020 to December 2020. The 252 patients included in our study were divided in to two groups. The patients in experimental group received Tab. doxazosin 4 mg daily for 4 weeks and Tab. diclofenac sodium 50 mg B.D for 5 days and then on need basis. The patients in control group received Cap. tamsulosin 0.4 mg daily for 4 weeks and similarly Tab. diclofenac sodium 50 mg as in experimental group. All the patients were followed regularly for expulsion of ureteric stones for four weeks. Sex, age and stone size were matching, while stone expulsion was a research variable. Hypothesis was verified by McNemar chi-square test.Results: Out of 252 patients, 113 (89.68%) patients in experimental group, while 77 (61.11%) patients in control group passed the stones. There was statistically significant difference in efficacy in doxazosin group as compared to tamsulosin group (p-value=.0001).Conclusion: The use of doxazosin as the medical expulsion therapy for the lower ureteric stone proved to be more effective as compared to tamsulosin as demonstrated by our results.

Analysis of Voiding Impairment after Prostate Biopsy and the Effect of Doxazosin Treatment: Outcomes from a Regional Cancer Center

Introduction: The aim of this study was to investigate the association of transrectal ultrasound (TRUS)-guided prostate biopsy with voiding impairment and the efficacy of doxazosin treatment. Methods: A prospective observational study including 200 male patients undergoing TRUS-guided prostate biopsy was performed between May 2020 and December 2020. One hundred patients underwent biopsy with doxazosin (doxazosin group). The remaining 100 patients underwent biopsy without doxazosin (control group). All patients were questioned regarding post-biopsy voiding difficulty and acute urinary retention. The International Prostate Symptom Score (IPSS), maximal urinary flow rate (Q_max), and residual urine volume were recorded before biopsy and at 7 and 30 days after biopsy. Results: There were no significant differences in baseline parameters between the two groups. The rate of post-biopsy voiding difficulty in the doxazosin group was significantly lower than that in the control group. Compared with baseline values, doxazosin treatment significantly improved IPSS, quality of life scores, and Q_max after biopsy (p < 0.05). The baseline values of IPSS and prostate size may be risk factors for post-biopsy voiding difficulty. Conclusion: TRUS-guided prostate biopsy causes transient voiding impairments, which may be improved by doxazosin treatment.

The safety and efficacy of doxazosin in medical expulsion therapy for distal ureteric calculi: A meta-analysis.

Alpha-adrenergic receptor blockers can be effectively used in the context of medical expulsion therapy (MET) to treat ureteric stones. This study was designed to evaluate the safety and efficacy of doxazosin in MET relative to placebo or tamsulosin. We systematically searched the PubMed, the Cochrane Library, EMBASE, Chinese Academic Database, and Web of Science databases to select randomized controlled trials (RCT) that compared the use of doxazosin with placebo or tamsulosin to treat ureteric stones. All patients we included were limited to those diagnosed with visible stones in the distal ureter. The diameter of ureteric stones does not exceed 10 mm. Eight trials comparing doxazosin with placebo or tamsulosin containing 667 patients were assessed in the final analysis. The meta-analysis showed that doxazosin effectively treated ureteric stones and was better than placebo in terms of efficacy. Relative to the placebo group, the expulsion rate of stones from the distal ureter (OR = 3.00, 95% CI [2.15, 4.19], I2 = 0%, P < 0.00001) was significantly increased, and the expulsion time (days) was shortened (mean difference) (MD) = -4.03, 95% CI [-4.53, -3.53], P < 0.00001). The doxazosin group experienced fewer pain episodes (MD = -0.78, CI = [-0.94, -0.23], I2 = 0%, P < 0.00001) than the placebo group. A subgroup analysis showed that the doxazosin group had a higher expulsion rate (of 5-10 mm stones) compared with the placebo group. Although doxazosin resulted in significantly more adverse effects compared with the placebo, the patient's symptoms were mild and no further medical interventions were required. Moreover, the expulsion time (days) was shorter for patients receiving doxazosin (MD = -0.61, 95% CI [-0.97, -0.24], I2 = 39%, P = 0.001) than those receiving tamsulosin. Compared with the placebo group, patients receiving doxazosin had a greater expulsion rate, a reduced expulsion time, and fewer pain episodes. The expulsion time of doxazosin was shorter than that of tamsulosin.

Doxazosin treatment in cocaine use disorder: pharmacogenetic response based on an alpha-1 adrenoreceptor subtype D genetic variant

ABSTRACTBackground: The α1 antagonist doxazosin reduces cocaine use in individuals with cocaine use disorder (CUD) through a functional polymorphism of the α1 adrenoreceptor. The regulatory role of the α1 adrenoreceptor subtype D (ADRA1D) gene polymorphism in CUD is uncharacterized.Objectives: To study how the genetic variant of ADRA1D gene (T1848A, rs2236554) may affect the treatment efficacy of doxazosin in reducing cocaine use.Methods: This 12-week pilot trial included 76 participants with CUD with ADRA1D (T1848A, rs2236554) AA (N = 40) or AT/TT genotype (N = 36). Participants were randomized to doxazosin (8 mg/day, N = 47) or placebo (N = 29), and followed with thrice weekly urine toxicology and once weekly cognitive behavioral psychotherapy.Results: The AA and the AT/TT groups had comparable baseline rates of cocaine positive urines at weeks 1–2 (~ 76%). In the placebo group, an increase of cocaine positive urines in the AT/TT group was found as compared to the AA group (24% vs. 9%). In the doxazosin group, a greater decrease in cocaine positive urines was found in the AT/TT group relative to the AA group. The difference between the doxazosin and placebo groups in cocaine negative urines became evident at weeks 5–6 and peaked at weeks 9–10 (~35% difference). The AT/TT group demonstrated a significant medication and time by medication effect (p < .001), whereas the AA group did not.Conclusion: The T-allele carriers showed a greater reduction of cocaine use after treatment with doxazosin in participants with the ADRA1D gene polymorphism (T1848A), suggesting that this SNP may serve as a pharmacogenetic marker in pharmacotherapy of CUD.

Efficacy of α-Blockers on Hemodynamic Control during Pheochromocytoma Resection: A Randomized Controlled Trial.

ContextPretreatment with α-adrenergic receptor blockers is recommended to prevent hemodynamic instability during resection of a pheochromocytoma or sympathetic paraganglioma (PPGL).ObjectiveTo determine which type of α-adrenergic receptor blocker provides the best efficacy.DesignRandomized controlled open-label trial (PRESCRIPT; ClinicalTrials.gov NCT01379898)SettingMulticenter study including 9 centers in The Netherlands.Patients134 patients with nonmetastatic PPGL.InterventionPhenoxybenzamine or doxazosin starting 2 to 3 weeks before surgery using a blood pressure targeted titration schedule. Intraoperative hemodynamic management was standardized.Main Outcome MeasuresPrimary efficacy endpoint was the cumulative intraoperative time outside the blood pressure target range (ie, SBP >160 mmHg or MAP <60 mmHg) expressed as a percentage of total surgical procedure time. Secondary efficacy endpoint was the value on a hemodynamic instability score.ResultsMedian cumulative time outside blood pressure targets was 11.1% (interquartile range [IQR]: 4.3–20.6] in the phenoxybenzamine group compared to 12.2% (5.3–20.2)] in the doxazosin group (P = .75, r = 0.03). The hemodynamic instability score was 38.0 (28.8–58.0) and 50.0 (35.3–63.8) in the phenoxybenzamine and doxazosin group, respectively (P = .02, r = 0.20). The 30-day cardiovascular complication rate was 8.8% and 6.9% in the phenoxybenzamine and doxazosin group, respectively (P = .68). There was no mortality after 30 days.ConclusionsThe duration of blood pressure outside the target range during resection of a PPGL was not different after preoperative treatment with either phenoxybenzamine or doxazosin. Phenoxybenzamine was more effective in preventing intraoperative hemodynamic instability, but it could not be established whether this was associated with a better clinical outcome.

A Randomized, Open-Label, Comparative Study of Efficacy and Safety of Tolterodine Combined with Tamsulosin or Doxazosin in Patients with Benign Prostatic Hyperplasia.

BackgroundBenign prostatic hyperplasia (BPH), a common disease in men over age 50 years, often causes bladder outlet obstruction and lower urinary tract symptoms (LUTS). Alpha blockers in combination with muscarinic receptor antagonists may have the potential to improve symptoms. This study aimed to assess the efficacy and safety of doxazosin or tamsulosin combined with tolterodine extend release (ER) in patients with BPH and LUTS.Material/MethodsIn a prospective, randomized, open-label study (ChiCTR-IPR-15005763), 220 consecutive men with BPH and LUTS were allocated to receive doxazosin 4 mg and tolterodine ER 4 mg per day (doxazosin group) or tamsulosin 0.2 mg and tolterodine ER 4 mg per day (tamsulosin group). Treatment lasted 12 weeks. The primary endpoint was the international prostatic symptom score (IPSS). Secondary endpoints were quality of life (QoL) and maximum flow rate (Qmax), which were evaluated at 0, 6, and 12 weeks, and urodynamic parameters assessed at 0 and 12 weeks.ResultsA total of 192 patients completed the trial. Baseline measurements showed no differences between the groups. After 6 weeks, IPSS improved in both groups and QoL was significantly better in the doxazosin group (P=0.01). After 12 weeks, Qmax, IPSS, QoL, intravesical pressure (Pves), and bladder compliance (BC) in the doxazosin group were significantly better than in the tamsulosin group (P=0.03, P<0.001, P<0.001, P=0.027, and P=0.044, respectively).ConclusionsAdministration of alpha blockers combined with muscarinic receptor blocker for 12 weeks improved LUTS in men with BPH.

Anterior segment morphologic changes related to α-1 adrenergic receptor antagonists use.

To investigate possible changes in anterior segment parameters with the Pentacam in patients taking tamsulosin or doxazosin for benign prostatic hyperplasia. This prospective, cross-sectional study was conducted at Necip Fazil City Hospital, Kahramanmaras, Turkey. Patients included in the study were grouped as follows: 29 patients treated with tamsulosin (group 1), 27 patients treated with doxazosin (group 2), and 40 untreated controls (group 3). Right eyes of each patient were included in the study. All patients underwent examination with the Pentacam under standard dim light conditions and with undilated pupils. Anterior chamber depth (ACD), anterior chamber volume (ACV), anterior chamber angle (ACA) width, central corneal thickness (CCT), corneal volume (CV), and pupil diameter (PD) were recorded. Mean duration of treatments was 2.7 ± 1.2 (1-5) and 2.4 ± 0.9 (1-5) years in groups 1 and 2 (p = 0.276). The ACD, ACV, ACA width, and PD were statistically significantly decreased in groups 1 and 2 when compared to group 3 (p&lt;0.05). There were no statistically significant differences among the groups in mean values of CCT and CV. In this study, decreased ACD, ACV, ACA width, and PD values were detected in tamsulosin and doxazosin groups when compared to controls. These findings should be considered during anterior segment examinations and surgeries.

Effects of doxazosin as the third agent on morning hypertension and position-related blood pressure changes in diabetic patients with chronic kidney disease

We conducted a prospective study to assess the effects of doxazosin, as the third agent, on morning and position-related blood pressure (BP) in 77 diabetic patients with chronic kidney disease, who were allocated randomly to doxazosin and diuretics groups. Doxazosin decreased morning BP but diuretics could not decrease pre-awakening diastolic BP. Only doxazosin improved sympathovagal balance. Doxazosin and diuretics decreased standing and sitting BP but only doxazosin improved sympathovagal balance regardless of body positions. Doxazosin did not decrease absolute BP changes shortly after standing. In diabetic patients, doxazosin decreased morning BP through improving sympathovagal balance without causing significant orthostatic hypotension (ClinicalTrials.gov number, NCT00295555).Trial registration: ClinicalTrials.gov identifier: NCT00295555.

Intraoperative floppy iris syndrome (IFIS): what complication rates can we expect?

Dear Editor, In a very interesting paper, Haridas et al. have shown that patients with intraoperative floppy iris syndrome (IFIS) receiving tamsulosin or doxazosin differ in terms of morbidity rates [1]. Among 2,785 cataract operations performed in 2,028 patients, the authors identified 52 (1.9 %) cases treated with tamsulosin and 109 (3.9 %) cases in which doxazosin was administered. They compared morbidity rates between these two groups. In our opinion, however, some aspects of this study need to be discussed. In their retrospective analysis, the authors found at least one IFIS feature in 17 out of 106 eyes (16 %) from the doxazosin group and in 25 out of 52 eyes (48 %) from the tamsulosin group. Alpha-1 antagonists, used in the symptomatic treatment of benign prostatic hyperplasia, may increase the surgical difficulties and risk of iris damage, corneal edema, posterior or anterior capsule rupture, and postoperative increase in intraocular pressure [2–4]. Nevertheless, analysis of data expressed as percentages can be misleading and provide false information on the prevalence of IFIS and expected intraoperative morbidity rate. In Table 1 of their paper, Haridas et al. presented data on the size of the pupil and status of the iris in the tamsulosin and doxazosin groups [1]. However, the prevalence of various abnormalities (large or small pupil, iris prolapse, etc.) was expressed as a percentage of IFIS cases in a given group, i.e. per 25 and 17 eyes in tamsulosin and doxazosin group, respectively. In our opinion, however, the prevalence should be rather expressed per the whole group administered a given agent, i.e. per 52 and 106 eyes of patients treated with tamsulosin and doxazosin, respectively. Only in this way can we estimate the potential risk of intraoperative complications in patients treated with α-1 antagonists. Furthermore, it should be noted that expressing seven cases of intraoperative complications in the tamsulosin group as 13.5 % (7 out of 52 eyes) suggests that such morbidity can be expected in patients subjected to cataract surgeries. This is not true, as intraoperative complications documented in the tamsulosin IFIS group (iris damage – 5 cases, anterior capsule rupture – 1 case, corneal edema – 1 case) corresponded to only 0.3 % of all 2,785 operated eyes, the average rate of cataract complications in non-IFIS patients. Takmaz analyzed a group of 858 operated eyes and identified intraoperative complications in 6 eyes of patients who were treated with tamsulosin [8]. However, he emphasized the lack of significant differences in the morbidity rates of tamsulosin-treated patients with and without IFIS (p = 0.245). According to Haridas et al., patients treated with tamsulosin differed significantly from the controls in terms of the morbidity rates (13.5 %, i.e. 7 out of 52 eyes vs. 3.3 %, i.e. 5 out of 150 eyes; p = 0.014) [1]. However, we postulate that statistical analyses are not justified in the case of such a large disproportion in group size. Furthermore, this analysis was not adjusted for surgeon’s experience and other intraoperative factors. Table 1 Studies reporting the rate of intraoperative floppy iris syndrome (IFIS) complications The exact data on the type and prevalence of intraoperative complications is missing in available literature. (Table 1) Chang et al. spoke to the intraoperative use of retractors in five cases but did not provide any data on the percentage of postoperative iris damage in patients with IFIS [2]. In turn, the report by Oshika et al. not only lacks any data on postoperative morbidity rates but does not provide any information about intraoperative strategies of performing cataract phacoemulsification in patients with IFIS [6]. Concluding: Although the use of α-1 antagonists, especially tamsulosin, can constitute a potential risk of intraoperative complications in cataract surgery, such complications occur sporadically, and therefore, the morbidity rates should be presented in a uniform manner in order to avoid their inadvertent overestimation.

Comparing the effectiveness of intranasal desmopressin and doxazosin in men with nocturia: a pilot randomized clinical trial.

We aimed to compare the effectiveness of intranasal desmopressin and doxazosin treatments in patients with nocturia and benign prostatic hyperplasia (BPH). Thirty one men with BPH and three or more episodes of nocturia were randomized to receive 2 mg doxazosin at night for two weeks increasing to 4 mg for a further two weeks versus 20 μg intranasal desmopressin at night. For all patients, number of nocturia, urinary flow rate, residual urine volume and quality of life score were checked. Outcomes were measured at two months. The comparison of before and after treatment changes between the groups were done by student's t-test. In doxazosin group, mean number of nocturia were 3.2 &plus mn; 0.4 (3-4 times) times per night and 1.2 +/- 0.8 (0-3 times) times per night before and after treatment, respectively. In desmopressin group, mean number of nocturia were 3.4 +/- 0.5 (3-4 times) and 1.5 +/- 0.6 (1-3 times) times per night before and after treatment, respectively. In doxazosin group, mean residual urine volumes were 44.3 +/- 35.9 ml (range 0-120 ml) and 23.1 +/- 18.8 ml (range 0-50 ml) before and after treatment, respectively. In desmopressin group, mean residual urine volumes were 36.6 +/- 32.4 ml (range 0-120 ml) and 14.0 +/- 26.9 ml (range 0-90 ml) before and after treatment, respectively. Improvements in number of nocturia, residual urine volume, quality of life scores and peak urinary flow rates weren't statistically significant between two groups, whereas change in international prostate symptom score (IPSS) score was more significant in doxazosin group. Intranasal desmopressin, is an effective symptomatic treatment of men with BPH complaining of nocturia, as well as doxazosin treatment.

Intraoperative floppy iris syndrome (IFIS) in patients receiving tamsulosin or doxazosin—a UK-based comparison of incidence and complication rates

The association between intraoperative floppy iris syndrome (IFIS) and tamsulosin has been well-described. The rate of IFIS in association with other α-1 antagonists needs further clarification. The objective of this study was to determine the incidence of IFIS and associated cataract surgery complications in patients taking tamsulosin or doxazosin. Patients receiving tamsulosin or doxazosin, and an equivalent number of controls, were identified using the electronic patient record for cataract surgery performed over 2 years. The presence of IFIS and intraoperative complications were ascertained. Modifications of surgical technique in the form of preoperative 1 % atropine, intraoperative diluted phenylephrine, iris hooks, or highly viscous viscoelastic materials were recorded. Of the 2,785 cataract operations performed in 2,028 patients, 52 cases (1.9 %) were on tamsulosin and 109 were on doxazosin (3.9 %). In the doxazosin group (excluding three cases with incomplete data), significantly more eyes (17 of 106 eyes, 16 %) showed at least one IFIS characteristic than controls, six eyes (6 %) required adjustment of surgical technique, and intraoperative complications occurred in two eyes (1.9 %). In the tamsulosin group, significantly more eyes (25 of 52 eyes, 48 %) demonstrated at least one IFIS feature than control or doxazosin eyes; 18 eyes (35 %) needed adjustment of surgical technique, and seven (13.5 %) suffered intraoperative complications. Incidence of IFIS was significantly higher in tamsulosin and doxazosin patients. The presence of IFIS was associated with a significantly higher complication rate. We would advise that all patients receiving α1 antagonists (not only those receiving tamsulosin) should be identified preoperatively, receive appropriate modifications in preparation, and have alternative techniques and a senior surgeon available at the time of surgery.

Above Which Blood Pressure Level Does the Risk of Atrial Fibrillation Increase?

See related article, pp 198–204 Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, occurs in 1% to 2% of the general population,1 and its incidence is growing. Mostly because of the progressive aging of the population, the prevalence of AF is expected to double over the next 50 years.1 AF is a potentially devastating condition for several reasons. It portends a 5-fold risk of stroke,2 and ischemic strokes that occur in people with AF are often fatal or leave surviving patients generally more disabled and at higher risk of recurrences compared with other causes of stroke. AF triples the risk of heart failure,3 doubles the risk of dementia, and markedly increases the risk of all-cause mortality.4 For the above reasons, prevention of AF through appropriate control of its modifiable risk factors is a public health priority. Unfortunately, despite numerous experimental and clinical studies, the individual risk of developing AF in a given time frame is still difficult to estimate.5 Hypertension is a well-known modifiable risk factor for AF,3,4 although it is unclear above which blood pressure (BP) level the risk of AF definitely increases and, even more important, which target BP level should be pursued to reduce the risk of AF in treated hypertensive patients. In a population based, case-control study of 433 patients with incident AF and 899 controls, the risk of AF doubled in participants with systolic BP ≥150 …

Doxazosin Versus Tizanidine for Treatment of Dysfunctional Voiding in Children: A Prospective Randomized Open-labeled Trial

To examine the efficacy and tolerability of tizanidine for the treatment of dysfunctional voiding in children compared with those of doxazosin. A total of 40 children with dysfunctional voiding were enrolled in a prospective, randomized, 2-parallel group, flexible-dose study. The evaluations were performed in accordance with the International Children's Continence Society guidelines. The children were followed up after 1 week and then monthly for 6 months for the clinical, urine culture, and urodynamic parameters. The degree of improvement was assessed using a satisfaction scale that ranged from 0 (no improvement at all) to 10 (total improvement). A total of 40 patients with a mean±SD age of 7±2.6 years were enrolled. The clinical and urodynamic parameters were comparable between both groups. At the last follow-up visit, both groups had had similar improvement in the severity of symptoms, satisfaction scale, and noninvasive flowmetry parameters. In the doxazosin group, urge episodes was the only symptom that showed a significant reduction compared with the baseline values (P=.028). However, the incidence of nocturnal enuresis, urgency attacks, and daytime incontinence were significantly reduced compared with baseline in the tizanidine group (P=.003, P=.008, and P=.017, respectively). Adverse effects were recorded in 6 patients (15%). Epigasteric pain was reported in 2 children (10%) who received doxazosin. In the tizanidine group, a loss of appetite was noted in 2 children (10%), epigastric pain in 1 (5%), and headache in 1 (5%). Tizanidine could be a safe and effective treatment of children with dysfunctional voiding due to pelvic floor/skeletal sphincter dysfunction. More placebo-controlled trails with larger sample sizes are needed.

Clinical effectiveness and safety of combined therapy with an alpha-blocker and an anticholinergic drug for patients with benign prostatic hyperplasia

To evaluate the effectiveness and safety of the combined therapy of doxazosin and tolterodine for BPH patients with dominant storage symptoms. From May 2009 to April 2010, 76 patients diagnosed as benign prostatic hyperplasia (BPH) by International Prostate Symptom Score (IPSS), flowmetry, ultrasound for prostate volume, residual urine and other methods were included in the study, all of them fulfilled the study's inclusive/exclusive criteria. The principal exclusive criteria were prostate volume > 50 ml, maximum flow rate (Qmax) < 10 ml/s and residual urine > 100 ml. All 76 patients had bothering storage symptoms and divided randomly into two groups:doxazosin group (n = 36) in which patients were treated with doxazosin 2 mg once daily for 8 weeks, and combination group (n = 40) in which patients were treated with doxazosin 2 mg once daily and tolterodine 2 mg twice daily for 8 weeks. At baseline, there was no significant differences. The IPSS was significantly improved in the two groups after treatment, but the reduction of IPSS in combination group was significantly greater (18.7 ± 2.2 vs 12.7 ± 3.9) than that in doxazosin group (18.6 ± 3.0 vs 15.2 ± 3.8) (P < 0.05), and the decreased storage IPSS was the main contribution to the reduction of IPSS in combination group. There was no difference between the groups for Qmax and residual urine. Combined therapy with doxazosin plus tolterodine for BPH patients with dominant storage symptoms can improve the IPSS, especially the storage IPSS, without any negative effects on uroflow rate and residual urine.

Selective α1-adrenoceptor antagonist (controlled release tablets) in preoperative management of pheochromocytoma

The objective of this article is to evaluate the efficacy of Doxazosin Mesylate Controlled Release Tablets for preoperative treatment of patients with pheochromocytoma. Between 2003 and 2008, 67 patients with confirmed diagnoses of pheochromocytoma were enrolled in this study. According to the drug used in preoperative management, patients were divided into two groups: Doxazosin Mesylate pretreatment group (n=36) and Phenoxybenzamine pretreatment group (n=31). Surgery was performed only in patients who met the optimal preoperative condition. The hematocrit decreased significantly (P<0.001) after antiadrenergic therapy in patients pretreated with phenoxybenzamine or doxazosin. There was no significant difference between the fluid intakes during operation in both groups. The systolic arterial pressures both before and after induction of anesthesia were all significantly higher in the doxazosin patients than in the phenoxybenzamine group (P<0.05). After tumor removed, the lowest systolic arterial pressure was significantly higher in doxazosin group than in phenoxybenzamine group (P<0.05). The fluctuation of systolic arterial pressure during operation was more stable in doxazosin group than in phenoxybenzamine group (P<0.05). Doxazosin mesylate controlled release tablet was as effective as phenoxybenzamine in preoperative volume expansion. Although phenoxybenzamine provided better arterial pressure control, patients pretreated with DOX experienced more stable perioperative hemodynamic changes, shorter preoperative management periods and more simple medication.

Risk Factors for Hemodynamic Instability during Surgery for Pheochromocytoma

Surgery on pheochromocytoma carries a risk for hemodynamic (HD) instability. The aim of this study was to identify preoperative risk factors for intraoperative HD instability. In addition, efficacy of pretreatment with the alpha-adrenergic receptor (alpha) antagonists phenoxybenzamine (PXB) and doxazosin (DOX) was compared with respect to reduction of intraoperative HD instability. Seventy-three patients operated in Erasmus Medical Center between 1995 and 2007 were included. Parameters studied were catecholamine type and concentration, tumor diameter, mean arterial pressure (MAP) before and after (MAP(alpha)) pretreatment with alpha-antagonist, postural fall in blood pressure (BP) after pretreatment, type of alpha-blockade, type of operation, and presence of a familial polytumor syndrome. HD instability was assessed by measuring the number and time period MAP was below 60 mm Hg and systolic BP (SBP) was above 160 mm Hg. A correlation was found between the intraoperative time periods of SBP above 160 mm Hg and plasma norepinephrine levels (r = 0.23; P < 0.05), tumor diameter (r = 0.36; P < 0.01), and postural BP fall (r = 0.30; P < 0.05). MAP at presentation and after alpha-blockade above 100 mm Hg (BP, 130/85 mm Hg) was related to more and longer episodes with a SBP above 160 mm Hg (P < 0.01). Type of operation or alpha-blockade and presence of a familial polytumor syndrome were not related to intraoperative HD instability. Postoperative MAP was lower in the DOX group than in the PXB group (P < 0.05). Risk factors for HD instability during surgery for pheochromocytoma include a high plasma NE concentration, larger tumor size, more profound postural BP fall after alpha-blockade, and a MAP above 100 mm Hg (130/85 mm Hg). Efficacy for preventing HD instability was identical for PXB and DOX.

Effects of (−)Doxazosin on Histomorphologic and Cell Apoptotic Changes of the Hyperplastic Prostate in Castrated Rats

Background(−)Doxazosin is one of the enantiomers of (±)doxazosin, and it was reported that (−)doxazosin possessed higher selectivity for lower urinary tract between the cardiovascular system and the urinary system in the animal experiments in comparison with that of (±)doxazosin and (+)doxazosin. Therefore, it is important to know whether (−)doxazosin has a therapeutic effect on the hyperplastic prostate. Methods(−)Doxazosin and (±)doxazosin were administered intragastrically to prostatic hyperplasia rats, induced by testosterone propionate for 4 weeks, and each experimental group contained 8 animals. The histomorphologic changes of the prostate were observed under light microscope, the quantitative analysis of the prostatic glandular cavity was performed using an image analysis system, and the cell apoptosis was detected by using flow cytometry. ResultsIn comparison with model-control group, the volume index of the prostate in (−)doxazosin 3.0mg/kg group became significantly smaller. The maximal diameter, perimeter, and area of the hyperplastic prostate glandular cavity, and the glandular epithelial cell height in (−)doxazosin (0.3, 1.0, and 3.0mg/kg) groups and (±)doxazosin group were significantly reduced. (−)Doxazosin and (±)doxazosin did not significantly affect cell cycle distribution and cell proliferation index of the hyperplastic prostate. However, apoptotic rates of the prostatic cells in (−)doxazosin (0.3, 1.0, and 3.0mg/kg) groups and (±)doxazosin group were significantly increased in comparison with those of model-control group. ConclusionsBoth (−)doxazosin and (±)doxazosin inhibit the prostatic hyperplasia induced by testosterone propionate in castrated rats. The induction of prostate cell apoptosis might be one of the mechanisms underlying the therapeutic role of (−)doxazosin.