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Frontiers in Pediatrics 2022Pediatric urolithiasis is a common condition, and medical expulsive therapy has grown to be accepted by many parents. We carried out a meta-analysis to identify the... (Review)
Review
OBJECTIVE
Pediatric urolithiasis is a common condition, and medical expulsive therapy has grown to be accepted by many parents. We carried out a meta-analysis to identify the efficacy and safety of α-adrenergic blockers for the treatment of pediatric urolithiasis.
METHODS
We identified related articles from the PubMed, Embase, and Cochrane Library databases. All published randomized controlled trials (RCTs) describing the use of α-adrenergic blockers and placebo treatment for pediatric distal urolithiasis were involved. The outcomes included stone expulsion rate, stone expulsion time, pain episodes, need for analgesia, adverse events, and related subgroup analyses.
RESULTS
A total of nine RCTs were involved in our study, including 586 patients. We found that α-adrenergic blockers could significantly increase the rate of stone expulsion [odds ratio (OR), 3.49; 95% confidence interval (CI), 2.38-5.12; < 0.00001], reduce the stone expulsion time [mean difference (MD), -5.15; 95% CI, -8.51 to -1.80; = 0.003], and decrease pain episodes (MD, -1.02; 95% CI, -1.33 to -0.72; < 0.00001) and analgesia demand (MD, -0.92; 95% CI, -1.32 to -0.53; < 0.00001) but had a higher incidence of side effects (MD, 2.83; 95% CI, 1.55 to 5.15; = 0.0007). During subgroup analyses, different medications (tamsulosin, doxazosin, and silodosin) also exhibited better efficiencies than placebo, except for doxazosin, which showed no difference in expulsion time (MD, -1.23; 95% CI, -2.98 to 0.51; = 0.17). The three kinds of α-adrenergic blockers also appeared to be better tolerated, except for tamsulosin with its greater number of adverse events (MD, 2.85; 95% CI, 1.34 to 6.03; = 0.006). Silodosin led to a better expulsion rate than tamsulosin (OR, 0.42; 95% CI, 0.20 to 0.92; = 0.03). In addition, α-adrenergic blockers increased the stone expulsion rate regardless of stone size and decreased the expulsion time of stones measuring <5 mm (MD, -1.71; 95% CI, -2.91 to -0.52; = 0.005), which was not the case for stones measuring >5 mm in expulsion time (MD, -3.61; 95% CI, -10.17 to 2.96; = 0.28).
CONCLUSION
Our review suggests that α-adrenergic blockers are well-tolerated and efficient for treating pediatric distal urolithiasis. We also conclude that silodosin is the best choice of drug, offering a better expulsion rate, but it remains to be evaluated further by future studies.
PubMed: 35498769
DOI: 10.3389/fped.2022.809914 -
Urology Journal Aug 2020Alpha-blockers have been proven as an effective method for increasing the stone expulsion rate of distal ureteral stones. Limited studies have focused on doxazosin; its... (Meta-Analysis)
Meta-Analysis
PURPOSE
Alpha-blockers have been proven as an effective method for increasing the stone expulsion rate of distal ureteral stones. Limited studies have focused on doxazosin; its efficacy remained unclear. We performed this meta-analysis to investigate the efficacy and safety of doxazosin for patients diagnosed with distal ureteral stones less than 10mm.
MATERIALS AND METHODS
We systematically searched Ovid MEDLINE®, Cochrane Library, EMBASE, and PubMed for articles comparing doxazosin and conventional care or tamsulosin for distal ureteral stones through October 2019. The outcome measures were stone expulsive rate (SER), stone expulsive time (SET), pain episodes, analgesics consumption, and adverse events.
RESULTS
We included 12 studies involving 836 participants with distal ureteral stones less than 10mm in our review. The present meta-analysis showed doxazosin could significantly increase SER [RR=1.64,95%CI (1.32, 2.04), P < 0.00001], shorten SET [WMD=-3.97,95% CI (-5.68, -2.27), P < 0.00001] compared with conventional care. In the subgroup analyses, doxazosin showed no benefit in the children subgroup (<16 years old) [RR=1.63,95% CI (0.73,3.64), P =0.23]. No statistically significant difference was observed regarding the effectiveness of doxazosin and tamsulosin in SER, SET, and safety. 9 in 286 participants reported doxazosin-related adverse events; most were mild to moderate.
CONCLUSION
This meta-analysis may suggest that doxazosin is a safe and effective MET for distal ureteral stones less than 10mm. It is not demonstrated to have any significant difference with tamsulosin in SER, SET, and safety. However, it showed no benefits for patients<16 years old.
Topics: Adrenergic alpha-1 Receptor Antagonists; Doxazosin; Humans; Treatment Outcome; Ureteral Calculi
PubMed: 32869260
DOI: 10.22037/uj.v16i7.5958 -
Clinical Interventions in Aging 2006We evaluated the efficacy and safety of alpha 1--blocker doxazosin for treatment of lower urinary tract symptoms (LUTS) compatible with benign prostatic hypertrophy... (Review)
Review
We evaluated the efficacy and safety of alpha 1--blocker doxazosin for treatment of lower urinary tract symptoms (LUTS) compatible with benign prostatic hypertrophy (BPH). Fourteen randomized controlled trials enrolled 6261 men, average age 64 years, who had moderately severe LUTS and flow impairment. Compared with baseline measures and placebo effect, doxazosin resulted in a statistically significant improvement in both LUTS and flow. However, when compared with placebo, the average magnitude of symptom improvement (International Prostate Symptom Score [IPSS] improvement < 3 points) typically did not achieve a level detectable by patients. Combined doxazosin and finasteride therapy improved LUTS and reduced the risk of overall clinical progression of BPH compared to each drug separately in men followed over 4 years. Reported mean changes from baseline in the IPSS were -7.4, -6.6, -5.6, and -4.9 points for combination therapy, doxazosin, finasteride, and placebo, respectively. Combination therapy reduced the need for invasive treatment for BPH and the risk of long-term urinary retention. The absolute reductions compared with placebo were less than 4% and primarily seen in men with prostate gland volume > 40 mL or PSA levels > 4 ng/mL. Efficacy was comparable with other alpha 1--blockers. Withdrawals from treatment for any cause were comparable to placebo. Dizziness and fatigue occurred more frequently with doxazosin compared to placebo.
Topics: Adrenergic alpha-Antagonists; Doxazosin; Drug Combinations; Enzyme Inhibitors; Finasteride; Humans; Male; Middle Aged; Prostatic Hyperplasia; Urinary Tract; Urodynamics
PubMed: 18046916
DOI: 10.2147/ciia.2006.1.4.389 -
Endocrine Practice : Official Journal... Sep 2022Phenoxybenzamine (nonselective, noncompetitive alpha-blocker) is the preferred drug for preoperative treatment of pheochromocytoma, but doxazosin (selective, competitive...
OBJECTIVE
Phenoxybenzamine (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.
METHODS
We 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.
RESULTS
Twenty-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.
CONCLUSION
Phenoxybenzamine 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.
Topics: Adrenal Gland Neoplasms; Adrenergic alpha-Antagonists; Case-Control Studies; Doxazosin; Humans; Phenoxybenzamine; Phenylephrine; Pheochromocytoma; Prospective Studies
PubMed: 35809774
DOI: 10.1016/j.eprac.2022.06.013 -
JACC. Cardiovascular Imaging Feb 2015Angina without coronary artery disease (CAD) has substantial morbidity and is present in 10% to 30% of patients undergoing angiography. Coronary microvascular... (Review)
Review
Angina without coronary artery disease (CAD) has substantial morbidity and is present in 10% to 30% of patients undergoing angiography. Coronary microvascular dysfunction (CMD) is present in 50% to 65% of these patients. The optimal treatment of this cohort is undefined. We performed a systematic review to evaluate treatment strategies for objectively-defined CMD in the absence of CAD. We included studies assessing therapy in human subjects with angina and coronary flow reserve or myocardial perfusion reserve <2.5 by positron emission tomography, cardiac magnetic resonance imaging, dilution methods, or intracoronary Doppler in the absence of coronary artery stenosis ≥50% or structural heart disease. Only 8 papers met the strict inclusion criteria. The papers were heterogeneous, using different treatments, endpoints, and definitions of CMD. The small sample sizes severely limit the power of these studies, with an average of 11 patients per analysis. Studies evaluating sildenafil, quinapril, estrogen, and transcutaneous electrical nerve stimulation application demonstrated benefits in their respective endpoints. No benefit was found with L-arginine, doxazosin, pravastatin, and diltiazem. Our systematic review highlights that there is little data to support therapies for CMD. We assess the data meeting rigorous inclusion criteria and review the related but excluded published data. We additionally describe the next steps needed to address this research gap, including a standardized definition of CMD, routine assessment of CMD in studies of chest pain without obstructive CAD, and specific therapy assessment in the population with confirmed CMD.
Topics: Coronary Angiography; Coronary Circulation; Diagnosis, Differential; Humans; Magnetic Resonance Imaging, Cine; Microcirculation; Microvascular Angina; Myocardial Revascularization; Positron-Emission Tomography; Practice Guidelines as Topic; Regional Blood Flow
PubMed: 25677893
DOI: 10.1016/j.jcmg.2014.12.008 -
JAMA Neurology Apr 2021Parkinson disease (PD) is a common neurodegenerative disease. A treatment that prevents or delays development of PD is a critical unmet need. Terazosin and closely... (Observational Study)
Observational Study
IMPORTANCE
Parkinson disease (PD) is a common neurodegenerative disease. A treatment that prevents or delays development of PD is a critical unmet need. Terazosin and closely related drugs were recently discovered to enhance glycolysis and reduce PD progression in animal models and human clinical databases.
OBJECTIVE
To determine whether use of terazosin, doxazosin, and alfuzosin is associated with a decreased risk of developing PD.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used active comparator control and propensity score-matched data from Danish nationwide health registries, including the Danish National Prescription Registry, the Danish National Patient Registry, and the Danish Civil Registration System, from January 1996 to December 2017 and data from the Truven Health Analytics MarketScan database from January 2001 to December 2017. Men without PD who newly initiated terazosin/doxazosin/alfuzosin therapy or tamsulosin therapy, which is used for a similar indication (benign prostatic hyperplasia or unspecified urinary problems) but does not enhance glycolysis, and had at least 1 year of follow-up after medication start were included. In Denmark, the database included all residents, while the Truven database is a compilation of insurance claims across the US. Data were analyzed from February 2019 to July 2020.
EXPOSURES
Patients who used terazosin/doxazosin/alfuzosin vs tamsulosin. Additional dose-response analyses were carried out.
MAIN OUTCOMES AND MEASURES
Differences in the hazard of developing PD identified by diagnoses or use of PD-specific medications between patients who ever used terazosin/doxazosin/alfuzosin or tamsulosin.
RESULTS
A cohort of 52 365 propensity score-matched pairs of terazosin/doxazosin/alfuzosin and tamsulosin users were identified in the Danish registries, of which all were male and the mean (SD) age was 67.9 (10.4) years, and 94 883 propensity score-matched pairs were identified in the Truven database, of which all were male and the mean (SD) age was 63.8 (11.1) years. Patients in the Danish cohort who used terazosin/doxazosin/alfuzosin had a hazard ratio (HR) for developing PD of 0.88 (95% CI, 0.81-0.98), and patients in the Truven cohort had an HR of 0.63 (95% CI, 0.58-0.69). There was a dose-response association with short-duration, medium-duration, and long-duration use of terazosin/doxazosin/alfuzosin users having a decreasing HR in both the Danish cohort (short: HR, 0.95; 95% CI, 0.84-1.07; medium: HR, 0.88; 95% CI, 0.77-1.01; long: HR, 0.79; 95% CI, 0.66-0.95) and Truven cohort (short: HR, 0.70; 95% CI, 0.64-0.76; medium: HR, 0.58; 95% CI, 0.52-0.64; long: HR, 0.46; 95% CI, 0.36-0.57).
CONCLUSIONS AND RELEVANCE
These data suggest that users of terazosin/doxazosin/alfuzosin are at lower hazard of developing PD compared with users of tamsulosin. Future work is needed to further assess this association.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adult; Aged; Aged, 80 and over; Cohort Studies; Databases, Factual; Denmark; Doxazosin; Female; Follow-Up Studies; Glycolysis; Humans; Male; Middle Aged; Parkinson Disease; Prazosin; Quinazolines; Registries; Risk Factors; Tamsulosin; United States
PubMed: 33523098
DOI: 10.1001/jamaneurol.2020.5157 -
EClinicalMedicine Jun 2022Pharmacological treatments for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are empirically used. However, the quantitative comparative effectiveness and...
BACKGROUND
Pharmacological treatments for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are empirically used. However, the quantitative comparative effectiveness and safety of multiple pharmacological treatments is lacking.
METHODS
PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched from inception to March 22, 2022. Randomised controlled trials comparing two or more oral pharmacological treatments for patients with CP/CPPS were included. Title, abstract, and full-text screening were independently screened by four reviewers. Primary outcomes were efficacy (the National Institutes of Health Chronic Prostatitis Symptom Index [NIH-CPSI] total score, pain score, urinary score, and quality of life score [QoL]) and safety (adverse events). This study was registered with PROSPERO, CRD42020184106.
FINDINGS
25 studies (3514 patients) assessed 26 treatments. Low to very low quality evidence indicated that doxazosin (Mean difference [MD], -11.4, 95% Credible interval [CrI], -17.5 to -5.1) and the doxazosin, ibuprofen, and thiocolchicoside combination (MD, -11.6, CrI, -18.1 to -5.3) were significantly more effective than placebo in the NIH-CPSI total score. Other NIH-CPSI relative outcomes (pain, urinary, and QoL scores) showed a similar pattern. Low and very low quality evidence suggested that combination treatment including doxazosin, ibuprofen, and thiocolchicoside (odds ratios [OR], 3.2, CrI, 0.5 to 19.3) and the tamsulosin and dapoxetine combination (OR, 6.0, CrI, 0.7 to 67.3) caused more adverse events. In half of all comparisons regarding NIH-CPSI pain scores and quality of life scores, heterogeneity was minimal or low. Heterogeneity was high in both NIH-CPSI total symptom scores ( = 78.0%) and pain scores ( = 87. 0%) for tamsulosin versus placebo. There was also high heterogeneity in NIH-CPSI urine scores for the combination of tamsulosin and ciprofloxacin versus tamsulosin ( = 66.8%), tamsulosin and levofloxacin versus tamsulosin ( = 93.3%), and tamsulosin versus placebo ( = 83%).
INTERPRETATION
Pharmacological treatments have little evidence supporting efficacy in CP/CPPS. Future studies could personalise therapy for individuals according to specific symptoms and identify non-pharmacological targets for CP/CPPS.
FUNDING
Dr Jiani Wu received funding for this project from the China Association for Science and Technology (2017QNRC001), the China Academy of Chinese Medical Sciences (ZZ13-YQ-027), and the National Natural Science Foundation of China (82105037).
PubMed: 35706494
DOI: 10.1016/j.eclinm.2022.101457 -
Andrology Nov 2022Rat isolated vas deferens releases 6-nitrodopamine (6-ND), and the spasmogenic activity of this novel catecholamine is significantly reduced by tricyclic compounds such...
BACKGROUND
Rat isolated vas deferens releases 6-nitrodopamine (6-ND), and the spasmogenic activity of this novel catecholamine is significantly reduced by tricyclic compounds such as amitriptyline, desipramine, and carbamazepine and by antagonists of the α -adrenergic receptors such as doxazosin, tamsulosin, and prazosin.
OBJECTIVES
To investigate the liberation of 6-ND by human epididymal vas deferens (HEVDs) and its pharmacological actions.
METHODS
The in vitro liberation of 6-ND, dopamine, noradrenaline, and adrenaline from human vas deferens was evaluated by LC-MS/MS. The contractile effect of the catecholamines in HEVDs was investigated in vitro. The action of tricyclic antidepressants was evaluated on the spasmogenic activity ellicited by the catecholamines and by the electric-field stimulation (EFS). The tissue was also incubated with the inhibitor of nitric oxide (NO) synthase L-NAME and the release of catecholamines and the contractile response to EFS were assessed.
RESULTS
6-ND is the major catecholamine released from human vas deferens and its synthesis/release is inhibited by NO inhibition. The spasmogenic activity elicited by EFS in the human vas deferens was blocked by tricyclic antidepressants only at concentrations that selectively antagonize 6-ND induced contractions of the human vas deferens, without affecting the spasmogenic activity induced by dopamine, noradrenaline, and adrenaline in this tissue. Incubation of the vas deferens with L-NAME reduced both the 6-ND release and the contractions induced by EFS.
DISCUSSION AND CONCLUSION
6-ND should be considered a major endogenous modulator of human vas deferens contractility and possibly plays a pivotal role in the emission process of ejaculation. It offers a novel and shared mechanism of action for tricyclic antidepressants and α -adrenergic receptor antagonists.
Topics: Adrenergic Antagonists; Amitriptyline; Animals; Antidepressive Agents, Tricyclic; Carbamazepine; Chromatography, Liquid; Desipramine; Dopamine; Doxazosin; Epinephrine; Humans; Male; Muscle Contraction; Muscle, Smooth; NG-Nitroarginine Methyl Ester; Nitric Oxide; Norepinephrine; Prazosin; Rats; Receptors, Adrenergic; Tamsulosin; Tandem Mass Spectrometry; Vas Deferens
PubMed: 35934935
DOI: 10.1111/andr.13263 -
PloS One 2021Alpha-adrenergic receptor blockers can be effectively used in the context of medical expulsion therapy (MET) to treat ureteric stones. This study was designed to... (Meta-Analysis)
Meta-Analysis
PURPOSE
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
Topics: Doxazosin; Humans; Randomized Controlled Trials as Topic; Safety; Ureteral Calculi
PubMed: 33493214
DOI: 10.1371/journal.pone.0245741 -
BMC Geriatrics Sep 2022Adrenergic alpha-1 receptor antagonists (alpha-1 antagonists) are frequently used medications in the management of lower urinary tract symptoms (LUTS) suggestive of... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of adrenergic alpha-1 receptor antagonists in older adults: a systematic review and meta-analysis supporting the development of recommendations to reduce potentially inappropriate prescribing.
BACKGROUND
Adrenergic alpha-1 receptor antagonists (alpha-1 antagonists) are frequently used medications in the management of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and in the management of therapy-resistant arterial hypertension, two conditions frequently found in older adults. This systematic review aims at presenting a complete overview of evidence over the benefits and risks of alpha-1 antagonist treatment in people ≥ 65 years, and at deriving recommendations for a safe application of alpha-1 antagonists in older adults from the evidence found.
METHODS
A comprehensive literature search was performed (last update March 25 2022) including multiple databases (Medline/Pubmed, Embase, the Cochrane Library) and using the PICOS framework to define search terms. The selection of the studies was done by two independent reviewers in a two-step approach, followed by a systematic data extraction. Quality appraisal was performed for each study included using standardised appraisal tools. The studies retrieved and additional literature were used for the development of recommendations, which were rated for strength and quality according to the GRADE methodology.
RESULTS
Eighteen studies were included: 3 meta-analyses, 6 randomised controlled trials and 9 observational trials. Doxazosin in the management of arterial hypertension was associated with a higher risk of cardiovascular disease, particularly heart failure, than chlorthalidone. Regarding treatment of LUTS suggestive of BPH, alpha-1 antagonists appeared to be effective in the relief of urinary symptoms and improvement of quality of life. They seemed to be less effective in preventing disease progression. Analyses of the risk profile indicated an increase in vasodilation related adverse events and sexual adverse events for some agents. The risk of falls and fractures as well as the effects of long-term treatment remained unclear. All meta-analyses and 5 out of 6 interventional studies were downgraded in the quality appraisal. 7 out of 9 observational studies were of good quality.
CONCLUSIONS
It cannot be recommended to use doxazosin as first-line antihypertensive agent neither in older adults nor in younger patients. In the management of BPH alpha-1 antagonists promise to effectively relieve urinary symptoms with uncertainty regarding their efficacy in preventing long-term progression events.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Aged; Antihypertensive Agents; Chlorthalidone; Doxazosin; Humans; Hypertension; Inappropriate Prescribing; Lower Urinary Tract Symptoms; Male; Prostatic Hyperplasia; Quality of Life
PubMed: 36171560
DOI: 10.1186/s12877-022-03415-7