Alpha-adrenergic Receptor Blocker Research Articles

Tamsulosin use in benign prostatic hyperplasia and risks of Parkinson's disease, Alzheimer's disease and mortality: An observational cohort study of elderly Medicare enrollees.

To study the effects of benign prostatic hyperplasia treatments, namely: alpha-adrenergic receptor blockers, 5-alpha-reductase inhibitors and phosphodiesterase-5 inhibitors on the risk of Parkinson's disease, Alzheimer's disease and mortality. All male Medicare enrollees aged 65 or above who were diagnosed with benign prostatic hyperplasia and received one of the study drugs between 2007-2020 were followed-up for the three outcomes. We used Cox regression analysis to assess the relative risk of each of the outcomes for each study drug compared to the most prescribed drug, tamsulosin, while controlling for demographic, socioeconomic and comorbidity factors. The study analyzed 1.1 million patients for a mean follow-up period of 3.1 years from being prescribed one of the study drugs. For all outcomes, patients on tamsulosin were used as the reference for comparison. For mortality, alfuzosin was associated with 27% risk reduction (HR 0.73, 95%CI 0.68-0.78), and doxazosin with 6% risk reduction (HR 0.94, 95%CI 0.91-0.97). For Parkinson's disease, terazosin was associated with 26% risk reduction (HR 0.74, 95%CI 0.66-0.83), and doxazosin with 21% risk reduction (HR 0.79, 95%CI 0.72-0.88). For Alzheimer's disease, terazosin was associated with 27% risk reduction (HR 0.73, 95%CI 0.65-0.82), and doxazosin with 16% risk reduction (HR 0.84, 95%CI 0.76-0.92). Tadalafil was associated with risk reduction (27-40%) in all 3 outcomes. More research is needed to elucidate the underlying mechanisms of these observations. Given the availability of safer alternatives for treating benign prostatic hyperplasia, caution should be exercised when using tamsulosin in elderly patients, especially those with an increased risk of developing neurodegenerative diseases.

Isolated angioedema due to face mask and other cases of isolated angioedema.

Isolated angioedema can be divided into two groups as mast cell-mediated angioedema and bradykinin-mediated angioedema according to the known mechanisms of occurrence. However, angioedema can also occur with mechanisms whose cause is unknown. Treatment varies according to the mechanism of angioedema formation. In this prospective study, we present the causes of 80 isolated angioedema cases admitted to our clinic during the pandemic period. We would like to emphasize the causes that we found in our cases but which are rare in the literature. For example: angioedema due to allergy to nickel in the mask used during the pandemic period, T cell-mediated angioedema, alpha adrenergic receptor blocker use, and patients diagnosed with collagen tissue disease presenting with angioedema as the first clinical finding.

Prenatal Morphine Exposure Increases Cardiovascular Disease Risk and Programs Neurogenic Hypertension in the Adult Offspring.

The opioid overdose and opioid use disorder epidemics are concomitant with increased metabolic and CVD risk. Although opioid use disorder causes adverse pregnancy outcomes, the offspring's cardiovascular health is understudied. We hypothesized that offspring exposed to in utero morphine exposure (IUME) would show increased CVD risk factors and endogenous opioid system dysregulation. Sprague Dawley dams were treated with saline (vehicle, n=10) or escalating doses of morphine (5-20 mg/kg per day, SC, n=10) during gestation. Cardiovascular and metabolic parameters were assessed in adult offspring. Litter size and pups' birth weight were not different in response to IUME. Female and male IUME offspring showed reduced body length at birth (P<0.05) and body weight from weeks 1 to 3 of life (P<0.05), followed by a catch-up growth effect. By week 16, female and male IUME rats showed reduced tibia length (P<0.05) and fat mass. IUME increases the mean arterial pressure and the depressor response to mecamylamine (5 mg/kg per day, IP) induced by IUME were abolished by a chronic treatment with an alpha-adrenergic receptor blocker (prazosin; 1 mg/kg per day, IP). Although circulating levels of angiotensin peptides were similar between groups, IUME exacerbated maximal ex vivo Ang (angiotensin) II-induced vasoconstriction (P<0.05) and induced endothelial dysfunction in a sex-specific manner (P<0.05). Proenkephalin, an endogenous opioid peptide that lowers blood pressure and sympathetic-mediated vasoconstriction, showed reduced mRNA expression in the heart, aorta, and kidneys from morphine versus vehicle group (P<0.05). Among the effects of IUME, neurogenic hypertension, vascular dysfunction, and metabolic dysfunction could be associated with the dysregulation of the endogenous opioid system.

Regional binding of [3H]‐MK801 to NMDA receptors in young and aged rat brain membranes

Norepinephrine (NE) and dopamine (DA) are essential neuromodulators in the central nervous system. They regulate several crucial physiological processes, including arousal/attention, focus, neuroendocrine functions, and the sleep‐wake cycle; they also play complex roles in regulating cognition and affect; therefore, dysfunctions in catecholaminergic neurotransmission are associated with various neurological consequences. Previously, we confirmed that in brain slices from aged Fischer 344 rats, there is an age‐related decrease in glutamate‐stimulated NE release in the cerebral cortex and hippocampus (Gonzales et al., 1991 &amp; Dezfuli et al., 2019) and a regionally specific decline in glutamate‐stimulated DA release, with a deficit in the striatum but not in the olfactory tubercle (Aljohani et al., 2021a). Importantly, our studies demonstrated that NMDA receptors mediate glutamate‐stimulated NE and DA release. We also have shown that the alpha‐2 adrenergic receptors agonist clonidine decreases this glutamate‐stimulated NE release in a concentration‐dependent manner; while in contrast, blockade of these receptors with phentolamine, an alpha‐1 and alpha‐2 adrenergic receptor blocker, or with idazoxan, a selective alpha‐2 receptor blocker, markedly potentiates glutamate‐stimulated NE release in cortical brain slices (Aljohani et al., 2021b). Since aging has heterogeneous effects on NMDA receptors in different brain areas, we have now begun to examine [3H]‐MK801 binding to NMDA receptors to compare changes in receptor density and responsiveness during aging in the cortex, hippocampus, striatum, and olfactory tubercle, as a possible mechanistic explanation for the changes in NE and DA release. The data from cortical membrane preparations suggest that young and old rats have similar NMDA receptor densities but may differ in their response to stimulation with glutamate/glycine.

The neurogenic bladder characteristics and treatment approaches in the patients with multiple sclerosis

ObjectivesTo analyze the neurogenic bladder characteristics and the treatment approaches in patients with multiple sclerosis (MS) to facilitate proper and reasonable decisions in relevant patients. DesignRetrospective study. SettingDepartment of Physical Medicine and Rehabilitation, Ankara Training and Research Hospital, Ankara, Turkey. ParticipantsSeventy-five patients diagnosed with MS between 2002 and 2015 were included in the study. InterventionUrodynamic examination. Outcome MeasureThe detrusor type, detrusor compliance, sense of bladder fullness, storage disorder, emptying disorder, voided volume, post-void residual volume, urine culture, emptying method, and medical treatments were recorded. ResultsThe study included 53 females and 22 males with a mean age of 36 ± 10.1 years. Urodynamic examinations indicated that 74.7% of the patients had detrusor overactivity, 74.7% had detrusor hypocompliance, 77.3% had storage dysfunction, and 81.3% had emptying dysfunction. An anticholinergic medication was recommended to 74.7% of the patients, while alpha-adrenergic receptor blockers were recommended to 69.3%. The detrusor hypocompliance was more common in the group with a disease duration of ≥10 years (p = 0.045). The use of external collector systems was more common, and urine culture was more frequently positive for infections in the female patients (p = 0.001 and p = 0.049, respectively). The frequency of normal bladder-filling sensation was higher in women (p = 0.01). The frequencies of detrusor overactivity and storage and emptying disorders, voided and postvoid volumes (mL), and bladder emptying methods were not significantly different among the subgroups (p > 0.05). ConclusionThe study revealed a significant neurogenic bladder dysfunction and an inadequate management of this dysfunction in MS patients. Considering that the symptoms may progress over time, the urinary systems of MS patients should be evaluated periodically, and necessary modifications should be made in their treatments.

Intraoperative floppy iris syndrome: an updated review of literature.

Intraoperative Floppy iris syndrome(IFIS) remains a challenge for surgeons during phacoemulsification. Initially, it was related to the use of tamsulosin, an alpha adrenergic receptor blocker used in benign prostatic hyperplasia. Subsequently, other alpha adrenergic receptor such as alfuzosin, terazosin and doxazosin alongwith different other class of medications and systemic risk factors were identified. Other class of medications includes 5-alpha reductase inhibitor, angiotensin receptor antagonist, benzodiazepines, antipsychotics and antidepressants. Other risk factors include increasing age, male gender, diabetes, hypertension and decreased preoperative pupil diameter. It is very important for surgeons to identify these risk factors preoperatively and take appropriate preoperative and intraoperative measures to tackle the dreaded complications of IFIS. Sometimes, it is important for an ophthalmologist to work in cooperation with physician and urologist to minimize the complications. In conclusion, awareness of the risk factors associated with IFIS, their detailed preoperative assessment and intraoperative measures and surgical intervention is crucial in addressing IFIS. Lack of awareness can turn a routine, uneventful surgery into one with significant visual morbidity.

Clinical profile of pheochromocytoma and paraganglioma with normal plasma free metanephrines

Plasma free metanephrines (MNs) have been widely used as an initial test for pheochromocytoma and paraganglioma (PPGL). PPGL without MNs elevation has been reported on rare occasions. The objective of this study was to analyze the clinical profile of sporadic PPGL patients with normal MNs. In the study, 104 patients with sporadic PPGL diagnosed by histopathology in Peking University First Hospital from March 2015 to January 2020 were enrolled. All the patients had plasma MNs result, of whom, eight (7.69%) were with normal MNs. The reasons for their medical visits, clinical manifestations, the levels of plasma free MNs, 3-methoxytyramine (3-MT), catecholamines and chromogranin A (CgA), and the imaging findings were documented. Their preoperative diagnosis, perioperative medical management, and intraoperative blood pressure were analyzed. All the data mentioned above were compared with the MNs elevated group. The postoperative follow-up for MNs normal patients were applied. For the eight PPGL patients with normal plasma MNs, the most common clinical symptoms were sweating (3/8), abdominal and back pain (3/8), headache (2/8), palpitations (2/8), and fatigue (2/8). There were no significant differences in plasma free 3-MT and catecholamines' diagnostic positive rate between the MNs normal group and MNs elevated group, but the rate for plasma CgA was significantly decreased in the MNs normal group (2/5 vs. 41/43, P=0.005). No significant difference was found for the incidence of typical findings by enhanced CT between the two groups. In these eight MNs normal patients, six were diagnosed with PPGL by the previous history of PPGL, typical symptoms and CT findings, or elevation of 3-MT, CgA levels or positive results of PET-CT; two patients were misdiagnosed as nonfunctioning adenoma or primary aldosteronism. All these MNs normal patients underwent preoperative management with alpha adrenergic receptor blockers, of whom, one had an average intraoperative arterial pressure < 60 mmHg during surgery. The median follow-up time for the eight patients was 1.5 (0.5－4.5) years. No evidence of new tumors was found on the enhanced CT scans. Two MNs normal patients' plasma 3-MT and (or) CgA decreased to normal. For patients with adrenal or retroperitoneal tumors, typical symptoms or a previous history of PPGL, normal plasma MNs is not a sufficient exclusion for PPGL. Plasma 3-MT, catecholamine, CgA results and the imaging findings are helpful for the diagnosis of PPGL. We recommend patients with suspected MNs normal PPGL take alpha adrenergic receptor blockers as preoperative blockade, but should avoid overdose. Postoperative follow-up for patients with normal MNs should focus on the positive biochemical markers before surgery.

Preoperative Use of Alpha-1 Receptor Blockers in Male Patients Undergoing Extracorporeal Shock Wave Lithotripsy for a Ureteral Calculus.

In this retrospective single-center cohort study, we investigated the impact of preoperative use of an alpha-1 adrenergic receptor (AR) blocker on the outcome of single-session extracorporeal shock wave lithotripsy (SWL) in 193 male patients who underwent SWL for a single ureteral calculus between 2006 and 2016. We reviewed their medical records to obtain the data on the preoperative use of alpha-1 AR blockers. The primary outcome was treatment success after single-session SWL. We performed a multivariable logistic regression analysis adjusting for clinically important confounders to examine the association between preoperative use of alpha-1 AR blockers and the treatment success of SWL. Among the 193 patients, 15 (7.8%) were taking an alpha-1 AR blocker preoperatively. A multivariable analysis showed that preoperative use of an alpha-1 AR blocker was a significant negative predictor for treatment success of SWL (adjusted odds ratio 0.17; 95% confidence intervals, 0.04-0.74). Our findings suggest that the preoperative use of an alpha-1 AR blocker was a negative predictor of treatment success of SWL in male patients with a single ureteral calculus. Clinicians should pay more attention to the preoperative drug use in determining an appropriate stone therapy modality.

Phenylephrine induces relaxation of longitudinal strips from small arteries of goat legs.

Alpha adrenergic stimulation is known to produce vasoconstriction. We have earlier shown that, in spiral strips of small arteries Phenylephrine (PE) caused vasorelaxation under high nitric oxide (NO) environment. However, on further experimentation it was realized that the PE-induced vasorelaxant response occurred only with longitudinal strips of small arteries even under normal NO environment while circular strips showed contraction with PE even under high NO environment. Such PE-induced vasorelaxation of longitudinal strips was blocked by Phentolamine, an alpha-adrenergic receptor blocker. On delineation of specific receptor subtype, PE-induced relaxation was found to be mediated through alpha 1D receptor. However, this phenomenon is specific to small artery, as longitudinal smooth muscle of aorta showed only contractile response to adrenergic stimulation. There is no prior report of longitudinal smooth muscle in small artery up to our knowledge. The results of this study and histological examination of vessel sections suggest the presence of longitudinal smooth muscle in small artery and their relaxant response to alpha adrenergic stimulation is a novel phenomenon.

Elucidation of prazosin biodegradation by isolated &lt;i&gt;Bacillus&lt;/i&gt; spp. from the tropical environment

Prazosin (PRZ), a drug used to treat hypertensive patients, is an emergent contaminant in water systems. PRZ is an alpha-adrenergic receptor blocker used to treat anxiety, and is believed to reach the environment through human excretion, irresponsible disposal of unused medicine, and waste products from manufacturing plants. The purpose of this research was to isolate and characterize potential microbes for PRZ biodegradation and to identify the degradation pathway. After screening, isolated strain STP3 showed a capability for PRZ degradation and was chosen for further analysis. Resting cell assays with PRZ were conducted to identify the intermediate metabolites formed from biodegradation by Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) analysis. Two metabolites degraded from PRZ by STP3 were successfully found, and as these metabolites are derived from the main structure of PRZ, their presence proved PRZ degradation. Draft genome sequencing analysis of STP3 was performed to identify potential enzymes for PRZ biodegradation based on the metabolites found.

Alpha-1 Adrenergic Receptor Blockers for the Treatment of Lower Urinary Tract Symptoms in Women: A Systematic Review and Meta-Analysis.

PurposeTo assess the effectiveness of alpha-1 adrenergic receptor blockers (α1-blockers) in the treatment of female lower urinary tract symptoms (LUTS).MethodsA literature search was conducted using the PubMed/MEDLINE, Embase, and Cochrane Library databases. Fourteen studies with 1,319 patients were ultimately included. The study comprised 2 analyses: a comparison of urinary symptom scores, maximal flow rate (Qmax), and postvoid residual (PVR) urine volume before and after α1-blocker administration in 8 prospective, open-label studies and 5 randomized clinical trials (RCTs); and an evaluation of the same variables in α1-blocker and placebo groups in 4 RCTs.ResultsThe first meta-analysis showed that, following treatment, patients exhibited statistically significant symptom relief (mean difference [MD], -5.85; 95% confidence interval [CI], -7.71 to -3.99; P<0.00001), increased Qmax (MD, 3.67 mL/sec; 95% CI, 2.76–4.59 mL/sec; P<0.00001), and decreased PVR volume (MD, -28.46 mL; 95% CI, -34.99 to -21.93 mL; P<0.00001). In the second meta-analysis, α1-blockers demonstrated significant symptom relief relative to placebo (MD, -1.60; 95% CI, -2.68 to -0.51; P=0.004). However, no significant differences were observed in Qmax (MD, 0.05 mL/sec; 95% CI, -0.74 to 0.83 mL/sec, P=0.91) and PVR (MD, -8.10 mL; 95% CI, -32.32 to 16.12 mL, P=0.51) between the α1-blocker and placebo groups.ConclusionsThese analyses suggest that α1-blockers are effective in the treatment of female LUTS patients. However, the effect of α1-blockers on female LUTS should be assessed according to the underlying cause, and the role of α1-blockers in combination therapy with other drugs should also be investigated.

Efficacy and safety of 5 alpha-reductase inhibitor monotherapy in patients with benign prostatic hyperplasia: A meta-analysis.

BackgroundAlthough combination therapy with 5 alpha-reductase inhibitor (5ARI) and alpha-blocker is one of the standard interventions in symptomatic benign prostatic hyperplasia (BPH), 5ARI monotherapy is seldom the focus of attention. Adverse events associated with 5ARI include depression and suicidal attempts in addition to persistent erectile dysfunction. The aim of this study is to update our knowledge of clinical efficacy and incidence of adverse events associated with 5ARI treatment in symptomatic BPH.Methods and findingsA meta-analysis of randomized controlled clinical trials (RCTs) from 1966 until March, 2017 was performed using database from PubMed, Cochrane Collaboration and Embase. A total of 23395 patients were included in this study and the inclusion criteria were: RCTs with 5ARI and placebo in symptomatic BPH patients. Parameters included prostate specific antigen (PSA), prostate volume (PV), International Prostate Symptom Score (IPPS), post-void residual urine (PVR), voiding symptoms of IPSS (voiding IPSS), maximum urinary flow rate (Qmax), and adverse events (AEs). A meta-analysis with meta-regression was performed for each effect size and adverse events, sensitivity analysis, cumulative analysis along with the analysis of ratio of means (ROM) in the placebo group.A total of 42 studies were included in this study for review, and a total of 37 studies were included in the meta-analysis, including a total of 23395 patients (treatment group: 11392, placebo group: 12003). The effect size of all variables except PVR showed a significant improvement following 5ARI treatment compared with placebo. However, the effect size of differences showed declining trend in PV, IPSS and Qmax according to recent years of publication. In ROM analysis, PV showed no significant increase in the placebo group, with a ROM of 1.00 (95% CI, 0.88, 1.14). The 5ARI treatment resulted in a significantly higher incidence of decreased libido (OR = 1.7; 95% CI, 1.36, 2.13), ejaculatory disorder (OR = 2.94; 95% CI, 2.15, 4.03), gynecomastia (OR = 2.32; 95% CI, 1.41, 3.83), and impotence (OR = 1.74; 95% CI, 1.32, 2.29). Our study has the following limitations: included studies were heterogeneous and direct comparison of efficacy between alpha blocker and 5ARI was not performed. Adverse events including depression or suicidal attempt could not be analyzed in this meta-analysis setting.ConclusionsAlthough there was a significant clinical benefit of 5ARI monotherapy compared with placebo, the effective size was small. Moreover, the risk of adverse events including sexually related complications were high. Additional head-to-head studies are needed to re-evaluate the clinical efficacy of 5ARI compared with alpha-adrenergic receptor blockers.

Is Tamsulosin Linked to Dementia in the Elderly?

Lower urinary tract symptoms (LUTS) result from age-related changes in detrusor function and prostatic growth that are driven by alterations in the ratio of circulating androgens and estrogens. Alpha-adrenergic receptor blockers are commonly used to treat LUTS because they influence urethral tone and intra-urethral pressure. Molecular cloning studies have identified three α1-adrenergic receptor subtypes (α1A, α1B, and α1D). The α1A subtype is predominant in the human prostate but is also present in many parts of the brain that direct cognitive function. Tamsulosin is the most widely used α1-adrenergic receptor antagonist with 12.6 million prescriptions filled in 2010 alone. When compared to the other common types of α1-adrenergic receptor antagonists (i.e., terazosin, doxazosin, and alfuzosin), tamsulosin is 10- to 38-fold more selective for the α1A versus the α1B subtype. Duan et al. have recently shown that men taking tamsulosin have a higher risk of developing dementia when compared to men taking other α-adrenergic antagonists or no α-adrenergic antagonists at all (HR 1.17; 95% CI 1.14-1.21). Based upon this retrospective analysis, we believe that tamsulosin, because of its unique affinity for α1A-adrenergic receptors, may increase the risk of developing dementia when used for an extended period of time. If these findings are confirmed, they carry significant public health implications for an aging society.

THE EFFECTS OF ANGIOTENSIN CONVERTING ENZYME INHIBITION AND ALPHA 1-ADRENERGIC RECEPTOR BLOCKADE ON HAEMOSTASIS AND INFLAMMATION IN MILD-TO-MODERATE HYPERTENSION

Objective: Hypertension is associated with oxidative stress and low-grade chronic inflammation, contributing to phenotypical alterations of the endothelium to a proconstrictive, proinflammatory and prothrombotic phenotype. Antihypertensive therapy improves vascular structure and function, and reduces cardiovascular complications. However, the relative contribution of antihypertensive therapy on vascular inflammation, thrombogenic mechanisms, and endothelial dysfunction remains unclear. We have previously demonstrated that treatment of hypertensive patients with ramipril, an ACE inhibitor, reduced thrombin generation compared to placebo treatment. This study aimed to extend these observations and to investigate the possible contribution of blocking the RAAS on haemostasis and systemic inflammation beyond the effects of lowering blood pressure. Design and method: We examined 59 individuals with mild-to-moderate hypertension randomized to receive double blind ramipril 10 mg od or the alpha 1-adrenergic receptor blocker doxazosin 8 mg od for 12 weeks. Haemostasis (plasminogen activator inhibitor-1 activity, tissue plasminogen activator antigen, thrombin-antithrombin complex, and thrombin generation by calibrated automated thrombogram) and inflammatory markers (interleukin-6, soluble interleukin-6 receptor, interleukin-8, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and C-reactive protein) were assessed. Results: Treatment reduced blood pressure in both groups. Thrombin-antithrombin complex decreased by treatment, and this was dependent on a reduction in thrombin-antithrombin complex in the ramipril group alone (figure). Changes in thrombin-antithrombin complex by treatment did not relate to changes in blood pressure. There were no changes in plasminogen activator inhibitor-1 activity, while tissue plasminogen activator antigen increased by ramipril and decreased by doxazosin. Only minor changes were observed in systemic inflammation by treatment.Conclusions: These results extend our previous findings to suggest that antihypertensive treatment with ramipril reduces thrombin generation beyond the effects on blood pressure reduction alone. Thus, drugs blocking the RAAS may reduce atherothrombotic complications beyond their effects to reduce blood pressure. Furthermore, doxazosin might have beneficial profibrinolytic effects. The antihypertensive treatment effects on inflammatory markers, however, were small.

Efficacy of an Alpha-Blocker for the Treatment of Nonneurogenic Voiding Dysfunction in Women: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

PurposeTo evaluate the efficacy of an alpha-1 adrenergic receptor (α1-AR) blocker for the treatment of female voiding dysfunction (FVD) through a pressure-flow study.MethodsThis was a randomized, double-blind, placebo-controlled trial. Women aged ≥18 years with voiding symptoms, as defined by an American Urological Association symptom score (AUA-SS) ≥15 and a maximum flow rate (Qmax) <15 mL/sec with a voided volume of >100 mL and/or a postvoid residual (PVR) volume >150 mL, were randomly allocated to either the alfuzosin or placebo group. After 8 weeks of treatment, changes in the AUA-SS, Bristol female lower urinary tract symptoms (BFLUTS) questionnaire, Qmax/PVR, and voiding diary were compared between groups. Patients’ satisfaction with the treatment was compared. Patients were categorized into 3 groups according to the Blaivas-Groutz bladder outlet obstruction (BOO) nomogram: none, mild, and moderate to severe. Subgroup comparisons were also made.ResultsOf a total of 187 women, 154 (79 alfuzosin, 75 placebo) were included in the analysis. After 8 weeks of treatment, the AUA-SS decreased by 7.0 in the alfuzosin group and by 8.0 in the placebo group. Changes in AUA-SS subscores, BFLUTS (except the I-sum), the voiding diary, and Qmax/PVR were not significantly different between groups. Approximately 54% of the alfuzosin group and 62% of the placebo group were satisfied with the treatment. No significant difference was observed between groups according to the presence or grade of BOO.ConclusionsAlfuzosin might not be more effective than placebo for treating FVD. The presence or the grade of BOO did not affect the results. A further study with sufficient power is needed to determine the efficacy of α1-AR blockers for the treatment of FVD.

Clinical study of duloxetine hydrochloride combined with doxazosin for the treatment of pain disorder in chronic prostatitis/chronic pelvic pain syndrome

To explore the safety and efficacy of the selective 5-serotonin and norepinephrine reuptake inhibitor duloxetine hydrochloride and alpha-adrenergic receptor blocker (alpha-blocker) doxazosin mesylate-controlled tablets in the treatment of pain disorder in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).In all, 150 patients were enrolled and 126 patients completed the study (41 patients in the doxazosin group, 41 patients in the sertraline group, and 44 patients in the duloxetine group). This was an open randomized 6-month study. CP/CPPS patients who met the diagnostic criteria were randomized into 3 groups. The patients in the duloxetine group received doxazosin 4 mg + duloxetine 30 mg once a day, and the dosage of duloxetine was increased to 60 mg after a week. The patients in the doxazosin group received doxazosin 4 mg once a day. The patients in the sertraline group received doxazosin 4 mg + sertraline 50 mg once a day. National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score, the short-form McGill Pain questionnaire (SF-MPQ), and the hospital anxiety and depression scale (HAD) were applied for evaluations during follow-up of 1, 3, and 6 months after treatment.There were slight positive significant correlations between NIH-CPSI scores and HAD scores, moderate positive significant correlations between the quality of life (QOL) and SF-MPQ, and slight positive significant correlations between HAD and QOL. The effective rate in the doxazosin group was 4.88%, 19.51%, and 56.10% after 1, 3, and 6 months, respectively (P < 0.05). The SF-MPQ score in the doxazosin group decreased to 1.80 ± 1.29, 2.66 ± 1.57, and 3.24 ± 1.67 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the doxazosin group decreased to 2.24 ± 2.17, 4 ± 2.11, and 4.90 ± 2.62 after 1, 3, and 6 months, respectively (P < 0.05). The effective rate in the sertraline group was 9.76%, 36.59%, and 63.41% after 1, 3, and 6 months, respectively. The SF-MPQ score in the sertraline group decreased to 1.76 ± 1.28, 3.07 ± 2, and 3.93 ± 2.53 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the sertraline group decreased to 3.56 ± 4.11, 5.73 ± 5.26, and 7.27 ± 6.50 after 1, 3, and 6 months, respectively (P < 0.05). The effective rate in the duloxetine group was 36.36%, 88.64%, and 88.64% after 1, 3, and 6 months, respectively. The SF-MPQ score in the duloxetine group decreased to 3.61 ± 2.54, 6.05 ± 3.66, and 7.41 ± 4.26 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the duloxetine group decreased to 3.14 ± 3.28, 6.93 ± 3.90, and 9.43 ± 4.67 after 1, 3, and 6 months, respectively (P < 0.05). There were significant differences in the reduction of the NIH-CPSI score and the SF-MPQ score between the duloxetine group and the sertraline group and between the duloxetine group and the doxazosin group (P < 0.01). There were significant differences in the reduction of the HAD score at 3 months between the duloxetine group and the doxazosin group, and there were significant differences in the reduction of the HAD score at 6 months among the groups (P < 0.05). The incidence rates of adverse reactions in the duloxetine group, the sertraline group, and the duloxetine group were 29.5%, 17%, and 7.3%, respectively, with adverse events ranging from mild to moderate.There was a clear relationship between the extent of pain and mental factors in CP/CPPS with the main symptom of pain. Doxazosin combined with duloxetine exhibited good safety and efficacy in the treatment of pain disorder in CP/CPPS.

Clinical efficacy of combination therapy of Tamsulosin plus Tolterodine sustained-release capsules on benign prostatic hyperplasia with overactive bladder in elderly men

Objective To evaluate the efficacy of combination therapy of cholinergic receptor blocker Tolterodine and Alpha-adrenergic receptor blocker Tamsulosin sustained-release capsules on benign prostatic hyperplasia(BPH)with overactive bladder(OAB)in elderly men. Methods A total of 97 male BPH patients aged 80 years and over(80~98 years old, mean 87.7 years old)were enrolled in this study, who met the diagnosis and treatment guidelines of OAB formulated by Chinese Urological Association and were admitted to our hospital from Jan. 2015 to July. 2015. Patients were randomly divided into Tamsulosin group(n=51, treated with Tamsulosin)and combination group(n=46, treated with Tamsulosin and Tolterodine). Results In Tamsulosin group after treatment, the international prostate symptom score(IPSS)was reduced from(18.3±2.7)to(13.3±3.1)(t=14.94, P 0.05). The total incidences of adverse events(mainly mouth dryness)had no significant differences between the Tamsulosin group and the combination group(8.7% vs. 5.9%, χ2=99.47, P>0.05). No acute urinary retention was found in the two groups. Conclusions The combination therapy of Tamsulosin and Tolterodine has better efficacy and safety than single Tamsulosin application in the treatment of BPH with OAB in elderly men. Key words: Prostatic hyperplasia; Urinary bladder, overactive; Muscarinic antagonists; Adrenergic alpha- antagonists

Blood pressure lowering efficacy of dual alpha and beta blockers for primary hypertension.

Drugs with combined alpha and beta blocking activity are commonly prescribed to treat hypertension. However, the blood pressure (BP) lowering efficacy of this class of beta blockers has not been systematically reviewed and quantified. To quantify the dose-related effects of various types of dual alpha and beta adrenergic receptor blockers (dual receptor blockers) on systolic and diastolic blood pressure versus placebo in patients with primary hypertension. We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ClinicalTrials.gov for randomized controlled trials up to October 2014. The WHO International Clinical Trials Registry Platform (ICTRP) is searched for inclusion in the Group's Specialised Register. Randomized double blind placebo controlled parallel or cross-over trials. Studies contained a beta blocker monotherapy arm with a fixed dose. Patients enrolled in the studies had primary hypertension at baseline. Duration of the studies was from three to 12 weeks. Drugs in this class of beta blockers are carvedilol, dilevalol and labetalol. Two review authors (GW and AL) confirmed the inclusion of studies and extracted the data independently. RevMan 5.3 was used to synthesize data. We included eight studies examining the blood pressure lowering efficacy of carvedilol and labetalol in 1493 hypertensive patients. Five of the included studies were parallel design; three were cross-over design. The two largest included studies were unpublished carvedilol studies. The estimates of BP lowering effect (systolic BP/diastolic BP millimeters of mercury; SPB/DBP mm Hg) were -4 mm Hg (95% confidence intervals (CI) -6 to -2)/-3 mm Hg (95% CI -4 to -2) for carvedilol (>1000 subjects) and -10 mm Hg (95% CI -14 to -7)/-7 mm Hg (95% CI -9 to -5) for labetalol (110 subjects). The effect of labetalol is likely to be exaggerated due to high risk of bias. Carvedilol, within the recommended dose range, did not show a significant dose response effect for SBP or DBP. Carvedilol had little or no effect on pulse pressure (-1 mm Hg) and did not change BP variability. Overall, once and twice the starting dose of carvedilol and labetalol lowered BP by -6 mm Hg (95% CI -7 to -4) /-4 mm Hg (95% CI -4 to -3) (low quality evidence) and lowered heart rate by five beats per minute (95% CI -6 to -4) (low quality evidence). Five studies (N = 1412) reported withdrawal due to adverse effects; the risk ratio was 0.88 (95% CI 0.54 to 1.42) (moderate quality evidence). This review provides low quality evidence that in patients with mild to moderate hypertension, dual receptor blockers lowered trough BP by an average of -6/-4 mm Hg and reduced heart rate by five beats per minute. Due to the larger sample size from the two unpublished studies, carvedilol provided a better estimate of BP lowering effect than labetalol. The BP lowering estimate from combining carvedilol once and twice the starting doses is -4/-3 mm Hg. Doses higher than the recommended starting dose did not provide additional BP reduction. Higher doses of dual receptor blockers caused more bradycardia than lower doses. Based on indirect comparison with other classes of drugs, the blood pressure lowering effect of dual alpha- and beta-receptor blockers is less than non-selective, beta1 selective and partial agonist beta blockers, as well as thiazides and drugs inhibiting the renin angiotensin system. Dual blockers also had little or no effect on reducing pulse pressure, which is similar to the other beta-blocker classes, but less than the average reduction of pulse pressure seen with thiazides and drugs inhibiting the renin angiotensin system. Patients taking dual receptor blockers were not more likely to withdraw from the study compared to patients taking placebo.

Rhythmic Aortic Contractions Induced by Electrical Stimulation In Vivo in the Rat.

For over a century, the behavior of the aorta and other large arteries has been described as passive elastic tubes in which no active contraction occurs in the smooth muscle wall. In response to pulsatile pressure changes, the vessels undergo a 'passive' elastic dilatation–contraction cycle, described as a “Windkessel” effect. However, Mangel and colleagues have presented evidence that is contrary to this view. They reported that in the rabbit, the aorta undergoes rhythmic 'active' (contraction) during the cardiac cycle; but these findings have been largely ignored. In the present study, we observed spontaneous contractions in synchrony with the heartbeat in another species (rat). In addition we demonstrate that aorta contractions are of neurogenic origin. Electrical stimulation of the aorta evoked contractions that occur at a rate that is in the range of the animal's heartbeat and are suppressed by tetrodotoxin and the alpha-adrenergic receptor blocker, phentolamine. Altogether, these findings indicate that aortic contractions are under neural control from the heart.

Resistant hypertension in the elderly-second line treatments: aldosterone antagonists, central alpha-agonist agents, alpha-adrenergic receptor blockers, direct vasodilators, and exogenous nitric oxide donors.

Resistant hypertension (RH) is a prevalent medical problem across all ages but is more frequent in elderly patients. This entity has to be distinguished from clinical settings which may simulate it such as apparent hypertension (pseudohypertension) or apparently resistant hypertension (pseudoresistant hypertension) [1]. An appropriate therapy for RH can be achieved by the addition of second line antihypertensive drugs: antialdosteronic diuretics, central agents, alpha blockers, direct vasodilating agents, and exogenous nitric oxide donors. These antihypertensive drugs are considered as second line drugs since they are less effective as monotherapy to reduce blood pressure (they induce counte regulatory responses that limit their antihypertensive effect such as volume expansion or reflex tachycardia) and prevent cardiovascular events, or due to significant adverse effects (postural hypotension, sedation, hyperkalemia). Second line drugs are also used when there is allergy or intolerance to the first line ones [2, 3].