Alpha Receptor Antagonist Research Articles

Alpha-1 adrenergic antagonists and the risk of hospitalization or death in non-hospitalized patients with COVID-19: A population-based study.

Alpha-1 receptor antagonists may interfere with IL-6 signaling and could therefore be a potential treatment for COVID-19. However, the effectiveness of these drugs in mitigating the risk of clinical deterioration among non-hospitalized patients with COVID-19 is unknown. The aim of this study is to examine the association between alpha-1 antagonist exposure and the 30-day risk of a hospital encounter or death in nonhospitalized patients with COVID-19. We conducted a population-based cohort study of Ontario residents aged 35 years and older who were eligible for public drug coverage and who had a positive test for SARS-CoV-2 between January 1, 2020, and March 1, 2021. We matched each individual receiving an alpha-1 antagonist at the time of their positive test with two non-exposed individuals using propensity scores. Our outcome was a composite of a hospital admission, emergency department visit, or death, 1 to 30 days following the positive test. We matched 3289 alpha-1 antagonist exposed patients to 6189 unexposed patients. Overall, there was no difference in the 30-day risk of the primary outcome among patients exposed to alpha-1 antagonists at the time of their diagnosis relative to unexposed individuals (28.8% vs. 28.0%; OR 1.00, 95% CI 0.91 to 1.11). In a secondary analysis, individuals exposed to alpha-1 antagonists had a lower risk of death in the 30 days following a COVID diagnosis (OR 0.79; 95% CI 0.66 to 0.93). Alpha-1 antagonists did not mitigate the 30-day risk of clinical deterioration in non-hospitalized patients with COVID-19. Our findings do not support the general repurposing of alpha-1 antagonists as a treatment for such patients, although there may be subgroups of patients in whom further research is warranted.

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.

Natural moisturising factor constituents in South African nursing students.

The majority of South African healthcare workers are Black Africans with dark-pigmented skin. Studies on how the markers of skin barrier function and natural moisturising factor (NMF) compare between dark and light-pigmented skin are limited. Quantifying NMF in a nursing student population during their practical training at university may provide valuable insight into their potential susceptibility to skin conditions associated with low NMF. The objectives of this study were to quantify and compare NMF content of Black African, Mixed Race and White nursing students from their dominant dorsal hand. Forty-nine White, 32 Black African and 5 Mixed Race nursing students participated in this study. Tape strip samples were collected from the participants' dominant dorsal hand and NMF content was measured, including histidine (HIS), pyrrolidone carboxylic acid (PCA), trans-urocanic acid (t-UCA) and cis-urocanic acid (c-UCA), as well as cytokines interleukin-1 alpha (IL-1α) and interleukin-1 receptor antagonist (IL-1RA). No statistically significant differences in PCA, t-UCA, c-UCA, IL-1α or IL-1RA were found between Black African and White nursing students. HIS was significantly (p = 0.001) higher in White nursing students when compared to Black African students. The ratio of tot-UCA/HIS was significantly higher in Black Africans (p = 0.0002) when compared to White nursing students. No significant differences were established in NMF content between White and Black African nursing students, other than HIS which was significantly higher in White students than in Black African students. Different HIS levels between the racial groups suggest variation in histidase activity which may be related to skin pH and pigmentation. This finding may suggest that nursing students at the beginning of their careers may have similar susceptibility to skin diseases related to NMF.

Association of silodosin, tamsulosin, and naftopidil with delirium: analysis of the pharmacovigilance database in Japan.

An association between adrenergic alpha-1 receptor antagonists and delirium has been suggested, but the details are unclear. This study investigated the association between adrenergic alpha-1 receptor antagonists and delirium in patients with benign prostatic hyperplasia using the Japanese Adverse Drug Event Report database. First, disproportionality analysis compared the frequency of delirium in the adrenergic alpha-1 receptor antagonists silodosin, tamsulosin, and naftopidil. Next, multivariate logistic analysis was performed to examine the association between delirium and adrenergic alpha-1 receptor antagonists where disproportionality was detected. A disproportionality in delirium was observed in patients receiving tamsulosin (reporting odds ratio [ROR] 1.85, 95% confidence interval [CI] 1.38-2.44, P < 0.01) compared with those who did not, and also in patients receiving naftopidil (ROR 2.23, 95% CI 1.45-3.28, P < 0.01) compared with those who did not. Multivariate logistic analysis revealed that in addition to previously reported risk factors for delirium, delirium in patients receiving tamsulosin was significantly increased with concomitant use of anticholinergics (odds ratio 2.73, 95% CI 1.41-5.29, P < 0.01) and delirium in patients receiving naftopidil was significantly increased with concomitant use of beta3-adrenergic receptor agonists (odds ratio 4.19, 95% CI 1.66-10.6, P < 0.01). Anticholinergics or beta3-adrenergic receptor agonists to treat overactive bladder in patients receiving tamsulosin and naftopidil was strongly associated with delirium. Confirming the medical history and concomitant medications of patients receiving tamsulosin or naftopidil may contribute to preventing delirium in patients with benign prostatic hyperplasia and to improving their outcomes.

Noradrenergic modulation of play in Sprague-Dawley and F344 rats.

For many mammals, engaging in social play behavior as a juvenile is important for cognitive, social, and emotional health as an adult. A playful phenotype reflects a dynamic interplay between genetic framework and experiences that operate on hard-wired brain systems so the relative lack of play in an otherwise playful species may be useful for identifying neural substrates that modulate play behavior. The inbred F344 rat has been identified as a strain that is consistently less playful than other strains commonly used in behavioral research. Norepinephrine (NE) acting on alpha-2 receptors has an inhibitory effect on play and F344 rats differ from a number of other strains in NE functioning. As such, the F344 rat may be particularly useful for gaining insight into NE involvement in play. The objective of this study was to determine whether the F344 rat is differentially sensitive to compounds that affect NE functioning and that are known to affect play behavior. Using pouncing and pinning to quantify play, the effects of the NE reuptake inhibitor atomoxetine, the NE alpha-2 receptor agonist guanfacine, and the NE alpha-2 receptor antagonist RX821002 on play behavior were assessed in juvenile Sprague-Dawley (SD) and F344 rats. Atomoxetine and guanfacine reduced play in both SD and F344 rats. RX821002 increased pinning to a comparable extent in both strains but F344 rats were more sensitive to the play-enhancing effects of RX821002 on pounces. Strain differences in NE alpha-2 receptor dynamics may contribute to the lower levels of play in F344 rats.

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

BackgroundAdrenergic 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.MethodsA comprehensive literature search was performed (last update March 25th 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.ResultsEighteen 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.ConclusionsIt 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.

The Efficacy of Camelina sativa Defatted Seed Meal against Colitis-Induced Persistent Visceral Hypersensitivity: The Relevance of PPAR α Receptor Activation in Pain Relief.

Brassicaceae are natural sources of bioactive compounds able to promote gut health. Belonging to this plant family, Camelina sativa is an ancient oil crop rich in glucosinolates, polyunsaturated fatty acids, and antioxidants that is attracting renewed attention for its nutraceutical potential. This work aimed at investigating the therapeutic effects of a defatted seed meal (DSM) of Camelina sativa on the colon damage and the persistent visceral hypersensitivity associated with colitis in rats. Inflammation was induced by the intrarectal injection of 2,4-dinitrobenzenesulfonic acid (DNBS). The acute administration of Camelina sativa DSM (0.1–1 g kg−1) showed a dose-dependent pain-relieving effect in DNBS-treated rats. The efficacy of the meal was slightly enhanced after bioactivation with myrosinase, which increased isothiocyanate availability, and drastically decreased by pre-treating the animals with the selective peroxisome proliferator-activated receptor alpha (PPAR α) receptor antagonist GW6471. Repeated treatments with Camelina sativa DSM (1 g kg−1) meal counteracted the development, as well as the persistence, of visceral hyperalgesia in DNBS-treated animals by reducing the intestinal inflammatory damage and preventing enteric neuron damage. In conclusion, Camelina sativa meal might be employed as a nutraceutical tool to manage persistent abdominal pain in patients and to promote gut healing.

Do adrenergic alpha-antagonists increase the risk of poor cardiovascular outcomes? A systematic review and meta-analysis.

Due to concerns regarding neurohormonal activation and fluid retention, adrenergic alpha-1 receptor antagonists (A1Bs) are generally avoided in the setting of heart disease, namely, symptomatic heart failure (HF) with reduced ejection fraction (HFrEF). However, this contraindication is mainly supported by ancient studies, having recently been challenged by newer ones. We aim to perform a comprehensive meta-analysis aimed at ascertaining the extent to which A1Bs might influence cardiovascular (CV) outcomes. We systematically searched PubMed, Cochrane Central Register of Controlled Trials and Web of Science for both prospective and retrospective studies, published until 1 December 2020, addressing the impact of A1Bs on both clinical outcomes-namely, acute heart failure (AHF), acute coronary syndrome (ACS), CV and all-cause mortality-and on CV surrogate measures, specifically left ventricular ejection fraction (LVEF) and exercise tolerance, by means of exercise duration. Both randomized controlled trials (RCTs) and studies including only HF patients were further investigated separately. Study-specific odds ratios (ORs) and mean differences (MDs) were pooled using traditional meta-analytic techniques, under a random-effects model. A record was registered in PROSPERO database, with the code number CRD42020181804. Fifteen RCTs, three non-randomized prospective and two retrospective studies, encompassing 32851, 19287, and 71600 patients, respectively, were deemed eligible; 62256 patients were allocated to A1B, on the basis of multiple clinical indications: chronic HF itself [14 studies, with 72558 patients, including seven studies with 850 HFrEF or HF with mildly reduced ejection fraction (HFmrEF) patients], arterial hypertension (four studies, with 44184 patients) and low urinary tract symptoms (two studies, with 6996 patients). There were 25998 AHF events, 1325 ACS episodes, 955 CV deaths and 33567 all-cause deaths. When considering only RCTs, A1Bs were, indeed, found to increase AHF risk (OR 1.78, [1.46, 2.16] 95% CI, P<0.00001, i2 2%), although displaying no significant effect on neither ACS nor CV or all-cause mortality rates (OR 1.02, [0.91, 1.15] 95% CI, i2 0%; OR 0.95, [0.47, 1.91] 95% CI, i2 17%; OR 1.1, [0.84, 1.43] 95% CI, i2 17%, respectively). Besides, when only HF patients were evaluated, A1Bs revealed themselves neutral towards not only ACS, CV, and all-cause mortality events (OR 0.49, [0.1, 2.47] 95% CI, i2 0%; OR 0.7, [0.21, 2.31] 95% CI, i2 21%; OR 1.09, [0.53, 2.23] 95% CI, i2 17%, respectively), but also AHF (OR 1.13, [0.66, 1.92] 95% CI, i2 0%). As for HFrEF and HFmrEF, A1Bs were found to exert a similarly inconsequential effect on AHF rates (OR 1.01, [0.5-2.05] 95% CI, i2 6%). Likewise, LVEF was not significantly influenced by A1Bs (MD 1.66, [-2.18, 5.50] 95% CI, i2 58%). Most strikingly, exercise tolerance was higher in those under this drug class (MD 139.16, [65.52, 212.8] 95% CI, P<0.001, i2 26%). A1Bs do not seem to exert a negative influence on the prognosis of HF-and even of HFrEF-patients, thus contradicting currently held views. These drugs' impact on other major CV outcomes also appear trivial and they may even increment exercise tolerance.

Alpha Blocker-Associated Intraoperative Floppy Iris Syndrome

Objective To evaluate the literature related to the use of alpha1-blockers and the risk of intraoperative floppy iris syndrome (IFIS), particularly in cataract surgery. IFIS is characterized by floppiness or billowing of the iris, iris prolapse, and progressive miosis, possibly leading to severe complications. It is thought to be associated with adrenergic alpha-1 receptor antagonists commonly used to treat lower urinary tract symptoms in patients with benign prostatic hyperplasia. Data Sources A literature search was conducted in Pubmed, EMBASE, and Web of Science through May 2021 with MeSH terms and keywords 'intraoperative floppy iris syndrome,' ' adrenergic alpha-1 receptor antagonists,' and 'cataract surgery.' Study Selection and Data Extraction Relevant articles were reviewed and included. In addition, reference lists from identified publications were reviewed to identify additional reports and studies of interest. Data Synthesis Numerous reports have linked IFIS to multiple risk factors including age, gender, hypertension, and the use of adrenergic alpha-1 receptor antagonists, most notably tamsulosin. Tamsulosin selectively blocks the adrenergic alpha-1 receptor in the iris dilator muscle, preventing mydriasis during cataract surgery. Other adrenergic alpha-1 receptor antagonists, including terazosin, doxazosin, alfuzosin, and sildosin, have also been linked to IFIS; however, their relationship to IFIS is not as well defined. Conclusion Patients should be educated regarding potential adverse effects and discuss this with their health care providers prior to cataract surgery. In addition, health care providers should be aware of the adverse effect and take steps to reduce the risk of surgical complications.

A Neuromodulatory System that Links Opioid‐Induced Sedation and Respiratory Depression

The main cause of death from opioid overdose is respiratory depression, mediated by mu‐opioid‐receptors located in the respiratory brainstem. Opioids also cause sedation, which further reduces respiratory drive through largely unknown mechanisms. The Kölliker‐Fuse nucleus (KF) in the pons is highly susceptible to inhibition by opioids and significantly contributes to opioid‐induced respiratory rate depression and associated changes in breathing pattern. Taking advantage of cell‐type specific retrograde neural tracing, we characterized anatomical projections between the main noradrenergic arousal center of the brain, the locus coeruleus (LC) and the KF, which represent a potential link between arousal/sedation and breathing. Our results show that 30% of noradrenergic LC neurons send projections to the KF. To begin to understand the functional role and to define the neurochemical identity of LC to KF projections, we used whole‐cell patch clamp recordings from the KF combined with optogenetic stimulation of LC neurons. Optical stimulation of LC axon terminals induces light‐evoked glutamatergic excitatory postsynaptic currents in KF neurons. Pharmacological isolation of LC to KF synapses suggests that this pathway is monosynaptic. The glutamatergic excitatory postsynaptic currents are dependent on vesicular glutamate transporter 2 expression in noradrenergic LC neurons. Additionally, prolonged optical stimulations lead to noradrenergic excitatory postsynaptic currents that are blocked by alpha1 receptor antagonist. Thus, LC may drive KF neuron activity via glutamate and/or noradrenaline release. This direct excitatory drive in the LC‐KF circuit is sensitive to opioids, which can directly inhibit KF neuron somas, as well as inhibit neurotransmitter release from presynaptic LC terminals. This work provides exciting evidence for an excitatory pathway between the LC and the KF, that may play an important link between opioid‐induced sedation and respiratory depression.

A Comparative Study of the Efficacy of Silodosin Versus Tamsulosin Versus Oral Hydration Therapy in Medical Expulsion Therapy for Ureteral Calculi

Purpose: The use of various alpha-receptor antagonists (α-blocker) drugs as medical expulsive therapy (MET) for spontaneous clearance of ureteral calculi of various sizes has been extensive in the last decade by urologists across the world. Among all, α-blocker tamsulosin has been used widely. In contrast silodosin which is recently introduced in the market and more selective alpha-receptor antagonist and cardioselective drug but it has not been used widely as MET. In this study, silodosin (8 mg), tamsulosin (0.4 mg), and oral hydration therapy were compared in terms of efficacy and safety as MET in the management of ureteric stone along with rate of stone clearance, expulsion time, analgesic requirements, and adverse effects for treating ureteral stones size between ≥4 mm and ≤10 mm in diameter. Materials and Methods: Prospective randomized study was conducted between September 2018 and August 2020 with a total of 240 patients (80 patients in each arm) in tertiary care center of eastern India. First group received a single dose of silodosin (8 mg) daily, second group received a single dose of tamsulosin (0.4 mg) daily and third group received oral hydration therapy for 4 weeks. Results: There is no difference in the stone expulsion rate (SER), stone expulsion time (SET), and surgical intervention between tamsulosin, silodosin and oral hydration therapy group for ureteric stones ≤5 mm size. For ureteric stones of size 6 mm–10 mm, silodosin has better SER than tamsulosin with no difference in terms of SET. Analgesic requirement and pain episodes were more in the oral hydration group with no adverse effects (statistically significant). Conclusion: The proportion of passed-out stone was significantly higher among the patients treated with silodosin (65.0%) in comparison to other two groups (P &lt; 0.05) with no difference in SET.

Prazosin use in a patient with rare Neurobeachin gene deletion shows improvement in paranoid behavior: a case report

BackgroundDisruption of the Neurobeachin gene is a rare genetic mutation that has been implicated in the development of autism and enhanced long-term potentiation of the hippocampal CA1 region, causing a heightened conditioned fear response and impaired fear extinction. Prazosin, an alpha-1 receptor antagonist, has been used in patients with posttraumatic stress disorder to mitigate the increased alpha-1 activity involved in fear and startle responses. Here we report a case of a patient with a rare Neurobeachin gene deletion, who demonstrated marked and sustained improvement in paranoid behavior within days of prazosin initiation.Case presentationThe patient is a 27-year-old White male with autism spectrum disorder, obsessive–compulsive disorder, and schizophrenia, with a chromosome 13q12 deletion including deletion of the Neurobeachin gene, who presented to the emergency department due to worsening functional status and profound weight loss as a result of only eating prepackaged foods. He had not showered or changed clothes in several months prior to presentation. He was hospitalized in the inpatient psychiatric unit for 2 months before prazosin was initiated. During that time, he demonstrated paranoia as evidenced by heightened sensitivity to doors opening, guarded interactions, and limited communication with providers and other patients. He also exhibited poor grooming habits, with aversion to showering, shaving, and changing clothes. Since initiating prazosin, he has demonstrated a brighter affect, initiates and maintains conversations, showers and changes clothes on a regular basis, and eats a variety of foods. At the time of this report, the patient was discharged to live in an apartment with a caregiver after a 7-month inpatient hospitalization.ConclusionsLow-dose prazosin shows rapid and sustained improvement in paranoid behavior in a patient with a rare Neurobeachin gene deletion. Prazosin has a relatively favorable side effect profile with once-daily dosing and low cost. Prazosin may provide clinical improvement in patients with Neurobeachin gene deletions due to its theoretical attenuation in fear response through alpha-1 antagonism.

Cardiac Depressant and Vasodialatory Effect of Flaxseed - Basis for the Medicinal use in Hypertension

Linum usitatissimum (Flaxseed) is known to be traditionally used for managing hypertension. In this study, we aim to provide a mechanistic basis for the medicinal use of Flaxseed in hypertension. The high-performance liquid chromatography (HPLC) analysis that we carried out during our study showed the presence of polar compounds (quercetin, nicotinic acid, and nicotinamide) in Flaxseed’s crude extract (Fs.Cr; aqueous methanolic). In anesthetized rats, Fs.Cr reduced arterial blood pressure (BP) dose-dependently (10-100 mg/kg). When tested for its mechanism of action ex vivo, Fs.Cr inhibited both the force and rate of spontaneous contractions in the dose range of 1-10 mg/mL in isolated guinea-pig atria, similar to how verapamil, a standard Ca+2 channel blocker does it. Further, Fs.Cr showed vasodilator effect against the contractions induced by phenylephrine (PE, 1 μM) in rat aortic ring preparations (concentration range: 1-10 mg/mL), whereas no effect was observed against the contractions induced by low K+ (25 mM) as well as high K+ (80 mM). This selective inhibitory effect of Fs.Cr against PE was tested for endothelium-dependent nitric oxide (NO) and/or cholinergic component involvement. The vasodilator effect of Fs.Cr against PE was retested in the absence and presence of atropine in endothelium (E)-intact and E-denuded aorta, but no significant shift was observed in the inhibitory effect of Fs.Cr. Further, Fs.Cr shifted the PE-induced concentration-response curves (CRCs) to the right in a dose-dependent manner (1 and 3 mg/mL). This effect was similar to that of prazosin. All these findings indicate that Flaxseed may mediate its antihypertensive activity by the alpha-1 receptor antagonist and Ca+2 channel blocking-like activity, which may account for its efficacy in hypertension.

Tamsulosin vs placebo to prevent postoperative urinary retention following female pelvic reconstructive surgery: a multicenter randomized controlled trial

Postoperative urinary retention is common after female pelvic reconstructive surgery. Alpha receptor antagonists can improve dysfunctional voiding by relaxing the bladder outlet and may be effective in reducing the risk of postoperative urinary retention. This study aimed to determine whether tamsulosin is effective in preventing postoperative urinary retention in women undergoing surgery for pelvic organ prolapse. This was a multicenter, double-blind, randomized controlled trial between August 2018 and June 2020, including women undergoing surgery for pelvic organ prolapse. Patients were excluded from recruitment if they had elevated preoperative postvoid residual volume, history of postoperative urinary retention, or a contraindication to tamsulosin. Those who experienced cystotomy were excluded from analysis. Participants were randomized to a 10-day perioperative course of tamsulosin 0.4 mg vs placebo, beginning 3 days before surgery. A standardized voiding trial was performed on postoperative day 1. The primary outcome was the development of postoperative urinary retention, as defined by the failure of the voiding trial or subsequent need for catheterization to empty the bladder. Secondary outcomes included the rate of urinary tract infection and the impact on lower urinary tract symptoms as measured by the American Urological Association Symptom Index. Of 119 patients, 57 received tamsulosin and 62 received placebo. Groups were similar in regard to demographics, preoperative prolapse and voiding characteristics, and surgical details. Tamsulosin was associated with a lower rate of postoperative urinary retention than placebo (5 patients [8.8%] vs 16 patients [25.8%]; odds ratio, 0.28; 95% confidence interval, 0.09-81; P=.02). The number needed to treat to prevent 1 case of postoperative urinary retention was 5.9 patients. The rate of urinary tract infection did not differ between groups. American Urological Association Symptom Index scores significantly improved after surgery in both groups (median total score, 14 vs 7; P<.01). Scores related to urinary stream improved more in the tamsulosin group than in placebo (P=.03). In this placebo-controlled trial, tamsulosin use was associated with a reduced risk of postoperative urinary retention in women undergoing surgery for pelvic organ prolapse.

Evaluation of low dose prazosin for PTSD-associated nightmares in children and adolescents

IntroductionKnowledge about fundamental sleep disorders and dysregulation that occurs in children with PTSD is limited. Prazosin is an alpha-1 receptor antagonist often used off label for the treatment of PTSD-associated nightmares in adults; however, evaluation of its use in pediatrics and adolescents is limited. The primary objective of this study was to assess the impact of prazosin on nightmares associated with PTSD in this population. Secondary objectives included assessing side effects, changes in blood pressure, and 30-day readmission rates.MethodsThis was a retrospective, single-center chart review of inpatients diagnosed with PTSD nightmares from January 1, 2017, to July 31, 2019. Patients 4 to 18 years old with a PTSD diagnosis, experiencing nightmares, and initiating any dose of prazosin were assessed to determine efficacy and tolerance.ResultsForty-two patients were evaluated to determine symptom improvement after initiation of prazosin for PTSD nightmares in children and adolescents. Of the 42 patients, 24 (57.1%) reported improvement in nightmares (average dose 1.05 mg). For secondary results, 38 (90.5%) patients continued prazosin at discharge, and 2 (5%) were readmitted within 30 days for reasons other than PTSD-associated nightmares. Thirty-four (81%) reported having no adverse effects to prazosin. There was no significant difference in systolic (P = .1883) or diastolic (P = .2777) blood pressure preinitiation and postinitiation of prazosin.DiscussionDespite the limitations of this retrospective study, the data suggests that prazosin may be associated with an improvement in nightmares in children and adolescents with PTSD. Adverse events were rarely reported, and there was no significant change in blood pressure with initiation of prazosin.

Re: Identification and Local Delivery of Vasodilators for the Reduction of Ureteral Contractions.

No AccessJournal of UrologyUrological Survey1 Dec 2020Re: Identification and Local Delivery of Vasodilators for the Reduction of Ureteral Contractions Anthony AtalaMD Anthony AtalaAnthony Atala More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001285.02AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Identification and Local Delivery of Vasodilators for the Reduction of Ureteral Contractions." The Journal of Urology, 204(6), p. 1385 Suggested Reading : Systemic and topical drug administration in the pig ureter: effect of phosphodiesterase inhibitors alpha1, beta and beta2-adrenergic receptor agonists and antagonists on the frequency and amplitude of ureteral contractions. J Urol 2001; 166: 714. Link, Google Scholar © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 204Issue 6December 2020Page: 1385-1385 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anthony Atala More articles by this author Expand All Advertisement PDF DownloadLoading ...

Molecular modeling studies of benzothiophene-containing derivatives as promising selective estrogen receptor downregulators: a combination of 3D-QSAR, molecular docking and molecular dynamics simulations

Selective estrogen receptor downregulators (SERDs) for the treatment of positive breast cancer can act both as estrogen alpha receptor (ERα) antagonists and degraders. In this study, the optimal antagonist models (CoMFA-A, q2 = 0.660, r2 = 0.996; CoMSIA-A, q2 = 0.728, r2 = 0.992) and degrader models (CoMFA-D, q2 = 0.850, r2 = 0.996; CoMSIA-D, q2 = 0.719, r2 = 0.995) of a series of potent benzothiophene-containing SERDs were constructed to explore the three-dimensional quantitative structure–activity relationship. Internal and external validation indicated that all models exhibited good applicability, high predictive ability and robustness. Contour maps revealed the relationships between the essential structural features and antagonistic and degradation activities. Additionally, molecular docking, molecular dynamics and free energy calculation studies were further performed to investigate the detailed binding mode. Results indicated that several key residues, ARG394, GLU353, PHE404 and ILE424, were crucial for the stability of the ligand binding domain. The hydrophobic, electrostatic and Van der Waals interactions played significant effect on the binding affinity. Finally, ten novel compounds were designed based on above findings, where the predicted activity of compound D8 was equivalent to that of the compound LSZ102. 3D-QSAR, ADMET and bioavailability predictions indicated that all designed compounds with good predicted activity, good physicochemical and bioavailability could be potential candidates for SERDs. These results and combinations of computational methods provided guidance for the rational drug design of novel potential SERDs. Communicated by Ramaswamy H. Sarma

Histopathology, pharmacotherapy, and predictors of prostatic malignancy in elderly male patients with raised prostate-specific antigen levels - A prospective study.

Background:Prostate cancer is the second most common cancer among adult men in the world, and the diagnosis requires biopsy. Prostate-specific antigen (PSA) test along with digital rectal examination (DRE) increases the detection rate of prostate cancer than DRE alone. The objective of this study was to correlate serum PSA level with histopathological diagnosis, identify the predictors of malignancy, and describe the pharmacotherapy of patients with serum PSA levels >4 ng/ml.Materials and Methods:This was a hospital-based observational study done among patients who presented with lower urinary tract symptoms and PSA levels >4 ng/ml who were planned to undergo prostatic biopsy. DRE followed by transrectal ultrasound (TRUS) assessment and guided sextant (6-core) prostatic biopsy was performed.Results:One hundred and four patients were screened and 87 were included. Nineteen patients were diagnosed with malignancy, and among them, eight had bone metastasis. Spearman's correlation coefficient between PSA and malignancy was 0.449 (P ≤ 0.001). Multivariate analysis suggested that the factors (adjusted odds ratio; 95% confidence interval; P value) such as increasing age (1.127; 1.013, 1.253; 0.027), nodular prostate (22.668; 4.655, 110.377; P < 0.001), and PSA (1.034; 1.004, 1.064; 0.024) were significant predictors of prostate cancer. All patients with benign prostatic hyperplasia were advised a combination therapy with 5-alpha reductase inhibitor and selective alpha-1 receptor antagonist while those with malignancy were prescribed androgen deprivation therapy with antiosteoporosis therapy.Conclusion:In elderly patients with raised PSA levels or suspicious DRE findings, TRUS-guided prostate is recommended to rule out malignancy and plan appropriate management.

Adrenergic alpha-2 receptor antagonists cease augmented oxidation of plasma proteins and anxiety of rats caused by chronic noise exposure.

Background:Noise is one of the environmental factors, which is considered as a powerful stressor for the organism. Generally, the acoustic stress affects the behavior and physiological state of humans and animals.Aims:The goal of this study is to investigate the relationship between chronic noise exposure and the effects of adrenergic alpha-2 receptor antagonists, beditin and mesedin, on the anxiety and oxidation of plasma proteins and fibrinogen in rats.Methods:The experiments were carried out on non-linear albino male rats, divided into four groups (six animals in each): 1. Healthy controls 2. Exposed to noise of a level 91 dB(A), eight hours daily, during 7, 30 and 60 days; 3. Injected with 2 mg/kg of beditin (2-(2-amino-4-thiazolyl)-1,4-benzodioxane hydrochloride)); 4. Injected with 10 mg/kg mesedin (2-(2-methyl-amino-thiozolyl)-1,4-benzodioxane hydrochloride). For evaluating the cognitive impairment, the Any-maze test was applied. The level of carbonylation of proteins was assessed by reaction with 2,4-dinitrophenylhydrazine, spectrophotometrically.Results:Chronic noise decreased locomotor activity and increased anxiety and oxidation of plasma protein and fibrinogen. Intensity of these changes were dependent on the duration of noise exposure.Conclusion:The Alpha 2 adrenoblockers alleviate oxidative modification of plasma proteins and reduce the cognitive impairment caused by chronic exposure to noise.

Therapeutic Potential of Dupilumab in the Treatment of Chronic Rhinosinusitis with Nasal Polyps: Evidence to Date.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is one of the most severe forms of chronic rhinosinusitis. CRSwNP is characterized by nasal and facial congestion, loss of sense of smell, rhinorrhea, and post-nasal drip. Treatments have been ineffective at controlling disease recurrence, despite multiple courses of medical and surgical therapies. Oral glucocorticoid therapy is often used to control exacerbations leaving the patient exposed to steroid-induced adverse effects. Thus, there is a clear unmet need for new treatments to achieve better control of the disease. Advances in understanding Type 2 inflammatory processes that occur in about 80% of the Western world patients with CRSwNP have resulted in new avenues for disease control. Biologics in the form of monoclonal antibodies, which target Type 2 inflammation, have helped control the severest forms of atopic dermatitis and asthma. Treatment regimes for CRSwNP now include biologics. In July 2019, dupilumab was the first monoclonal antibody to gain FDA approval for the treatment of CRSwNP. In this review, we summarize the proof of concept clinical trials and Phase 3 trials leading to approval of dupilumab, an anti-IL4 alpha receptor antagonist that blocks the actions of both IL4 and IL13. These studies show that dupilumab is a proven treatment option to control disease. Collective studies demonstrate a high safety profile. Questions arise as to the best use of dupilumab in the context of current treatment paradigms, and for which sub-population of the varied heterogeneous endotypes of CRSwNP patients. Recognizing the high cost of biologics forces the need for cost-effectiveness analysis.