Prospective analysis of anatomic features predisposing patients to intraoperative floppy iris syndrome.

PURPOSE: To aid preoperative risk assessment by identifying anatomic parameters corresponding with a higher risk of intraoperative floppy iris syndrome (IFIS) during cataract surgery. METHODS: Prospective cohort study of 55 patients with α1-adrenergic receptor antagonist (α1-ARA) treatment and 55 controls undergoing cataract surgery. Anterior segment optical coherence tomography (AS-OCT), video pupilometer, and biometry measurements were performed preoperatively and analyzed regarding anatomic parameters that corresponded with a higher rate of IFIS. Those statistically significant parameters were evaluated with logistic regression analysis and receiver operating characteristic (ROC) curve. RESULTS: Pupil diameter was significantly smaller in patients who developed IFIS compared to those who did not develop IFIS (AS-OCT 3.29 ± 0.85 vs. 3.63 ± 0.68, p = 0.03; Pupilometer 3.56 ± 0,87 vs. 3.95 ± 0.67, p = 0.02). Biometric evaluation revealed shallower anterior chambers in the IFIS group (ACD 3.12 ± 0.40 vs. 3.32 ± 0.42, p = 0.02). Cutoff values for 50% IFIS probability (p = 0.5) were PD = 3.18 mm for pupil diameter and ACD = 2.93 mm for anterior chamber depth. ROC curves of combined parameters were calculated for α1-ARA medication with pupil diameter and anterior chamber depth, which yielded an AUC of 0.75 for all IFIS grades. CONCLUSION: The combination of biometric parameters with history of α1-ARA medication can improve assessment of risk stratification for IFIS incidence during cataract surgery.

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

BACKGROUND: An association between adrenergic alpha-1 receptor antagonists and delirium has been suggested, but the details are unclear. AIM: 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. METHOD: 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. RESULTS: 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). CONCLUSION: 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.

A Double-Blind Randomized Controlled Trial of Doxazosin for Co-Occurring PTSD and Alcohol Use Disorder in Veterans.

Objective: The aim of this study was to determine the efficacy of doxazosin, an α1-adrenergic antagonist, for the treatment of co-occurring posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD).Methods: This 12-week, double-blind, randomized controlled trial of doxazosin (16 mg/d) was conducted between June 2016 and December 2019 at the Ralph H. Johnson VA Medical Center in Charleston, South Carolina. Participants were military veterans (N = 141) who met DSM-5 criteria for current PTSD and AUD and were randomly assigned to receive doxazosin (n = 70) or placebo (n = 71). Primary outcome measures were the Clinician Administered PTSD Scale (CAPS-5), the PTSD Checklist for DSM-5 (PCL-5), and the Timeline Follow-Back (TLFB).Results: Findings from the intent-to-treat analyses revealed that participants in both groups demonstrated statistically significant reductions in CAPS-5 and PCL-5 scores (P < .0001), but, contrary to hypotheses, no significant differences were observed between groups. Percent drinking days and percent heavy drinking days also decreased significantly during treatment, but there were no differences between groups (P < .0001). Abstinence during treatment was significantly higher in the doxazosin versus the placebo group (22% vs 7%, P = .017); however, participants in the doxazosin group consumed a greater number of drinks on drinking days (6.15 vs 4.56, P = .0096). A total of 74.5% of the sample completed the treatment phase, and there were no group differences in retention or adverse events.Conclusions: Doxazosin was safe and tolerable but was not more effective than placebo in reducing PTSD or AUD severity in this dually diagnosed sample. Clinical considerations such as heterogeneity of PTSD and AUD presentation and potential moderators are discussed in the context of future research directions.Trial Registration: ClinicalTrials.gov Identifier: NCT02500602.

Evolving Role of Silodosin for the Treatment of Urological Disorders - A Narrative Review.

Use of α-androgenic receptor blockers remains a mainstay therapeutic approach for the treatment of urological diseases. Silodosin is recommended over other α-blockers for the treatment of lower urinary tract symptoms (LUTS) and benign prostate hyperplasia (BPH), due to its high α1A uroselectivity. Current research data suggest that silodosin is efficacious in the management of various urological diseases. Thus, we herein review the current evidence of silodosin related to its efficacy and tolerability and appraise the available literature that might ultimately aid in management of various urological conditions at routine clinical practice. Literature reveals that silodosin is beneficial in improving nocturia events related to LUTS/BPH. Silodosin exerts effect on relaxing muscles involved in detrusor obstruction, therefore prolonging the need for patients undergoing invasive surgery. Silodosin treatment, either as a monotherapy or combination, significantly improves International Prostate Symptom Score (IPSS) including both storage and voiding symptoms in patients with BPH/LUTS. Patients on other treatment therapies such as phosphodiesterase 5 inhibitors or other α-blockers are well managed with this drug. Steadily, silodosin has proved beneficial in the treatment of other urological disorders such as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), overactive bladder/acute urinary retention (AUR), premature ejaculation (PE), and prostate cancer post brachytherapy-induced progression. In patients with distal ureteral stones, silodosin treatment is beneficial in decreasing stone expulsion time without affecting stone expulsion rate or analgesic need. Moreover, there were significant improvements in intravaginal ejaculation latency time, quality of life scores, and decrease in PE profile among patients with PE. Silodosin has also demonstrated promising results in increasing the likelihood of successful trial without catheter in patients with AUR and those taking antihypertensive drugs. Reports from Phase II studies have shown promising role of silodosin in the treatment of CP/CPPS as well as facilitating ureteral stone passage. From the robust data in this review, further silodosin treatment strategies in the management of different urological conditions need to be focused on.

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 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. 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.

Factors predisposing to intraoperative floppy-iris syndrome: An up-to-date meta-analysis.

Intraoperative floppy-iris syndrome (IFIS) is an increasingly recognized condition that is proven to lead to higher rates of intraoperative complications. This study provides an updated systematic review and meta-analysis regarding all the identified factors predisposing to IFIS. The study was performed in accordance with the PRISMA guidelines. 38 studies were finally included in the meta-analysis. The factors that were found to predispose to IFIS significantly were male sex (odds ratio [OR], 4.25; CI, 2.58-7.01), hypertension (OR, 1.55; CI, 1.01-2.37), tamsulosin (OR, 31.06; CI, 13.74-70.22), finasteride (OR, 4.60; CI, 1.97-10.73), benzodiazepines (OR, 2.88; CI, 1.17-7.12), and antipsychotics intake (OR, 6.91; CI, 2.22-21.50). A decreased dilated pupil preoperatively was found predisposing to IFIS (weighted mean difference -0.93; CI, -1.19 to -0.67). Intracameral epinephrine, which was investigated as a potential prophylactic measure for preventing IFIS, did not reach statistical significance (OR, 0.29; CI, 0.08-1.06). A comprehensive preoperative assessment of all risk factors is vital to stratify the surgical risk, which is crucial in addressing IFIS because unanticipated IFIS could turn a routine surgery into one of significant visual morbidity.

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.

Tamsulosin and risk of priapism: A causality assessment using Austin Bradford Hill Criteria.

Tamsulosin hydrochloride, a selective alpha-adrenergic blocking agent has been previously associated with priapism. Priapism is a medically serious condition that, if not intervened, can cause permanent erectile dysfunction. This study was conducted to investigate whether the association of tamsulosin and priapism is causal. All currently available evidence such as experimental, biological, toxicological, published studies, and safety data mined from the WHO global pharmacovigilance database was systematically organized into the Austin Bradford Hill causality assessment framework. In the international pharmacovigilance database, a strong association between tamsulosin and priapism (IC025  = 4.1; PRR025  = 19.9; ROR025  = 20) was observed. There were 122 cases of priapism associated with tamsulosin submitted to the database from 23 countries. In 87.7% of the cases, tamsulosin was reported as a 'sole suspect,' and in 50.8%, it was the only drug administered. In several patients, priapism resolved following discontinuation of tamsulosin and recurred after its reintroduction. Both in the published and unpublished data, for majority of the cases, the time to onset of priapism was within few days following the first intake of tamsulosin. Cases of priapism, particularly those published, were consistent in their clinical features with patients experiencing prolonged painful erection that required aspiration of cavernosal blood, irrigation of the corpora cavernosa, and treatment with vasopressors. Other alpha-adrenergic blocking agents that are structurally analogous with tamsulosin have also been associated with priapism. In several cases, tamsulosin was used off-label, for the treatment of ureteral calculi expulsion. Eight patients experienced priapism that ended up with serious complications such as ejaculation disorders and erectile dysfunction. The currently available totality of evidence suggests that the association of tamsulosin and priapism is causal. Healthcare professionals are therefore recommended to cautiously prescribe tamsulosin and ensure that consumers are aware of the potential risk of priapism.

[Intraoperative floppy iris syndrom (IFIS) associated with tamsulosin]. / Intraoperatives Floppy Iris Syndrom (IFIS) bei Tamsulosineinnahme.

BACKGROUND: Tamsulosin is one of the most commonly prescribed alpha-1A antagonists for the treatment of benign prostatic syndrome (BPS). Patients treated with tamsulosin often develop intraoperative floppy iris syndrome (IFIS) during cataract surgery. This leads to increasing miosis and an undulating iris, which increases the risk of complications significantly and can cause permanent damage. AIM OF THE WORK: The aim is to raise awareness for the effects of tamsulosin intake before cataract surgery. MATERIAL AND METHODS: We conducted a critical review of publications on the association of IFIS in cataract surgery with alpha-receptor blockers. RESULTS AND DISCUSSION: Tamsulosin has a risk of complications of up to 80 %, whereas doxazosin and alfuzosin only have a 15-20 % chance of complications. Tamsulosin therefore represents a significant risk factor for permanent secondary damage after cataract surgery. Even after discontinuing tamsulosin, IFIS was still observed after up to 3 years. Nevertheless, pausing of tamsulosin intake is recommended. An alternative preparation should therefore be preferred in patients who have not yet had cataract surgery. If patients are already pseudophakic, tamsulosin can be given without concern.

Dealing with floppy iris syndrome.

PURPOSE OF REVIEW: The aim of this study was to review and summarize recent findings and advancements regarding intraoperative floppy iris syndrome (IFIS). Although many improvements have been made for the management of IFIS, it remains a challenging condition for surgeons. An understanding of the syndrome as well as the multitude of tools to mitigate risk of complication is important for surgeons operating on high-risk patients. RECENT FINDINGS: A variety of management approaches have been modified and improved or further supported with new data, such as intracameral compounds, intraoperative devices and surgical techniques. SUMMARY: An understanding of risk factors is important for the identification of at-risk patients. A variety of approaches can greatly reduce incidence of IFIS complications. Multiple management strategies should be utilized to further reduce risk during these difficult surgeries.

Preoperative atropine and non-steroidal anti-inflammatory drugs for the prevention of intraoperative floppy iris syndrome.

PURPOSE: To examine the efficacy of preoperative administration of topical atropine 1% and non-steroidal anti-inflammatory drugs (NSAIDs) for prevention of intraoperative floppy iris syndrome (IFIS). METHODS: In this retrospective cohort study, patients who underwent cataract surgery by phacoemulsification between July 2019 and February 2020 in two hospitals were included. Both hospitals are located in central Israel, have similar patient demographics and employ similar surgical techniques. They, however, differ in policy of IFIS prevention. In Meir Medical Center no preventive medications are given pre-operatively, while in Shamir Medical Center patients at-risk for IFIS receive topical atropine 1% once daily and non-steroidal anti-inflammatory drugs (NSAIDs) thrice daily for 3 days preoperatively. RESULTS: Overall, 207 eyes of 207 patients with history of alpha-antagonist use were included. Mean age was 74.9 ± 7.8 years and 82.1% (n = 170) were male. Among patients from the pretreating center 86.8% (n = 92/106) were pre-treated with either NSAIDs or atropine preoperatively, while in the non-pretreating center no treatment was prescribed (n = 0/101). IFIS rate among the non-pretreating center was 29.7% (n = 30/101) compared to 15.1% (n = 16/106) in the pretreating center (p = 0.012). When strictly comparing treated to untreated patients, the treated group had an IFIS rate of 12.0% compared to 30.4% among untreated (p = 0.001). Adjusted for age and gender results remain consistent (odds ratio 0.329 for treated patients, 95% confidence interval: 0.150-0.720; p = 0.005). CONCLUSIONS: IFIS rates were significantly lower in the pretreating center compared to the non-pretreating center. When comparing strictly treated to untreated patients, differences were even more pronounced.

Silodosin as a predisposing factor of intraoperative floppy iris syndrome (IFIS): an observational propensity score-matching cohort study.

PURPOSE: To evaluate the correlation between silodosin and intraoperative floppy iris syndrome (IFIS) and compare it with other a1-adrenergic receptor antagonists (a1-ARAs) and other factors predisposing to IFIS. METHODS: From the patients who underwent phacoemulsification between 2014 and 2020, we identified all patients who, during their preoperative assessment, reported an a1-ARAs intake (exposed group). These patients were matched utilizing a propensity score matching analysis with an otherwise homogenous group of patients (control group) based on demographics and systemic/ocular comorbidities. RESULTS: A total of 350 patients were included in each group. In the exposed group, 177 (50.6%) patients were exposed to tamsulosin, 105 (30%) to alfuzosin, 43 (12.2%) to silodosin. Regarding IFIS, it was observed in 21.5% of patients on tamsulosin (38/177), 11.4% on alfuzosin (12/105), 37.2% on silodosin (16/43), and 3.4% in the controlled group (12/350). In a multiple regression model analysis, the only two factors significantly associated with IFIS development were silodosin and tamsulosin yielding an adjusted odds ratio of 8.471 (95%CI 4.005-17.920) and 3.803 (95%CI 2.231-6.485), respectively. CONCLUSION: Silodosin has been demonstrated as a predisposing factor, strongly correlated with IFIS development. These results should increase cataract surgeons' awareness to assess their patients preoperatively for exposure to silodosin carefully and employ the appropriate prophylactic measures to ameliorate the impact of silodosin intake on the surgical outcome.

Association of alpha-1-adrenergic antagonist use with the risk of gout development in benign prostatic hyperplasia patients: a population-based cohort study.

BACKGROUND: Men are more likely to develop benign prostatic hyperplasia (BPH) and gout as they age. However, the role of alpha-1-adrenergic antagonists, the medication for BPH, in the development of gout is uncertain. OBJECTIVE: To investigate the effect of alpha-1-adrenergic antagonist use on the risk of developing gout in BPH patients. METHODS: Data of patients with newly diagnosed BPH were retrieved from Taiwan's 2000-2013 National Health Insurance Research Database (total number: 15,390 patients; 7,695 patients in each cohort). Propensity score matching was conducted according to age, comorbidities, medication history for cohorts that received or did not receive alpha-1-adrenergic antagonists. Hazard ratios (HRs) were assessed for gout development using Cox proportional hazards regression models. RESULTS: Use of alpha-1-adrenergic antagonists was not associated with gout development in BPH patients (HR = 0.92; 95% confidence interval [CI], 0.78-1.10; P = 0.35). However, after stratification according to the average number of days of alpha-1-adrenergic antagonist use per year, patients with an average of >300 days had a significantly higher risk of gout development than patients who did not receive alpha-1-adrenergic antagonists (adjusted HR = 1.57; 95% CI, 1.25-1.97; P < 0.001). Patients with more days of medication use per year had a higher risk of gout development than those with fewer days of medication use (P < 0.001). CONCLUSION: Patients who received more doses of alpha-1-adrenergic antagonists per year had a higher risk of developing gout. A causal proof of the role of alpha-1-adrenergic antagonists use in gout development should be analysed in future studies designed as double blind randomized controlled trials.

Free combination of dutasteride plus tamsulosin for the treatment of benign prostatic hyperplasia in South Korea: analysis of drug utilization and adverse events using the National Health Insurance Review and Assessment Service database.

OBJECTIVE: To assess the use and safety of free combination therapy (dutasteride and tamsulosin), dutasteride monotherapy, or tamsulosin monotherapy in patients with benign prostatic hyperplasia (BPH). METHODS: This non-interventional retrospective cohort study used claims data from the Korea Health Insurance Review and Assessment-National Patient Sample database. Patients with BPH ≥ 40 years of age receiving combination therapy (dutasteride 0.5 mg and tamsulosin 0.4 mg daily) or dutasteride 0.5 mg, or tamsulosin 0.4 mg daily dose between 2012 and 2017 were included. The frequency, duration of treatment and risk of any adverse event (AE) or serious AE (SAE) was compared for combination therapy versus each monotherapy using non-inferiority testing. RESULTS: Of 14,755 eligible patients, 1529 (10.4%) received combination therapy, 6660 (45.1%) dutasteride monotherapy, and 6566 (44.5%) tamsulosin monotherapy. The proportion of patients treated with combination therapy exceeded the pre-specified 3% threshold for 'frequent' use. Safety results indicated a similar risk of any AE and SAE irrespective of treatment group. The adjusted relative risk for any AE over the treatment observation period comparing combination therapy with dutasteride monotherapy was 1.07 (95% confidence interval [CI] 1.03, 1.12), and with tamsulosin monotherapy was 0.98 (95% CI 0.95, 1.02) demonstrating non-inferiority. The adjusted relative risk for any SAE was 1.07 (95% CI 0.66, 1.74) and 0.90 (95% CI 0.56, 1.45), compared with dutasteride and tamsulosin monotherapy, respectively. Although the SAE results did not statistically demonstrate non-inferiority of combination therapy based on pre-specified margins, the 95% CI for the risk ratio estimates included the null with a lower limit below the non-inferiority margins, indicating no meaningful differences in SAE risk between groups. Absolute SAE risks were low. CONCLUSION: Combination therapy with dutasteride and tamsulosin is frequently used in real-world practice in South Korea for treatment of BPH and demonstrates a safety profile similar to either monotherapy.

Intraoperative Floppy Iris Syndrome Induced by Tamsulosin: The Risk and Preventive Strategies.

Tamsulosin is an antagonist of a subtype-specific alpha-1A- and alpha-1D-adrenoceptor (AR) that is expressed in the prostate gland, urethra, and bladder. Several reports have shown a possible relationship between ophthalmologic adverse effects and the use of alpha-1-receptor medicines, including tamsulosin. This descriptive review evaluates the intraoperative floppy iris syndrome (IFIS) associated with tamsulosin. A search of the Medline and PubMed databases was conducted to identify control trials, case reports, and observational examinations published in English. The publication dates were restricted (January 1, 2000, to January 1, 2020). Keywords (tamsulosin, alpha-blocker, ocular, eye, adverse reaction, and IFIS) were used in the searches. The searches identified 66 studies including in vitro or in vivo studies, trials, and observational studies. Twenty-two (33.33%) studies were articles citing tamsulosin and IFIS as having confirmed potential risk to ocular safety. The results of this review, including a comprehensive summary of published research on tamsulosin use in different populations, have identified several articles showing associations between tamsulosin and IFIS that merit further investigation. Suspending of potential causative pharmacological treatment of IFIS before ocular surgery including tamsulosin, proper identification of at-risk patients, preoperative prophylaxis treatments, and surgical technique modifications clearly can mitigate the anticipated risk of IFIS induced by tamsulosin.

Blood Pressure Control in Acute Stroke: Labetalol or Nicardipine?

PURPOSE: To assess the safety and efficacy of continuous infusion (CIV)-labetalol compared to -nicardipine in controlling blood pressure (BP) in the acute stroke setting. MATERIALS: Patients were eligible if they had a diagnosis of an acute stroke and were administered either CIV-labetalol or CIV-nicardipine. Study outcomes were assessed within the first 24 h of the antihypertensive infusion. RESULTS: A total of 3,093 patients were included with 3,008 patients in the CIV-nicardipine group and 85 in the CIV-labetalol group. No significant difference was observed in percent time at goal BP between the nicardipine (82%) and labetalol (85%) groups (p = 0.351). There was also no difference in BP variability between nicardipine (37%) and labetalol (39%) groups (p = 0.433). Labetalol was found to have a shorter time to goal BP as compared to nicardipine (24 min vs. 40 min; p = 0.021). While CIV-nicardipine did have a higher incidence of tachycardia compared to labetalol (17% vs. 4%; p <0.001), the incidence of hypotension (13% vs. 15%; p = 0.620) and bradycardia (24% vs. 22%; p = 0.797) were similar. CONCLUSIONS: These results indicate that CIV-labetalol and CIV-nicardipine are comparable in safety and efficacy in controlling BP for patients with acute stroke.

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.

Parkinson disease among patients treated for benign prostatic hyperplasia with α1 adrenergic receptor antagonists.

BACKGROUNDRecently the α1 adrenergic receptor antagonist terazosin was shown to activate PGK1, a possible target for the mitochondrial deficits in Parkinson disease related to its function as the initial enzyme in ATP synthesis during glycolysis. An epidemiological study of terazosin users showed a lower incidence of Parkinson disease when compared with users of tamsulosin, an α1 adrenergic receptor antagonist of a different class that does not activate PGK1. However, prior research on tamsulosin has suggested that it may in fact potentiate neurodegeneration, raising the question of whether it is an appropriate control group.METHODSTo address this question, we undertook an epidemiological study on Parkinson disease occurrence rate in 113,450 individuals from the United States with 5 or more years of follow-up. Patients were classified as tamsulosin users (n = 45,380), terazosin/alfuzosin/doxazosin users (n = 22,690), or controls matched for age, sex, and Charlson comorbidity index score (n = 45,380).RESULTSIncidence of Parkinson disease in tamsulosin users was 1.53%, which was significantly higher than that in both terazosin/alfuzosin/doxazosin users (1.10%, P < 0.0001) and matched controls (1.01%, P < 0.0001). Terazosin/alfuzosin/doxazosin users did not differ in Parkinson disease risk from matched controls (P = 0.29).CONCLUSIONThese results suggest that zosins may not confer a protective effect against Parkinson disease, but rather that tamsulosin may in some way potentiate Parkinson disease progression.FUNDINGThis work was supported by Cerevel Therapeutics.

Triple Therapy with Tamsulosin, Dutasteride, and Imidafenacin for Benign Prostatic Hyperplasia in Patients with Overactive Bladder Symptoms Refractory to Tamsulosin: Subgroup Analyses of the DIrecT Study.

AIM: To verify if the efficacy of the triple therapy with tamsulosin, dutasteride, and imidafenacin (TDI) is influenced by any background characteristics in patients with overactive bladder (OAB). METHODS: A subanalysis of data from the DIrecT study was conducted. Superiority of TDI over tamsulosin and dutasteride in terms of efficacy based on the Overactive Bladder Symptom Score (OABSS), total International Prostate Symptom Score (IPSS), IPSS quality of life index, and postvoid residual (PVR) was evaluated in binary subgroups. RESULTS: In the treatment groups, there was a significant interaction of total OABSS with testosterone level (≥4.8 vs. <4.8 ng/mL, p = 0.043) and PVR (≥20 vs. <20 mL, p = 0.018). For the total IPSS, no significant interaction was found except for the IPSS QOL index. For the IPSS QOL index, a significant interaction was found with testosterone level (≥4.8 vs. <4.8 ng/mL, p < 0.0001) as well as with total IPSS and total OABSS. For the PVR, no significant interaction was found except with total OABSS. CONCLUSIONS: Triple therapy with TDI is suggested to be a therapeutic option for benign prostatic hyperplasia in patients with residual OAB symptoms refractory to tamsulosin and in patients with various background characteristics regardless of severity of OAB symptoms. Trial Registry No. UMIN 000011980.

Pharmacokinetics and pharmacodynamics of MT-1207, a novel multitarget blocker of α1 receptor, 5-HT2A receptor, and calcium channel, in healthy subjects.

BACKGROUND: MT-1207 is a novel multitarget blocker of α1 receptor, 5-HT2A receptor, and calcium channel that is currently under development for the treatment of hypertension. In this study, we evaluated the tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of MT-1207 in healthy Chinese subjects. RESEARCH DESIGN AND METHODS: We examined the effects of a single-ascending dose (SAD) of MT-1207 (5-40 mg) and MT-1207 (40 mg) administered in combination with food in 56 healthy subjects. RESULTS: No serious adverse events or discontinuations due to adverse events (related to MT-1207) occurred in either study. MT-1207 was rapidly absorbed (median Tmax: 0.5-1.25 h). The mean t1/2 of MT-1207 was approximately 4-7 hours. Systemic exposure (Cmax and AUC) to MT-1207 increased in proportion to dose. Food had little effect on the pharmacokinetics of MT-1207, such as t1/2 and AUC. For 4h-24 h after administration, the blood pressure reduction in the MT-1207 group was higher than that in the placebo group, showing the antihypertensive effect. Blood pressure reduction after MT-1207 administration showed some dose-dependent trend in the 5-20 mg groups. CONCLUSIONS: MT-1207 was well tolerated in all subjects. PD measurements demonstrated the antihypertensive effects of MT-1207.