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Aims: Prazosin is an antihypertensive medication which can be used to help with post-traumatic stress disorder (PTSD) symptoms. Little data is currently available on its safety in pregnancy. The aim of this study was to assess the fetal and pregnancy safety associated with prazosin exposures in early pregnancy., Methods: Subjects were 11 patients who took prazosin during pregnancy and were counselled at the FRAME clinic in London Health Sciences Centre (Ontario, Canada) between 1 January 2000 and 31 December 2021. Data on their other exposures and pregnancy outcomes were collected from medical records and through telephone questionnaires., Results: It was found that 6/11 (54.5%) subjects did not report any adverse outcomes and experienced uneventful pregnancies. There were two miscarriages. Birthweights were within the normal range for the remaining nine pregnancies. Adverse events reported were consistent with background population expectation, including: one postpartum haemorrhage, one case of preeclampsia, one preterm birth, two NICU admissions, and two caesarean sections., Conclusions: For these 11 subjects, pregnancy outcomes after exposure to prazosin were consistent with typical outcomes from unexposed pregnancies. More data are needed to conclude that prazosin is safe for use in pregnant subjects. However, the lack of adverse effects above baseline is reassuring to future patients who may be unintentionally exposed to prazosin while pregnant. Therefore, this study contributes valuable data towards monitoring safety of prazosin in pregnancy., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Patients on alpha-blockers (ABs) treatment may have an increased risk of adverse events (AEs). Aim of our study was to compare real-life data on neuro-vascular and sexual AEs associated with ABs based on Eudra-Vigilance reported AEs., Methods: Eudra-Vigilance (EV) database is the system for managing and analyzing information on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). We recorded the number of sexual and neuro-vascular AEs for tamsulosin, alfuzosin, silodosin, prazosin and doxazosin per category and severity until July 30 th , 2022. Pooled Relative Risk (PRR) was used to compare data between drugs., Results: Overall the number of AEs were 2842 for Alfuzosin, 11,086 for tamsulosin, 792 for terazosin, 572 for prazosin and 4641 for doxazosin. Different percentages of AEs were obtained for each drug and in different age groups according to EV sub-groups (≤65, 65-85, ≥85). On PRR analysis, the risk of ejaculatory disorders for Silodosin (11%) is 18.5 times higher (PRR 18.5 95%CI; 10.7-31.8; P<0.05) when compared to alfuzosin and the risk of orthostatic hypotension is 2 times lower (PRR=1,84 95%CI 1.32-2.57; P<0.05)., Conclusions: Real life data is consistent with registry studies regarding side effects related to alpha-blockers. Alfuzosin is safer in terms of ejaculatory disorders while silodosin and tamsulosin in terms of orthostatic hypotension. Clinicians should consider these data when prescribing ABs especially in younger and older patients.

Objective: The study aimed to develop a rapid, simple and sensitive LC/ESI-MS/MS method to measure prazosin concentration in human plasma and apply bedside sampling in bioequivalence study of two prazosin tablets to resolve the adverse effect of orthostatic hypotension., Significance: The LC/ESI-MS/MS prazosin method was highly sensitive and selective. Bedside sampling reduced the orthostatic hypotension incidence and subject dropout rate., Methods: After sample preparation, prazosin and terazosin (IS) were detected on mass spectrometer operating in multiple reaction monitoring mode using positive ionization. Mobile phase flow rate was set at 0.40 mL/min with sample run time of 1.75 min. The bioanalytical method was validated as per EMEA and FDA guidelines. Bedside sampling was performed in bioequivalence study for the first 4 h after dosing. The three primary pharmacokinetic parameters, C max , AUC 0- t and AUC 0-∞ and 90% confidence interval were determined., Results: The small injection volume of 1 μL minimized instrumentation contamination and prolonged the analytical column lifespan. Linearity was obtained between 0.5 and 30.0 ng/mL, with coefficient of determination, r 2 ≥ 0.99. The mean extraction recovery of prazosin and IS was >92%, with precision value (CV, %) ≤ 10.3%. Only two orthostatic hypotension adverse events were reported. The two prazosin formulations were found to be bioequivalent., Conclusion: The LC/ESI-MS/MS method has shown robustness and reliability exemplified by the incurred sample re-analysis result. Bedside sampling should be proposed for bioequivalence or pharmacokinetic studies of drugs demonstrating adverse event of orthostatic hypotension.

Objective: To evaluate the efficacy of prazosin for posttraumatic stress disorder (PTSD)-related nightmares in veterans and to analyze subgroup benefit/risk to guide prescribing., Methods: Patients with a previous prescription for prazosin between 1 June 2007 and 30 June 2017 were collected from the institution's electronic records. Efficacy (including nightmare frequency, and clinical PTSD rating scales) and safety (including blood pressure) data were retrospectively analyzed., Results: Eighty-four patients were included in the analysis. The primary outcome, item 2 of the PTSD checklist, decreased from 4.00 to 3.19 (on a scale of 1-5), which was statistically significant (p < 0.05). Nightmare frequency was found to have a statistically significant decrease from four to two times per week on average (p = 0.00002, 95% CI 2.36 [1.39-3.33]). Of the patients who reported the greatest response (n = 23), 91% (n = 21) were on an antidepressant and 61% (n = 14) were receiving concurrent psychotherapy. This is compared to 90% (n = 76) and 44% (n = 37) of the total cohort, respectively. No significant differences were found in blood pressure or suicidal ideation (p = 0.58 and p = 0.22, respectively)., Conclusion: Prazosin may be considered as an adjunct option to decrease nightmare frequency in patients already receiving first-line treatment., (© 2021 John Wiley & Sons Ltd.)

A 35-year-old African-American man, who was an active duty service member, presented to the Troop Medical Clinic with a 4-hour history of priapism. He had been taking sertraline 100 mg and prazosin 10 mg nightly for 4 months to treat his posttraumatic stress disorder (PTSD) with no reported adverse effects. These doses were titrated 2 months prior to presentation. The patient reported that he took his usual medication doses before bed and awoke at 3 am with a penile erection. At 7 am, he presented to the clinic because of pain from the continued erection.

Background: In randomized trials, prazosin, an α 1 -adrenoreceptor antagonist, has been effective in alleviating nightmares associated with post-traumatic stress disorder (PTSD) in military veterans., Methods: We recruited veterans from 13 Department of Veterans Affairs medical centers who had chronic PTSD and reported frequent nightmares. Participants were randomly assigned to receive prazosin or placebo for 26 weeks; the drug or placebo was administered in escalating divided doses over the course of 5 weeks to a daily maximum of 20 mg in men and 12 mg in women. After week 10, participants continued to receive prazosin or placebo in a double-blind fashion for an additional 16 weeks. The three primary outcome measures were the change in score from baseline to 10 weeks on the Clinician-Administered PTSD Scale (CAPS) item B2 ("recurrent distressing dreams"; scores range from 0 to 8, with higher scores indicating more frequent and more distressing dreams); the change in score from baseline to 10 weeks on the Pittsburgh Sleep Quality Index (PSQI; scores range from 0 to 21, with higher scores indicating worse sleep quality); and the Clinical Global Impression of Change (CGIC) score at 10 weeks (scores range from 1 to 7, with lower scores indicating greater improvement and a score of 4 indicating no change)., Results: A total of 304 participants underwent randomization; 152 were assigned to prazosin, and 152 to placebo. At 10 weeks, there were no significant differences between the prazosin group and the placebo group in the mean change from baseline in the CAPS item B2 score (between-group difference, 0.2; 95% confidence interval [CI], -0.3 to 0.8; P=0.38), in the mean change in PSQI score (between-group difference, 0.1; 95% CI, -0.9 to 1.1; P=0.80), or in the CGIC score (between-group difference, 0; 95% CI, -0.3 to 0.3; P=0.96). There were no significant differences in these measures at 26 weeks (a secondary outcome) or in other secondary outcomes. At 10 weeks, the mean difference between the prazosin group and the placebo group in the change from baseline in supine systolic blood pressure was a decrease of 6.7 mm Hg. The adverse event of new or worsening suicidal ideation occurred in 8% of the participants assigned to prazosin versus 15% of those assigned to placebo., Conclusions: In this trial involving military veterans who had chronic PTSD, prazosin did not alleviate distressing dreams or improve sleep quality. (Funded by the Department of Veterans Affairs Cooperative Studies Program; PACT ClinicalTrials.gov number, NCT00532493 .).

Objective: Maternal and environmental factors control the epigenetic fetal programming of the embryo, thereby defining the susceptibility for metabolic or endocrine disorders in the offspring. Pharmacological interventions required as a consequence of gestational problems, e.g. hypertension, can potentially interfere with correct fetal programming. As epigenetic alterations are usually only revealed later in life and not detected in studies focusing on early perinatal outcomes, little is known about the long-term epigenetic effects of gestational drug treatments. We sought to test the consequences of maternal α1-adrenergic antagonism during pregnancy, which can occur e.g. during hypertension treatment, for the endocrine and metabolic phenotype of the offspring., Methods: We treated C57BL/6NCrl female mice with the α1-adrenergic antagonist prazosin during pregnancy and analyzed the male and female offspring for endocrine and metabolic abnormalities., Results: Our data revealed that maternal α1-adrenergic blockade caused dwarfism, elevated body temperature, and insulin resistance in male offspring, accompanied by reduced IGF-1 serum concentrations as the result of reduced hepatic growth hormone receptor (Ghr) expression. We subsequently identified increased CpG DNA methylation at the transcriptional start site of the alternative Ghr promotor caused by the maternal treatment, which showed a strong inverse correlation to hepatic Ghr expression., Conclusions: Our results demonstrate that maternal α1-adrenergic blockade can constitute an epigenetic cause for dwarfism and insulin resistance. The findings are of immediate clinical relevance as combined α/β-adrenergic blockers are first-line treatment of maternal hypertension., (Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background and Purpose: Nightmares associated with posttraumatic stress disorder (PTSD) are a hallmark symptom among U.S. military veterans who have seen combat. Management of combat-related nightmares can be difficult and current pharmacologic options are limited and tend to have adverse side effects. The aim of this review is to explore recent literature regarding the efficacy of prazosin for the treatment of nightmare disorder in the veteran population., Methods: Recent literature consisting of three systematic reviews was reviewed, as well as current clinical guidelines published by The Department of Veterans Affairs (VA) and The Department of Defense (DoD) and the American Academy of Sleep Medicine (AASM)., Conclusions: Prazosin has been shown to be effective in the treatment of PTSD trauma-related nightmares. As a result of its low side effect profile and abilities to improve both sleep and reduce trauma nightmares, prazosin has been recommended as an adjunct therapy., Implications for Practice: Prazosin should be initiated as an adjunctive treatment to promote sleep in those suffering from PTSD nightmares. It should be initiated at 1 mg and then titrated upward until absence or desired reduction of nightmares is achieved, with a maximum dosage recommendation of 20 mg at bedtime and 5 mg midmorning., (©2016 American Association of Nurse Practitioners.)

Objectives: To assess urologists' awareness of intraoperative floppy iris syndrome., Materials and Methods: A questionnaire composed of 21 questions was emailed to all of the Urology residency programs in the U.S. and all members of the Western section of the American Urological Association. Responses were collected and analyzed using statistical software., Results: A total of 175 responses were collected from residents, fellows, and attending physicians from a wide range of geographic locations, subspecialties, and practice settings. Thirty percent of the urologists would routinely discuss intraoperative floppy iris syndrome with patients prior to start of benign prostate hyperplasia treatment. Twenty-one percent of the respondents never asked patients about ophthalmologic conditions prior to benign prostate hyperplasia treatment. If patients had concurrent visual complaints, only 37% of the respondents would routinely encourage patients to speak to an ophthalmologist and only 13% would routinely refer patients to an ophthalmologist. A comparison among the subgroups based on training status and practice settings further showed that a significantly higher percentage of residents would not ask about visual complaints or refer patients with visual complaints to an ophthalmologist compared with fellows and attending physicians (P <.01); however, there was no significant difference between urologists in academic and nonacademic settings (P >.05)., Conclusion: Despite continuing effort to educate physicians about intraoperative floppy iris syndrome, there still exists a knowledge gap that may compromise patient care and further education is needed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We describe a 71-year-old male patient who developed acute myocardial infarction (AMI) due to a dynamic left ventricular outflow tract obstruction induced by terazosin. After receiving terazosin, the patient had a syncope followed by angina. The electrocardiogram showed Q waves and ST segment elevation in the precordial and inferior leads. Coronary angiography evidenced a chronically occluded left anterior descending artery. Doppler-echocardiography revealed apical akinesia, hyperdynamic basal segments, systolic anterior motion of the mitral valve (SAM) and dynamic left ventricular outflow tract obstruction. Therapy with intravenous fluids and atenolol resulted in marked clinical improvement. Acute myocardial infarction resulted from low coronary perfusion pressure in a patient with a chronically diminished coronary reserve.

Prazosin is increasingly being used off-label to treat nightmares in patients with posttraumatic stress disorder. The literature about the psychiatric adverse effects of prazosin is very limited. We present a case in which low-dose prazosin was associated with nightmares and sleep disturbances in an elderly patient without previously diagnosed mental illness or coexisting environmental risk factors for nightmares. Insomnia and hallucinations are listed as some of the rare side effects of prazosin by the manufacturer. Prazosin could be associated with rare psychiatric adverse effects and sleep disturbances. Particular attention is required in identifying these adverse effects, which can be difficult to distinguish from other drug-related side effects in the elderly particularly because they are often using multiple medications., (© 2016 American Academy of Sleep Medicine.)

Background: Posttraumatic stress disorder (PTSD) and alcohol dependence (AD) commonly co-occur and are associated with greater symptom severity and costs than either disorder alone. No pharmacologic interventions have been found to decrease both alcohol use and PTSD symptom severity relative to matched placebo. Prazosin, an alpha-1 adrenoreceptor antagonist, has demonstrated the efficacy of reducing PTSD and AD symptoms among individuals with one or the other disorder and may be useful in addressing comorbid PTSD/AD., Methods: Prazosin and matched placebo were compared in the context of an outpatient 6-week double-blind randomized controlled pilot trial involving 30 individuals with comorbid PTSD/AD. Medication was titrated to 4 mg q am, 4 mg q pm and 8 mg qhs by the end of week 2. Participants in both conditions received 5 medical management sessions. Information regarding alcohol use, craving, and PTSD was gathered daily using a telephone interactive voice response system., Results: Participants randomized to prazosin had a greater reduction in percent days drinking per week and percent days heavy drinking per week between baseline and week 6 than did placebo participants. No significant differences were detected within or between groups in change from weeks 1 to 6 in total PTSD symptoms. Participants in the prazosin condition reported drowsiness on significantly more days than those in the placebo condition., Conclusions: Consistent with the extant research evaluating medications for comorbid PTSD/AD, the current evaluation of prazosin also found decreased alcohol consumption but no medication effect on PTSD symptomatology., (Copyright © 2015 by the Research Society on Alcoholism.)

Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder that may develop after exposure to a life-threatening trauma. As veterans and armed forces may deal with diverse health problems compared with civilians, they have a greater risk for psychiatric disorders, including PTSD, than civilians, even if the disorder may be also frequent in the general population. PTSD is associated with significant comorbidity, especially with mood disorders and substance abuse. Moreover, the suicide risk is higher in PTSD patients than in the general population. Selective Serotonin Reuptake Inhibitors (SSRIs), atypical antipsychotics and benzodiazepines are commonly employed in the management of PTSD, but often these treatments fail or are discontinued due to adverse effects. It has been demonstrated that high noradrenergic activity may be associated with hyperarousal, trauma nightmares and sleep disturbances in PTSD subjects, probably through the stimulation of α -1 adrenergic receptors in the brain prefrontal cortex. The α -1 adrenoreceptor antagonist prazosin decreases noradrenaline effects at brain α-1 adrenoreceptors and may be a promising agent in the treatment of PTSD, as some studies have found it effective and well tolerated. Therefore, the present review is aimed to examine the role of noradrenergic system in the pathophysiology of PTSD. Moreover, we conducted a systematic review to evaluate the effectiveness and tolerability of prazosin in PTSD patients. Meta-analysis was used to combine data from multiple studies and better estimate the effect of prazosin on specific outcomes. We found prazosin to be significantly more efficacious than placebo in reducing distressing dreams in PTSD patients, even though our results should be interpreted with caution due to the small number of studies included in our quantitative synthesis.

Posttraumatic stress disorder (PTSD) often follows a chronic course, and the disorder is resistant to treatment with antidepressants and cognitive-behavioral therapy in a proportion of patients. Prazosin, an a1-adrenoceptor blocker, has shown some promise in treating chronic PTSD. A review of this literature was conducted via a search of MEDLINE and SUMMON, using keywords such as PTSD, prazosin, treatment, and resistance. At least 10 clinical studies of prazosin in the treatment of PTSD, including open-label and randomized controlled trials, have been published. All of these studies support the efficacy of prazosin either for treating nightmares and improving sleep or for reducing the severity of PTSD. Treatment of PTSD with prazosin is usually initiated at a dose of 1 mg, with monitoring for hypotension after the first dose. The dose is then gradually increased to maintenance levels of 2-6 mg at night. Studies of military patients with PTSD have used higher doses (e.g., 10-16 mg at night). Prazosin has also been studied in younger and older adults with PTSD and in patients with alcohol problems, in whom it was found to reduce cravings and stress responses. Prazosin offers some hope for treating resistant cases of PTSD in which recurrent nightmares are problematic, with a relatively rapid response within weeks. It is suggested that large-scale civilian trials of prazosin be done, as well as studies concerning the use of prazosin in acute PTSD and as a potential preventive agent.

Objectives: In light of the high prevalence of sleep disorders in patients suffering from posttraumatic stress disorder (PTSD), this study sought to compare the effect of prazosin and hydroxyzine on sleep quality in this patient group., Methods: A total of 100 patients suffering from PTSD were assessed (mean age = 35.51 years, SD = 6.41; 28% females). Next, they were randomly assigned to one of three treatment groups: prazosin (33 patients), hydroxyzine (34 patients) or placebo (33 patients). The trial lasted for 8 weeks. The patients' sleep quality was assessed using the Pittsburgh Sleep Quality Index. Items taken from the Mini International Neuropsychiatric Interview were used to operationalize PTSD., Results: Compared to controls, patients treated with prazosin and hydroxyzine reported improved sleep and less nightmares. Improvement was greatest in patients treated with prazosin compared to hydroxyzine and placebo. Improvement in sleep was associated with an amelioration of their PTSD symptoms., Conclusion: Both prazosin and hydroxyzine can be used to treat psychopharmacological sleep disorders and nightmares in patients suffering from PTSD, also leading to reductions in PTSD symptoms., (© 2014 S. Karger AG, Basel.)

Objective: The authors conducted a 15-week randomized controlled trial of the alpha-1 adrenoreceptor antagonist prazosin for combat trauma nightmares, sleep quality, global function, and overall symptoms in active-duty soldiers with posttraumatic stress disorder (PTSD) returned from combat deployments to Iraq and Afghanistan., Method: Sixty-seven soldiers were randomly assigned to treatment with prazosin or placebo for 15 weeks. Drug was titrated based on nightmare response over 6 weeks to a possible maximum dose of 5 mg midmorning and 20 mg at bedtime for men and 2 mg midmorning and 10 mg at bedtime for women. Mean achieved bedtime doses were 15.6 mg of prazosin (SD=6.0) and 18.8 mg of placebo (SD=3.3) for men and 7.0 mg of prazosin (SD=3.5) and 10.0 mg of placebo (SD=0.0) for women. Mean achieved midmorning doses were 4.0 mg of prazosin (SD=1.4) and 4.8 mg of placebo (SD=0.8) for men and 1.7 mg of prazosin (SD=0.5) and 2.0 mg of placebo (SD=0.0) mg for women. Primary outcome measures were the nightmare item of the Clinician-Administered PTSD Scale (CAPS), the Pittsburgh Sleep Quality Index, and the change item of the Clinical Global Impressions Scale anchored to functioning. Secondary outcome measures were the 17-item CAPS, the Hamilton Depression Rating Scale, the Patient Health Questionnaire-9, and the Quality of Life Index. Maintenance psychotropic medications and supportive psychotherapy were held constant., Results: Prazosin was effective for trauma nightmares, sleep quality, global function, CAPS score, and the CAPS hyperarousal symptom cluster. Prazosin was well tolerated, and blood pressure changes did not differ between groups., Conclusions: Prazosin is effective for combat-related PTSD with trauma nightmares in active-duty soldiers, and benefits are clinically meaningful. Substantial residual symptoms suggest that studies combining prazosin with effective psychotherapies might demonstrate further benefit.

Nineteen dogs with vesico-urethral reflex dyssynergia (VURD) were treated with prazosin or terazosin 0.5 mg/kg twice daily to compare efficacy and side effects. Dogs were referred because of signs of (partial) urethral obstruction. Physical examination, abdominal ultrasonography, urinalysis and a radiographic contrast study of bladder and urethra (urethrocystography) were routinely performed. If no mechanical causes of obstruction or disease of the distal urinary tract were observed, the diagnosis VURD was presumed and the dogs were included in our study. Follow-up information was obtained from owners or referring veterinarians. Significantly more side effects were seen in the dogs treated with terazosin (n=14; 93 per cent) compared with the dogs treated with prazosin (n=5; 20 per cent; P=0.002). Effects of the treatment were comparable between prazosin and terazosin. Labradors and dogs that were castrated surgically had a significant better survival (P<0.01) compared with other breeds and animals that were castrated chemically. There was a moderate to good effect in 60 per cent of the dogs treated with prazosin, and in 64 per cent of the dogs treated with terazosin.

A crossover study was conducted to identify the best α1-adrenoceptor (α1AR) antagonist for individual patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). One hundred thirteen patients (mean age 70.8 years) were enrolled. All patients met BPH clinical study guidelines. Seven agents were utilized:tamsulosin 0.2mg, silodosin 8mg, urapidil 60mg, naftopidil 50mg, prazosin 1mg, terazosin 2mg, and doxazosin 1mg. Patients were initially prescribed tamsulosin or silodosin for a week and then urapidil for a week. Two weeks later, they were prescribed the better of the 2 agents for a week and a new agent for the next week. This cycle was repeated until all 7 agents were tested. Efficacy was evaluated with the International Prostate Symptom Score. The agent rankings were doxazosin (25 [22%]), silodosin (22 [19%]), urapidil (19 [17%]), naftopidil (17 [15%]), terazosin (12 [11%]), tamsulosin (11 [10%]), prazosin (7 [6%]). Only 12 patients (11%) changed agents after the crossover study was completed. The major reason was adverse events (83%). We found that each of the 7 α1AR antagonists has its own supporters. Further, the one-week crossover study was useful in identifying the best agent for the treatment of each individual with LUTS.

Alteration of the oxidative stress of hepatocellular carcinoma (HCC) cells can influence the expressions of genes favored angiogenesis. Quinone reductase 2 which can activate quinones leading to reactive oxygen species production is a melatonin receptor known as MT3. Prazosin prescribed for benign prostate hyperplasia and hypertension is a potent antagonist for MT3. This study was to investigate the influence of therapeutic concentrations of prazosin (0.01 and 0.1μM) on cell proliferation and differential expressions of CCL2, CCL20, CXCL6, CXCL10, IL8 and IL6 genes related to inflammation and/or oxidative stress in human HCC cell lines. Two HCC cell lines including one without susceptible to amphotericin B-induced oxidative stress (cell line A; HCC24/KMUH) and one with this effect (cell line B; HCC38/KMUH) were investigated by 0.01 and 0.1μM prazosin. The premixed WST-1 cell proliferation reagent was applied for proliferation assay. Differential expressions of genes were examined by quantitative reverse transcriptase-polymerase chain reaction. Our results showed that both 0.01 and 0.1μM prazosin did not influence cell proliferation in both cell lines. Both 0.01 and 0.1μM prazosin in cell line A and 0.01μM prazosin in cell line B did not cause differential expressions of tested genes. However, 0.1μM prazosin caused remarkable up-regulation of IL6 gene and slightly up-regulation of CCL2 gene in cell line B. In conclusion, high therapeutic concentration of prazosin can up-regulate angiogenic IL6 and CCL2 genes in human HCC cells susceptible to amphotericin B-induced oxidative stress. Clinical application of prazosin in patients with HCC should consider this possibility., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: Stress, alcohol cues, and dysregulated stress responses increase alcohol craving and relapse susceptibility, but few pharmacologic agents are known to decrease stress- and cue-induced alcohol craving and associated stress dysregulation in humans. Here we report findings from a preliminary efficacy study of the alpha-1 receptor antagonist, prazosin, in modulating these relapse-relevant factors in alcohol-dependent individuals., Methods: Seventeen early abstinent, treatment-seeking alcohol-dependent individuals (12 men and 5 women) were randomly assigned to receive either placebo or 16 mg daily prazosin in a double-blind, placebo-controlled manner over 4 weeks. During week 4, all patients participated in a 3-day laboratory experiment involving 5-minute guided imagery exposure to stress, alcohol cue, and neutral-relaxing/control conditions, 1 exposure per day, on consecutive days in a random, counterbalanced order. Alcohol craving, anxiety, negative emotion, cardiovascular measures, and plasma hypothalamic-pituitary-adrenal (HPA; cortisol, adenocorticotropic hormone) were assessed repeatedly in each session., Results: The prazosin group (n = 9) versus the placebo group (n = 8) showed significantly lower alcohol craving, anxiety, and negative emotion following stress exposure. The placebo group also showed significantly increased stress- and cue-induced alcohol craving, anxiety, negative emotion, and blood pressure (BP), as well as a blunted HPA response relative to the neutral condition, while the prazosin group showed no such increases in craving, anxiety, negative emotion, and BP, and no blunted HPA response to stress and alcohol cue exposure., Conclusions: Prazosin appears efficacious in decreasing stress- and cue-induced alcohol craving and may normalize the stress dysregulation associated with early recovery from alcoholism. Further research to assess the efficacy of prazosin in reducing alcohol craving and stress-related relapse risk is warranted., (Copyright © 2011 by the Research Society on Alcoholism.)

Background: We examined whether intracoronary or intrafemoral administration of ranolazine produces local vasodilation., Methods and Results: Effects of intra-arterial ranolazine on coronary and femoral artery vasodilation and systemic hemodynamic function were studied in anesthetized pigs (n=27). Ranolazine, nitroglycerin, or saline (control) was injected into the left anterior descending (LAD) coronary artery or femoral artery (2-mL bolus in 10 seconds). Pretreatment with prazosin (300 μg/kg IV) allowed determination of α(1)-adrenergic receptor involvement (n=8). Rapid intracoronary administration of ranolazine (0.048 mg/kg) to achieve high local concentrations resulted in 91±11% increase in LAD coronary artery flow and 39±7% reduction in coronary vascular resistance (both, P<0.0001). This effect lasted 2-3 minutes without change in heart rate or rate-pressure product. Mean arterial pressure decreased marginally (by 2±1 mm Hg, P=0.01). Maximum systemic plasma concentration (0.93±0.29 μmol/L) remained in subtherapeutic range. Pretreatment with prazosin abolished these effects. Intracoronary nitroglycerin (100 μg) increased LAD coronary artery flow by 112±25% (P=0.02), but the effect lasted <2 minutes; mean arterial pressure decreased by 4±1 mm Hg (P=0.01). Intrafemoral injection of ranolazine (0.24 mg/kg, ie, one-tenth of the systemic bolus) resulted in a 70±19% increase in femoral artery flow (P=0.05) and 26±5% reduction in femoral artery resistance (P=0.004). At 2 minutes after the injection, the femoral flow remained 16±9% above the baseline and dilatory effects occurred without tolerance to repeated injections., Conclusions: Intracoronary or intrafemoral ranolazine bolus exerts a marked, 2- to 3-minute dilatory effect that is comparable to nitroglycerin in magnitude but more persistent, attributable primarily to α(1)-adrenergic blockade.

Background: This project aimed to provide an organized, sequential, and evidence-supported approach to the pharmacotherapy of posttraumatic stress disorder (PTSD), following the format of previous efforts of the Psychopharmacology Algorithm Project at the Harvard South Shore Program., Method: A comprehensive literature review was conducted to determine the best pharmacological choices for PTSD patients and to update the last published version (1999) of the algorithm. We focused on optimal pharmacological interventions to address the prominent symptoms of PTSD, with additional attention to the impact that common comorbidities have on treatment choices., Results: We found that SSRIs and SNRIs are not as effective as previously thought, and that awareness of their long-term side effects has increased. New evidence suggests that addressing fragmented sleep and nightmares can improve symptoms (in addition to insomnia) that are frequently seen with PTSD (e.g., hyperarousal, reexperiencing). Prazosin and trazodone are emphasized at this initial step; if significant PTSD symptoms remain, an antidepressant may be tried. For PTSD-related psychosis, an antipsychotic may be added. In resistant cases, two or three antidepressants may be used in sequence. Following that, or with partial improvement and residual symptomatology, augmentation may be tried; the best options are antipsychotics, clonidine, topiramate, and lamotrigine., Conclusion: This heuristic may be helpful in producing faster symptom resolution, fewer side effects, and increased compliance.

Purpose: To evaluate the effect of α1-adrenergic receptor antagonists (α1-ARAs) on pupil diameter and determine whether the diameter predicts intraoperative floppy-iris syndrome (IFIS)., Setting: Ophthalmology Section, Palermo University, Palermo, Italy., Design: Prospective cohort study., Methods: Male outpatients taking tamsulosin, α(1)-ARAs, or no α(1)-ARAs having phacoemulsification were recruited. Pupils were measured 1 month preoperatively, immediately preoperatively, and postoperatively under mesopic low (0.4 lux) and high (4.0 lux) illumination after pharmacologic dilation. The IFIS severity was graded., Results: Each group comprised 50 patients. Pharmacologic dilation in both α(1)-ARA groups was statistically significantly less than in the no α1-ARA group 1 month preoperatively, immediately before surgery, and postoperatively (P=.001, P<.0005, and P<.0005, respectively). The IFIS incidence differed significantly between the tamsulosin and other α(1)-ARA groups and the no α1-ARA group (P<.0005 and P=.017, respectively) and between the tamsulosin group and the other α1-ARA group (P=.027). On regression analysis, the hazard ratio for overall IFIS incidence was 3.8 in the other α(1)-ARA group (P=.012) and 10.1 in the tamsulosin group (P<.0005). Pupil size was inversely related to IFIS incidence and severity (P<.0005). A dilated pupil of 7.0 mm or smaller had 73% sensitivity and 95% specificity for predicting IFIS (P=.0001)., Conclusions: Pupil dilation was inhibited by α(1)-ARAs, in particular tamsulosin. For a pupil 7.0 mm or smaller, the risk for IFIS existed regardless of α(1)-ARAs treatment, which surgeons should take into consideration., (Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate risk factors (hypertension, diabetes mellitus, and current tamsulosin, alfuzosin, terazosin, or doxazosin use) for intraoperative floppy iris syndrome (IFIS) in patients undergoing phacoemulsification cataract surgery., Design: Systematic review and meta-analysis of the literature., Participants: Seventeen eligible studies (17 588 eyes) examining the association between IFIS and risk factors., Methods: Pertinent publications were identified through a systematic search of PubMed. All references of relevant reviews and eligible articles were also screened. Language restrictions were not used, and data were extracted from each eligible study by 2 investigators working independently. For medications, 2 separate analyses were performed: an analysis using a dichotomous criterion (use/non-use of the examined agent) and an alternative analysis performing comparisons with patients not receiving any α(1)-blocker. The fixed-effects model (Mantel-Haenszel method) or the random-effects (DerSimonian Laird) model was appropriately used to calculate the pooled odds ratio (OR). Publication bias was appropriately assessed., Main Outcome Measures: Pooled OR for the incidence of IFIS., Results: The pooled OR for IFIS after tamsulosin use was approximately 40-fold greater (or 16.5 at the alternative analysis) than that after alfuzosin use, that is, the second α(1)-blocker in order of effect size. Alfuzosin and terazosin were also associated with IFIS with comparable ORs; the effect of doxazosin reached formal statistical significance at the alternative analysis. Intraoperative floppy iris syndrome was positively associated with hypertension (pooled OR = 2.2, 95% confidence interval [CI], 1.2-4.2, fixed effects) but not with diabetes mellitus (pooled OR = 1.3, 95% CI, 0.7-2.2, fixed effects)., Conclusions: This meta-analysis has highlighted a hierarchy concerning the role of α(1)-blockers in IFIS, indicating an extremely sizeable effect size of tamsulosin; this may entail important physiologic implications. Alfuzosin, terazosin, and doxazosin presented with comparable effect sizes. Hypertension, but not diabetes mellitus, emerged as a risk factor for IFIS., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: Envenomation by Mesobuthus tamulus scorpion sting can result in serious cardiovascular effects. Scorpion antivenom is a specific treatment for scorpion sting. Evidence for the benefit of scorpion antivenom and its efficacy compared with that of commonly used vasodilators, such as prazosin, is scarce. We assessed the efficacy of prazosin combined with scorpion antivenom, compared with prazosin alone, in individuals with autonomic storm caused by scorpion sting., Design: Prospective, open label randomised controlled trial., Setting: General hospital inpatients (Bawaskar Hospital and Research Centre Mahad Dist-Raigad Maharashtra, India)., Participants: Seventy patients with grade 2 scorpion envenomation, older than six months, with no cardiorespiratory or central nervous system abnormalities., Intervention: Scorpion antivenom plus prazosin (n=35) or prazosin alone (n=35) assigned by block randomisation. Treatment was not masked. Analysis was by intention to treat., Main Outcome Measures: The primary end point was the proportion of patients achieving resolution of the clinical syndrome (sweating, salivation, cool extremities, priapism, hypertension or hypotension, tachycardia) 10 hours after administration of study drugs. Secondary end points were time required for complete resolution of clinical syndrome, prevention of deterioration to higher grade, doses of prazosin required overall and within 10 hours, and adverse events. The study protocol was approved by the independent ethics committee of Mumbai., Results: Mean (SD) recovery times in hours for the prazosin plus scorpion antivenom group compared with the prazosin alone groups were: sweating 3 (1.1) v 6.6 (2.6); salivation 1.9 (0.9) v 3 (1.9); priapism 4.7 (1.5) v 9.4 (1.5). Mean (SD) doses of prazosin in the groups were 2 (2.3) and 4 (3.5), respectively. 32 patients (91.4%, 95% confidence interval 76.9% to 97.8%) in the prazosin plus antivenom group showed complete resolution of the clinical syndrome within 10 hours of administration of treatment compared with eight patients in the prazosin group (22.9%, 11.8% to 39.3%). Patients from the antivenom plus prazosin group recovered earlier (mean 8 hours, 95% CI 6.5 to 9.5) than those in the control group (17.7 hours, 15.4 to 19.9; mean difference -9.7 hours, -6.9 to -12.4). The number of patients whose condition deteriorated to a higher grade was similar in both groups (antivenom plus prazosin four of 35, prazosin alone five of 35). Hypotension was reported in fewer patients in the antivenom plus prazosin group (12 of 35, 34.3%) than in the prazosin group (19 of 35, 54.3%), but the difference was not statistically significant. No difference was noted in change in blood pressure and pulse rate over time between two groups., Conclusion: Recovery from scorpion sting is hastened by simultaneous administration of scorpion antivenom plus prazosin compared with prazosin alone., Trial Registration Number: CTRI/2010/091/000584 (Clinical Trials Registry India).

Posttraumatic stress disorder (PTSD) is an anxiety disorder experienced by combat veterans. Nighttime symptoms are often unrelieved by selective serotonin reuptake inhibitor therapy, and increased use of prazosin or quetiapine for treatment is seen. The purpose of this study was to determine the short- and long-term effectiveness and safety of prazosin versus quetiapine for treating nighttime symptoms in veteran PTSD patients. This is a historical prospective cohort study using retrospective chart review. Three hundred twenty-four patients with a diagnosis of PTSD, based on International Classification of Diseases, Ninth Revision coding, who were initially prescribed prazosin or quetiapine for nighttime symptoms were screened for inclusion. Short-term effectiveness was determined by documentation of symptomatic improvement within 6 months, and long-term effectiveness if patients continued therapy to study end date. Safety was assessed by comparing incidence of adverse drug effects causing discontinuation of either study drug. This study included 237 patients: 62 received prazosin, and 175 received quetiapine. Short-term effectiveness was similar for prazosin (61.3%) and quetiapine (61.7%; P = 0.54). However, patients prescribed prazosin were significantly more likely to continue their therapy to study end date compared with quetiapine (48.4% vs 24%; P < 0.001; odds ratio, 3.0; 95% confidence interval, 1.62-5.45), thus achieving long-term effectiveness. Alternatively, patients in the quetiapine group were more likely to discontinue therapy because of adverse effects compared with the prazosin group (34.9% vs 17.7%; P = 0.008). Because of similar rate of short-term effectiveness, superior long-term effectiveness, and lower incidence of events leading to discontinuation, compared with quetiapine, prazosin should be used first-line for treating nighttime PTSD symptoms in a veteran population.

Purpose: To identify iris structural alterations associated with intraoperative floppy iris syndrome (IFIS) in patients using systemic alpha(1)-adrenergic receptor antagonists (alpha-1ARA)., Design: Cross-sectional study., Participants and Controls: Twenty-nine patients with current or past treatment with any systemic alpha-1ARA and 22 untreated controls., Methods: Consecutive eligible patients underwent slit-lamp-adapted optical coherence tomography in a masked fashion under standardized lighting conditions., Main Outcome Measures: Iris thickness at the dilator muscle region (DMR; measured at half of the distance between the scleral spur and the pupillary margin) and at the sphincter muscle region (SMR; 0.75 mm from the pupillary margin), the ratio between the DMR/SMR (to compensate for possible intersubject variability), and pupillary diameter., Results: Most treated patients were on tamsulosin (27/29). Mean age was similar in study and control groups (70.6+/-7.6 vs 67.1+/-9.1 years; P = 0.061). Photopic pupil diameter was reduced in the study group (2.06+/-0.5 vs 2.5+/-0.6 mm; P = 0.001). The SMR was similar between groups (P = 0.53). Significantly lower values were found in treated subjects for the DMR and the DMR/SMR ratio (P<0.001). These differences remained significant after adjusting for pupil diameter (P<0.001). Multiple regression analysis showed that a longer duration of alpha-1ARA treatment correlated to a reduced DMR/SMR ratio (P = 0.001; r = 0.47). Age and eye color were not significant in this model., Conclusions: Patients using systemic alpha-1ARA have significantly lower values of DMR thickness and DMR/SMR ratio and smaller pupil diameter when compared with age-matched controls. These differences seem to be related to the duration of drug exposure and provide evidence of structural alterations to the iris dilator muscle from this class of agents in IFIS., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Context: Passive diffusion of new medical innovations is an important mechanism by which knowledge transitions from research to clinical practice. Preliminary evidence has emerged about the effectiveness of the alpha(1)-adrenergic blocker prazosin hydrochloride in the treatment of nightmares and hyperarousal among patients with posttraumatic stress disorder (PTSD). This treatment has been neither widely accepted nor the subject of active dissemination efforts, and its efficacy was discovered in a discrete geographic location., Objectives: To evaluate the pace and reach of the passive dissemination of a promising technology within a national health care system., Design: Geographic surveillance data study., Setting: Academic research., Patients: We tracked the use of prazosin in the treatment of patients diagnosed as having PTSD in the Department of Veterans Affairs during fiscal years 2004 (n = 203 414) and 2006 (n = 319 670)., Main Outcome Measure: The percentage of patients diagnosed as having PTSD who received a prescription for prazosin., Results: Whereas 37.6% of patients with PTSD treated within the Veterans Affairs Puget Sound Health Care System, Tacoma, Washington, in 2004 were prescribed prazosin, only 18.2% were treated with prazosin at medical centers up to 499 miles (to convert miles to kilometers, multiply by 1.6) away, 6.7% at centers 500 to 999 miles away, 4.0% at centers 1000 to 2499 miles away, and 1.9% at centers 2500 miles away or farther. Adjusting for patient characteristics, patients with PTSD treated up to 499 miles from Puget Sound were about 49% less likely in 2006 and about 63% less likely in 2004 to be prescribed prazosin than their counterparts treated within Puget Sound, while those who were treated 2500 miles away or farther were about 94% less likely in 2006 and about 97% less likely in 2004 to be treated with prazosin than patients within Puget Sound., Conclusion: Passive diffusion of a new treatment can be rapid in the immediate area in which it is developed, but the geographic gradient of use seems to be steep and enduring even when cost and organizational barriers are minimal.

Background: Current medications for alcohol dependence (AD) show only modest efficacy. None target brain noradrenergic pathways. Theory and preclinical evidence suggest that noradrenergic circuits may be involved in alcohol reinforcement and relapse. We therefore tested the alpha-1 adrenergic receptor antagonist, prazosin, as a pharmacotherapy for AD., Methods: We randomized 24 participants with AD but without posttraumatic stress disorder to receive either prazosin or placebo in a 6-week, double-blind pilot study. Medication was titrated to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS by the end of week 2. Participants received 5 medical management treatment sessions. Participants were reminded 3 times each day via a text pager to take medications and to call a telephone monitoring system once daily to provide self-reports of alcohol consumption and craving, the primary outcome measures. Results were analyzed using mixed linear regression adjusted for drinking days per week at baseline and week number., Results: Twenty of the 24 (83%) subjects completed. Among the completers, the prazosin group reported fewer drinking days per week than the placebo group during the final 3 weeks of the study. Since only 1 woman was randomized to placebo and only three women completed the trial, the following results focus on the 17 male completers. The prazosin group reported fewer drinking days per week and fewer drinks per week during the final 3 weeks of the study; average total number of drinking days for the placebo group 5.7 (SEM 1.9) versus 0.9 (SEM 0.5) for the prazosin group, and average total number of drinks 20.8 (SEM 6.5) for the placebo group versus 2.6 (SEM 1.3) for the prazosin group. Rates of adverse events were equivalent across conditions., Conclusions: Prazosin holds promise as a pharmacologic treatment for AD and deserves further evaluation in a larger controlled trial.

Introduction: We assessed the efficacy of using an alpha-1A-specific blocker for improving the success rate in shock wave lithotripsy (SWL) for lower ureteral stones., Materials and Methods: This prospective study was conducted from June 2005 to December 2006 and involved 107 patients. All the patients underwent SWL with the PCK Stonelith. The patients were randomly divided into 3 groups: group 1 (34 patients) received tamsulosin, group 2 (35 patients) received terazosin, and group 3 (38 patients) received placebo. All patients were diagnosed by kidney-ureter-bladder X-ray, abdominal ultrasonography and intravenous urography. The number of colic episodes, lower urinary tract symptoms, analgesic dosage and days for spontaneous passage of the stones through the ureter were recorded by diary. Statistical analyses were performed using ANOVA, the chi(2) test, Fisher's exact test and the non-parametric Wilcoxon 2-sample t test., Results: There were no differences between the groups regarding age, stone size, expulsion time and expulsion rate. The number of colic episodes and the analgesic dosage were significantly lower in group 1 compared with groups 2 and 3. A statistically significant difference was observed in lower urinary tract symptoms: lower urinary tract symptoms were observed in 4 of 34 patients in group 1 (12%), in 8 of 35 in group 2 (23%), and in 13 of 38 in group 3 (34%). Adverse effects were noted in 5 of 32 patients in group 2 (16%), which was significantly different in comparison with group 3., Conclusions: Administration of an alpha-1A-specific blocker reduced analgesic dosage and colic episodes after SWL of lower ureteral stones. There was no benefit with regard to increasing stone expulsion rate or decreasing expulsion time., (Copyright 2009 S. Karger AG, Basel.)

Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous eruption mainly provoked by drugs. A case of AGEP in a 74-year-old male that was attributed to the ingestion of terazosin hydrochloride is presented. This is the first reported case of this association in medical literature. The history, clinical presentation, and pathogenesis of AGEP are discussed.

Background: Prazosin, a central nervous system (CNS) active alpha-1 adrenoreceptor antagonist, has reduced nightmares and sleep disturbance in placebo-controlled studies of combat-related posttraumatic stress disorder (PTSD). We evaluated objective sleep parameters and PTSD symptoms in a placebo-controlled prazosin trial for civilian trauma-related PTSD., Methods: Thirteen outpatients with chronic civilian trauma PTSD, frequent nightmares, and sleep disturbance participated in a randomized placebo-controlled crossover trial of prazosin. Sleep parameters were quantified at home with the REMView (Respironics, Pittsburgh, Pennsylvania). The PTSD symptoms were quantified with the Clinician Administered PTSD Scale (CAPS) "recurrent distressing dreams" and "disturbed sleep" items, a non-nightmare distressed awakenings scale, the PTSD Dream Rating Scale (PDRS), the PTSD Checklist-Civilian (PCL-C), and the Clinical Global Impression of Improvement (CGI-I)., Results: Prazosin compared with placebo significantly increased total sleep time by 94 min; increased rapid eye movement (REM) sleep time and mean REM period duration without altering sleep onset latency; significantly reduced trauma-related nightmares, distressed awakenings, and total PCL scores; significantly improved CGI-I scores; and changed PDRS scores toward normal dreaming., Conclusions: Prazosin reductions of nighttime PTSD symptoms in civilian trauma PTSD are accompanied by increased total sleep time, REM sleep time, and mean REM period duration in the absence of a sedative-like effect on sleep onset latency.

Alpha-adrenoceptor antagonists are used worldwide for the treatment of voiding dysfunction associated with benign prostatic hyperplasia. Recently, abnormal ejaculation, an adverse effect associated with their use, has attracted attention. Here, we simultaneously investigated the effects of alpha(1)-adrenoceptor antagonists on intraurethral pressure in the prostatic urethra and intraluminal pressure in the vas deferens in anesthetized male dogs, and compared their tissue selectivity. Phenylephrine, an alpha(1)-adrenoceptor agonist, induced simultaneous increases in intraurethral and intraluminal pressure. Alfuzosin, naftopidil, prazosin, silodosin and tamsulosin dose-dependently inhibited both responses. Comparison of ED(50) values in both tissues showed that silodosin had the highest selectivity for the vas deferens (7.5-fold), followed by naftopidil (4.3-fold), alfuzosin (3.8-fold), tamsulosin (2.6-fold) and prazosin (2.5-fold). These results suggest that alpha(1)-adrenoceptor antagonists inhibit contraction of not only the urethra but also the vas deferens in a dose-dependent fashion, and that their high tissue selectivity for the vas deferens over the urethra may contribute to the incidence of abnormal ejaculation.

Purpose: We determined the efficacy and safety of a relatively high dose of terazosin (5mg) in Korean patients with lower urinary tract symptoms (LUTS), with or without concomitant hypertension., Materials and Methods: From July to December 2006, 200 men who consecutively presented with LUTS were prospectively studied. Eight weeks after treatment, blood pressure (BP), uroflowmetry, and International Prostate Symptom Score (I-PSS) were assessed. For analysis purposes, patients were stratified according to concomitant hypertension. Of the 200 patients, 173 completed the scheduled eight-week treatment period., Results: At baseline, no differences were evident in the two groups in terms of I-PSS, Qmax, PVR and BP. After eight weeks of treatment-although I-PSS and uroflowmetry parameters were not significantly different in the two groups-systolic and diastolic BP in the non-hypertensive control group were higher than in the hypertensive group (p= 0.001 and p=0.0100, respectively). Changes in I-PSS, uroflowmetry parameters, and BPs measured at week eight post- treatment commencement did not significantly differ between the two groups. Moreover, the addition of 5mg of terazosin to antihypertensives did not cause a significant reduction in either systolic or diastolic BP in either group., Conclusion: Adding terazosin to existing antihypertensive regimens did not seem to increase the incidence of adverse events. Our findings suggest that 5mg terazosin is effective and that it has an acceptable safety profile as an add-on therapy for patients with LUTS and concomitant hypertension.

Introduction: Priapism has been reported as a rare effect of the commonly used alpha 1-antagonists through direct inhibition of the sympathetic input necessary for detumescence. Although previously reported as an adverse event in a patient with spinal cord injury, to the best of our knowledge, terazosin-induced priapism in an otherwise healthy man has not been previously described., Aim: We describe an otherwise healthy man with lower urinary symptoms who developed priapism after ingestion of the commonly prescribed alpha-blocker terazosin., Results: The priapism resolved after a combination of cavernosal aspiration and alpha-agonist administration., Conclusion: Priapism is an extremely rare side effect of alpha-blocker therapy and has previously been described in association with other alpha-blockers, as well as with terazosin, in a spinal cord-injured patient. We report a case of priapism specifically associated with terazosin prescribed for lower urinary tract symptoms in an otherwise healthy man.

The epidemiological survey shows that primary hypertension is one of the independent risk factors in the development and the progress of BPH, 25 percent of old male patients aged 60 or more suffer from the two diseases at the same time, which grievously affects their quality of life. There is little literature about the appropriate therapeutic regimen of BPH associated hypertension. The article reviews the progress in the studies of alpha1-adrenoceptor blocker for BPH associated hypertension, and explores the main problems facing us and ventures the prospects for the development in this field.

Objective: Aggressive behavior in dementia is a major clinical management problem., Method: Postmortem brain tissue was obtained from 24 patients with Alzheimer disease (AD) and 25 comparison cases. [3H] Prazosin binding to alpha1-AdR was determined., Results: Aggressive behavior was significantly correlated with alpha1-adrenoceptor number in patients with AD (R(s)=0.454, N=24). Furthermore, patients receiving ongoing neuroleptics had significantly higher Bmax for [3H] prazosin (21 +/- 2, N=9) than those who were not (16 +/- 1, N=15)., Conclusions: Upregulation of alpha1-AdR is associated with aggressive behavior and chronic treatment with neuroleptic medication.

Background: Terazosin is an alpha1-selective adrenoceptor blocking agent that has been reported in many clinical trials to be an effective choice for the treatment of benign prostatic hyperplasia (BPH). To improve cost-effectiveness, the development of an effective and well-tolerated generic formulation is needed., Objective: The aim of this study was to compare the efficacy and tolerability of branded versus generic terazosin hydrochloride in adult patients with symptomatic BPH in Taiwan., Methods: This randomized, open-label, 2-sequence, 2-period crossover study was conducted at the Urological Clinic, National Cheng Kung University Medical Center, Taman, Taiwan. Men newly diagnosed with symptomatic BPH who had not previously received treatment for BPH were recruited between August 2002 and April 2006. Patients were randomly assigned to 1 of 2 treatment sequences. Group A received generic terazosin during period 1 (6 weeks) and branded terazosin in period 2 (6 weeks); group B received the branded drug during period 1 and the generic during period 2. The 2 study periods were separated by a 1-week washout period. All treatments were given by mouth once daily (bedtime) at an initial dosage of 2 mg/d for the first 2 weeks. At the week-2 study visit in each treatment period, the dosage could be increased to 4 mg/d or decreased to 1 mg/d based on each patient's response and experience of adverse effects (AEs), based on the opinion of the investigator. Efficacy variables included the total score on the International Prostate Symptom Scale (IPSS), a 7-item instrument used to assess objective lower urinary tract symptoms, including quality of life. IPSS was measured at baseline and weeks 2 and 6 of each treatment period, and maximal and mean uroflow rates, measured at baseline and week 6. Tolerability was assessed at each time point using physical examination, including vital signs; laboratory analysis; and spontaneous reporting., Results: Fifty-three patients were randomized; 43 were included in the efficacy analysis (mean [SD] age, group A, 64.5 [7.7] years and group B, 62.9 [8.2] years; mean [SD] weight, group A, 66.4 [7.2] kg and group B, 67.1 [8.9] kg; all patients were Taiwanese). At 2 and 6 weeks, no significant between-product differences were found in mean (SD) decreases from baseline in IPSS total score (generic, 2.46 [0.84] and 2.46 [1.00], respectively; branded, 1.56 [0.60] and 2.87 [0.71]). At week 6, the between-product difference in mean increase from baseline in maximal uroflow rate was nonsignificant (generic, 2.36 [0.90] mL/s; branded, 2.03 [0.62] mL/s). A total of 86 treatment-emergent AEs were reported (45 with the generic drug; 41 with the branded drug), all of which were considered by the investigator as nonserious except for 1 case of acute epididymitis, which occurred with the generic drug. The most common AEs reported with the generic and branded formulations were dizziness (7/48 [14.6%] and 10/50 [20.0%], respectively) and peripheral edema (1/48 [2.1%] and 3/50 [6.0%]). No significant differences in the prevalences of AEs were found between the 2 treatments., Conclusion: In this group of Taiwanese patients with symptomatic BPH, the efficacy and tolerability of generic terazosin were similar to those of branded terazosin.

Background: The primary objectives of the treatment for the lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are to produce rapid, sustained, and safe improvements in the symptoms that affect the quality of life in the majority of men over 50. In this study, we evaluated the efficacy and safety of the combined therapy with terazosin (apha1-adrenergic receptor antagonist) and tolterodine (anticholinergic agent) for LUTS associated with BPH., Methods: This combination study included 69 patients diagnosed with LUTS associated with BPH based on the International Prostate Symptom Scores (IPSS), urinary flow rate, prostate volume, urinary residual, and their serum prostate-specific antigen levels. Initially, 191 patients were treated with terazosin 2 mg once daily for one week. Those patients with continued LUTS after the initial treatment were allocated randomly into two groups: terazosin group (n = 36) in which patients were treated with terazosin 2 mg once daily for six weeks, and combination group (n = 33) in which patients were treated with both terazosin 2 mg once daily and tolterodine 2 mg twice daily for 6 weeks., Results: The IPSS were significantly improved in both groups after treatment, and the reduction of IPSS in the combination group was significantly greater than that in the terazosin group (P < 0.01). A decrease in urgency, frequency and nocturia were the main contributory factors causing the reduction of IPSS in the combination group. The differences about the peak urinary flow rate and the residual urine from the baseline values were noted in both groups after treatment, but were not significant between the two groups. The incidence of adverse effects in the combination group was higher than that in the terazosin group. As expected the most common adverse effect was mouth dryness which was associated with anticholinergic drugs such as tolterodine., Conclusions: Patients with LUTS associated BPH appear the improved IPSS after combined therapy with terazosin and tolterodine. This study, although short term and limited numbers of patients, provides evidence that the combined therapy with terazosin plus tolterodine is a good approach for meeting the objectives of rapid, sustained, and safe improvements in the LUTS associated with BPH. And the profile of patients in this study might be used as the indication of such combined therapy for LUTS associated with BPH without urodynamic evaluation.

Low-flow priapism is a rare condition whereby there is a persistent, painful erection. The patient often presents late because of embarrassment. Failure to recognise this as an emergency and instigate immediate treatment may lead to cavernosal tissue ischaemia, fibrosis and subsequent long-term impotence. A case of low-flow priapism, that demonstrated a lack of urgency and understanding is discussed. An internet-based literature search provided a treatment regimen with resolution of tumescence.