-
The New England Journal of Medicine Feb 2018In randomized trials, prazosin, an α-adrenoreceptor antagonist, has been effective in alleviating nightmares associated with post-traumatic stress disorder (PTSD) in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In randomized trials, prazosin, an α-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 .).
Topics: Adrenergic alpha-1 Receptor Antagonists; Adult; Combined Modality Therapy; Dose-Response Relationship, Drug; Double-Blind Method; Dreams; Female; Hospitals, Veterans; Humans; Male; Middle Aged; Prazosin; Psychiatric Status Rating Scales; Psychotherapy; Sleep; Sleep Wake Disorders; Stress Disorders, Post-Traumatic; Suicidal Ideation; Treatment Failure; United States; Veterans
PubMed: 29414272
DOI: 10.1056/NEJMoa1507598 -
Journal of the American Veterinary... May 2022To determine if prazosin administration decreased the rate of recurrent urethral obstruction (rUO) before hospital discharge and within 14 days.
OBJECTIVE
To determine if prazosin administration decreased the rate of recurrent urethral obstruction (rUO) before hospital discharge and within 14 days.
ANIMALS
388 cats with urethral obstruction.
PROCEDURES
Veterinarians who either always or never prescribed prazosin (generally, 0.5 to 1 mg, PO, q 12 h for 14 days) were recruited to complete observational surveys. Patient data and characteristics of relieving the obstruction, including perception of a gritty feel within urethra or difficulty unobstructing the cat, were recorded. The rate of development of rUO before hospital discharge and by day 14 was compared between cats that received or did not receive prazosin with the Fisher exact test. Other variables were similarly compared between cats with and without rUO.
RESULTS
302 (78%) cats received prazosin, while 86 (22%) did not. There was no association between prazosin administration and risk of rUO prior to discharge, with 34 of 302 (11.3%) cats receiving prazosin and 5 or 86 (5.8%) not receiving prazosin developing rUO. Within 14 days, a significantly higher proportion of prazosin-treated cats (73/302 [24%]) developed an rUO, compared with the proportion of non-prazosin-treated cats (and 11/86 [13%]). The perception of a "gritty feeling urethra" or difficulty of performing the catheterization was associated with increased risk of rUO.
CLINICAL RELEVANCE
Prazosin administration increased the likelihood of rUO by 14 days; ongoing investigation of other therapies to decrease rUO in cats is warranted. Without specific indications, the use of prazosin for the prevention of rUO should be discouraged.
Topics: Animals; Cat Diseases; Cats; Prazosin; Urethra; Urethral Obstruction
PubMed: 35290210
DOI: 10.2460/javma.21.10.0469 -
The Journal of Clinical Investigation Oct 2019Parkinson's disease (PD) is a common neurodegenerative disease that lacks therapies to prevent progressive neurodegeneration. Impaired energy metabolism and reduced ATP...
Parkinson's disease (PD) is a common neurodegenerative disease that lacks therapies to prevent progressive neurodegeneration. Impaired energy metabolism and reduced ATP levels are common features of PD. Previous studies revealed that terazosin (TZ) enhances the activity of phosphoglycerate kinase 1 (PGK1), thereby stimulating glycolysis and increasing cellular ATP levels. Therefore, we asked whether enhancement of PGK1 activity would change the course of PD. In toxin-induced and genetic PD models in mice, rats, flies, and induced pluripotent stem cells, TZ increased brain ATP levels and slowed or prevented neuron loss. The drug increased dopamine levels and partially restored motor function. Because TZ is prescribed clinically, we also interrogated 2 distinct human databases. We found slower disease progression, decreased PD-related complications, and a reduced frequency of PD diagnoses in individuals taking TZ and related drugs. These findings suggest that enhancing PGK1 activity and increasing glycolysis may slow neurodegeneration in PD.
Topics: Adenosine Triphosphate; Aged; Aged, 80 and over; Animals; Brain; Disease Progression; Dopamine; Drosophila melanogaster; Female; Glycolysis; Humans; Induced Pluripotent Stem Cells; Male; Mice; Mice, Inbred C57BL; Nerve Degeneration; Parkinson Disease; Parkinsonian Disorders; Phosphoglycerate Kinase; Prazosin; Rats
PubMed: 31524631
DOI: 10.1172/JCI129987 -
International Journal of Environmental... Dec 2022Nightmares are highly prevalent and distressing for the sufferer, which underlines the need for well-documented treatments. A comprehensive literature review and... (Meta-Analysis)
Meta-Analysis Review
Nightmares are highly prevalent and distressing for the sufferer, which underlines the need for well-documented treatments. A comprehensive literature review and meta-analysis of the effects of different pharmacological placebo-controlled randomized clinical trials, covering the period up to 1 December 2022, was performed. Searches were conducted in PubMed, Embase, Web of Science, PsychInfo, Cinahl, and Google Scholar, resulting in the identification of 1762 articles, of which 14 met the inclusion criteria: pharmacological intervention of nightmares, based on a placebo-controlled randomized trial published in a European language, reporting outcomes either/or in terms of nightmare frequency, nightmare distress, or nightmare intensity, and reporting sufficient information enabling calculation of effect sizes. Most studies involved the effect of the α-adrenergic antagonist prazosin in samples of veterans or soldiers suffering from posttraumatic stress disorder. Other medications used were hydroxyzine, clonazepam, cyproheptadine, nabilone, and doxazosin. The vast majority of studies were conducted in the USA. The studies comprised a total of 830 participants. The Clinician-Administered PTSD Scale was the most frequently used outcome measure. The results showed an overall effect size of Hedges' = 0.50 (0.42 after adjustment for publication bias). The synthetic cannabinoid nabilone (one study) showed the highest effect size ( = 1.86), followed by the histamine H-antagonist hydroxyzine (one study), and prazosin (10 studies), with effect sizes of = 1.17 and = 0.54, respectively. Findings and limitations are discussed, and recommendations for future studies are provided.
Topics: Humans; Dreams; Randomized Controlled Trials as Topic; Prazosin; Adrenergic alpha-1 Receptor Antagonists; Stress Disorders, Post-Traumatic; Hydroxyzine
PubMed: 36613097
DOI: 10.3390/ijerph20010777 -
Drug Research Jul 2022Acute kidney injury (AKI) is a major medical challenge caused from renal ischemia-reperfusion (IR) injury connected with different cellular events in other distant...
Acute kidney injury (AKI) is a major medical challenge caused from renal ischemia-reperfusion (IR) injury connected with different cellular events in other distant organs. Renal IR-related oxidative stress and inflammation followed by cell apoptosis play a crucial role in IR-induced distant organ pathological damages. Prazosin has shown protective effects against IR-injuries. Thus, the current study intended to investigate the possible protective role of prazosin against the consequents of renal IR in the heart and brain tissues. To reach this goal, rats were randomly divided into 3 groups (n=7): Sham, IR and prazosin pretreatment-IR animals (1 mg/kg intraperitoneally injection of prazosin 45 min before IR induction). After 6 h reperfusion, lipid peroxidation and antioxidant markers levels were evaluated in the both, brain and heart tissue. Moreover, apoptotic pathway in the heart and brain tissues were assessed by western blotting. Accordingly, prazosin pretreatment in IR model rats could significantly increase the antioxidant capacity and attenuate apoptotic pathways by increasing the bcl-2 levels and decreasing the expression of Bax and caspase 3 enzymes (P<0.05). Thus, prazosin suppressed cellular damages of heart and brain tissues post kidney IR by anti-oxidative and anti-apoptotic effects, which suggests the plausible use of prazosin in improving the clinical outcomes during AKI after further investigations.
Topics: Acute Kidney Injury; Animals; Antioxidants; Apoptosis; Brain; Ischemia; Kidney; Oxidative Stress; Prazosin; Rats; Reperfusion; Reperfusion Injury
PubMed: 35426094
DOI: 10.1055/a-1806-1453 -
International Braz J Urol : Official... 2021To describe the otorhinolaryngological adverse effects of the main drugs used in urological practice. (Review)
Review
PURPOSE
To describe the otorhinolaryngological adverse effects of the main drugs used in urological practice.
MATERIALS AND METHODS
A review of the scientific literature was performed using a combination of specific descriptors (side effect, adverse effect, scopolamine, sildenafil, tadalafil, vardenafil, oxybutynin, tolterodine, spironolactone, furosemide, hydrochlorothiazide, doxazosin, alfuzosin, terazosin, prazosin, tamsulosin, desmopressin) contained in publications until April 2020. Manuscripts written in English, Portuguese, and Spanish were manually selected from the title and abstract. The main drugs used in Urology were divided into five groups to describe their possible adverse effects: alpha-blockers, anticholinergics, diuretics, hormones, and phosphodiesterase inhibitors.
RESULTS
The main drugs used in Urology may cause several otorhinolaryngological adverse effects. Dizziness was most common, but dry mouth, rhinitis, nasal congestion, epistaxis, hearing loss, tinnitus, and rhinorrhea were also reported and varies among drug classes.
CONCLUSIONS
Most of the drugs used in urological practice have otorhinolaryngological adverse effects. Dizziness was most common, but dry mouth, rhinitis, nasal congestion, epistaxis, hearing loss, tinnitus, and rhinorrhea were also reported. Therefore, doctors must be aware of these adverse effects to improve adherence to the treatment and to minimize damage to the health of patients.
Topics: Adrenergic alpha-Antagonists; Doxazosin; Humans; Male; Pharmaceutical Preparations; Prazosin; Prostatic Hyperplasia; Tadalafil; Tamsulosin
PubMed: 33566468
DOI: 10.1590/S1677-5538.IBJU.2021.99.06 -
The Primary Care Companion For CNS... Jul 2016To consolidate the evidence from the literature to evaluate the role of prazosin in the treatment of posttraumatic stress disorder (PTSD). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To consolidate the evidence from the literature to evaluate the role of prazosin in the treatment of posttraumatic stress disorder (PTSD).
DATA SOURCES
Major databases, including PubMed, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Ovid PsycINFO, and Scopus, were searched through August 2015 for studies reporting the role of prazosin in the treatment of PTSD with no language constraints. Keywords included (PTSD OR posttraumatic stress OR posttraumatic stress OR nightmares) AND prazosin.
STUDY SELECTION
Of 402 screened articles, 6 studies were included in the systematic review and meta-analysis.
DATA EXTRACTION
Two reviewers independently extracted relevant data (study characteristics, type of intervention, outcome measures, and follow-up) from the included studies using a standardized data extraction form. Only randomized controlled trials comparing prazosin to a placebo or control group in patients with PTSD were included.
RESULTS
The patients with PTSD receiving prazosin showed significant improvement in nightmares (standardized mean difference [SMD] = 1.01; 95% CI, 0.72-1.30), overall PTSD symptoms (SMD = 0.77; 95% CI, 0.48-1.06), and clinical global improvement (SMD = 0.94; 95%, CI 0.6-1.29) compared to the placebo/control group. Prazosin improved sleep quality (SMD = 0.87; 95% CI, 0.55-1.19), hyperarousal symptoms (SMD = 1.04; 95% CI, 0.23-1.84), dream content (SMD = 1.33; 95% CI, 0.69-1.97), and total sleep time (60.98 minutes; 95% CI, 18.69-103.26). Prazosin was fairly well tolerated. Minor side effects were reported, which were similar between the prazosin and placebo groups.
CONCLUSIONS
This study suggests that prazosin improves nightmares and overall PTSD symptoms including hyperarousal, sleep disturbances, total sleep time, and sleep quality.
Topics: Adult; Dreams; Female; Humans; Male; Middle Aged; Prazosin; Randomized Controlled Trials as Topic; Sleep Wake Disorders; Stress Disorders, Post-Traumatic; Treatment Outcome
PubMed: 27828694
DOI: 10.4088/PCC.16r01943 -
Mayo Clinic Proceedings Sep 2012Nightmares, frequently associated with posttraumatic stress disorder and clinically relevant in today's world of violence, are difficult to treat, with few pharmacologic... (Review)
Review
Nightmares, frequently associated with posttraumatic stress disorder and clinically relevant in today's world of violence, are difficult to treat, with few pharmacologic options. We performed a systematic review to evaluate the evidence for the use of prazosin in the treatment of nightmares. A comprehensive search was performed using the databases EMBASE, Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane Database of Systematic Reviews, from their inception to March 9, 2012, using keywords prazosin and nightmares/PTSD or associated terms (see text). Two authors independently reviewed titles and abstracts and selected relevant studies. Descriptive data and outcomes of interest from eligible studies were extracted by 1 author, and checked by 2 others. The risk of bias of randomized controlled trials (RCTs) was assessed independently by 2 reviewers. Articles met criteria for inclusion if prazosin was used to treat nightmares, and outcome measures included nightmares or related symptoms of sleep disorders. Our search yielded 21 studies, consisting of 4 RCTs, 4 open-label studies, 4 retrospective chart reviews, and 9 single case reports. The prazosin dose ranged from 1 to 16 mg/d. Results were mixed for the 4 RCTs: 3 reported significant improvement in the number of nightmares, and 1 found no reduction in the number of nightmares. Reduced nightmare severity with use of prazosin was consistently reported in the open-label trials, retrospective chart reviews, and single case reports.
Topics: Adrenergic alpha-1 Receptor Antagonists; Dreams; Humans; Prazosin; Sleep Wake Disorders; Stress Disorders, Post-Traumatic
PubMed: 22883741
DOI: 10.1016/j.mayocp.2012.05.015 -
Minerva Urology and Nephrology Aug 2023Patients 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...
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, 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.
Topics: Humans; Doxazosin; Tamsulosin; Hypotension, Orthostatic; Adrenergic alpha-Antagonists; Prazosin; Urogenital Diseases
PubMed: 37067186
DOI: 10.23736/S2724-6051.23.05225-4 -
Expert Opinion on Therapeutic Targets Dec 2011Mechanistic, translational and pharmacological studies led to the identification and discovery of the preferred localization, binding characteristics, structure and... (Review)
Review
INTRODUCTION
Mechanistic, translational and pharmacological studies led to the identification and discovery of the preferred localization, binding characteristics, structure and functional properties of α1-adrenoceptor (α1-AR) subtypes in the bladder neck, bladder and prostate gland. The evidence gathered on α1-ARs, provided a molecular platform for the development of subtype-selective antagonists, resulting in more effective approaches targeting those receptors for the treatment of outlet bladder obstruction and benign prostate hyperplasia.
AREAS COVERED
Advances over the last decade in the design and optimization of Prazosin, Doxazosin and Terazosin quinazoline-based derivatives as α1-AR antagonists. Evidence on the metabolic and growth interference action by these agents, in addition to their smooth-muscle-relaxing effects. The new action recognition emerges from data on the inhibitory effect of quinazoline-based antagonists on primary tumor growth and progression to metastasis. In addition to the cellular findings in the prostate, functional validation and therapeutic effects of selected lead pharmaceutically optimized derivatives in the context of impairing vascularity and triggering tumor apoptosis.
EXPERT OPINION
Knowledge on targeting intracellular signalling pathways driving the cellular response via an α1-AR-dependent and independent antagonistic action, must be invested towards the optimization of new agents that while bypassing AR, exhibit improved pharmacological efficacy against human cancer.
Topics: Adrenergic alpha-1 Receptor Antagonists; Antihypertensive Agents; Drug Design; Humans; Hypertension; Male; Prazosin; Prostatic Hyperplasia; Receptors, Adrenergic; Receptors, Adrenergic, alpha-1; Urinary Bladder Neck Obstruction
PubMed: 22148952
DOI: 10.1517/14728222.2011.641534