The Effects of Verapamil, Hydralazine, and Doxazosin on Renin, Aldosterone, and the Ratio Thereof.

PURPOSE: Hydralazine, doxazosin, and verapamil are currently recommended by the Endocrine Society as acceptable bridging treatment in those in whom full cessation of antihypertensive medication is infeasible during screening for primary aldosteronism (PA). This is under the assumption that they cause minimal to no effect on the aldosterone-to-renin ratio, the most widely used screening test for PA. However, limited evidence is available regarding the effects of these particular drugs on said ratio. METHODS: In the present study, we retrospectively assessed the changes in aldosterone, renin, and aldosterone-to-renin values in essential hypertensive participants before and after treatment with either hydralazine (n = 26) or doxazosin (n = 20) or verapamil (n = 15). All samples were taken under highly standardized conditions. RESULTS: Hydralazine resulted in a borderline significant rise in active plasma renin concentration (19 vs 25 mIU/L, p = 0.067) and a significant fall in the aldosterone-to-renin ratio (38 vs 24, p = 0.017). Doxazosin caused declines in both plasma aldosterone concentration (470 vs 330 pmol/L, p = 0.028) and the aldosterone-to-renin ratio (30 vs 20, p = 0.020). With respect to verapamil, we found no statistically significant effect on any of these outcome variables. CONCLUSION: We conclude that the assumption that these drugs can be used with little consequence to the aldosterone-to-renin cannot be substantiated. While it is possible that they are indeed the best option when full antihypertensive drug cessation is infeasible, the potential effects of these drugs must still be taken into account when interpreting the aldosterone-to-renin ratio.

Drug repositioning: doxazosin attenuates the virulence factors and biofilm formation in Gram-negative bacteria.

The resistance development is an increasing global health risk that needs innovative solutions. Repurposing drugs to serve as anti-virulence agents is suggested as an advantageous strategy to diminish bacterial resistance development. Bacterial virulence is controlled by quorum sensing (QS) system that orchestrates the expression of biofilm formation, motility, and virulence factors production as enzymes and virulent pigments. Interfering with QS could lead to bacterial virulence mitigation without affecting bacterial growth that does not result in bacterial resistance development. This study investigated the probable anti-virulence and anti-QS activities of α-adrenoreceptor blocker doxazosin against Proteus mirabilis and Pseudomonas aeruginosa. Besides in silico study, in vitro and in vivo investigations were conducted to assess the doxazosin anti-virulence actions. Doxazosin significantly diminished the biofilm formation and release of QS-controlled Chromobacterium violaceum pigment and virulence factors in P. aeruginosa and P. mirabilis, and downregulated the QS encoding genes in P. aeruginosa. Virtually, doxazosin interfered with QS proteins, and in vivo protected mice against P. mirabilis and P. aeruginosa. The role of the membranal sensors as QseC and PmrA was recognized in enhancing the Gram-negative virulence. Doxazosin downregulated the membranal sensors PmR and QseC encoding genes and could in silico interfere with them. In conclusion, this study preliminary documents the probable anti-QS and anti-virulence activities of doxazosin, which indicate its possible application as an alternative or in addition to antibiotics. However, extended toxicological and pharmacological investigations are essential to approve the feasible clinical application of doxazosin as novel efficient anti-virulence agent. KEY POINTS: • Anti-hypertensive doxazosin acquires anti-quorum sensing activities • Doxazosin diminishes the virulence of Proteus mirabilis and Pseudomonas aeruginosa • Doxazosin could dimmish the bacterial espionage.

REVIEW OF ADVERSE DRUG REACTIONS OF MEDICINES USED FOR THE TREATMENT OF BENIGN PROSTATIC HYPERPLASIA REPORTED TO HALMED.

Benign prostatic hyperplasia is one of the most common diseases in men, with a prevalence rate of 50% in their 50s to 80% in their 80s, and is mostly treated with chronic drug therapy. The aim of this study was to analyze adverse drug reactions (ADR) to drugs used in benign prostate hyperplasia (BPH) treatment reported to HALMED from 2008 to 2021. Data on ADR reports in Croatia were obtained from the VigiFlow national database and on the use of drugs for BPH in Croatia from Drug Utilization Reports from HALMED. In the observed period, the number of reports on each BPH drug, total number of reports, seriousness of reported ADR, patient age and sex, type of reporter, and most reported ADRs were analyzed. Results showed that 438 ADR reports were received, of which 45.95% on tamsulosin as the most frequently used drug for BPH. Of all reports, 84% were non-serious, 96% were reported in men and 82% in patients older than 45 years. The most frequently reported ADRs were consistent with the known safety profile of BPH drugs. Pharmacists were the most common (47%) reporters of ADRs for BPH drugs, while 33% were reported by physicians. Analysis of the reported ADRs showed that most frequently reported ones were in line with the known safety profile of BPH drugs. However, given the prevalence of the disease and the extent of the use of BPH drugs, it could be argued that the number of reports could be higher (i.e., 34 reports/year). Reporting on ADRs is necessary to better understand the safety profile of drugs in the post-authorization period, and more information on the safe use of medicines could be collected by raising awareness of healthcare professionals.

Determination of antihypertensive drugs irbesartan and doxazosin mesylate in healthcare products and urine samples using surface-enhanced Raman scattering.

In this paper, a surface-enhanced Raman scattering (SERS) strategy was constructed for the determination of antihypertensive drugs irbesartan (IRB) and doxazosin mesylate (DOX). ß-Cyclodextrin-capped silver nanoparticles (CD-AgNPs) are employed as SERS-active substrate. The introduction of ß-CD with hydrophobic cavity can capture drug molecules to form host-guest complex, making the drug molecules closer to the electromagnetic enhancement field of the AgNPs, thereby enhancing the SERS signal of drug molecules with low Raman cross-section. The vibrational modes of IRB and DOX are assigned by density functional theory calculations. The linear response from 3.0 × 10-7 to 1.0 × 10-5 mol L-1 for IRB and 3.0 × 10-7 to 2.0 × 10-5 mol L-1 for DOX and low limits of detection (LOD) 7.5 × 10-8 mol L-1 for IRB and 8.6 × 10-8 mol L-1 for DOX can be achieved. Meanwhile, this SERS approach can be applicable to determine IRB and DOX in commercial drug tablets, healthcare products, and human urine samples with recoveries of 90.8-115.7% and 90.0-113.5%, respectively, with relative standard deviation (RSD) less than 4.5%. This designed SERS strategy enables for the rapid determination of IRB and DOX in drug quality monitoring and illegal additives in healthcare products as well as clinical applications.

Analysis of Voiding Impairment after Prostate Biopsy and the Effect of Doxazosin Treatment: Outcomes from a Regional Cancer Center.

INTRODUCTION: The aim of this study was to investigate the association of transrectal ultrasound (TRUS)-guided prostate biopsy with voiding impairment and the efficacy of doxazosin treatment. METHODS: A prospective observational study including 200 male patients undergoing TRUS-guided prostate biopsy was performed between May 2020 and December 2020. One hundred patients underwent biopsy with doxazosin (doxazosin group). The remaining 100 patients underwent biopsy without doxazosin (control group). All patients were questioned regarding post-biopsy voiding difficulty and acute urinary retention. The International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), and residual urine volume were recorded before biopsy and at 7 and 30 days after biopsy. RESULTS: There were no significant differences in baseline parameters between the two groups. The rate of post-biopsy voiding difficulty in the doxazosin group was significantly lower than that in the control group. Compared with baseline values, doxazosin treatment significantly improved IPSS, quality of life scores, and Qmax after biopsy (p < 0.05). The baseline values of IPSS and prostate size may be risk factors for post-biopsy voiding difficulty. CONCLUSION: TRUS-guided prostate biopsy causes transient voiding impairments, which may be improved by doxazosin treatment.

Kidney, Cardiac, and Safety Outcomes Associated With α-Blockers in Patients With CKD: A Population-Based Cohort Study.

RATIONALE & OBJECTIVES: Alpha-blockers (ABs) are commonly prescribed for control of resistant or refractory hypertension in patients with and without chronic kidney disease (CKD). The association between AB use and kidney, cardiac, mortality, and safety-related outcomes in CKD remains unknown. STUDY DESIGN: Population-based retrospective cohort study. SETTINGS & PARTICIPANTS: Ontario (Canada) residents 66 years and older treated for hypertension in 2007 to 2015 without a prior prescription for an AB. EXPOSURES: New use of an AB versus new use of a non-AB blood pressure (BP)-lowering medication. OUTCOMES: 30% or greater estimated glomerular filtration rate (eGFR) decline; dialysis initiation or kidney transplantation (kidney replacement therapy); composite of acute myocardial infarction, coronary revascularization, congestive heart failure, or atrial fibrillation; safety (hypotension, syncope, falls, and fractures) events; and mortality. ANALYTICAL APPROACH: New users of ABs (doxazosin, terazosin, and prazosin) were matched to new users of non-ABs by a high dimensional propensity score. Cox proportional hazards and Fine and Gray models were used to examine the association of AB use with kidney, cardiac, mortality, and safety outcomes. Interactions by eGFR categories (≥90, 60-89, 30-59, and<30mL/min/1.73m2) were explored. RESULTS: Among 381,120 eligible individuals, 16,088 were dispensed ABs and matched 1:1 to non-AB users. AB use was associated with higher risk for≥30% eGFR decline (HR, 1.14; 95% CI, 1.08-1.21) and need for kidney replacement therapy (HR, 1.28; 95% CI, 1.13-1.44). eGFR level did not modify these associations, P interaction=0.3and 0.3, respectively. Conversely, AB use was associated with lower risk for cardiac events, which was also consistent across eGFR categories (HR, 0.92; 95% CI, 0.89-0.95; P interaction=0.1). AB use was also associated with lower mortality risk, but only among those with eGFR<60mL/min/1.73m2 (P interaction<0.001): HRs were 0.85 (95% CI, 0.78-0.93) and 0.71 (95% CI, 0.64-0.80) for eGFR of 30 to 59 and<30mL/min/1.73m2, respectively. LIMITATIONS: Observational design, BP measurement data unavailable. CONCLUSIONS: AB use in CKD is associated with higher risk for kidney disease progression but lower risk for cardiac events and mortality compared with alternative BP-lowering medications.

Hypertension in Pheochromocytoma and Paraganglioma: Evaluation and Management in Pediatric Patients.

PURPOSE OF REVIEW: The rare catecholamine-secreting tumors, pheochromocytomas and paragangliomas (PPGL), account for a minority of cases of secondary hypertension in pediatrics. As such, perioperative blood pressure (BP) management in pediatric patients presents a distinct challenge. This review will expand the practitioner's knowledge of antihypertensive treatment options for the pediatric patient with PPGL with a focus on literature in the past several years. RECENT FINDINGS: There continue to be only small case series and single-center experiences to provide guidelines regarding BP management. While phenoxybenzamine has been more routinely used, selective α1-blockers, such as doxazosin, as well as calcium channel blockers, have also been utilized with success in pediatric patients. While the concept of obligatory α-adrenergic blockade for adult patients has been recently challenged, international guidelines and current practice patterns among pediatric clinicians continue to support preoperative α-adrenergic blockade to ensure the best possible patient outcomes. Selective α1-blockers and calcium channel blockers are becoming more commonly used given the high cost, limited availability, and undesirable side effect profile of phenoxybenzamine.

Doxazosin and erlotinib have anticancer effects in the endometrial cancer cell and important roles in ERα and Wnt/ß-catenin signaling pathways.

ERα and Wnt/ß-catenin pathways are critical for the progression of most endometrial cancers. We aimed to investigate the cytotoxic and apoptotic effects of tamoxifen and quinazoline derivative drugs of doxazosin and erlotinib, and their roles in ERα and Wnt/ß-catenin signaling pathways in human endometrial cancer RL 95-2 cell. 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay and xCELLigence systems were performed to evaluate cytotoxicity. Furthermore, apoptotic induction was tested by Annexin V analysis. Caspase-3 and -9 activity and changes in the mitochondrial membrane potential were evaluated. The level of reactive oxygen species was measured by incubating with dichlorofluorescein diacetate. Protein ratios of p-ERα/ERα, GSK3ß/p-GSK3ß, and p-ß-catenin/ß-catenin and expression levels of ESR1, EGFR, c-Myc genes were evaluated to elucidate mechanisms in signaling pathways. We found that the tested drugs showed cytotoxic and apoptotic effects in the cells. Doxazosin significantly reduced ESR1 expression, slightly reduced the p-ß-catenin/ß-catenin ratio and c-Myc expression. Erlotinib significantly increased c-Myc expression while significantly decreasing the p-ß-catenin/ß-catenin and p-ERα/ERα ratio, and ESR1 expression. However, we observed that the cells develop resistance to erlotinib over a certain concentration, suggesting that ERα, ESR1, EGFR, and c-Myc may be a new target for overcoming drug resistance in the treatment of endometrial cancer. We also observed that erlotinib and doxazosin play an important role in the ERα signaling pathway and can act as potent inhibitors of PKA and/or tyrosine kinase in the Wnt/ß-catenin signaling pathway in RL 95-2 cell. In conclusion, doxazosin and erlotinib may have a possible therapeutic potential in human endometrial cancer.

Dimeric small molecule agonists of EphA2 receptor inhibit glioblastoma cell growth.

EphA2 receptor kinase could become a novel target for anti-glioblastoma treatment. Doxazosin previously identified acts like the endogenous ligand of EphA2 and induces cell apoptosis. Through lead structure modification a derivative of Doxazosin possessing unique dimeric structure showed an improvement in the activity. In the current study, we expanded the dimeric scaffold by lead optimization to explore the chemical space of the conjoining moieties and a slight variation to the core structure. 27 new derivatives were synthesized and examined with EphA2 overexpressed and wild type glioblastoma cell lines for cell proliferation and EphA2 activation. Three new compounds 3d, 3e, and 7bg showed potent and selective activities against the growth of EphA2 overexpressed glioblastoma cells. Dimer 3d modification replaces the long alkyl chain with a short polyethylene glycol chain. Dimer 7bg has a relatively longer polyethylene glycol chain in comparison to compound 3d and the length is more similar to the lead compound. Whereas dimer 3e has a rigid aromatic linker exploring the chemical space. The diversity of the linkers in the active suggest additional hydrogen binding sites has a positive correlation to the activity. All three dimers showed selective activity in EphA2 overexpressed cells, indicating the activity is correlated to the EphA2 targeting effect.

Doxazosin treatment in cocaine use disorder: pharmacogenetic response based on an alpha-1 adrenoreceptor subtype D genetic variant.

Background: The α1 antagonist doxazosin reduces cocaine use in individuals with cocaine use disorder (CUD) through a functional polymorphism of the α1 adrenoreceptor. The regulatory role of the α1adrenoreceptor subtype D (ADRA1D) gene polymorphism in CUD is uncharacterized.Objectives: To study how the genetic variant of ADRA1D gene (T1848A, rs2236554) may affect the treatment efficacy of doxazosin in reducing cocaine use.Methods: This 12-week pilot trial included 76 participants with CUD with ADRA1D (T1848A, rs2236554) AA (N = 40) or AT/TT genotype (N = 36). Participants were randomized to doxazosin (8 mg/day, N = 47) or placebo (N = 29), and followed with thrice weekly urine toxicology and once weekly cognitive behavioral psychotherapy.Results: The AA and the AT/TT groups had comparable baseline rates of cocaine positive urines at weeks 1-2 (~ 76%). In the placebo group, an increase of cocaine positive urines in the AT/TT group was found as compared to the AA group (24% vs. 9%). In the doxazosin group, a greater decrease in cocaine positive urines was found in the AT/TT group relative to the AA group. The difference between the doxazosin and placebo groups in cocaine negative urines became evident at weeks 5-6 and peaked at weeks 9-10 (~35% difference). The AT/TT group demonstrated a significant medication and time by medication effect (p < .001), whereas the AA group did not.Conclusion: The T-allele carriers showed a greater reduction of cocaine use after treatment with doxazosin in participants with the ADRA1D gene polymorphism (T1848A), suggesting that this SNP may serve as a pharmacogenetic marker in pharmacotherapy of CUD.

Validated RP-HPLC method for quantification of doxazosin in human plasma: Application in a bioequivalence study.

OBJECTIVES: The aim of the present study was to validate a simple, sensitive, HPLC method of analysis of doxazosin in human plasma with fluorescence detection. METHODS: The validated method employed one-step direct protein precipitation with acetonitrile. Chromatographic separation was attained using a reverse-phase 250mm×4.6mm 5µ Hypersil® BDS C 18 column and the mobile phase consisted of 10mm sodium dihydrogen phosphate dihydrate (pH=3.0) and acetonitrile at a ratio of (65:35 v/v). The method was evaluated in terms of linearity, precision, accuracy, selectivity and stability as per standard guidelines. The total run time was about 4.5min which make this method suitable for high throughput analyses. This method was applied to the bioequivalence study of two doxazosin tablets in healthy human volunteers. RESULTS: Good linear response was achieved over the range of 5.0-200ng/mL. The observed within- and between-day assay precision ranged from 0.64% to 14.73%; accuracy varied between 94.11% and 105%. The 90% confidence intervals for the ratio Cmax, and AUC 0-∞ of the test product over those of reference were within the acceptable range (0.8-1.25) for bioequivalence. CONCLUSION: The developed method was simple and could be applied to therapeutic drug monitoring of doxazosin.

Prostate Transition Zone Fibrosis is Associated with Clinical Progression in the MTOPS Study.

PURPOSE: Medications targeting androgen receptor activity (eg finasteride) or smooth muscle contractility (eg doxazosin) do not resolve lower urinary tract symptoms indicative of lower urinary tract dysfunction in an important subgroup of men. Recently fibrosis has been implicated as another pathobiology contributing to male lower urinary tract symptoms but to our knowledge no systematic studies have been done to assess fibrosis in the context of medical treatment. We determine whether fibrotic changes in the prostate transition zone are associated with an increased risk of clinical progression in participants treated with doxazosin, finasteride or finasteride plus doxazosin in the MTOPS (Medical Therapy of Prostatic Symptoms) study. MATERIALS AND METHODS: Transition zone biopsy tissues from men who did or did not experience clinical progression on placebo, doxazosin, finasteride or combination therapy were assessed for collagen content and architectural changes using picrosirius red birefringence and CT-FIRE (Curvelet Transform-Fiber Extraction) analysis. Correlations were made with annotated demographic and clinical data. Statistical analyses were done with the Pearson correlation coefficient, ANOVA and the t-test. RESULTS: High levels of wavy, aligned prostate transition zone collagen significantly correlated with an increased risk of clinical progression among MTOPS trial participants treated with doxazosin plus finasteride, particularly those with a high body mass index. CONCLUSIONS: Fibrotic changes in the prostate transition zone are associated with an increased risk of clinical progression in men treated with doxazosin plus finasteride. Antifibrotic therapeutics might provide a new treatment approach in men with lower urinary tract dysfunction who do not respond to current medical treatment approaches.

The Evidence Paradox of the Effectiveness between the Paediatric and Adult Stone-Forming Population: A Narrative Review.

AIM/OBJECTIVE: To identify trends in the evidence base regarding the effectiveness of using α-blockers in children versus adults and compare outcomes. METHODS: A literature search up using the key words including urolithiasis/renal/ureteric stone in children/paediatric population, medical expulsive treatment (MET), α-blocker/alfuzosin/tamsulosin/doxazosin. Included were randomized or controlled clinical trials in paediatric stone formers (aged ≤18 years). Outcome measures for assessment included the overall stone expulsion rate, expulsion time, the number of pain episodes and adverse drug effects and/or reactions. Further comparison of efficacy levels using respective studies from the adult population was performed in order to identify trends, similarities and differences. RESULTS: A total of 8,259 articles were identified. Full text evaluation was possible for 28 articles. Although the picture is clearer in the paediatric group, the lack of reproducible results in adults certainly poses serious questions about data collection, analysis and interpretation in each individual study. The apparent paradox is due to the methodological differences between studies. CONCLUSION: The effectiveness of α-blockers and other medication as MET needs to be studied in multi-institutional, double-blind, placebo-controlled studies that would aim to prove superiority to placebo in contemporary clinical situations, with realistic end points and standardized outcome measure determination.

Chitosan-TPP nanoparticles stabilized by poloxamer for controlling the release and enhancing the bioavailability of doxazosin mesylate: in vitro, and in vivo evaluation.

Objective: Control the release and enhance the bioavailability of chitosan-doxazosin mesylate nanoparticles (DM-NPs). Significance: Improve DM bioavailability for the treatment of benign prostatic hyperplasia and hypertension. Methods: Plackett-Burman design was utilized to screen the variables affecting the quality of DM-NPs prepared by ionic gelation method. The investigated variables were initial drug load (X1), chitosan percentage (X2), tripolyphosphate sodium (TPP) percentage (X3), poloxamer percentage (X4), homogenization speed (X5), homogenization time (X6) and TPP addition rate (X7). The prepared DM-loaded NPs have been fully evaluated for particle size (Y1), Zeta potential (Y2), production yield (Y3), entrapment efficiency (Y4), loading capacity (Y5), initial burst (Y6), and cumulative drug release (Y7). Finally, DM pharmacokinetic has been investigated on healthy albino male rabbits by means of non-compartmental analysis. Results: The combination of variables showed variability of Y1, Y2, and Y3 equal to 122-710 nm, 3.49-23.63 mV, and 47.31-92.96%, respectively. While Y4 and Y5, reached 99.87%, and 8.53%, respectively. The prepared NPs revealed that X2, X3, and X4 are the variables that play the important role in controlling the release behavior of DM from the NPs. The in vivo pharmacokinetic results indicated the enhancement in bioavailability of DM by 7 folds compared to drug suspension and the mean residence time prolonged to 23.72 h compared to 4.7 h of drug suspension. Conclusion: The study proved that controlling the release of DM from NPs enhance its bioavailability and improve the compliance of patients with hypertension or benign prostatic hyperplasia.

Three-Year Treatment Outcomes of Water Vapor Thermal Therapy Compared to Doxazosin, Finasteride and Combination Drug Therapy in Men with Benign Prostatic Hyperplasia: Cohort Data from the MTOPS Trial.

PURPOSE: We evaluated the long-term outcomes of treatment of lower urinary tract symptoms due to benign prostatic hyperplasia to compare a 1-time water vapor thermal therapy procedure with daily medical therapy in cohorts from the MTOPS (Medical Therapy of Prostatic Symptoms) study. MATERIALS AND METHODS: Results in the treatment arm of a randomized, controlled trial of thermal therapy using the Rezum® System were compared to MTOPS subjects treated with doxazosin and/or finasteride. Evaluations were restricted to medical therapy subjects, representing 1,140 of the original 3,047 (37.4%), with a prostate volume of 30 to 80 cc and an International Prostate Symptom Score of 13 or greater to include men who met key criteria of the Rezum and MTOPS trials. Outcomes were compared during 3 years for symptom changes and clinical progression rates. RESULTS: Thermal therapy improved symptom scores by approximately 50% throughout 36 months (p <0.0001). Symptom improvement was greater than with either drug alone but similar to that of combination drugs (p ≤0.02 and 0.73, respectively). The peak flow rate improved 4 to 5 ml per second after thermal therapy and doxazosin while thermal therapy was superior to finasteride and combination drugs for 24 and 12 months (p <0.001 and <0.01, respectively). Observed rates of clinical progression during 3 years corroborate these outcomes with approximately 5 times greater progression for any medical therapy vs a single thermal therapy procedure. CONCLUSIONS: A single water vapor thermal therapy procedure provided effective and durable improvements in symptom scores with lower observed clinical progression rates compared to daily long-term use of pharmaceutical agents.

A preliminary investigation into the effects of doxazosin on cognitive functioning in tobacco-deprived and -satiated smokers.

OBJECTIVE: To test the effects of doxazosin, an α1 antagonist, on cognitive functioning during tobacco withdrawal in smokers. METHODS: Participants (n = 35) were randomly assigned to receive placebo, 4-mg/day, or 8-mg/day doxazosin. They completed a continuous performance task and self-reported their withdrawal symptoms at baseline and twice following a medication titration period: once in a tobacco-deprived state and again in a nondeprived state. Ability to resist smoking was assessed using a laboratory smoking-lapse paradigm. RESULTS: Participants showed poorer cognitive performance on most measures taken from the continuous performance task when tobacco deprived. Eight-mg/day doxazosin improved inhibitory control during the nondeprivation session but did not affect sustained attention or reaction time. Participants receiving doxazosin reported fewer withdrawal symptoms during deprivation than those on placebo. Those showing the greatest improvement of inhibitory control under doxazosin were better able to resist smoking (i.e., latency to smoke) during a smoking lapse task. Self-reported withdrawal symptoms also were negatively associated with time to smoking. CONCLUSIONS: Doxazosin reduced symptoms of tobacco withdrawal according to self-report and cognitive assessment and improved inhibitory control above predrug levels. This research identifies potential mechanisms by which doxazosin might improve smoking outcomes.

Successful management of a third-trimester pregnancy complicated by pheochromocytoma: case report.

Pheochromocytoma (PH) is a tumor that arises from chromaffin cells of the adrenal medulla. Though being this benign neoplasm very rare in pregnancies, lack of treatment nevertheless causes high mortality rates for both the mother and the fetus. Classic symptoms related to PH are hypertension, abdominal pain, diaphoresis, and headache; but it can be easily misdiagnosed as gestational hypertension or preeclampsia. Its appearance is sporadic, but there are some genetic disorders that favor its onset (e.g. MEN 2A and 2B). Individual management is needed, because no single protocol is suitable in such a complex and rare condition. In this paper we describe our experience in the clinical and surgical management of a young pregnant patient affected by PH, and in particular the specific and unique pharmacological treatment with doxazosin, the use of corticosteroids and a close monitoring of fetal well-being, which proved being an effective approach.

Micellar enhanced spectrofluorimetric approach for nanogram detection of certain α1 -blocker drugs: Application in pharmaceutical preparations and human plasma.

Alpha1-adrenergic-blocking drugs, namely; alfuzosin hydrochloride (ALF), doxazosin mesylate (DOX) and terazosin hydrochloride (TER) are effective as antihypertensive agents as well as in management of benign prostatic hypertrophy. In this study, a simple, very fast, highly sensitive and cheap technique was optimized for assay of these drugs in pure states and pharmaceutical tablets. The proposed method is dependent on enhancement of the native fluorescence of investigated drugs using the polyoxyethylene 50 stearate (POE50S) micellar system. The method showed excitation at 325, 340 and 250 nm for ALF, DOX and TER, respectively and an emission maxima at 382 nm. The fluorescence intensity-concentration charts of studied drugs were attained utilizing concentration ranges (2.0-60.0 ng mL-1 ) for DOX and (4.0-100.0 ng mL-1 ) for ALF and TER with quantitation limits 2.9, 1.6 and 2.5 ng mL-1 for ALF, DOX and TER, respectively. The suggested technique was approved according to International Council for Harmonisation (ICH) standards and the United States Food and Drug Administration (US FDA) bioanalytical method validation and has been effectively applied for assay of these medications in their dosage forms as well as for content uniformity test. The developed procedure was also efficiently applied for determination of these drugs in real human plasma with high accuracy.

The effect of doxazosin and sildenafil citrate combination on bladder tissue contractility, alpha adrenergic receptor, and iNOS subtype expression in a male rat model of partially bladder outlet obstruction.

AIMS: Our aim was to investigate the effects of doxazosin, sildenafil, and their combination on bladder tissue contractility and adrenergic receptor (AR) and inducible nitric oxide synthase (iNOS) expression utilizing a male rat model of partial urethral obstruction (PUO). METHODS: Thirty male Sprague Dawley rats were divided into five groups. Except the SHAM group, all animals in remaining four groups underwent surgery for PUO. No further treatment was given to the first group (NT group). Remaining three groups received 6 weeks of treatment with 20 mg/kg doxazosin (D group), 20 mg/kg sildenafil (S group), 20 mg/kg doxazosin, and 20 mg/kg sildenafil combination (DS group), respectively via oral gavage. Then, bladder strips were harvested from each animal for isometric tension studies and for real time polymerase chain reaction studies of both AR subtypes and iNOS mRNA. RESULTS: Contractile responses to carbachol and electrical field stimulation at various concentrations/frequencies showed a significant increase after PUO. Any treatment helped to normalize these increased responses. Alpha 1a and 1d AR subtype expressions were found to be down- and up-regulated, respectively, in every group with PUO, compared to SHAM group. iNOS expression was similar in D and NT groups and significantly increased in S and DS groups. CONCLUSIONS: Contractile changes of rat bladder tissue due to PUO were prevented by sildenafil or doxazosin alone or in combination where combination treatment did not provide any additional advantage. Further studies are needed to clarify the role of phosphodiesterase inhibitors and combination treatment in the treatment of LUTS.

Perioperative α-receptor blockade in phaeochromocytoma surgery: an observational case series.

BACKGROUND: Mortality associated with surgery for phaeochromocytoma has dramatically decreased over the last decades. Many factors contributed to the dramatic decline of the mortality rate, and the influence of an α-receptor blockade is unclear and has never been tested in a randomized trial. We evaluated intraoperative haemodynamic conditions and the incidence of complications in patients with and without α-receptor blockade undergoing surgery for catecholamine producing tumours. METHODS: Haemodynamic conditions and perioperative complications were assessed in 110 patients with (B) and 166 without (N) α-receptor blockade. Data were analysed as a consecutive case series of 303 cases and subsequently via propensity score matching, and presented as mean and confidence interval (CI). RESULTS: No difference in maximal intraoperative systolic arterial pressures (B = 178 mm Hg (CI 169-187) vs N = 185 mm Hg (CI 177-193; P = 0.2542) and hypertensive episodes above 250 mm Hg were found (P = 0.7474) for the closed case series. No major complications occurred. Propensity score matching (75 pairs) revealed a significant difference of 17 mm Hg in maximal intraoperative systolic bp for these selected pairs (P = 0.024). CONCLUSIONS: Only a slight difference in mean maximal systolic arterial pressure was detected between patients with or without an α-receptor blockade. There was no difference in the incidence of excessive hypertensive episodes between groups and no major complications occurred. The basis for the general recommendation of perioperative α- receptor blockade for phaeochromocytoma surgery demands further study.