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12 h incubation of CD133(+)/CD133(-) co-cultures with doxazosin resulted in increase of apoptotic cells, while in CD133(+) cultures no changes were observed. Correlation between apoptotic cell number and doxazosin concentration in CD133(+)/ CD133(-) co-cultures group was high (R = 0.99).
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Previous studies have suggested that dopamine stimulates active ileal ion absorption via alpha 2-adrenergic or dopaminergic receptor activation. Identification of a dopamine 1a receptor on rat enterocytes located in intestinal crypts prompted this investigation of the effect of luminally administered dopamine on water and ion transport in the canine ileum. Absorption studies (n = 27) were performed in dogs with 25-cm ileal Thiry-Vella fistulas. Perfusion with [14C] PEG was used to calculate absorption of water and electrolytes from the Thiry-Vella fistula. Experiments consisted of three 1-hr periods: basal, luminal drug infusion at 10(-4) M, and recovery. Agonists used included dopamine (DOP: alpha-adrenergic, D1 and D2 receptor) and SKF 38393 (D1 receptor). Antagonists used included terazosin (TZ: alpha 1) and yohimbine (YOH: alpha 2). DOP caused significant increases in water and electrolyte absorption. TZ and YOH prevented the dopamine-induced proabsorptive response. Luminal DOP may serve as a proabsorptive modulator of ileal transport, acting via alpha 1, alpha 2, and dopaminergic receptors. The development of more potent proabsorptive dopamine analogs, which maintain the ability to broadly activate mucosal receptors, may be useful in such clinical situations as diabetic diarrhea, short gut syndrome, or following small bowel transplantation.
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Prostatitis can resemble various other medical conditions but proper classification and an understanding of the pharmacologic features and expectations of the medications used to treat it can help identify effective treatment strategies. Fluoroquinolones are the preferred agents for treating bacterial causes of prostatitis and have demonstrated efficacy in some cases of chronic prostatitis when an organism has not been identified. However, the use of agents with anti-inflammatory or antiadrenergic properties may be necessary in combination with or after trying antimicrobial agents.
Ninety-two male Sprague-Dawley rats were randomized to 1 of 5 groups: double-placebo control (n = 15), nicotine opposed by oral placebo (n = 26), nicotine opposed by subcutaneous placebo (n = 16), nicotine opposed by oral terazosin (n = 21), and nicotine opposed by subcutaneous terazosin (n = 14).
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Benign prostatic hyperplasia (BPH) is one of the most common diseases of aging men. It is estimated that by age 60 years, greater than 50% of men will have histologically documented evidence of the disease. Therapy for this disease has evolved considerably from its inception. Recent data from long-term population-based studies have shed new light on the treatment of this common problem in aging men. The authors review the current state of diagnosis of BPH and medical therapy for this condition in the primary care setting.
Terazosin was effective and superior to placebo in reducing symptoms and increasing the peak urinary flow rate. The effect of terazosin on the peak urinary flow rate was apparent in studies as short as 8 weeks. Most importantly, the effect of terazosin on symptoms and peak urinary flow rate was independent of the baseline prostate size for the range of prostate volumes reported.
Several interventions significantly improved IELT. Many interventions also improved sexual satisfaction and other outcomes. However, assessment of longer-term safety and effectiveness is required to evaluate whether or not initial treatment effects are maintained long term, whether or not dose escalation is required, how soon treatment effects end following treatment cessation and whether or not treatments can be stopped and resumed at a later time. In addition, assessment of the AEs associated with long-term treatment and whether or not different doses have differing AE profiles is required.
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These data suggest that exposure to quinazoline based alpha1-adrenoceptor antagonists significantly decreases the incidence of prostate cancer. This evidence suggests that the apoptotic and anti-angiogenic effects of these drugs may prevent the development of prostate cancer.
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The study subjects comprised 281 patients (60 with diabetes and 221 non-diabetics with clinically diagnosed BPH) who were treated with alpha1-blockers (doxazosin, terazosin, alfuzosin and tamsulosin). The international prostate symptom score (IPSS), bother score, maximum flow rate (Q(max)) and post-void residual urine volume (PVR) were determined at baseline and after treatment for a minimum of 6 months.
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For treating benign prostatic hyperplasia (BPH) 5 or 10 mg. terazosin hydrochloride daily has been routinely used in North America and Europe. We investigated the urodynamic effects of 2 mg. terazosin daily on Japanese patients with symptomatic BPH using pressure flow study.
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The risk of mortality and long-term morbidity, including loss of sexual function, associated with surgical procedures for symptomatic benign prostatic hyperplasia (BPH) has prompted research into alternative medical therapies. Phytotherapy involves the use of herbal formulations, where the mechanisms of action are usually obscure and although studies have confirmed their effectiveness in symptom relief and improving quality of life (QOL), few placebo-controlled trials exist. Both the 5 alpha-reductase inhibitor finasteride and alpha 1-adrenoceptor antagonists (e.g. alfuzosin, doxazosin, prazosin, tamsulosin and terazosin) have been recommended as appropriate treatment options for patients with lower urinary tract symptoms (LUTS) associated with benign prostatic obstruction (BPO), and their efficacy has been proven in several placebo-controlled trials. Finasteride reduces the static component of BPO--by reducing the size of the prostate--and, as a result, symptom relief is slow (6-12 months) and is predominantly restricted to patients with large prostates (> 40 g). The alpha 1-adrenoceptor antagonists, on the other hand, reduce the dynamic component of obstruction--relaxation of smooth muscle in the prostate, urethra and bladder neck--and provide rapid symptom relief after only a few doses, relieving LUTS more effectively than finasteride and irrespective of prostate size. All of the various alpha 1-adrenoceptor antagonists provide effective and comparable relief of LUTS, and an improvement in bothersomeness and symptom-related QOL. However, it is also important that the therapy is fast acting and acceptable to the patient, in that it does not interfere with other medication or produce unpleasant side effects. These documented properties of the alpha 1A-adrenoceptor antagonists make them an ideal choice for the medical treatment of symptomatic BPH.
Terazosin, a selective alpha 1-adrenergic antagonist, was administered intravenously to 10 patients undergoing cardiac catheterization to determine its short-term hemodynamic effects. Hemodynamic measurements were performed before and 30 minutes after three doses of the drug: 1, 1, and 3 mg. One milligram of terazosin reduced the blood pressure (systolic/diastolic, mean) from a mean of 152.0/86.3, 110.7 mm Hg by -24.3/-9.4, -15.3 mm Hg (p less than 0.05). In the five patients who received 5 mg of the drug, blood pressure declined in a dose-dependent manner by -21.8/-3.8, -11.6 mm Hg after 1 mg, and by -35.8/-14.8, -22.8 mm Hg (p less than 0.05) after all 5 mg of the drug. The changes in blood pressure paralleled the terazosin-induced decrease in systemic resistance. Similar changes were recorded for pulmonary artery and capillary wedge pressures and pulmonary vascular resistance. The greatest hemodynamic response was noted with the first drug dose; succeeding doses had a progressively diminished incremental effect. Cardiac output, heart rate, and maximum left ventricular dp/dt demonstrated little change, whereas left ventricular end-diastolic pressure decreased after all three doses, reaching significance after 2 mg (-3.4 +/- 0.9 mm Hg, p less than 0.05), and left ventricular ejection fraction tended to increase (+5.6% +/- 2.4%, p less than 0.05 after 1 mg) and showed a dose dependence analogous to that of systemic resistance. Although not generally reaching statistical significance, indexes of aortic stiffness and compliance displayed a favorable effect. These data are consistent with terazosin's specific alpha 1-antagonism. Left ventricular performance is improved by afterload reduction, since terazosin demonstrated no direct effect on cardiac contractility.(ABSTRACT TRUNCATED AT 250 WORDS)
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Quinazoline-based alpha1-adrenergic receptor antagonists may not act solely on smooth muscle contractility. We evaluated the in vivo effect of terazosin on the expression of caspase-3 in the rat ventral prostate.
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Pharmacotherapy for the treatment of BPH is currently being targeted to relax prostate smooth muscle (alpha blockade) and decrease prostate volume (androgen suppression). The objective of the present study was to determine the relative efficacy of terazosin vs. terazosin and flutamide (combination therapy) for the treatment of symptomatic BPH. Twenty-nine males with symptomatic BPH were enrolled into this 6-month open label study. The entry criteria included peak urinary flow rate between 4-15 ml/sec, a total Boyarsky symptom score greater than 7, and postvoid residual less than 300 ml. The daily dosage of terazosin was titrated to 5 mg over a 2-week interval. A 750 mg daily dosage of flutamide was added following 1 month of terazosin monotherapy. The dosages were lowered if significant adverse events developed. Efficacy assessments were performed at 1 month (terazosin alone), 6 months (combination therapy), or at the time of early withdrawal from the study. The efficacy of combination therapy was evaluable in 24 patients receiving combination therapy. At one month, the mean peak urinary flow rate and mean total Boyarsky symptom score improved 38% and 56% relative to baseline, respectively. The present study confirmed the previously observed efficacy and safety of terazosin for BPH. The addition of flutamide did not result in statistically significant improvements in the peak urinary flow rate or total Boyarsky symptom score. The adverse events related to flutamide resulted in 16 dose reductions and 14 premature withdrawals. The role of combination therapy will require a randomized placebo controlled study sufficiently powerful to identify clinically and statistically significant improvements in objective outcome parameters relative to the monotherapies.
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The severity of lower urinary tract symptoms (LUTS) has correlated with erectile dysfunction (ED) and ejaculatory dysfunction (EjD) in large-scale epidemiologic studies. ED and EjD are also side effects of some medical therapies for LUTS suggestive of benign prostatic hyperplasia (LUTS/BPH). These relationships were examined in a physician office-based population of men enrolled in the BPH Registry.
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Relevant randomized controlled trials were identified through searching PubMed, the Cochrane Library, Embase, and other sources. After quality assessment and data abstraction, direct comparison based on the Ureteral Stent-related Symptom Questionnaire (USSQ) between α-blockers and control was performed by RevMan 5.3. Indirect comparison between different types of α-blockers was performed by ITC 1.0. Sensitive and subgroup analyses were used to handle important clinical factors.
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Management of benign prostatic hyperplasia (BPH) is often complicated by concomitant hypertension, a life-threatening condition that must be managed optimally. Many of the alpha blockers used to treat BPH also decrease blood pressure, and terazosin and doxazosin have been shown to have significant cardiovascular side effects, such as asthenia/fatigue, postural hypotension, and dizziness when used to treat BPH patients. Furthermore, these drugs are not first-line therapies for hypertension, and the majority of hypertensive BPH patients will be receiving other antihypertensive agents. Therefore, it is possible that the introduction of these drugs will affect blood pressure control, at least temporarily, with possible adverse effects. In contrast, the selective alpha1A blocker tamsulosin does not appear to have significant cardiovascular side effects and produces minimal blood pressure reductions. Therefore, urologists can choose either to use alpha blockers to treat both hypertension and BPH or to treat BPH using alpha blockers that do not interact with antihypertensive therapy. This review focuses on the alpha blockers currently being used to treat BPH, their effects on the cardiovascular system, and their interaction with antihypertensive drugs.
Receipt of medical therapy for incident BPH (ie, selective α-1 blockers [prazosin (released 1976), terazosin (1987), doxazosin (1990), tamsulosin (1997), alfuzosin (2003), silodosin (2009)] and 5-ARIs [finasteride (1992) and dutasteride (2002)]).
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Healthy male volunteers were monitored in controlled, crossover studies. The effects of placebo or alpha blocker on phenylephrine (PE)-induced urethral and vascular responses, were determined. These were related to plasma drug concentrations and used with in vitro radioligand binding data to derive receptor occupancy.
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The number of questionnaires completed was 12,457. Of the completed questionnaires, 70% of the participants reported the use of multivitamins, and 21% reported the use of herbal supplements. Ten percent of all men reported the use of prescription medications for LUTS (AUA-SS greater than 15). Of the men reporting the use of prescription medications, 19% were taking finasteride, 17% doxazosin, 20% terazosin, 23% tamsulosin, and 22% other prescription medications. Moreover, the average AUA-SS was greater for the men taking herbs or supplements than for those who did not take herbs or supplements (P <0.001). Nonetheless, the Sexual Health Inventory for Men score did not show a positive correlation between the intake of alternative medications and the severity of erectile dysfunction.
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We report the synthesis and evaluation of novel alpha1a adrenoceptor subtype-selective antagonists. Systematic modification of the lipophilic 4,4-diphenylpiperidinyl moiety of the dihydropyridine derivatives 1 and 2 provided several highly selective and potent alpha1a antagonists. From this series, we identified the 4-(methoxycarbonyl)-4-phenylpiperidine analogue SNAP 5540 (-) [(-)-63] for further characterization. When examined in an isolated human prostate tissue assay, this compound was found to have a Ki of 2.8 nM, in agreement with the cloned human receptor binding data (Ki = 2.42 nM). Further evaluation of the compound in isolated dog prostate tissue showed a Ki of 3.6 nM and confirmed it to be a potent antagonist (Kb = 1.6 nM). In vivo, this compound effectively blocked the phenylephrine-stimulated increase in intraurethral pressure (IUP) in mongrel dogs, at doses which did not significantly affect the arterial pressure (diastolic blood pressure, DBP), with a DBP Kb/IUP Kb ratio of 16. In addition, (-)-63 also showed greater than 40 000-fold selectivity over the rat L-type calcium channel and 200-fold selectivity over several G protein-coupled receptors, including histamine and serotonin subtypes. These findings prove that alpha1a adrenoceptor-subtype selective antagonists such as (-)-63 may be developed as uroselective agents for an improved treatment of BPH over nonselective alpha1 antagonists such as prazosin and terazosin, with fewer side effects.
This study shows that terazosin inhibits not only prostate cancer cell growth but also its colony forming ability, both of which are main targets of clinical treatment. In addition, terazosin is shown to inhibit cell growth through G1 phase cell cycle arrest and the up-regulation of p27(KIP1).
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Tamsulosin, a selective alpha1A-adrenoceptor antagonist, and terazosin, a non-selective one, are effective for the treatment of urinary disturbance due to benign prostatic hypertrophy. In the present study, their alpha1-adrenoceptor-blocking effects on blood vessels, which may cause orthostatic hypotension, were investigated in 10 healthy males. After the subjects took orally 0.2 mg of tamsulosin, 1 mg of terazosin or a lactate capsule as the control in a randomized cross-over fashion, their finger tip vasoconstrictor response to cold stimulation and vasoconstrictor response of the dorsal hand vein to increasing doses of phenylephrine were examined. The finger tip vasoconstrictor response was significantly reduced and the infusion rate of phenylephrine producing a half-maximal constriction was significantly increased by terazosin, but tamsulosin had no significant effect on these parameters. These data suggest that the usual dose of tamsulosin exerts little alpha1-adrenoceptor-blocking activity on blood vessels, and orthostatic episodes might be mild, if any, during the treatment with tamsulosin.
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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.
The effect of adding surface-active agents to electrolytes containing terazosin, an antihypertensive drug, on the voltammetric response of glassy carbon electrode was studied. The current signal due to the oxidation process was a function of the amount of terazosin, pH of the medium, type of surfactant, and accumulation time at the electrode surface. Two surfactants were used, an anionic type, sodium dodecyl sulfate (SDS) and a cationic type, cetyl trimethyl ammonium bromide (CTAB). Addition of SDS to the terazosin-containing electrolyte was found to enhance the oxidation current signal while CTAB showed an opposite effect. Beside the interfacial interaction of the surfactant with the electrode surface in reference to the bias applied potential and the charge of surfactant, terazosin-surfactant interaction in the electrolytic solution was found to be critical to the magnitude of current signal. Addition of SDS to terazosin-containing buffer solution resulted in a decrease in the drug absorption spectrum both in the ultra-violet and visible (UV-vis) regions. Moreover, NMR measurements showed considerable chemical shifts for the aromatic protons of the quinazolinyl moiety of the terazosin in presence of SDS. The affected aromatic protons are positioned next to the interacting protonated amino-group of the terazosin with the charged sulfonate-group of SDS. On the other hand, addition of CTAB did not cause noticeable changes both to the UV-vis and NMR spectra of the drug. The use of SDS in the electrochemical determination of terazosin using linear sweep voltammetry and differential pulse voltammetry at solid glassy carbon electrode enhanced the detection limit from 6.00x10(-7)molL(-1) in absence of surfactant to 4.58x10(-9)molL(-1) when present. The validity of using this method in the determination of drug active ingredient in urine samples and tablet formulations was also demonstrated.
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We analyzed practice and referral patterns of primary care practitioners regarding the diagnosis of prostate cancer, and the evaluation and treatment of voiding dysfunction.
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Amlodipine alone or combined with terazosin might have the potential to alleviate lower urinary tract symptoms (LUTS). The combined therapy appears to be more suitable for LUTS with predominantly irritative symptoms.
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The results support the hypothesis that blockade of alpha(1)-receptors in the dorsal pons of mice produces inactivity by causing unopposed activity of alpha(2)-receptors. This condition may be relevant to inactive states seen after stress or during depressive illness.
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The prevalence of OH is very high in older veterans and significantly related to the number of concurrent causative medications used. Providers should be educated to reduce the amount of potentially causative medications in the elderly and better assess patients in which use of such medications is necessary to avoid symptomatic OH.
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Structural similarities were identified among AT(1) and α(1)-antagonists, initiating a speculation that α(1)-antagonists could possibly block the AT(1) receptor and vice-versa.