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To elucidate the vascular effect of tamsulosin hydrochloride (INN, tamsulosin), a selective alpha1A-adrenergic receptor antagonist, in humans, we examined the alpha1-adrenergic receptor antagonistic activity against blood vessels after oral intake of recommended and higher doses of the drug and evaluated the relation between its plasma concentrations and the effect.
On COS cells expressing human α(1) (A) -adrenoceptors and on human prostatic strips, ρ-Da1a inhibited adrenaline- and noradrenaline-induced effects. In anaesthetized rats, ρ-Da1a and tamsulosin administered i.v. 30 min before PHE significantly antagonized the effects of PHE on IUP. The pK(B) values for tamsulosin and ρ-Da1a for this effect were similar. With regards to AP, ρ-Da1a only reduced the effect of PHE on AP at the lowest dose tested (10 μg·kg(-1) ), whereas tamsulosin significantly reduced PHE effects at doses between 10 and 150 μg·kg(-1) .
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There have been few reports on the relationship between the prostatic tissue components and the effect of alpha adrenergic blocker on urination. The present study was undertaken to correlate the rates of the prostatic tissue components and the clinical response to alpha adrenergic blocker in benign prostatic hyperplasia.
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We evaluated the efficacy of the alpha1-adrenergic antagonist tamsulosin for conservative expulsive therapy in patients with ureteral colic due to juxtavesical stones.
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To prospectively evaluate the effectiveness of tamsulosin in treating women with voiding difficulty.
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To identify the alpha1-adrenoceptor subtypes present in the human urethra, by comparing the affinity of prazosin for alpha1-adrenoceptors in the rabbit, dog and human prostatic urethra, and in the dog and human prostate.
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In prostate cancer, tumor-stroma interactions play a critical role in the promotion of tumorigenesis, and thus the prevention of those interactions is a promising target to suppress tumor growth. Several studies demonstrated that alpha(1)-adrenoceptor (α(1)-AR) antagonists, therapeutic drugs for benign prostatic hyperplasia, have growth inhibitory effects on human prostate cancer (PCa) cells through induction of apoptosis or G(1) cell-cycle arrest. However, their direct actions on stromal cells surrounding cancer cells have not yet been elucidated. In this study, we investigated the effects of subtype-selective α(1)-AR antagonists (naftopidil, tamsulosin, and silodosin) on prostate tumor growth with a focus on the role of stroma, using commercially available fibroblast cells (PrSC). Tumorigenic studies in vivo showed significant reductions in tumor growth when E9 cells (an androgen low-sensitive LNCaP subline) grafted with PrSC were treated with naftopidil. In in vitro analyses, naftopidil and silodosin showed antiproliferative effects on PCa cells regardless of androgen sensitivity and α(1)-AR subtype expression. In PrSC, a strong growth inhibitory effect was observed with naftopidil but not silodosin. Flow cytometric analysis revealed that naftopidil, but not silodosin, induced G(1) cell-cycle arrest in both PCa cells and PrSC. In naftopidil-treated PrSC, total interleukin-6 protein was significantly reduced with increased suppression of cell proliferation. Silodosin induced weak early apoptosis only in PCa cells. These findings demonstrated that naftopidil strongly suppressed cell proliferation of stromal cells, resulting in decreased tumorigenic soluble factor, suggesting that naftopidil might be effective in preventing stromal support of tumor cells.
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Tamsulosin has beneficial effects in a significant proportion of women with voiding difficulty.
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5-alpha-Reductase inhibitors, alpha1-adrenoreceptors blockers and herbal drugs, like lipid extracts from saw palmetto fruits, are used to treat benign prostatic hyperplasia (BPH). D-004, a lipid extract from the Royal palm fruits, prevented prostate hyperplasia (PH) induced with testosterone and the atypical PH induced with phenylephrine (PHE) in the rat, its effect in this last model being comparable to that of saw palmetto, but lesser than that of tamsulosin (CAS 106133-20-4). It was investigated whether single doses of D-004, tamsulosin and their combined therapy can prevent urodynamic changes induced with PHE in the rat. Firstly, the effects of PHE on rat volume voided per micturition (VM) were explored in rats that were distributed in three groups: a negative control and two groups injected s. c. with PHE (5 and 10 mg/kg, respectively). In the other two experiments, rats were distributed in four groups: a negative control and three groups injected with PHE (a positive control and two groups treated with either tamsulosin 0.05 and 0.1 mg/kg, or D-004 400 and 800 mg/kg. In another experiment, the effects of the combined therapy were assessed using four groups: a negative control, a positive control and three groups treated orally with tamsulosin 0.05 mg/kg, D-004 400 mg/kg or D-004 400 mg/kg + tamsulosin 0.05 mg/kg, respectively. Sixty min later, all rats (except negative controls) were injected s. c. with PHE (5 mg/kg), and all (including the negative controls) received a fluid-loading dose. Thirty min later, they were placed in metabolic cages and theVM was measured for 1 h. The VM was significantly reduced with PHE (5 and 10 mg/kg), the high dose producing anuria in 50% of the rats. The reduction of VM was significantly and dose-dependently prevented with tamsulosin (0.05 and 0.1 mg/kg) (42.9% and 60.3%, respectively) and with D-004 (400 and 800 mg/kg) (25.2% and 43.1%, respectively). The inhibition reached (70.9%) with the combined therapy was greater than that reached with each monotherapy and also greater than the sum (56.8%) of the inhibitions reached with tamsulosin (35%) or D-004 (21.8%) alone. In conclusion, tamsulosin (0.05 and 0.1 mg/kg) and D-004 (400-800 mg/kg) dose-dependently inhibited the VM reduction induced with PHE, their combined therapy producing the greater effects.
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The article presents the results of the study aimed to the evaluation the efficacy of combination therapy with alpha1-blocker (tamsulosin) and phosphodiesterase type 5 inhibitor (sildenafil) in patients with urination disorders and erectile dysfunction (ED). A pilot observational study involving 60 men aged from 50 and 80 years divided into 3 groups of 20 people was performed. Group 1 of patients received sildenafil 25 mg daily (dynamico), Group 2--tamsulosin 0.4 mg daily (Omnic-Ocas), and Group 3--tamsulosin 0.4 mg (Omnic-Ocas) and sildenafil 25 mg (dynamico) daily. The visits were carried out at the stage of screening, further--every 10 days (a total number--4 visits). Combination therapy of urination disorders and ED contributed to the significant improvement in uroflowmetry, the stopping of complaints according to the IPSS and IIEF-15 questionnaires, and improving the quality of life (according to the QoL questionnaire). Combination therapy significantly decreased obstructive and irritative symptoms, increased the maximum urine flow rate within the period of observation, as well as significantly decreased the residual urine volume, more pronounced when compared with monotherapy. Significant positive effect on erectile component and all components of the overall satisfaction in the sexual sphere were registered, that as a consequence led to the positive impact on the quality of life in patients treated with PDE5 inhibitor. Given the high prevalence of urinary disorders and erectile dysfunction, combined therapy with alpha1-blockers and PDE5 inhibitors in this case should be a promising area for drug therapy.
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Patients were identified from referral-based practices of urologists. One hundred ninety-six men with a National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score of at least 15 and a mean of 6.2 years of symptoms were enrolled. Patients had received substantial previous treatment.
Benign prostatic hyperplasia (BPH) is a complex disease that is progressive in many men. BPH is commonly associated with bothersome lower urinary tract symptoms; progressive disease can also result in complications such as acute urinary retention (AUR) and BPH-related surgery. It is therefore important to identify men at increased risk of BPH progression to optimise therapy. Several factors are associated with progression, including age and prostate volume (PV). Serum prostate-specific antigen level is closely correlated with PV, making it useful for determining the risk of BPH progression. Medical therapy is the most frequently used treatment for BPH. 5-alpha-reductase inhibitors impact the underlying disease and decrease PV; this results in improved symptoms, urinary flow and quality of life, and a reduced risk of AUR and BPH-related surgery. Alpha-blockers achieve rapid symptom relief but do not reduce the overall risk of AUR or BPH-related surgery, presumably because they have no effect on PV. Combination therapy provides greater and more durable benefits than either monotherapy and is a recommended option in treatment guidelines. The Combination of Avodart and Tamsulosin (CombAT) study is currently evaluating the combination of dutasteride with tamsulosin over 4 years in a population of men at increased risk of BPH progression. A preplanned 2-year analysis has shown sustained symptom improvement with combination therapy, significantly greater than with either monotherapy. CombAT is also the first study to show benefit in improving BPH symptoms for combination therapy over the alpha-blocker, tamsulosin, from 9 months of treatment.
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1. The absorption, excretion and metabolism of tamsulosin hydrochloride (TMS), a potent alpha 1-adrenoceptor blocking agent, were studied in four healthy male subjects after a single oral administration of 14C-TMS at a dose of 0.2 mg. 2. Plasma and blood radioactivity concentrations attained peak levels (Cmax) within 1 h after dosing and then declined biphasically. Mean terminal elimination half-lives were 11.8 h for plasma and 9.1 h for blood. The respective mean area under the radioactivity concentration-time curves (AUC0-infinity) were 122.8 and 57.8 ng equivalents h/ml. 3. Mean plasma Cmax of unchanged TMS was 13.0 ng/ml. Plasma levels of TMS declined biphasically. Mean terminal elimination half-life and AUC0-infinity were 8.4 h and 90.3 ng h/ml. The percentage of unchanged TMS to total radioactivity was 91% for Cmax and 74% for AUC0-infinity indicating small amounts of metabolites in plasma. 4. By 1 week post-dosing, 76.4% of the administered radioactivity was recovered in urine and 21.4% in faeces. The major part of radioactivity excreted in urine was recovered within the first 24 h (62.2% of the dose). 5. Unchanged TMS and 11 metabolites in 0-24-h urine samples were quantified. TMS accounted for 8.7% of the dose. Extensive excretion of the sulphate of the O-deethylated metabolite (M-1-Sul) and o-ethoxyphenoxy acetic acid (AM-1) was seen, accounting for 15.7 and 7.5% of the dose respectively.
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Silodosin is a highly selective alpha1A-adrenoceptor antagonist approved for the treatment of the signs and symptoms of benign prostatic hyperplasia. Its clinical pharmacology profile offers a number of advantages, including uroselectivity, once-daily (QD) dosing, a standard dose of 8 mg QD that does not need to be adjusted according to age, and the feasibility of concomitant treatment with phosphodiesterase type 5 (PDE5) inhibitors and antihypertensive agents. Three phase 3 double-blind, randomised trials using the dosage regimen of 8 mg QD in > 800 patients have shown that silodosin is significantly more effective than placebo (p < 0.001) and at least as effective as tamsulosin (0.4 mg QD) in improving International Prostate Symptom Score (IPSS) total score, storage subscore, and voiding subscore. It is significantly more effective than tamsulosin in inducing simultaneous improvement of bothersome lower urinary tract symptoms such as incomplete emptying, frequency, and nocturia (p = 0.03). Safety data collected in 1581 patients exposed to chronic treatment with silodosin 8 mg QD have shown that the drug is safe and well tolerated. As was to be expected with a uroselective compound, cardiovascular effects have been minimal. The most common adverse reaction is "retrograde ejaculation" (anejaculation), which led to treatment discontinuation in only 3.9% of patients. The rare, drug class-related safety issue of intraocular floppy iris syndrome can be satisfactorily managed by warning patients simply to inform their ophthalmologist that they are or were on treatment with an alpha1-adrenoceptor blocker.
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The mean (SD) maximum stone dimension was 7.8 (1.5), 8.1 (1.3), 7.9 (1.6) and 8.0 (1.4) mm in Groups I, II, III and IV, respectively. Groups II and IV had significantly higher stone-free rates than Groups I and III (P < 0.05), whilst there were no statistically significant differences between Groups I and III or between Groups II and IV. There was no statistical difference among the four groups for the time to stone expulsion. Three patients in Group II and two patients in Group IV developed transient hyperglycaemia, which resolved after cessation of methylprednisolone.
Ten healthy subjects were investigated in a randomized, single-blind, three-way cross-over design and received a single dose of 0.4 mg tamsulosin, 5 mg terazosin or placebo on 3 study days at least 1 week apart. Before and 1, 3, 5, 7, 10 and 23.5 h after drug intake, alterations of diastolic blood pressure and other haemodynamic parameters in response to a graded infusion of the alpha1-adrenoceptor agonist phenylephrine were determined non-invasively.
The freeze dried extracts of B. biternata had significant antidiarrheal effects in the castor oil induced diarrhea model (p<0.01) with the highest activity being observed at the 400mg/kg dosage level (1.66±0.81g vs. 4.54±0.51g control, p=0.01). B. biternata extract had significant effects on intestinal motility in the charcoal meal test compared to the control group (43.61±4.42% vs. 60.54±3.33%: p<0.05). B. biternata extract had a significant effect on PGE2 induced enteropooling (3.06±0.07ml vs. 4.74±0.10ml; p<0.001). The freeze dried extracts of B. biternata had a significant negative effect on the contractility of the isolated rabbit jejunum (p<0.001). The effects of the extract were significantly attenuated by tamsulosin (53.94±4.20% vs. 80.57±4.09%; p<0.01) and naloxone (53.94±4.20% vs. 73.89±7.26%; p<0.05). Yohimbine (p>0.05) and propranolol (p>0.05) however did not have any significant effect on the contractile activity of the extract.
To review the physiology of micturition, the pathophysiology of micturition disorders, and current pharmacological agents used to treat these disorders. To discuss different urinary catheterization techniques, along with the risks of catheter-associated urinary tract infections attributed with these techniques.
Determination of the prostate volume and MRI findings of the inner prostate gland were useful in predicting Q(max) responders to the alpha-blocker in men with BPH. In contrast, there were no clinical characteristics of the IPSS responders. IPSS responders without a Q(max) response should be closely followed while continuing the alpha-blocker therapy for a long duration.
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There was a statistically significant higher expulsion rate in group B compared with group A (83.6% vs 65.5%; P-value = 0.031) and a shorter time to expulsion (14.9 ± 4.4 days vs 16.7 ± 4.8 days; P-value = 0.003). Statistically significant differences were noted in terms of the number of hospital visits and analgesic requirement in favor of group B. There was no serious adverse event. An improvement in erectile function was noted in patients of group B compared with those of group A.