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IPSS, IPSS4, OAB symptoms, QoL score, PVR, and Qmax scores of the groups did not differ. After one year treatment, there was significant improvement in IPSS, IPSS4, OAB symptoms, QoL and Qmax values in Group 2. No significant improvement was noted for the same parameters in Group 1.
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Retrospective case-control study.
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To corroborate this speculation, we screened prototypical α(1)-antagonists such as prazosin, doxazosin, and terazosin for antagonism of angiotensin II on rat aortic strips. We also examined the AT(1) antagonists losartan, valsartan, and olmesartan for their possible antagonistic effect, on contractions of rat aortic strips induced by phenylephrine.
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To assess the mechanistic relationship between doxazosin (alpha(1)-receptor antagonist) and receptor occupancy and a measure of pharmacological effect (Q(max), the maximum urinary flow rate) and to compare the mean receptor occupancy ratio at clinical doses of doxazosin, tamsulosin, terazosin and prazosin in benign prostatic hyperplasia (BPH).
A crossover study was conducted to identify the best α1-adrenoceptor (α1AR) antagonist for individual patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). One hundred thirteen patients (mean age 70.8 years) were enrolled. All patients met BPH clinical study guidelines. Seven agents were utilized:tamsulosin 0.2mg, silodosin 8mg, urapidil 60mg, naftopidil 50mg, prazosin 1mg, terazosin 2mg, and doxazosin 1mg. Patients were initially prescribed tamsulosin or silodosin for a week and then urapidil for a week. Two weeks later, they were prescribed the better of the 2 agents for a week and a new agent for the next week. This cycle was repeated until all 7 agents were tested. Efficacy was evaluated with the International Prostate Symptom Score. The agent rankings were doxazosin (25 [22%]), silodosin (22 [19%]), urapidil (19 [17%]), naftopidil (17 [15%]), terazosin (12 [11%]), tamsulosin (11 [10%]), prazosin (7 [6%]). Only 12 patients (11%) changed agents after the crossover study was completed. The major reason was adverse events (83%). We found that each of the 7 α1AR antagonists has its own supporters. Further, the one-week crossover study was useful in identifying the best agent for the treatment of each individual with LUTS.
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On the basis of the author's personal experience with migraine, and occasional reports in the literature suggesting that alpha 1-adrenergic blocking drugs may have a beneficial effect in the prophylaxis of migraine, 10 patients with migraine in a general neurology practice were placed on either terazosin or doxazosin. A decrease in migraine frequency or severity or both was seen in all but 1 patient, but 5 patients discontinued the drug due to side effects. No serious adverse reactions were reported. This anecdotal experience with the alpha 1-adrenergic blockers warrants a controlled, double-blind study of this class of drugs for the prophylaxis of migraine.
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The mean age of Group 1 was 44 years and Group 2 was 39 years. The median stone size was 6.9 +/- 2.3 mm in Group 1 and 6.6 +/- 3.1 mm in Group 2, which was not significantly different. Stone expulsion rate was 90.62% in Group 1 and 62.5% in Group 2, with a significant statistical difference (p=0.041). The mean expulsion time was 76.3 +/- 60 hours and 141 +/- 64 hours in Groups 1 and 2, (p=0.001). Extra analgesic (pethidine) requirement averaged 34.4 +/- 12.7 mg and 62.1 +/- 10.5 mg in Groups 1 and 2 (p=0.036). Seven patients in Group 1 and 15 patients in Group 2 required ureteroscopy after 4 weeks due to lack of the stone passage.
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Four groups, with 10 rats each, were designed to receive terazosin, tamsulosin, doxazosin, and no medication. Dilated pupil diameter (PD) measurements were performed 24 hr before, 24 hr after, and 30 days after the initiation of medication, and after 30 days of washout. The intergroup and intragroup differences in PD were evaluated using one-way ANOVA and Wilcoxon signed rank test, respectively.
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Medical treatment of distal ureteral calculi with alfuzosin, doxazosin and terazosin resulted in a significantly increased stone-expulsion rate and decreased expulsion time when compared with HBB. HBB seems to have a negative effect on stone-expulsion rate.
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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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For male patients with LUTS associate with hypertension, all of amlodipine (APVR = 6.8) , terazosin (APVR = 7. 6), and combination group (APVR = 8.8) can significant reduced the PVR (P < . 0.1), but no significant difference was found among three groups.
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Thirty-five rats were implanted with electroencephalogram and neck electrodes to record sleep-wake states and GG and diaphragm electrodes for respiratory muscle recordings. Microdialysis probes were inserted into the HMN.
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Male rats were randomly divided into seven groups: normal, model, finasteride (0.5 mg/ kg), terazosin (0.5 mg/kg), and FHT (10, 5, 2.5 g/kg). Rats were administered testosterone (0.5 mg sc) for 6 weeks after orchiectomy, excluding the normal group. All rats were intragastrically administered assigned drugs for 4 weeks from the third week. Urodynamics were assessed in rats under anesthesia. Serum dihydrotestosterone (DHT) and prostatic acid phosphatase (PAP) were measured. The prostate index (PI), bladder index (BI), and pathological detection were evaluated.
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A total of 42,769 men with incident BPH received any selective α-1 blocker or 5-ARI. Tamsulosin and dutasteride were the most widely prescribed agents of their respective drug classes. Predicted probabilities showed that urologists were more likely to prescribe alfuzosin (24.0% vs. 7.8%; P<0.001) and silodosin (2.3% vs. 0.4%; P<0.001) when compared with primary care providers (PCPs) at 6 months after diagnosis. Urologists were more likely to prescribe 5-ARIs but less likely to prescribe older α-1 blockers (terazosin, prazosin, and doxazosin) than PCPs at 6 months postdiagnosis.
An on-line SPE-HPLC method, using a monolithic poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) (poly(GMA-EDMA)) based weak cation-exchange (WCX) column, was developed for simultaneous determination of alpha1-adrenergic receptor antagonists in human plasma. The monolithic WCX column was prepared by an in-situ polymerization protocol and modified stepwise with ethylenediamine and chloroacetic acid. On connecting this column to an injection valve, an on-line SPE protocol could be established for removal of matrices (mainly proteins and lipids) and preconcentration of four alpha1-adrenergic receptor antagonists in human plasma. This method was validated and then used for determination of terazosin, alfuzosin, prazosin, and doxazosin in clinical plasma samples. For all analytes, each calibration curve was found to be linear over a range of 0.005-5 microg/mL (R>0.997), and the limit of detection for each analyte was 0.5 ng/mL. Recovery (>80%) and precision (RSD<15%) for inter- and intra-day assay were tested at three concentration levels of each analyte and showed acceptable results for quantitative assay. Real samples from hypertensive patients were monitored and results were in agreement with those of the conventional liquid-liquid extraction-HPLC method. Furthermore, due to its good permeability and biocompatibility, the monolithic WCX sorbent could be reused more than 300 times. The proposed method was especially appropriate for multi-analyte monitoring in plasma samples.
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An Internet-based decision support tool was developed to help patients with benign prostatic hypertrophy (BPH) determine whether they wanted to use alpha blockers. The Internet site incorporates a meta-analytic model of the results of randomized trials of the alpha blocker terazosin. The site describes alternative treatments for BPH and potential adverse effects of alpha blockers. The site then measures patients' current symptoms and desired level of symptom reduction. In response, the site computes and displays the probability of a patient's achieving his objective by means of terazosin or placebo treatment.
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We conducted a systematic review to evaluate the effectiveness and adverse effects of the alpha-blocker, terazosin, for treatment of urinary symptoms associated with BPO.
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Tamsulosin, alfuzosin slow release and silodosin do not require dose titration. Alfuzosin, terazosin, doxazosin and silodosin have all been shown to be effective in relieving LUTS/BPH independent of prostate size. Low incidence of orthostatic hypotension has been reported for silodosin, but abnormal ejaculation is the most commonly reported adverse effect.
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The total number of reports used was 1,260,182. Signal scores suggested the associations of alfuzosin, doxazosin, tamsulosin, and terazosin with dizziness/vertigo, orthostatic hypotension, erectile dysfunction, ejaculation dysfunction (EjD), thirst/dry mouth, and constipation; however, reports on naftopidil, silodosin, and urapidil were not enough to compare with the other 4 A1Bs. Signal scores for EjD were higher for tamsulosin, and those for dizziness/vertigo were lower for doxazosin than for the other 3 drugs.
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At most time points tamsulosin inhibited phenylephrine-induced diastolic blood pressure elevations significantly less than terazosin (5 h time point: median difference in inhibition 35%, 95% CI: 18.7-50.3%). On the other hand, phenylephrine-induced changes of cardiac output, heart rate and stroke volume were similar during both active treatments.
The authors concluded that treatment with terazosin was associated with greater peak urinary flow rate and lower symptom score than treatment with placebo. There was no variability of efficacy of terazosin as a result of prostrate volume, and measurement of prostrate volume was not essential before initiation of therapy.
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We compared the efficacy of once a day administration of terazosin hydrochloride with that of twice a day administration for benign prostatic hyperplasia (BPH) patients. Forty-two patients with BPH were randomly assigned to receive a maximum dose of 2 mg terazosin either once (n = 21) or twice (n = 21) a day. International prostate symptom score (IPSS), uroflowmetry and side effect profile were determined before and 4 weeks after randomization. Both groups were similar with respect to patient age, baseline IPSS and prostate volume. After 4 weeks of treatment with terazosin, significant improvement in IPSS, maximum flow rate and mean flow rate were observed in both groups. However, these improvements did not differ significantly between them. In addition, there were no differences in side effects between the groups. In conclusion, once a day administration of terazosin hydrochloride is as effective and safe as twice a day administration in patients with BPH.
AUA-SS (0 to 35 point scale) improved from a baseline mean of 20.1 points by 37.8% during terazosin (n=976) and by 18.4% during placebo (n=973) treatment (P<0.001). Similarly, statistically superior improvements were observed in regard to the AUA-BS, BII, and the QQL score in the terazosin-treated patients. Peak urinary flow rate improved from a baseline of 9.6 mL/s (both regional treatment groups) by 2.2 mL/s in the terazosin group (n=137) and by 0.7 mL/s in the placebo group (n=140) (P< or = 0.05). Treatment failure occurred in 11.2% of terazosin- and 25.4% of placebo-treated patients (P<0.001; Kaplan-Meier adjusted withdrawal rates of 365 days). Withdrawal from study drug treatment due to adverse events occurred in 19.7% of terazosin- and 15.2% of placebo-treated patients (P<0.001).
Dosing regimen is an important determinant of both drug cost and patient compliance. This retrospective analysis evaluated dosing regimens and drug acquisition costs for 101 patients identified from medical records in a large metropolitan hospital as having hypertension and/or benign prostatic hyperplasia and receiving alpha-blocker therapy with either doxazosin or terazosin. Although once-daily administration is generally recommended for both drugs, 25 (38%) of 66 patients receiving terazosin were treated twice daily compared with 6 (17%) of 35 patients treated twice daily with doxazosin. This difference was statistically significant. The average (mean +/- SD) daily treatment cost per patient for all individuals receiving terazosin during the period of the record review was $1.68 +/- 0.60. For patients treated with doxazosin, the average was $0.96 +/- 0.65-a highly statistically significant result. If all 66 patients receiving terazosin had been converted to doxazosin at the beginning of the study, annual savings would have been $17,345.00. These results demonstrate the importance of reviewing actual dosing regimens. The fact that doxazosin could be administered to a significantly higher percentage of patients once daily rather than twice daily substantially decreased its cost relative to terazosin. A once-daily treatment regimen may also enhance patient compliance, thereby improving the chances of therapeutic success.
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Hypertension may worsen LUTS and may decrease the improvement of symptoms by terazosin.
Randomized, double-blind, multicenter (eight government and private facilities), placebo-controlled study.
Terazosin kinetics were followed in normal subjects after intravenous doses of 0.5, 1.0, and 2.0 mg and oral doses of 1.0 mg. Plasma and urine samples were collected for the first 48 and 24 hours. The samples were analyzed by a sensitive HPLC assay developed in our laboratory. Mean calculated peak plasma levels from the 0.5, 1.0, and 2.0 mg intravenous doses were 25.0, 44.1, and 83.3 ng/ml. After a 1 mg oral dose the mean peak level was 19.6 ng/ml. Data were fit to a two-compartment open model with mean elimination phase t1/2 values of 7.9, 8.9, and 10.1 hours for the ascending intravenous doses and 11.6 hours for the oral dose. Mean 0 to 24-hour urinary recovery after the intravenous doses was 14%, 13%, and 11%. It is concluded that terazosin kinetics are linear after oral and intravenous doses.
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Randomised controlled trials (RCTs) provide the best available external evidence for the use of alpha1-blockers in treating lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). Placebo-controlled and actively-controlled RCTs evidenced the efficacy of alpha1-blockers in augmenting urine flow, relieving symptoms, reducing bother and improving quality of life in patients with LUTS. This improvement involves both filling (irritative) and voiding (obstructive) symptoms, occurs promptly and is well-maintained over time. Treatment benefit is independent of prostate size and baseline prostate specific antigen (PSA). There is no evidence of relevant differences between the different alpha1-blockers in this regard and all alpha1-blockers can be accepted as appropriately efficacious at the presently recommended doses. The best available external evidence for relevant differential properties of alpha1-blockers relates to their clinical selectivity in terms of the absence/presence of ancillary cardiovascular, i.e. anti-hypertensive effects. Anti-hypertensive alpha1-blockers (terazosin and doxazosin in particular) are more likely to cause dizziness and other cardiovascular untoward effects, eventually leading to premature treatment discontinuation. Alfuzosin (although primarily developed as an anti-hypertensive agent) and tamsulosin in contrast, are better tolerated; the former nevertheless carries a more distinct risk of symptomatic impairment of blood pressure control. Although indirect comparisons between different studies suggest a higher risk of retrograde ejaculation with tamsulosin, this hypothesis failed to be confirmed in direct comparative RCTs.