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In this large cohort, we observed no association between the use of thiazolidinediones or metformin and new medical or surgical treatment for BPH compared to sulfonylureas.
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In men with benign prostatic hyperplasia, terazosin was effective therapy, whereas finasteride was not, and the combination of terazosin and finasteride was no more effective than terazosin alone.
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To clarify the influence of hypertension on lower urinary tract symptoms (LUTS) we examined the relationship between blood pressure, LUTS, and the effect of terazosin on LUTS in patients with benign prostatic hyperplasia (BPH).
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Our findings revealed that terazosin may be effective in decreasing sweating severity in patients using sertraline.
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The four alpha(1)-adrenoceptor antagonists were evaluated against norepinephrine-induced phasic contractions in mouse isolated ureteral preparations and against phenylephrine-induced sustained contractions in hamster isolated ureteral preparations using a functional experimental technique.
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In order to characterize inverse agonism at alpha1B-adrenoceptors, we have compared the concentration-response relationships of several quinazoline and non-quinazoline alpha1-adrenoceptor antagonists at cloned hamster wild-type (WT) alpha1B-adrenoceptors and a constitutively active mutant (CAM) thereof upon stable expression in Rat-1 fibroblasts. Receptor activation or inhibition thereof was assessed as [3H]inositol phosphate (IP) accumulation. Quinazoline (alfuzosin, doxazosin, prazosin, terazosin) and non-quinazoline alpha1-adrenoceptor antagonists (BE 2254, SB 216,469, tamsulosin) concentration-dependently inhibited phenylephrine-stimulated IP formation at both WT and CAM with Ki values similar to those previously found in radioligand binding studies. At CAM in the absence of phenylephrine, the quinazolines produced concentration-dependent inhibition of basal IP formation; the maximum inhibition was approximately 55%, and the corresponding EC50 values were slightly smaller than the Ki values. In contrast, BE 2254 produced much less inhibition of basal IP formation, SB 216,469 was close to being a neutral antagonist, and tamsulosin even weakly stimulated IP formation. The inhibitory effects of the quinazolines and BE 2254 as well as the stimulatory effect of tamsulosin were equally blocked by SB 216,469 at CAM. At WT in the absence of phenylephrine, tamsulosin did not cause significant stimulation and none of the other compounds caused significant inhibition of basal IP formation. We conclude that alpha1-adrenoceptor antagonsits with a quinazoline structure exhibit greater efficacy as inverse agonists than those without.
Terazosin, a new long-acting selective alpha 1-receptor antagonist, was studied in a crossover trial to assess the effect of age on oral and intravenous pharmacokinetics. Thirty healthy male and female volunteers between the ages of 23 and 75 years received 1-mg oral and intravenous doses of terazosin. For both routes of administration, the only pharmacokinetic variables significantly correlated with age were terminal elimination rate constant and the area under the plasma concentration-time curve (AUC). However, the differences in half-life and AUC between the youngest and oldest subjects were modest and not of practical clinical significance. There was no evidence of an enhanced pharmacologic or toxic effect in older subjects. From these data, we conclude that the dosage of terazosin does not need to be adjusted on the basis of age alone; the dose of terazosin is titrated in all patients to the lowest effective dose that is well tolerated.
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The quinazoline family of alpha1-blockers (prazosin, doxazosin, and terazosin) induce apoptosis of prostate cells through an alpha1-adrenoceptor-independent mechanism. The objective of this study was to gain insight into the non-adrenergic, apoptotic mechanism of action of doxazosin in the prostate and the induction of anoikis by doxazosin. Primary cultures of benign prostate stromal and epithelial cells and the LNCaP (androgen sensitive) and PC-3 (androgen insensitive) prostate carcinoma cell lines were treated with doxazosin (0-50 microM). The effects of doxazosin on cell morphology, caspase-3 activity, and the expression levels of focal adhesion kinase (FAK) and integrin-linked kinase (ILK) were examined. Doxazosin induced changes in morphology consistent with anoikis in both benign and cancerous prostatic cells and increased caspase-3 activity. The effects were similar comparing benign cells (which express alpha1-adrenoceptors) and cancer cells (which do not express alpha1-adrenoceptors), but were more robust in benign cells. Norepinephrine had no effect on doxazosin-induced cell morphology or caspase-3 activity. Treatment of PC-3 cells with doxazosin significantly reduced the protein levels of FAK but did not significantly affect the levels of ILK. These findings suggest that doxazosin induces apoptosis and anoikis of prostate cancer cells by a mechanism of action that is alpha1-adrenoceptor independent. The apoptosis of cancer cells induced by doxazosin counteracts cell proliferation and may have the potential of retarding or reversing prostate cancer cell growth.
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The efficacy and safety of terazosin were compared with those of other antihypertensive drugs in three parallel-group, randomized, double-blind studies in which 133 patients with mild to moderate hypertension participated. In two studies, terazosin monotherapy was compared with placebo and prazosin (study M79-073), or with hydrochlorothiazide (study M80-012). In a third study (M80-013), the combination of terazosin plus hydrochlorothiazide was compared with the combination of prazosin plus hydrochlorothiazide. Doses of study medications were administered twice daily and were increased at weekly intervals until the average supine diastolic blood pressure was 90 mm Hg or less, with a decrease from baseline of at least 10 mm Hg, or until the maximum specified dosage of a given study drug was reached. In general, all active treatments resulted in significant decreases from baseline in supine and standing blood pressures. There was no significant difference between terazosin- and prazosin-treated patients for changes from baseline to the final visit in supine or standing blood pressure measurements (study M79-073). Hydrochlorothiazide had a significantly greater effect on supine diastolic blood pressure when compared with terazosin (study M80-012). Otherwise, there were no significant differences between active treatment groups. Overall, no regimen caused clinically important changes in pulse rates, body weights, laboratory test results, physical examinations, or electrocardiograms. The incidence of side effects was approximately the same for all drugs; the most common side effects were headache, dizziness, malaise, asthenia, and nasal congestion. The results of these studies suggest that terazosin exhibits antihypertensive activity that is quantitatively similar to that of prazosin in patients with mild to moderate hypertension, and that a dose of 1 to 10 mg twice daily is well tolerated.
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Cystometry was performed in conscious female rats recording bladder volume capacity (BVC), evaluated as the amount of saline infused between two voiding cycles, and micturition volume (MV). Changes in frequency and amplitude of spontaneous non-voiding bladder contractions (NVC) were also recorded. The effects of the intravenous administration of suramin (100 mg/kg), BMY 7378 (1 mg/kg), and terazosin (0.3 mg/kg) on NVC, BVC and MV were evaluated in obstructed rats with bladder infusion of saline. The effects of infravesical infusion of suramin (3-10 micromol/L), terazosin (1 micromol/L) and BMY 7378 (10 micromol/L) were also evaluated and compared with values observed in control rats during saline infusion into the bladder.
Current guidelines recommend α1-adrenoreceptor blockers (A1Bs) for treating lower urinary tract symptoms suggestive of benign prostatic hyperplasia, but their adverse effects can be problematic. In this study, reports submitted to the US Food and Drug Administration Adverse Event Reporting System (FAERS) between 1997 and 2011 were reviewed to assess the safety profiles of A1Bs.
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For various reasons, the alpha 1-receptor blocker prazosin has been used infrequently as initial therapy for hypertension. The introduction of additional agents of this class with properties different from prazosin provides slower onset of action, which should reduce the degree of first-dose and postural hypotension and a longer duration of action, which allows for once-a-day dosage. A summary of the published data on efficacy, side effects, and special properties of this class of agents indicates that they will probably be used more extensively, particularly because of their ability to improve lipid and glucose-insulin metabolism.
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In a previous study, we showed that electroacupuncture (EA) applied to the SI-6 point on the contralateral forelimb produces long-lasting and powerful analgesia in pain caused by ankle sprain in a rat model. To investigate the underlying mechanism of EA analgesia, the present study tested the effects of various antagonists on known endogenous analgesic systems in this model. Ankle sprain was induced in anesthetized rats by overextending their right ankle with repeated forceful plantar flexion and inversion of the foot. When rats developed pain behaviors (a reduction in weight-bearing of the affected hind limb), EA was applied to the SI-6 point on the contralateral forelimb for 30 min under halothane anesthesia. EA significantly improved the weight-bearing capacity of the affected hind limb for 2h, suggesting an analgesic effect. The alpha-adrenoceptor antagonist phentolamine (2mg/kg, i.p. or 30 microg, i.t.) completely blocked the EA-induced analgesia, whereas naloxone (1mg/kg, i.p.) failed to block the effect. These results suggest that EA-induced analgesia is mediated by alpha-adrenoceptor mechanisms. Further experiments showed that intrathecal administration of yohimbine, an alpha(2)-adrenergic antagonist, reduced the EA-induced analgesia in a dose-dependent manner, whereas terazosin, an alpha(1)-adrenergic antagonist, did not produce any effect. These data suggest that the analgesic effect of EA in ankle sprain pain is, at least in part, mediated by spinal alpha(2)-adrenoceptor mechanisms.
To determine whether postjunctional alpha1- and alpha2-adrenoceptors mediate vasoconstrictor responses in the cutaneous vasculature of the human forearm.
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The concept of a tonic drive activating respiratory muscle in wakefulness but not sleep has been an important and enduring notion in respiratory medicine, not least because it is useful in modeling sleep effects on breathing and understanding the pathogenesis of sleep-related breathing disorders such as obstructive sleep apnea. However, a neurotransmitter substrate mediating respiratory muscle activation across sleep-wake states has not been identified.
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Chi-square test was used to determine the statistical significance of resolution of upper tract stasis. Student's t test for 2-paired samples was used to evaluate whether urodynamic parameters differed significantly before and after treatment with alpha1-blockers.
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Clinical trials are currently underway to evaluate the efficacy of terazosin for the treatment of symptomatic benign prostatic hyperplasia (BPH). Terazosin is a potent and selective alpha 1 adrenergic blocking agent structurally similar to prazosin. The alpha adrenergic binding properties of terazosin were studied in human prostate adenomas and canine brains using radioligand receptor binding methods. Saturation analyses were performed at varying concentrations of [125I]-Heat and [3H]rauwolscine [( 3H]Ra) in human prostate adenomas and canine brains. The binding of [125I]-Heat and [3H]Ra in the human prostates and canine brains was consistently saturable and of high affinity. The equilibrium dissociation constant (Kd) for [125I]-Heat binding in the canine brains and human prostate adenomas was 84.4 +/- 4.3 pM and 65.4 +/- 19.2 pM, respectively (p greater than 0.05). The (Kd) for [3H]Ra binding in the human prostate adenomas and canine brains was 1.21 +/- 0.23 nM and 1.52 +/- 0.28 nM, respectively (p greater than 0.05). The density of alpha 1 (0.37 +/- 0.15 fmol/mg. wet wt.) and alpha 2 (0.29 +/- 0.09 fmol/mg. wet wt. adrenergic binding sites in the human adenomas were similar (p greater than 0.05). The IC50 corrected (IC50 corr) of terazosin for [125I]-Heat and [3H]Ra binding sites in the human prostate was 2.5 nM and 1.0 micron., respectively. The IC50 corr of terazosin for [125I]-Heat and [3H]Ra binding sites in the canine brain was 2.0 nM and 0.8 microM, respectively. The competitive binding assays indicate that terazosin binds selectively to alpha 1 adrenergic binding sites in the human prostate and canine brain.
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The effectiveness and safety of the combined therapy of terazosin and tolterodine for LUT/BPH patients with dominant storage symptoms was evaluated.
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The objective of this open randomized clinical study was to compare the short-term efficacy and safety of three alpha-1 blockers, prazosin, terazosin and tamsulosin, in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).
Drugs were administered transdermally by iontophoresis in the forearm of 20 healthy participants. Phenylephrine and clonidine were administered at sites pretreated with the relevant antagonist (terazosin and rauwolscine), and at additional untreated sites and sites pretreated with saline. To enhance the contrast between sites, the forearm was heated to 42 degrees C before flow was measured with the laser Doppler technique.
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The purpose of this investigation was to determine the effectiveness of alpha-1 blockade in the treatment of bladder outlet obstruction in the spinal cord injured (SCI) patient. We evaluated terazosin, a selective alpha-1 blocker, in 15 normotensive SCI patients. Detrusor-external sphincter dyssynergia (DESD), without obstruction of the bladder neck or prostate, was documented in all patients using video-urodynamic evaluation. Urodynamic testing was performed both before and during treatment with terazosin (5 mg nightly). Voiding pressure before and during terazosin therapy averaged 92 +/- 17 and 88 +/- 27 cm H2O, respectively (p = 0.48). After subsequent external sphincterotomy or sphincter stent placement, the voiding pressure was reduced to 38 +/- 15 cm H2O (p < 0.001). Nine other patients suffered from persistent difficulty voiding after previous sphincterotomy. Each was subsequently treated with oral terazosin. In five patients who improved with this treatment, urodynamic parameters demonstrated obstruction only at the bladder neck, with no evidence of obstruction at the level of the external sphincter. The four patients who failed to improve were documented to have an open bladder neck but obstruction at the level of the external sphincter. Our data show that alpha-1 sympathetic blockade has no effect on external sphincter function and does not significantly relieve functional obstruction caused by DESD. It was also noted that terazosin is helpful in diagnosing and treating internal sphincter (bladder neck and prostate) obstruction especially in patients who have persistent difficulty voiding after external sphincterotomy.
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To assess differences in pupil diameter between men taking systemic α(1)-adrenoreceptor antagonists and controls.