According to the baseline, the IPSS and Qmax were significantly correlated to the prostatic volume and transitional zone volume (P < 0.01). At average follow-up of 6 months, significant improvements in IPSS, QOL, Qmax and residual urine volume were observed in each therapeutic group, and no difference in IPSS improvement was found among the groups. Prostatic volume and transitional zone volume were significant decreased in 5alpha-reductase inhibitor groups (P < 0.05). In patients with baseline TPV greater than 35.5 cm3, the improvement of Qmax was more significant than that in patients with TPV less than 35.5 cm3 in finasteride group (P < 0.01) (5.7 ml/s and 2.2 ml/s respectively), and more significant symptomatic improvements were also found in cernilton, doxazosin and naftopidil group. In each group, the improvement of symptom were more significant in patients with IPSS higher than 20 points (P < 0.01).
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alpha-Adrenoceptor agonists decreased mean arterial pressure when injected into the arterial blood supply of the paraspinal sympathetic ganglia of pentobarbital-anesthetized open-chest dogs. The hypotensive response occurred concomitantly with selective decreases of vascular resistance in the vessels innervated by neurons arising from these ganglia, and both of these responses were blocked by the ganglionic blocking agent, hexamethonium. The hypotensive response to phenylephrine was selectively blocked by terazosin; alpha 1 selective agonist, and antagonist, respectively, while the hypotension produced by intra-arterial clonidine was blocked by rauwolscine; alpha 2 selective agonist and antagonist, respectively. Either terazosin or rauwolscine reduced the hypotension produced by noradrenaline or dopamine. These results demonstrated the presence of both alpha 1- and alpha 2-adrenoceptors in the paraspinal sympathetic ganglia. Activation of either alpha-adrenoceptor subtype inhibited ganglionic transmission.
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Brain alpha1-adrenoceptors have been shown to be essential for motor activity and movement in mice using intraventricular injection of alpha1-antagonists. To facilitate subsequent neuroanatomical mapping of these receptors, the present study was undertaken to replicate these effects in the rat. Rats were administered the alpha1-antagonist, terazosin, in the absence and presence of the alpha1-agonist, phenylephrine, in the IVth ventricle and were tested for their motor activity responses to an environmental change. Terazosin was found to produce a dose-dependent, virtually complete cessation of behavioral activity that was reversed by coinfusion of phenylephrine. The results could not be explained by sedation. It is concluded that central alpha1-adrenoceptors are essential for behavioral activation in rats as in mice.
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Terazosin treatment did not affect the weight of the ventral prostate gland. The prostate contains hyaluronic acid, chondroitin sulfate (CS), dermatan sulfate (DS), and heparan sulfate (HS), MMP-2, TIMP-1, and TIMP-2, but not MMP-9. Terazosin caused a significant increase in the relative content of DS and a significant decrease in the relative content of CS and to a lesser extent of HS. Terazosin evoked a significant increase in the activity of proMMP-2 and MMP-2 but did not affect TIMP.
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Relevant information was identified through a search of MEDLINE (1966-June 2010), International Pharmaceutical Abstracts (1970-June 2010), and EMBASE (1947-June 2010). Randomized, controlled trials that examined prostate cancer, benign prostatic hypertrophy, or procedures related to the prostate (ie, biopsies) were excluded.
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The present study included 69 patients diagnosed as LUT/BPH by IPSS, flowmetry, ultrasound for prostate volume, residual urine, serum PSA and other methods, all of them fulfilled the study's inclusive/exclusive criteria. The principal exclusive criteria were prostate volume > 50 ml, Qmax < 10 ml/s and residual urine > 50 ml. All 69 patients had bothering storage symptoms after initial treatment with terazosin 2 mg once daily for one week., they were divided randomly into two groups. Terazosin group in which patients were treated with terazosin 2 mg once daily for six weeks, and combination group in which patients were treated with terazosin 2 mg once daily and tolterodine 2 mg twice daily for 6 weeks.
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Terazosin is a new long-acting, selective alpha 1-adrenergic antagonist. Its pharmacokinetic and pharmacodynamic profiles are similar to those of prazosin, but terazosin has a half-life three to four times longer. This allows once daily dosing of terazosin and a potential advantage in ensuring patient compliance to treatment. Terazosin has been evaluated alone and in combination with other drugs for the treatment of mild to moderate hypertension. Terazosin has been shown to have favorable lipid and side effect profiles. Unlike prazosin, the drug is available (but not yet marketed) in parenteral form. Its gradual onset of action with intravenous use would limit its potential application in hypertensive emergencies. Other possible uses for terazosin might include treatment of congestive heart failure and Raynaud's phenomenon, but definitive studies are needed.
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Previous studies suggest that activation of the CNS melanocortin system reduces appetite while increasing sympathetic activity and arterial pressure. The present study tested whether endogenous activity of the CNS melanocortin 3/4 receptors (MC3/4-R) contributes to elevated arterial pressure in the spontaneously hypertensive rat (SHR), a model of hypertension with increased sympathetic activity. A cannula was placed in the lateral ventricle of male SHR and Wistar (WKY) rats for chronic intracerebroventricular (ICV) infusions (0.5 muL/h). Mean arterial pressure (MAP) and heart rate (HR) were recorded 24 hour/d using telemetry. After 5-day control period, rats were infused with MC3/4-R antagonist (SHU-9119, 1 nmol/h-ICV) for 12 days, followed by 5-day posttreatment period. MC3/4-R antagonism increased food intake in SHR by 90% and in WKY by 125%, resulting in marked weight gain, insulin resistance, and hyperleptinemia in SHR and WKY. Despite weight gain, MC3/4-R antagonism reduced HR in SHR and WKY ( approximately 40 bpm), while lowering MAP to a greater extent in SHR (-22+/-4 mm Hg) than WKY (-4+/-3 mm Hg). SHU9119 treatment failed to cause further reductions in MAP during chronic adrenergic blockade with propranolol and terazosin. These results suggest that endogenous activity of the CNS melanocortin system contributes to the maintenance of adrenergic tone and elevated arterial pressure in SHR even though mRNA levels for POMC and MC4R in the mediobasal hypothalamus were not increased compared to WKY. These results also support the hypothesis that weight gain does not raise arterial pressure in the absence of a functional MC3/4-R.
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Treatment with different types of antihypertensive drugs during second month age has not prevented development of arterial hypertension and myocardial hypertrophy in the adult rats with inherited stress-induced arterial hypertension. At 6 months of age, the 11% attenuation of basal blood pressure has beet achieved only in the rats treated with angiotensin-converting enzyme inhibitor enalapril. Nevertheless, they expressed the most pronounced left ventricular hypertrophy. The unfavorable tissue and ultrastructural abnormalities were revealed in the myocardium of the rats which received the alpha1-adrenoceptor blocker terazosin. The delayed effects of losartan (angionetsin II receptor antagonist) and corinfar (calcium channel antagonist) on the myocardial structure were inessential.
Finasteride improves long-term urinary symptoms versus placebo, but is less effective than doxazosin. Long-term combination therapy with alpha blockers (doxazosin, terazosin) improves symptoms significantly better than finasteride monotherapy. Finasteride + doxazosin improves symptoms equally - and clinically - to doxazosin alone. In comparison to doxazosin, finasteride + doxazosin appears to improve urinary symptoms only in men with medium (25 to < 40 mL) or large prostates (≥ 40 mL), but not in men with small prostates (25 mL).Comparing short to long-term therapy, finasteride does not improve symptoms significantly better than placebo at the short term, but in the long term it does, although the magnitude of differences was very small (from < 1.0 point to 2.2 points). Doxazosin improves symptoms better than finasteride both short and long term, with the magnitude of differences ∼2.0 points and 1.0 point, respectively. Finasteride + doxazosin improves scores versus finasteride alone at both short and long term, with mean differences ∼2.0 points for both time points. Finasteride + doxazosin versus doxazosin improves scores equally for short and long term.Drug-related adverse effects for finasteride are rare; nevertheless, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder, versus placebo. Versus doxazosin, which has higher rates of dizziness, postural hypotension, and asthenia, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder. Finasteride significantly reduces asthenia, postural hypotension, and dizziness versus terazosin. Finasteride significantly lowers the risk of asthenia, dizziness, ejaculation disorder, and postural hypotension, versus finasteride + terazosin.
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In this group of Taiwanese patients with symptomatic BPH, the efficacy and tolerability of generic terazosin were similar to those of branded terazosin.
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We constructed a retrospective cohort of 192,457 male veterans newly prescribed either rosiglitazone, pioglitazone, metformin, or a sulfonylurea. We used Cox proportional hazard regression to assess the association between thiazolidinedione or metformin use and the risk of requiring medical or surgical treatment for BPH compared to sulfonylurea use. New BPH treatment was defined by either a new prescription for a α-1 blocker or 5α-reductase inhibitors or a surgical procedure indicated for severe BPH.
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A total of 100 females 20 to 70 years old who met the inclusion criteria of total International Prostate Symptom Score 8 or greater, symptom duration 1 or more months, and did not meet any exclusion criteria were entered into the study. Subjects were randomized to receive terazosin or placebo in titrated dose from 1 mg od, 1 mg twice daily to 2 mg twice daily during 14 weeks. Successful treatment outcomes use primary end point of International Prostate Symptom Score quality of life 2 or less and secondary end point of total International Prostate Symptom Score 7 or less. Other outcome measures included International Prostate Symptom Score individual item scores, King's Health Questionnaire quality of life domains, objective assessment parameters of 24-hour frequency volume chart, maximum flow rate and post-void residual urine.
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alpha(1)-Adrenoceptors of the locus coeruleus (LC) have been implicated in behavioral activation in novel surroundings, but the endogenous agonist that activates these receptors has not been established. In addition to the canonical activation of alpha(1)-receptors by norepinephrine (NE), there is evidence that dopamine (DA) may also activate certain brain alpha(1)-receptors. This study examined the contribution of DA to exploratory activity in a novel cage by determining the effect of infusion of various dopaminergic and adrenergic drugs into the mouse LC. It was found that the D2/D3 agonist, quinpirole, which selectively blocks the release of CNS DA, produced a dose-dependent and virtually complete abolition of exploration and all movement in the novel cage test. The quinpirole-induced inactivity was significantly attenuated by coinfusion of DA but not by the D1 agonist, SKF38390. Furthermore, the DA attenuation of quinpirole inactivity was blocked by coinfusion of the alpha(1)-adrenergic receptor antagonist, terazosin, but not by the D1 receptor antagonist, SCH23390. LC infusions of either quinpirole or terazosin also produced profound inactivity in DA-beta-hydroxylase knockout (Dbh -/-) mice that lack NE, indicating that their behavioral effects were not due to an alteration of the release or action of LC NE. Measurement of endogenous DA, NE, and 5HT and their metabolites in the LC during exposure to the novel cage indicated an increase in the turnover of DA and NE but not 5HT. These results indicate that DA is a candidate as an endogenous agonist for behaviorally activating LC alpha(1)-receptors and may play a role in the activation of this nucleus by novel surroundings.
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The prostate dihydrotestosterone concentrations were decreased by the administration of all antiandrogens. Treatment with CMA, finasteride, flutamide, or bicalutamide reduced the prostatic blood supply by 50% to 65%. The parallel reduction in luminal areas of the true capillaries was observed in rats treated with CMA. Treatment with alpha-blockers did not affect the prostate androgen content, prostatic blood supply, or capillary luminal area.
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To compare the effects of the doxazosin and terazosin on total International Prostate Symptom Score (IPSS) and maximum urinary flow rate (Qmax) in treating patients with lower urinary tract symptoms (LUTS) and compare this effectivity by switching the drugs in the patients who did not benefit from either the first or the second drug.
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The effect of finasteride treatment on improvements in total symptom severity, frequency score, and peak urinary flow rate was consistent across all six trials and similar among men with similar prostate volumes at baseline. Symptom severity improved by 1.8 points (95% confidence interval [CI], 0.7 to 2.9) in men with prostate volumes less than 20 cc (n = 72), while the improvement was 2.8 points (95% CI, 2.1 to 3.5) for men with volumes greater than 60 cc (n = 272) on the Quasi-IPSS Scale (range 0 to 30). Similarly, improvements in peak urinary flow rate ranged from 0.89 mL/s (95% CI, -0.05 to 1.83) for men with prostate volumes less than 20 cc to 1.84 mL/s (95% CI, 1.37 to 2.30) in men with volumes greater than 60 cc. The difference in the magnitude of improvement between finasteride and placebo becomes significant (that is, no overlap in 95% CI) for men with a baseline prostate volume assessed by either transrectal ultrasonography or magnetic resonance imaging of greater than 40 cc, which encompasses approximately 50% of the entire population. Baseline prostate volume is a key predictor of treatment outcomes: approximately 80% of the variation in the treatment effects noted between studies could be attributed to differences in mean prostate volumes at baseline. Variation in entry criteria results in large differences in baseline symptom severity status, prostate volume, and consequently apparent inconsistencies in the overall outcomes of these trials.
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To evaluate the cost-effectiveness and functional status effects of terazosin, an alpha(1)-adrenoceptor antagonist, compared with placebo in the treatment of men with moderate to severe, symptomatic, benign prostatic hyperplasia (BPH).
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alpha1-Adrenergic blockers have recently been shown to increase the rate of spontaneous passage of distal ureteral stones. We compared efficacy of 3 different alpha1-adrenergic blockers for this purpose.
Male lower urinary tract symptoms (LUTS) are one of the most common causes for a consultation with a health care provider, and one of the most common causes of male LUTS is benign prostatic hyperplasia (BPH). In recent decades, medical therapy has established itself as viable and cost effective for the majority of men. For the treatment of male LUTS in the United States, the 5 currently available alpha-adrenergic receptor blockers are alfuzosin, doxazosin, silodosin, terazosin, and tamsulosin. alpha-Blockers remain one of the mainstays in the treatment of male LUTS and clinical BPH. They exhibit an early onset of efficacy (within less than 1 week) with regard to both symptoms and flow rate improvement, maintain such improvements in open-label and controlled trials for up to 5 years, and have been shown to prevent symptomatic progression.
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The order of highest to lowest agonist induced tensile forces was NE, dopamine, acetylcholine, bethanechol, histamine and serotonin. Excitatory concentration EC(50) values were determined for each agonist tested. Significant differences were found between specific alpha-1 adrenergic receptor blockers (terazosin, prazosin and the experimental drug LY253352). In addition, many other agents antagonized the alpha-1 adrenergic receptor. Inhibitory concentration IC(50) values were obtained and the order of alpha-1 adrenergic antagonistic strengths from strongest to weakest was LY253352, prazosin, terazosin, ketanserin, SCH23390, diphenhydramine, DO710, dopamine, serotonin and histamine.
Trials were eligible if they (1) randomized men with BPH to receive tamsulosin in comparison with placebo, other BPH medications or surgical interventions and (2) included clinical outcomes such as urologic symptom scales, symptoms, or urodynamic measurements, and (3) had a treatment duration of 30 days or longer. Eligibility was assessed by at least two independent observers.
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Pertinent English-language articles were identified through a search of MEDLINE (1966-week 2, May 2006) using such search terms as 5alpha-reductase inhibitor, alpha-blocker, benign prostatic hyperplasia, dutasteride, efficacy, enlarged prostate, finasteride, and safety.
The incidence of both systolic and diastolic hypertension is increased in elderly patients, therefore antihypertensive drugs are commonly used in this population. In addition to changes in blood pressure, the aging process also causes numerous changes in other physiological parameters, resulting in altered pharmacokinetic and pharmacodynamic responses to the drugs. The dosage regimens for thiazide diuretics and amiloride must be individually titrated in the elderly patient, since the elimination of these agents decreases concurrently with decreased renal function, as indicated by compromised creatinine clearance. The initial doses of the calcium antagonists should be decreased in elderly patients, since representative compounds from all 3 chemically heterogeneous classes have been shown to have decreased clearance in these patients which appears to be primarily due to the status of hepatic function in the patient. However, with verapamil, the dosage should be further decreased in association with compromised renal function. The dosage of the angiotensin converting enzyme (ACE) inhibitors should be adjusted according to renal function rather than age. Lisinopril, which is primarily eliminated unchanged, is usually given in lower doses in the elderly, and doses of both captopril and enalapril may need to be reduced, depending on renal function. While there is no need to adjust the dosage regimen for the alpha-adrenoceptor blocking drugs (prazosin, terazosin), caution should be used with the beta-adrenergic blockers, particularly the hydrophilic agents, since they are renally eliminated. Labetalol may be a suitable alternative beta-blocker for the elderly patient, since its pharmacodynamic properties of decreased systemic vascular resistance without changes in heart rate or stroke volume are preferential for the elderly patient, and its pharmacokinetics are relatively unchanged in this population. Drugs that act primarily through the central nervous system, such as clonidine, methyldopa and guanfacine, require smaller doses in the presence of renal dysfunction. In contrast, guanabenz is metabolised primarily by the liver, so it would appear to be useful in elderly patients with renal dysfunction despite the lack of studies in this population. Guanadrel, an adrenergic neuron blocking drug, also requires a dosage reduction in patients with impaired renal function. In addition to the pharmacokinetic changes that occur in the elderly patient, pharmacodynamic changes may also be anticipated due to receptor modifications. Older patients have a decrease in beta-receptor sensitivity, while alpha-receptor sensitivity does not change. When designing the dosage regimen for a senior patient with hypertension, the combination of all these variables must be considered.
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After discussion with the patients and their carers, terazosin was prescribed with a starting dose of 1 mg in an adult and 0.5 mg in a child administered nocte. The patients were observed for (1) drug-induced hypotension; (2) clinical symptoms due to side effects of terazosin; and (3) continued occurrence of dysreflexic symptoms. Step-wise increments of the dose of terazosin (1 mg in case of adults, and 0.5 mg in a child) was carried out at intervals of 3-4 days, if a patient continued to develop dysreflexia but did not manifest any serious side effect.
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A randomized, parallel-controlled, multicenter clinical trial was conducted. From September 2002 to December 2003 906 BPH patients were enrolled into 7 therapeutic groups, including selective-adrenoceptor antagonist (terazosin, doxazosin tamsulosin and naftopidil), 5 alpha-reductase inhibitor (finasteride and epristeride) and natural product (cernilton). International Prostate Symptom Score (IPSS) and Quality of Life (QOL), uroflowmetry, total prostatic volume (TPV) and transitional zone volume and residual urine were used as efficacy criteria.