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Diabetic patients had a lower baseline Q(max) than non-diabetics (p < 0.001), while the IPSS, bother score and PVR did not differ significantly between the two groups. After treatment with alpha1-blockers, lower urinary tract symptoms improved significantly. The improvement rates of the IPSS and bother score were significantly higher in the diabetic patients than in the non-diabetics (p < 0.01). The relationship between the duration of diabetes and the effect of alpha1-blockers on IPSS, bother score, Q(max) and PVR was not statistically significant (p > 0.05).
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Over the past years new formulations of several α1-adrenoceptor blockers were introduced to the market. Five long-acting α1-blockers are currently approved by the Food and Drug Administration for treatment of symptomatic LUTS/BPH: terazosin, doxazosin, tamsulosin, alfuzosin and silodosin. Silodosin is the only adrenoceptor blocker that exhibits true selectivity for the α1-adrenoceptor subtypes. This unique adrenoceptor selectivity profile likely accounts for the very favorable cardiovascular safety profile.
Groups of untreated or chronically deoxycorticosterone acetate (DOCA)-salt-treated female Sprague-Dawley rats were used. Rats were anaesthetized with Inactin (barbiturate); drugs were administered via a jugular venous catheter; blood pressure was monitored via a carotid arterial catheter.
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Four groups of eight rats each were selected for this study and treated with saline solution (control), doxazosin mesylate, finasteride and combination of the drugs, during 10 months. After this time, the prostate was removed, weighed and sent for histological analysis. Prostate sections were stained with Masson trichrome. With an image analyzer, the percentage of smooth muscle, collagen, epithelium, acinar lumen and interstitial space was measured. Also, the minimum, medium and maximum epithelial thickness, number of acini per field, mean acinar area and the presence of papillary projections were evaluated.
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The implication of a single adrenoceptor subtype in the contractility of prostatic and urethral smooth muscle cells led to the concept that drugs with selectivity for this subtype may exhibit functional uroselectivity. Comparison of the affinities of the alpha1-adrenoceptor antagonists revealed that few compounds show selectivity for one of the three cloned alpha1-adrenoceptor subtypes (alpha1a/A, alpha1b/B, alpha1d/D) whereas most of them had a similar affinity for the three subtypes. Moreover, data supporting a relationship between selectivity for the alpha1a/A-adrenoceptor subtype and functional uroselectivity are still lacking and recent data challenged the relevance of the selectivity for a given cloned alpha1-adrenoceptor subtype in predicting functional uroselectivity. In vivo data showed that alpha1-adrenoceptor antagonists without adrenoceptor subtype selectivity, like alfuzosin or to a minor extent doxazosin, showed functional uroselectivity whereas prazosin and terazosin were not shown to be uroselective. Compounds considered to be selective for the alpha1a/A-adrenoceptor, like tamsulosin or 5-Me-urapidil, did not show functional uroselectivity since they modified urethral and blood pressures in a manner which was not correlated to their selectivity for the cloned alpha1-adrenoceptor subtypes. Meanwhile, the identification in prostatic tissue, of a new sub-family of alpha1-adrenoceptors with low affinity for prazosin and denominated alpha1L gave rise to numerous studies. However, its functional role as well as the affinity of the known antagonists for this receptor subtype remains to be clarified. In conclusion, the existing alpha1-adrenoceptor antagonists have different pharmacological profiles in vivo which are yet not predictable from their receptor pharmacology based on the actual state of knowledge of the alpha1-adrenoceptor classification.
A search of Medline and EMBASE were performed using the keywords 'OROS' and 'osmotic delivery' for the period January 1990 to June 2005. Data were also obtained from the manufacturers' websites and associated publications.
Prospective cohort 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.
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The use of alpha-blockers for all prescriptions began to decrease after the closure of the alpha-blocker (doxazosin) arm of ALLHAT in January 2000. Prescriptions for the thiazide-type diuretics immediately increased after the ALLHAT publication in December 2002. During the first 6 months of 2003, the percentages of thiazide-type diuretics were statistically significantly higher compared with the predicted values. This pattern held for all as well as for new antihypertensive prescriptions.
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This retrospective study involved 181 outpatients with resistant hypertension (defined as a failure of blood pressure [BP] control despite treatment with three drugs, one of which was a diuretic) who received additional spironolactone (n=88) or doxazosin (n=93).
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The authors determined whether increasing alpha 1-adrenergic blockade resulted in progressively less arrhythmic activity in the canine halothane-epinephrine arrhythmia model. Dogs (n = 7) were anesthetized with halothane (1.5%) in oxygen. Stepwise increases in steady-state plasma levels of either of two alpha 1-adrenoceptor antagonists (droperidol, doxazosin) were produced by applying Wagnerian principles to the known pharmacokinetic parameters of these drugs. At each steady state plasma level of these antagonists, the extent of the alpha 1-adrenergic blockade produced was assessed by defining a phenylephrine (PE) dose pressor response curve. The degree of alpha 1-blockade produced was quantitated as the dose of PE that caused a 25-mmHg increase in mean arterial pressure (ED25) as derived by polynomial regression analysis. By analysis of variance (ANOVA) the ED25 increased significantly for each targeted steady state plasma level of either droperidol (P less than 0.001) or doxazosin (P less than 0.001). For an assessment of the antiarrhythmic activity of these alpha 1-antagonists, the arrhythmogenic dose of epinephrine (ADE) was determined at each of the states of alpha 1-adrenergic blockade previously defined. By ANOVA there was a significant increase in the ADE over the range of alpha blockade produced for either droperidol (P less than 0.001) or doxazosin (P less than 0.001). A close correlation (r2) existed between the ED25 and the ADE for the target steady state levels that were achieved for either droperidol (0.99) or doxazosin (0.74).(ABSTRACT TRUNCATED AT 250 WORDS)