Preoperative Use of Alpha-1 Receptor Blockers in Male Patients Undergoing Extracorporeal Shock Wave Lithotripsy for a Ureteral Calculus.

In this retrospective single-center cohort study, we investigated the impact of preoperative use of an alpha-1 adrenergic receptor (AR) blocker on the outcome of single-session extracorporeal shock wave lithotripsy (SWL) in 193 male patients who underwent SWL for a single ureteral calculus between 2006 and 2016. We reviewed their medical records to obtain the data on the preoperative use of alpha-1 AR blockers. The primary outcome was treatment success after single-session SWL. We performed a multivariable logistic regression analysis adjusting for clinically important confounders to examine the association between preoperative use of alpha-1 AR blockers and the treatment success of SWL. Among the 193 patients, 15 (7.8%) were taking an alpha-1 AR blocker preoperatively. A multivariable analysis showed that preoperative use of an alpha-1 AR blocker was a significant negative predictor for treatment success of SWL (adjusted odds ratio 0.17; 95% confidence intervals, 0.04-0.74). Our findings suggest that the preoperative use of an alpha-1 AR blocker was a negative predictor of treatment success of SWL in male patients with a single ureteral calculus. Clinicians should pay more attention to the preoperative drug use in determining an appropriate stone therapy modality.

Sonographic Parameters Predicting the Outcome of Patients With Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia Treated With Alpha1-Adrenoreceptor Antagonist.

OBJECTIVE: To define prostate and bladder sono-morphologic parameters that best predict the outcome of benign prostatic hyperplasia (BPH) in men treated with alpha1-adrenoreceptor antagonist. MATERIALS AND METHODS: Patients with BPH, candidates for medical treatment, were prospectively enrolled. Besides basic evaluation measures, all patients underwent transrectal ultrasonography. The main outcome was the response to treatment on the basis of International Prostatic Symptom Score, quality of life score, and maximum urine flow rate after taking daily oral dose of tamsulosin 0.4 mg for 6 months. The influences of baseline parameters on treatment response were statistically analyzed. RESULTS: A total of 166 patients completed the study. From these, 59 (35.5%) had ineffective treatment after 6 months. According to logistic regression analysis, baseline International Prostatic Symptom Score storage subscore, maximum urine flow rate, and transrectal ultrasonography-measured sono-morphologic parameters (bladder wall thickness [BWT], ultrasound estimated bladder weight [UEBW], and intravesical prostatic protrusion [IPP]) were the independent predictors of ineffective treatment (P < .05). Using receiver operating characteristics analysis, BWT, UEBW, and IPP had adequate area under the curve (0.939, 0.897, and 0.876, respectively). At cutoff values of 9.3 mm, 34.5 g, and 12.9 mm, the positive and negative predictive values for BWT, UEBW, and IPP were 83.6% and 92.4%; 78.2% and 85.6%; 80.3% and 90.5%; respectively. Combination of these sono-morphologic parameters increased their positive predictive value to 97.6%. CONCLUSION: Sonographic measurements of BWT, UEBW, and IPP might aid in determining patients with BPH at high risk of alpha1-adrenoreceptor antagonist monotherapy failure, in turn determining the initial need for additional medical therapy or surgical intervention.

Chronic bladder ischemia and oxidative stress: new pharmacotherapeutic targets for lower urinary tract symptoms.

Chronic bladder ischemia is potentially a common cause of lower urinary tract symptoms in the elderly. Epidemiological studies have shown a close association between lower urinary tract symptoms and vascular risk factors for atherosclerosis, and investigations using transrectal color Doppler ultrasonography have shown a negative correlation between decreased lower urinary tract perfusion and International Prostate Symptom Score in elderly patients with lower urinary tract symptoms. Bladder blood flow is also known to decrease in men with bladder outlet obstruction as a result of benign prostatic hyperplasia. Studies in animal models suggest that chronic bladder ischemia and repeated ischemia/reperfusion during a micturition cycle might produce oxidative stress, leading to denervation of the bladder and the expression of tissue-damaging molecules in the bladder wall, which could be responsible for the development of bladder hyperactivity progressing to bladder underactivity. The effects of drugs with different mechanisms of action; for example, α1-adrenoceptor antagonists, phosphodiesterase type 5 inhibitors, free radical scavengers and ß3-adrenoceptor agonist, have been studied in animal models of chronic bladder ischemia. The drugs, representing different treatment principles for increasing blood flow and decreasing oxidative stress, showed protective effects not only on urodynamic parameters, but also on negative effects on muscle contractility and on detrimental structural bladder wall changes. Improvement of lower urinary tract perfusion and control of oxidative stress can be considered new therapeutic strategies for treatment of bladder dysfunction induced by chronic ischemia.

Bunazosin, a selective alpha1-adrenoceptor antagonist, as an anti-glaucoma drug: effects on ocular circulation and retinal neuronal damage.

Bunazosin hydrochloride is a potent and selective alpha1-adrenoceptor antagonist that has been clinically used both as a systemic antihypertensive as well as an ocular hypotensive drug. In a number of studies, we have examined some effects of bunazosin hydrochloride that might indicate its potential as an anti-glaucoma drug. In normal rabbit eyes, topically instilled bunazosin hydrochloride reached the posterior retina by local penetration at concentrations sufficient to attenuate the phenylephrine- or endothelin-1 (ET-1)-induced constriction of retinal arteries. Furthermore, bunazosin hydrochloride improved the impairment of optic nerve head (ONH) blood flow, the prolongation of visual-evoked potentials (VEP) implicit time, the enlargement of the optic disk cup, and the decrease in the number of retinal ganglion cell layer cells induced by repeated injections of ET-1 in rabbits. Topically instilled bunazosin hydrochloride improved the reductions in ONH capillary blood flow and VEP amplitude induced in rabbit eyes by nitric oxide synthase inhibition. In rat primary retinal cultures, bunazosin hydrochloride reduced glutamate-induced neuronal cell death, presumably through a Na+ channel blocking effect. In healthy humans, topically instilled bunazosin hydrochloride reportedly increases blood velocity in the ONH, retina and choroid, without significantly altering either blood pressure or heart rate. These results indicate that bunazosin hydrochloride exerts both an improvement effect within the ocular circulation and a direct neuroprotective effect. Hence, bunazosin hydrochloride may be useful as a therapeutic drug against ischemic retinal diseases (such as glaucoma and retinal vascular occlusive diseases) that are associated with disturbances of the ocular circulation.

Attenuation of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)-induced rhabdomyolysis with alpha1- plus beta3-adrenoreceptor antagonists.

1. Studies were designed to examine the effects of alpha(1) (alpha(1)AR)- plus beta(3)-adrenoreceptor (beta(3)AR) antagonists on 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)-induced hyperthermia and measures of rhabdomyolysis (creatine kinase (CK)) and renal function (blood urea nitrogen (BUN) and serum creatinine (sCr)) in male Sprague-Dawley rats. 2. MDMA (40 mg x kg(-1), s.c.) induced a rapid and robust increase in rectal temperature, which was significantly attenuated by pretreatment with the alpha(1)AR antagonist prazosin (100 microg x kg(-1), i.p.) plus the beta(3)AR antagonist SR59230A (5 mg x kg(-1), i.p.). 3. CK levels significantly increased (peaking at 4 h) after MDMA treatment and were blocked by the combination of prazosin plus SR59230A. 4. At 4 h after MDMA treatment, BUN and sCr levels were also significantly increased and could be prevented by this combination of alpha(1)AR- plus beta(3)AR-antagonists. 5. The results from this study suggest that alpha(1)AR and beta(3)AR play a critical role in the etiology of MDMA-mediated hyperthermia and subsequent rhabdomyolysis.

Impact of alpha1-blockers in men with spinal cord injury and upper tract stasis.

OBJECTIVE: Our objective was to determine the effectiveness of alpha1-blockers on upper tract stasis in men with spinal cord injury (SCI) who use reflex voiding for bladder management. METHODS: A retrospective chart review of men with SCI at or above T6, who used reflex voiding for bladder management and had upper tract stasis diagnosed by renal scan. Inclusion was based on the availability of the following tests both before and after alpha1-receptor blockade: renal scan, urodynamic studies, and arterial pressures. Part I evaluated the impact of alpha1-blockers on upper tract stasis. Part II evaluated the impact of alpha1-blockers on urodynamic parameters in those with and without resolution of stasis. STATISTICAL METHODS: 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. MAIN OUTCOME MEASURES: Urodynamic parameters evaluated included mean changes in opening pressure, maximum detrusor voiding pressure, and duration of uninhibited contraction. RESULTS: Ten men with upper tract stasis were identified (15 renal units). After >6 months on alpha1-receptor antagonist therapy, upper tract stasis resolved in 8 of the 10 men (11 renal units) and persisted in 2 men (4 renal units). (P = .00026). The only urodynamic parameter that significantly changed in those with resolution of upper tract stasis was the duration of the uninhibited contraction (resolution of stasis: -57 seconds; P < .001), persistence of stasis: +12 seconds (P < .05). No significant change in opening pressures occurred in either those with resolution of stasis or persistent stasis (P < .78). Maximum arterial pressures during voiding statistically decreased with the use of alpha1-blockers (152 mmHg vs 135 mmHg; P < .01). CONCLUSIONS: alpha1-Receptor-antagonist therapy improved upper tract stasis in men with SCI. The urodynamic parameter that changed in those with resolution of upper tract stasis was the duration of uninhibited contractions, which decreased significantly.

A 6-month large-scale study into the safety of tamsulosin.

AIMS: Tamsulosin is an alpha1-adrenoceptor antagonist for the treatment of symptomatic benign prostatic hyperplasia with a tolerability similar to that of placebo in short-term, placebo-controlled studies with limited patient numbers. The present study was designed to test the safety of tamsulosin treatment in a large cohort of men during a prolonged period of time, particularly with regard to comedications. METHODS: A multicentre, open-label phase IIIb study with 1784 patients receiving 0.4 mg o.d. tamsulosin for 6 months was performed according to good clinical practice guidelines. The analysis was performed on an intention-to-treat basis and powered to detect adverse events (AE) occurring in 0.15% of patients with 95% confidence. RESULTS: During a total drug exposure time of 811 patient years, 386 AE were recorded in 253 patients (14.2%; 95% confidence intervals [CI] 12.0-15.2%). Twenty-nine patients suffered 44 serious AE including five fatal events (CI 0.12-0.73%) due to myocardial infarction (n = 3) and to pneumonia and a car accident (one each), but all deaths were judged to be unlikely to be related to study medication. The frequency of AE in patients without any comedication (n = 1095) was 13.0% (CI 11.3-14.9%). In a logistic regression analysis beta-adrenoceptor blockers, converting enzyme inhibitors, antidiabetics and diuretics did not significantly affect the odds ratio for having AE. However, concomitant alpha-adrenoceptor antagonists (a protocol violation) and treatment with verapamil (which also has alpha-adrenoceptor antagonist activity) significantly enhanced the odds ratio for having AE to 3.87 (CI 1.52-9.85) and 3.17 (CI 1.52-6.58), respectively. Minor increases in the odds ratio, which did not reach statistical significance, were also observed for Ca2+ antagonists other than verapamil and for nitrates. CONCLUSIONS: We conclude that tamsulosin has a good safety profile relative to AE rates in the placebo arms of previous studies on tamsulosin even in the presence of most potentially complicating comedications. No major unexpected severe AE were recorded during our 6 months study.