High blood pressure. Causes, symptoms, treatments

Angiotensin receptors in the brain.

2017-04-07

α(1)-AR antagonists cause EjD as a class effect that depends on affinity for α(1A)-AR. Differences in α(1A)-AR selectivity would be unlikely to be related to the incidence of EjD.

To review key trials of monotherapy and combination therapy of alpha(1)-adrenergic receptor antagonists (alpha(1)-ARAs), 5alpha-reductase inhibitors (5alphaRIs) and anti-muscarinic agents in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). To assess the safety and efficacy of combination therapies for LUTS associated with BPH, a search of the MEDLINE and Cochrane databases (1976-2008) was conducted for relevant trials and reviews using the terms benign prostatic hyperplasia, lower urinary tract symptoms, alpha(1)-adrenergic receptor antagonists, 5alpha-reductase inhibitors, anti-muscarinics, anticholinergics, combination therapy, alfuzosin, doxazosin, tamsulosin, terazosin, dutasteride, finasteride, tolterodine, flavoxate, propiverine, oxybutynin, erectile dysfunction, sildenafil, vardenafil and tadalafil. Data from the Medical Therapy of Prostatic Symptoms (MTOPS) study indicated a role for long-term use of alpha(1)-ARAs and 5alphaRIs in combination. In the MTOPS study, combination therapy with the alpha(1)-ARA doxazosin and the 5alphaRI finasteride was significantly more effective than either component alone in reducing symptoms (P=0.006 vs doxazosin monotherapy; P<0.001 vs finasteride monotherapy) and in lowering the rate of clinical progression (P<0.001 vs either monotherapy). These findings were confirmed by the 2-year preliminary results of the Combination of Avodart and Tamsulosin study. In this study, combination therapy of the alpha(1)-ARA tamsulosin and the 5alphaRI dutasteride resulted in a significantly greater decrease in International Prostate Symptom Score (IPSS) when compared with either monotherapy. Several recent trials have studied the efficacy of combining alpha(1)-ARAs and anti-muscarinic agents in the treatment of BPH. These studies have found this combination to result in statistically significant benefits in quality of life scores, patient satisfaction, urinary frequency, storage symptoms and IPSS scores. Studies have not shown an increased risk of urinary retention associated with the use of anti-muscarinics in a highly select cohort of men with BPH. The available data suggest that combination therapy can be beneficial in the treatment of BPH and associated LUTS. The greatest efficacy for the alpha(1)-ARA and 5alphaRI combination was shown in patients with larger prostate size and more severe symptoms. The combination of alpha(1)-ARAs and 5alphaRIs appears to prevent disease progression in these patients. The combination of alpha(1)-ARAs with anti-muscarinic agents is useful for relieving symptoms of bladder outlet obstruction and detrusor overactivity. Theoretic concerns regarding the risk of acute urinary retention have been refuted in several recent clinical trials; however, it must be noted that the patients in these trials were a highly select cohort of men. Men with overactive bladder and BPH who are not receiving adequate alleviation of symptoms from the first-line alpha(1)-ARAs may benefit from the addition of an anti-muscarinic agent.

We included in the study 239 outpatients; 118 of them were affected by concomitant cardiovascular illness, 37 by neurologic diseases, 29 by neoplastic diseases and 55 refused surgery for the possible general or specific complications like retrograde ejaculation. All subjects have been checked every six months by transabdominal ultrasonography of the urinary tract, evaluation of the prostate volume and percent of post-micturitional residue, associated with uroflussometry. The patients have been divided into three groups and treated by finasteride, mepartricin, alfuzosin, doxazosin. The enlistment concluded in December 1995 and the follow-up extended up to December 1999.

Of the 2618 men analysed, 1875 (71.6%) had spontaneous AUR (sAUR) and 743 (28.4%) had precipitated AUR (pAUR), mainly after surgery with locoregional or general anaesthesia. BPH was revealed by AUR in 52.3% of men with pAUR and 25.9% of men with sAUR. A urethral catheter was inserted in most cases (82.7%) while only 16.7% had a suprapubic catheter. After initial catheterization, 72.8% of men had a TWOC (pAUR 89.4%, sAUR 66.2%, P < 0.001) after a median of 3 days of catheterization, 17.9% had elective surgery after a median of 8 days of catheterization (pAUR 7.1%, sAUR 22.1%, P < 0.001), 5.7% had immediate surgery after a median of 4 days of catheterization (pAUR 1.1%, sAUR 7.5%, P < 0.001), 0.4% had a urethral stent inserted and 1.1% had an indwelling catheter. Of the 1906 men who had a TWOC, 79% received an alpha(1)-blocker (mainly alfuzosin) before catheter removal. The TWOC was successful in 50.2% of men (pAUR 52.3%, sAUR, 49.0%, P = 0.17) and the success rate was significantly higher in men receiving an alpha(1)-blocker (53.0% vs 39.6%, P < 0.001) before the TWOC. If the TWOC failed, 33.4% had a second TWOC (pAUR 39.9%, sAUR 30.2%, P = 0.003) after a median of 7 days re-catheterization, 57.5% had elective surgery (pAUR 49.1%, sAUR, 61.7%, P < 0.001) after a median of 8 days re-catheterization, 1.5% had a stent inserted and 1.1% had an indwelling catheter. The overall success rate of a second TWOC was 25.9% (pAUR 32.2%, sAUR 21.9%, P = 0.04). Men catheterized for >3 days had a slightly lower success rate for TWOC, greater comorbidity and double the rate of prolonged hospitalization due to adverse events than those catheterized for < or = 3 days.