Combination Treatment With an α-Blocker Plus an Anticholinergic for Bladder Outlet Obstruction: A Prospective, Randomized, Controlled Study

Athanasopoulos, Anastasios; Gyftopoulos, Kostis; Giannitsas, Konstantinos; Fisfis, J.; Perimenis, Petros; Barbalias, George A.

doi:10.1097/01.ju.0000067541.73285.eb

Cited by 242 publications

(175 citation statements)

References 18 publications

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“…This synergistic mechanism may contribute to the prevention of urinary reflux into the ureter and increase outflow closure pressure, as the trigone is sited to regulate both functions. This synergy may explain why combination therapies of antimuscarinic and α-receptor blockers agents are particularly effective in reducing LUTS symptoms, even in men with outflow tract obstruction (Athanasopoulos et al, 2003;Lee et al, 2004;Kaplan et al, 2007;Royner et al, 2008), where there has been reluctance to prescribe antimuscarinic agents for fear of urinary retention.…”

Section: The Bladder Basementioning

confidence: 99%

The physiological function of lower urinary tract smooth muscle

Fry

Meng

Young

2010

Autonomic Neuroscience

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Section: The Bladder Basementioning

confidence: 99%

The physiological function of lower urinary tract smooth muscle

Fry

Meng

Young

2010

Autonomic Neuroscience

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“…45 Combination therapy with the α-blocker tamsulosin and the anticholinergic tolterodine in 25 men with BOO and detrusor instability was shown to improve quality of life over treatment in 25 patients with α-blocker alone. 46 A risk of using anticholinergics in men with LUTS secondary to BOO is precipitating urinary retention. This question was recently addressed in a study in which 221 men with BOO were randomized to tolterodine immediate release compared with placebo.…”

Section: Men With Lutsmentioning

confidence: 99%

COMBINED USE OF Α-Adrenergic AND MUSCARINIC ANTAGONISTS FOR THE TREATMENT OF VOIDING DYSFUNCTION

2005

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Purpose-We provide an overview of the medical literature supporting the combined use of muscarinic and α-adrenergic antagonist therapy for the treatment of voiding dysfunction. The MEDLINE database (1966 of the United States National Library of Medicine was searched for pertinent studies. Materials and Methods-Results-Although the mechanism of action of α-adrenergic antagonist therapy for voiding dysfunction has traditionally been assumed to be relaxation of the periurethral, prostatic and bladder neck smooth muscle, substantial evidence supports action at extraprostatic sites involved in micturition, including the bladder dome smooth muscle, peripheral ganglia, spinal cord and brain. Likewise the mechanism of action of anticholinergic therapy has been traditionally assumed to be inhibition of the M 3 muscarinic receptor subtypes that mediate normal bladder contractions. However, M 2 receptor mediates hypertrophied bladder contractions and there is evidence for an M 2 component to the suprasacral control of voiding.Conclusions-Based on the physiology of α-adrenergic and muscarinic receptors the inhibition of each one would be expected to be more beneficial than that of either alone because they would work on 2 components of detrusor function. Patients who would likely benefit from this combination therapy are men with lower urinary tract symptoms, women with urgency/frequency syndrome (overactive bladder), patients with uninhibited bladder contractions due to neurogenic bladder, and patients with pelvic pain and voiding symptoms, ie interstitial cystitis and chronic prostatitis/chronic pelvic pain syndrome. Keywordsbladder; prostate; adrenergic alpha-antagonists; muscarinic antagonists; urination disorders The wide range of patients who might benefit from this type of treatment combination is considered to be large, perhaps several times the estimated 17 million patients in the United States with overactive bladder. 1 A patent application has been filed for the treatment of lower urinary tract (LUT) symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) with this combination. 2

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“…As DO is thought to contribute to symptoms in 40-70% of patients with BOO, 6 it is rational to expect that combination therapy with an a 1 -ARA and an antimuscarinic would alleviate LUTS and improve QoL. 46 A study 46 of 50 men with urodynamically proven mild or moderate BOO and DO investigated the use of an a 1 -ARA (tamsulosin) in combination with an antimuscarinic (tolterodine). Patients were initially treated with tamsulosin (0.4 mg d À1 ) for 1 week.…”

mentioning

confidence: 99%

“…Statistically significant differences in maximum detrusor pressure and maximum unstable contraction pressure were present only in the combination therapy group. 46 Another group randomly assigned 211 men with OAB and urodynamically proven BOO to receive doxazosin controlled release 4 mg d À1 or doxazosin controlled release 4 mg d…”

mentioning

confidence: 99%

The role of combination medical therapy in benign prostatic hyperplasia

Greco

McVary

2008

Int J Impot Res

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To review key trials of monotherapy and combination therapy of a 1 -adrenergic receptor antagonists (a 1 -ARAs), 5a-reductase inhibitors (5aRIs) 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 was conducted for relevant trials and reviews using the terms benign prostatic hyperplasia, lower urinary tract symptoms, a 1 -adrenergic receptor antagonists, 5a-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 a 1 -ARAs and 5aRIs in combination. In the MTOPS study, combination therapy with the a 1 -ARA doxazosin and the 5aRI finasteride was significantly more effective than either component alone in reducing symptoms (P ¼ 0.006 vs doxazosin monotherapy; Po0.001 vs finasteride monotherapy) and in lowering the rate of clinical progression (Po0.001 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 a 1 -ARA tamsulosin and the 5aRI 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 a 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 a 1 -ARA and 5aRI combination was shown in patients with larger prostate size and more severe symptoms. The combination of a 1 -ARAs and 5aRIs appears to prevent disease progression in these patients. The combination of a 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 a 1 -ARAs may benefit from the addition of an antimuscarinic agent.

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Combination Treatment With an α-Blocker Plus an Anticholinergic for Bladder Outlet Obstruction: A Prospective, Randomized, Controlled Study

Cited by 242 publications

References 18 publications

The physiological function of lower urinary tract smooth muscle

The physiological function of lower urinary tract smooth muscle

COMBINED USE OF Α-Adrenergic AND MUSCARINIC ANTAGONISTS FOR THE TREATMENT OF VOIDING DYSFUNCTION

The role of combination medical therapy in benign prostatic hyperplasia

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