Prostatic α1-adrenoceptors and uroselectivity

Andersson, Karl‐Erik; Lepor, Herbert; Wyllie, Michael G.

doi:10.1002/(sici)1097-0045(19970215)30:3<202::aid-pros9>3.0.co;2-n

Cited by 142 publications

(138 citation statements)

References 88 publications

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“…36 Finally, selectivity observed pharmacologically and physiologically in preclinical in vitro and animal-model settings will not necessarily play out in humans. 21 In fact, Figure 1 Pharmacological selectivity of alfuzosin, doxazosin, tamsulosin, and terazosin. 31 Figure 2 Physiological selectivity of alfuzosin, doxazosin, tamsulosin, and terazosin.…”

Section: Alpha-blockers and Uroselectivitymentioning

confidence: 99%

Alpha–1–adrenoceptor blockade in the treatment of benign prostatic hyperplasia

Lowe

1999

Prostate Cancer Prostatic Dis

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In light of the growing interest in the concept of`uroselectivity' and in the increased worldwide use of alpha-blockers for benign prostatic hyperplasia (BPH), this review evaluates the relative bene®ts of various alpha-blocking agents in the treatment of BPH. The pharmacological and physiological selectivity as well as the clinical ef®cacy and safety of alfuzosin, doxazosin (Cardura 1 ), tamsulosin (Flomax 1 ), and terazosin (Hytrin 1 ) are compared. In reviewing ef®cacy and safety, emphasis is given to 17 placebo-controlled, doubleblind trials of these alpha-blockers published in peer-reviewed journals. This review also considers long-term data, effects on blood pressure, costs, and dose ranges.

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Section: Alpha-blockers and Uroselectivitymentioning

confidence: 99%

Alpha–1–adrenoceptor blockade in the treatment of benign prostatic hyperplasia

Lowe

1999

Prostate Cancer Prostatic Dis

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“…8 This is in contrast to what has been found in the human prostate. 9 The fact that drugs acting selectively on prostatic a 1 -ARs may have little effect on lower urinary tract symptoms (LUTS) can theoretically be explained if they did not block the a 1 -ARs of the bladder. Considering the doubtful functional importance of the bladder a 1 -ARs, this seems unlikely.…”

Section: Bladder and Urethramentioning

confidence: 99%

“…9 If this is the case, a model of increased sympathetic activity should be useful for study of the role of the sympathetic nervous system in the pathogenesis of LUTS. Such a model may be the spontaneously hypertensive rat (SHR).…”

Section: Bladder and Urethramentioning

confidence: 99%

The pharmacological perspective: role for the sympathetic nervous system in micturition and sexual function

1999

Prostate Cancer Prostatic Dis

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The predominant effects of the sympathetic innervation of the lower urinary tract in man are mediation of contraction of the bladder base and the urethra and inhibition of the parasympathetic pathways at spinal and ganglion levels. Sympathetic tone also mediates the contractility of smooth muscle ®bres in the prostatic stroma, and it has an important role in maintaining the penis in a¯accid state and in ejaculation. In the detrusor muscle of most species, b-adrenoceptors (b-ARs) mediating relaxation normally dominate over a-ARs mediating contraction, and the effect of noradrenaline (NA) is relaxation. The human detrusor is able to express b 1 -, b 2 -and b 3 -ARs and stimulation of b 3 -ARs causes relaxation. Low, but reproducible expression of a 1 -ARs (a 1a and a 1d ) has been found in human detrusor muscle, but the a 1 -AR subtypes mediating contraction have not been established. The sympathetic pathways to the penis may mediate antierectile as well as erectile effects. Although a 1 and a 2 -ARs have been demonstrated in human corpus cavernosum tissue, available information supports the view of a functional predominance of a 1 -ARs. The human vas deferens also has an important adrenergic innervation and a 1A -ARs seem to mediate contraction.

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“…sustained-release (SR) alfuzosin [10]. Alfuzosin acts on the dynamic component of BPO by decreasing the sympathetically controlled tone of prostatic smooth muscle [9,11,12]. Alfuzosin has a rapid onset of action, with evidence of ef®cacy from the ®rst dose [13,14].…”

Section: Introductionmentioning

confidence: 99%

The clinical uroselectivity of alfuzosin is not significantly affected by the age of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia

et al. 2000

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The clinical uroselectivity of alfuzosin is not signi®cantly affected by the age of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia i.e. <56, 56±65, 66±75 and >75 years. All groups of patients showed a mean IPSS decrease of 11±12 (55.8±65.4% from baseline) at the end of the study, while the QoL decreased by 2±3 points (55.6±63.6% from baseline). There were no relevant effects of age on the ef®cacy of the treatment. Moreover, alfuzosin was well tolerated independently of the age of the patient; 1.2% of the patients enrolled withdrew because of adverse events. The qualitative distribution of vasodilatory/nonvasodilatory adverse events was similar in all age groups. The incidence of asymptomatic orthostatic hypotension was low (0.58%) and not affected by the age of the patients. Conclusion This study con®rms that the clinical uroselectivity of SR-alfuzosin, already described in randomized controlled studies, is not signi®cantly affected in clinical practice by the age of the patients. This is considered particularly relevant to the characteristics of patients with BPH, as they are mostly elderly men.

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Prostatic α1-adrenoceptors and uroselectivity

Cited by 142 publications

References 88 publications

Alpha–1–adrenoceptor blockade in the treatment of benign prostatic hyperplasia

Alpha–1–adrenoceptor blockade in the treatment of benign prostatic hyperplasia

The pharmacological perspective: role for the sympathetic nervous system in micturition and sexual function

The clinical uroselectivity of alfuzosin is not significantly affected by the age of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia

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