de Mey C
Applied Clinical Pharmacology Services, Mainz-Kastel, Germany.
Eur Urol. 1998;34 Suppl 2:18-28; discussion 47.
Alpha-adrenoceptor antagonists (alpha-blockers) are efficacious in treating lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO), also termed symptomatic benign prostatic hyperplasia (BPH), causing bladder outlet obstruction (BOO). There is little difference among the various alpha-blockers in terms of efficacy in treating LUTS. However, conventional quinazoline derivatives such as terazosin, doxazosin and alfuzosin, originally developed for hypertension, have inherent cardiovascular extension effects, which influence the well being and safety of patients with LUTS by impairing physiological blood pressure (BP) control, even when their effect on unchallenged BP may be quite low. Preclinically, tamsulosin, a sulphonamide-substituted phenethylamine, has a relative selectivity for the alpha 1-adrenoceptors of the lower urinary tract. Clinically, this is associated with fewer cardiovascular extension effects with tamsulosin (modified release capsule) 0.4 mg once daily. This allows the use of convenient regimens of 0.4 mg tamsulosin administered once daily after breakfast from initiation of treatment without the need for 'step-up' increases of dose to avoid 'first-dose' hypotension. Extensive investigation, including multiple orthostatic stress testing (which otherwise is unusual in the characterization of alpha-blockers because of their inherent safety), confirms that tamsulosin 0.4 mg definitely carries a lower risk of impaired BP control.
α-肾上腺素能受体拮抗剂(α阻滞剂)在治疗提示良性前列腺梗阻(BPO)的下尿路症状(LUTS)方面有效,BPO也被称为有症状的良性前列腺增生(BPH),可导致膀胱出口梗阻(BOO)。各种α阻滞剂在治疗LUTS的疗效方面差异不大。然而,传统的喹唑啉衍生物,如最初用于治疗高血压的特拉唑嗪、多沙唑嗪和阿夫唑嗪,具有固有的心血管扩张作用,即使它们对未受刺激的血压影响可能很低,但会通过损害生理性血压(BP)控制来影响LUTS患者的健康和安全。临床前研究表明,坦索罗辛(一种磺酰胺取代的苯乙胺)对下尿路的α1-肾上腺素能受体具有相对选择性。临床上,这与服用0.4mg坦索罗辛(缓释胶囊)每日一次时较少的心血管扩张作用相关。这使得从治疗开始就可以采用方便的给药方案,即早餐后每日一次服用0.4mg坦索罗辛,而无需“逐步增加”剂量以避免“首剂”低血压。广泛的研究,包括多次直立位应激试验(由于α阻滞剂固有的安全性,这种试验在α阻滞剂的特性描述中并不常见)证实,0.4mg坦索罗辛确实具有较低的血压控制受损风险。