Info

Reproduced with kind permission from Lowe, F. C. Clin. Ther. 2004, 26, 1701-1713.

Reproduced with kind permission from Lowe, F. C. Clin. Ther. 2004, 26, 1701-1713.

As a result of the key role that ^-adrenoceptors play in BPH and LUTS, a number of agents that target these receptors (e.g., aradrenoceptor antagonists) have been developed as treatments (see Section 6.24.7.2). Theoretically, an ideal agent (i.e., one with an optimal clinical profile) would be 'uroselective,' having high binding affinity for a1A-and a1D-adrenoceptors and low affinity for a1B-adrenoceptors. ^-Adrenoceptor antagonists (or a1,-blockers) can be classified based on their receptor specificity (see Table 3).

A number of other receptors are also being examined for their role in BPH and as potential treatment targets. Of clinical importance is the recent finding that estradiol and androgen receptors have different subcellular distribution in the prostate of patients with BPH and prostate cancer. Vitamin D receptors, which are expressed by the human bladder, are also being investigated as a treatment target,42 and bradykinin receptors, part of the kallikrein-kinin system, which are expressed in normal human prostate and have a role to play in cell proliferation via activation of extracellular signal-related kinases (ERK)-1/2 pathways, are also being explored.43 For more information on choosing targets see Chapter 2.19.

6.24.7.2 Pharmacotherapy 6.24.7.2.1 a1 - Adrenoceptor antagonists a^Adrenoceptor antagonists 'block' the adrenoceptors in the prostate and bladder neck, causing the smooth muscle to relax, which results in an improvement in urine flow and a decrease in residual bladder volume. The four ar adrenoceptor antagonists recommended by both the EAU and AUA guidelines are alfuzosin, doxazosin, terazosin (quinazoline derivatives), and tamsulosin (sulfonamide derivative) (see Figure 14 for structures). Indirect comparisons of placebo-controlled studies using the a^adrenoceptor antagonists alfuzosin, doxazosin, terazosin, and tamsulosin have shown that they have comparable efficacy; symptom scores are improved by 30-45% and Qmax by 15-30% versus baseline.44 More recently, there is evidence to suggest that doxazosin and terazosin also have proapoptotic effects in the prostate epithelium and stroma.45

ch3o.

ch3o

Diabetes Sustenance

Diabetes Sustenance

Get All The Support And Guidance You Need To Be A Success At Dealing With Diabetes The Healthy Way. This Book Is One Of The Most Valuable Resources In The World When It Comes To Learning How Nutritional Supplements Can Control Sugar Levels.

Get My Free Ebook


Post a comment