Latest treatment for lower urinary tract dysfunction: Therapeutic agents and mechanism of action

Authors


Correspondence: Osamu Yamaguchi M.D., Ph.D., Division of Bioengineering and LUTD Research, Nihon University School of Engineering, Koriyama 963-8642, Japan. Email: yamaosa@ee.ce.nihon-u.ac.jp

Abstract: 

Recent studies suggest that antimuscarinics might suppress bladder afferent activity by blocking muscarinic receptors in the urothelium, myofibroblasts and detrusor, thereby improving overactive bladder symptoms. β3-Adrenoceptors are predominantly expressed in the human bladder and mediate relaxation of detrusor muscle. β3-Adrenoceptor agonists increase bladder capacity and prolong micturition interval. It is assumed that β3-adrenoceptor agonists could exert an inhibitory effect on bladder afferent through β3-adrenoceptors in the urothelium and detrusor, which eventually improve the symptom of urgency. Mirabegron is a potent and selective β3-adrenoceptor agonist. A Japanese phase 3 study showed that mirabegron has excellent efficacy and safety for treating overactive bladder. α1-Adrenoceptor antagonists (α1-blockers) have become a mainstay of male lower urinary tract symptoms treatment. The α1A subtype is known to mediate functional obstruction as a result of benign prostatic enlargement. Recent studies have suggested that α1A-adrenoceptors are additionally involved in the generation of storage symptoms. The α1D subtype is thought to play a role in the facilitation of voiding reflex; that is; storage symptoms. α1-Blockers often fail to alleviate overactive bladder symptoms. In this context, combination therapy with α1-blockers and antimuscarinics has been recommended. Treatment with 5α-reductase inhibitor for 1 year improves urinary symptoms and flow rate by reducing prostatic volume in men with benign prostatic enlargement. A pooled analysis showed that the long-term (2 or 4 years) treatment with 5α-reductase inhibitor reduced the rate of progression to acute urinary retention and surgery. Combination therapy with 5α-reductase inhibitor and α1-blocker was shown to provide a rapid improvement in lower urinary tract symptoms, and reduce the relative risk of acute urinary retention and benign prostatic hyperplasia-related surgery. Phosphodiesterase inhibitors might target a nitric oxide–cyclic guanosine monophosphate pathway in the prostate, urethra and bladder. Phosphodiesterase-5 inhibitors (sildenafil or tadalafil) were shown to provide clinically relevant improvements in both male lower urinary tract symptoms and erectile dysfunction.

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