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Latest treatment for lower urinary tract dysfunction: therapeutic agents and mechanism of action.
Int J Urol. 2013 Jan; 20(1):28-39.IJ

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. β(3)-Adrenoceptors are predominantly expressed in the human bladder and mediate relaxation of detrusor muscle. β(3)-Adrenoceptor agonists increase bladder capacity and prolong micturition interval. It is assumed that β(3)-adrenoceptor agonists could exert an inhibitory effect on bladder afferent through β(3)-adrenoceptors in the urothelium and detrusor, which eventually improve the symptom of urgency. Mirabegron is a potent and selective β(3)-adrenoceptor agonist. A Japanese phase 3 study showed that mirabegron has excellent efficacy and safety for treating overactive bladder. α(1)-Adrenoceptor antagonists (α(1)-blockers) have become a mainstay of male lower urinary tract symptoms treatment. The α(1)(A) subtype is known to mediate functional obstruction as a result of benign prostatic enlargement. Recent studies have suggested that α(1)(A)-adrenoceptors are additionally involved in the generation of storage symptoms. The α(1)(D) subtype is thought to play a role in the facilitation of voiding reflex; that is; storage symptoms. α(1)-Blockers often fail to alleviate overactive bladder symptoms. In this context, combination therapy with α(1)-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 α(1)-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.

Authors+Show Affiliations

Division of Bioengineering and LUTD Research, Nihon University School of Engineering, Koriyama, Japan. yamaosa@ee.ce.nihon-u.ac.jp

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

23190275

Citation

Yamaguchi, Osamu. "Latest Treatment for Lower Urinary Tract Dysfunction: Therapeutic Agents and Mechanism of Action." International Journal of Urology : Official Journal of the Japanese Urological Association, vol. 20, no. 1, 2013, pp. 28-39.
Yamaguchi O. Latest treatment for lower urinary tract dysfunction: therapeutic agents and mechanism of action. Int J Urol. 2013;20(1):28-39.
Yamaguchi, O. (2013). Latest treatment for lower urinary tract dysfunction: therapeutic agents and mechanism of action. International Journal of Urology : Official Journal of the Japanese Urological Association, 20(1), 28-39. https://doi.org/10.1111/iju.12008
Yamaguchi O. Latest Treatment for Lower Urinary Tract Dysfunction: Therapeutic Agents and Mechanism of Action. Int J Urol. 2013;20(1):28-39. PubMed PMID: 23190275.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Latest treatment for lower urinary tract dysfunction: therapeutic agents and mechanism of action. A1 - Yamaguchi,Osamu, Y1 - 2012/11/28/ PY - 2012/10/15/received PY - 2012/10/16/accepted PY - 2012/11/30/entrez PY - 2012/11/30/pubmed PY - 2013/7/3/medline SP - 28 EP - 39 JF - International journal of urology : official journal of the Japanese Urological Association JO - Int J Urol VL - 20 IS - 1 N2 - 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. β(3)-Adrenoceptors are predominantly expressed in the human bladder and mediate relaxation of detrusor muscle. β(3)-Adrenoceptor agonists increase bladder capacity and prolong micturition interval. It is assumed that β(3)-adrenoceptor agonists could exert an inhibitory effect on bladder afferent through β(3)-adrenoceptors in the urothelium and detrusor, which eventually improve the symptom of urgency. Mirabegron is a potent and selective β(3)-adrenoceptor agonist. A Japanese phase 3 study showed that mirabegron has excellent efficacy and safety for treating overactive bladder. α(1)-Adrenoceptor antagonists (α(1)-blockers) have become a mainstay of male lower urinary tract symptoms treatment. The α(1)(A) subtype is known to mediate functional obstruction as a result of benign prostatic enlargement. Recent studies have suggested that α(1)(A)-adrenoceptors are additionally involved in the generation of storage symptoms. The α(1)(D) subtype is thought to play a role in the facilitation of voiding reflex; that is; storage symptoms. α(1)-Blockers often fail to alleviate overactive bladder symptoms. In this context, combination therapy with α(1)-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 α(1)-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. SN - 1442-2042 UR - https://www.unboundmedicine.com/medline/citation/23190275/Latest_treatment_for_lower_urinary_tract_dysfunction:_therapeutic_agents_and_mechanism_of_action_ L2 - https://doi.org/10.1111/iju.12008 DB - PRIME DP - Unbound Medicine ER -