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

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. beta 3-Adrenoceptors are predominantly expressed in the human bladder and mediate relaxation of detrusor muscle. beta 3-Adrenoceptor agonists increase bladder capacity and prolong micturition interval. It is assumed that beta 3-adrenoceptor agonists could exert an inhibitory effect on bladder afferent through beta 3-adrenoceptors in the urothelium and detrusor, which eventually improve the symptom of urgency. Mirabegron is a potent and selective beta 3-adrenoceptor agonist. A Japanese phase 3 study showed that mirabegron has excellent efficacy and safety for treating overactive bladder. a1-Adrenoceptor antagonists (a1-blockers) have become a mainstay of male lower urinary tract symptoms treatment. The a1A subtype is known to mediate functional obstruction as a result of benign prostatic enlargement. Recent studies have suggested that a1A-adrenoceptors are additionally involved in the generation of storage symptoms. The a1D subtype is thought to play a role in the facilitation of voiding reflex; that is; storage symptoms. a1-Blockers often fail to alleviate overactive bladder symptoms. In this context, combination therapy with a1-blockers and antimuscarinics has been recommended. Treatment with 5a-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 5a-reductase inhibitor reduced the rate of progression to acute urinary retention and surgery. Combination therapy with 5a-reductase inhibitor and a1-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 oxidecyclic 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.