Current and emerging pharmacological targets for medical expulsive therapy

Abstract

The primary goals of medical expulsive therapy are to increase the rate of stone expulsion along the ureter to avoid ureteral obstruction and reduce ureteral colic and thus avoid the need for surgical and more invasive interventions. This review focussed on the findings from in vivo and in vitro animal and human studies that have investigated the pharmacological mechanisms controlling ureteral motility and their translation to current and potentially new clinically used drugs for increasing the rate of stone expulsion along the ureter. The complicated contractility profile of the ureter, which alters with age, tissue segment region, orientation and species contributes to the difficulty of interpreting studies on ureteral pharmacology, which translates to the complexity of discovering ideal drug targets for medical expulsive therapy. Nevertheless, the current drug classes clinically used for patients with stone lodgement include α1‐adrenoceptor antagonists, calcium channel blockers and NSAIDS, whilst there are promising targets for drug development that require further clinical investigations including the phosphodiesterase type 5 enzyme, β‐adrenoceptors and 5‐HT receptors.

Is Silodosin a Better Alternative to Tamsulosin as a Part of Medical Expulsion Therapy in Patients with Lower Uretic Calculi?

“…The frequency of ureteric peristalsis is enhanced by stimulation of alpha 1 AR precisely in the ureter. Tamsulosin has been in use for the treatment of lower uretic calculi for patients that have stones less than 10mm in size [13][14] . Previous studies have shown that it improves the rate of stones explosion, and the rate is increased with less pain and less need of analgesics 15 .…”

Translational pharmacology: Closing the mechanistic gap

“…Chua et al 4 similarly consider a common side-effect to chemotherapy, namely peripheral neuropathy, focusing on microtubule-targeting agents and how translational genetic studies covering both genome-wide association studies and functional genomic studies using pluripotent stem cells will bring us forward in our understanding of chemotherapy-induced neuropathy. Lim et al 5 review pharmacological agents of current or potential future use as medical expulsive therapy in urolithiasis, leveraging both in vitro and in vivo studies to provide recommendations for candidate drug classes for further clinical investigation. Eisenmann et al 6 review how pharmacokinetic knowledge can be used to improve the oral bioavailability of anticancer drugs by deploying intentional drug-drug interactions.…”

Safety and Efficacy of Mirabegron in Treatment of Nocturnal Enuresis in Children

“…It has been established that mirabegron is safe, efficient, and well-tolerated. In almost all trials, it produced outcomes that were comparable to placebo in terms of the prevalence of dry mouth (3) . The bladder's detrusor smooth muscle relaxes as a result of the beta-3 adrenergic receptor agonist mirabegron, which also improves bladder capacity.…”