Silodosin, Tadalafil Alone vs. Silodosin Plus Tadalafil as MET for Lower Ureteric Stones

The global incidence of urolithiasis, a disease with a high recurrence rate, is increasing. Urolithiasis is one of the most common disorders of the urinary tract with a lifetime prevalence of up to 15% with men affected three times more than women.

Urolithiasis causes recurrent stone formers to experience a decline in quality of life, and there is an increasing socioeconomic burden associated with the management of urolithiasis. Improved quality of life may also have increased its prevalence. A significant proportion, about 1/5th of urinary tract stones, is found in the ureter, of which 2/3rd is seen in the distal ureter. Initially, a colicky pain of various grades presents with ureteric stone. It is one of the most common problems that compel a patient to an emergency room.

Methods to manage ureteral stones include conservative treatment, pharmacological treatment (e.g., medical expulsive therapy), shock wave lithotripsy, and surgical treatment. Thus, urologists must select the appropriate treatment for each patient (i.e., non-surgical or surgical). Today, medical expulsive therapy has become the most used modality of treatment for urolithiasis. During this treatment, the ureter smooth muscle is treated via various drugs by different mechanisms.

Blocking alpha-(α-) 1 adrenergic receptor, especially in the distal third decreases basal smooth muscle contraction and causes propulsive antegrade peristalsis helping stone expulsion. By increasing the intraureteral pressure gradient around the stone, alpha-1 adrenergic receptor antagonists eject distal ureteral stones.

Significant pathological changes can occur when ureteric stones are impacted. +is can cause an inflammatory reaction with mucosal edema which could further worsen the ureteric obstruction, increasing the risk of impaction and retention. However, selective alpha-1 blockers, such as tamsulosin and silodosin, have been the treatment of choice, with proven efficacy in multiple clinical trials. Silodosin is a more selective α-1A adrenoceptor blocker with a better stone expulsion rate than tamsulosin.

Recently, a newer Phosphodiesterase type 5 inhibitor, tadalafil, has shown action on the nitric oxide-cyclic guanosine monophosphate signaling pathway of smooth muscles, resulting in increased levels of cyclic guanosine monophosphate, causing ureteric relaxation.

Due to its smooth muscle relaxation mechanism, tadalafil has received US Food and Drug Administration approval to treat many urinary tract diseases. Therefore, the combination of silodosin and tadalafil drugs is aimed to facilitate stone passage by better ureteric relaxation and reducing intramural ureter pressure. Although there have been few similar studies using various combinations, comparing the efficacy of silodosin and tadalafil vs. silodosin are very few, and these studies have taken longer duration of treatment (4 to 6 weeks) which might have affected the outcome.