Using Drugs to Expel Stones
Medical expulsion therapy increased stone passage rate by 29%, meta-analysis showed.
Alpha blockers improve stone passage rates, decrease time to expulsion.
In 2007, an international panel convened by the American Urological Association (AUA) and the European Association of Urology (EAU) updated the AUA ureteral stone guidelines.
Most notably, the new guidelines reflect a pragmatic addition to the urologist's armamentarium: medical expulsive therapy (MET). MET is defined as the use of pharmaceutical agents to improve urinary stone passage rates and the time to stone passage in select individuals.
Most small stones will pass spontaneously without the need for intervention. From 71%-98% of stones less than 5 mm in size will pass without surgery.1 However, stones can induce ureteral spasm, which can hinder stone passage.2 The ureter has several types of receptors and cell to cell interactions that may play a role.
Alpha receptors are present in the human ureter, and selective alpha blockers such as tamsulosin have been shown to inhibit basal tone and decrease the frequency and amplitude of peristalsis in the ureter.3
The AUA/EAU guidelines included a meta-analysis of the randomized controlled trials (RCT) available evaluating alpha blockers as medical expulsive agents. This analysis found that use of MET significantly increased stone passage rate by 29%.4 One study compared three available alpha blockers (tamsulosin, terazosin, and doxazosin) in a clinical RCT and found similar stone passage rates among them.5
Not only do alpha blockers appear to improve stone passage rates, but they also decrease the time to stone expulsion. A study by Porpiglia et al compared tamsulosin to nifedipine in 86 patients with distal ureteral calculi measuring less than 1 cm. Patients were randomized to receive deflazacort (a corticosteroid) with either nifedipine or tamsulosin or to a control group. Stone passage was observed in 80% in the nifedipine group, 85% in the tamsulosin group and 43% in the control group. Average expulsion time was 9.3, 7.7 and 12 days for the three groups, respectively.6
The majority of the published RCTs combined a corticosteroid with an alpha blocker to improve spontaneous stone passage rates. Dellabella et al evaluated the efficacy of tamsulosin with deflazacort in patients with distal stones. Sixty patients were randomized to receive a combination of phloroglucinol-trimethoxybenzene (an oral antispasmolytic), deflazacort, and cotrimoxazole, or this combination plus tamsulosin 0.4 mg daily. The tamsulosin group showed a significantly higher stone-expulsion rate (100% vs. 70%) and a shorter stone expulsion time (65.7 vs. 111.1 hours). No drug-related side effects were reported and hospital stays were dramatically decreased in the tamsulosin group.7
The benefits of alpha blockers are not just limited to stone patients who are able to take corticosteroids concurrently. A meta-analysis of the available MET data by Hollingsworth et al suggests that the additive benefit of corticosteroids as an adjunct to alpha blocker therapy is small, and that MET also provided the advantage of fewer pain episodes, lower analogue pain scores, and lower analgesic dose requirements.8
Dellabella et al described the additional benefit of steroids as an increase in expulsion rate from 90% with tamsulosin alone to 96.7% in patients receiving the alpha blocker plus deflazacort. The patients taking the tamsulosin/deflazacort combination also decreased their time to stone passage to 72 hours compared with 120 hours in those on tamsulosin monotherapy. They concluded that both regimens were highly effective.9
These studies, along with others, have made tamsulosin a commonly used agent. The rationale for this is based on efficacy, tolerability, and the comfort level urologists have in using tamsulosin for BPH management.