Comparison between Rowatinex and Tamsulosin as a Medical Expulsion Therapy for Ureteral Stone

The objective of this study is to evaluate the efficacy and safety of rowatinex and tamsulosin in the treatment of patients with ureteric stone. Forty patients with ureteric stone ranged (412) mm, were included in this study. They were randomized into two groups where the first group includes twenty patients treated with Rowatinex three times daily (Group 1), and the second group includes twenty patients treated with tamsulosin 0.4mg/day (Group 2). All patients were randomly assigned to receive the designed standard medical therapy for a maximum of 3 weeks. Each group was given an antibiotic as prophylaxis and an injectable non-steroidal anti-inflammatory drug used on demand. At the outpatient clinic all subjects were assessed by CT-scan at baseline and evaluated every 7 days by physical examination, plain abdominal X-ray (KUB), and abdominal ultrasonography. Data were analyzed by using Student t-test method to compare the results; differences in the success rate between treatments were compared with the chi-square test for 2× 2 tables. The results showed that tamsulosin significantly increases the expulsion rate, and reduce expulsion time of ureteric stone when compared with rowatinex group. Tamsulosin results in a better control of renal colic pain, and decreases in endoscopic procedures performed to remove the stone.


Introduction
Urolithiasis is a common disease worldwide and its incidence in Western countries is growing (1) .Urolithiasis has been considered as a significant source of morbidity , affecting all geographical,cultural, and racial groups.The risk of developing urolithiasis throughout lifetime is about 10 -15% in the developed countries, but can be as high as 20 -25% in the Middle East.
The increased risk of dehydration in hot climates, coupled with a diet that is 50% lower in calcium and 250% higher in oxalates compared to Western diets, accounts for the higher net risk in the Middle East . (2)Stones <3 mm in diameter have a better chance to pass spontaneously in the majority of cases, whereas stones>6 mm in the ureter are unlikely to pass in most situations (3) .
Many factors are involved in the interaction between the ureter and stones, therefore it is useful to understand mechanisms involved in the contraction and relaxation of the ureter.These mechanisms would possibly lead to discovery of new drugs that might facilitate stone passage, relieve symptoms and act as an adjunctive treatment to existing conventional modalities (4) .
Minimal invasive treatment strategies such as extracorporeal shockwave lithotripsy and ureteroscopy are frequently applied procedures in ureteral stone disease.However, indications for watchful waiting might be extended by addition of so-called 'medical expulsive therapy'(MET).
MET developed from several physiologic and pathophysiologic premises.Alpha 1 adrenoceptors (AR) have also been reported to mediate contractile responses in the ureter, and there is evidence that α-1 receptors predominate in ureteral smooth muscle (5,6) .
Alpha-adrenoceptors (AR) -1A,-1B and -1D subtypes were found to be localized in human ureter irrespective of location. (7).Sympathetic nerve bundles were distributed throughout the entire ureter.Therefore, a1-adrenergic receptor antagonists may act on the entire ureter, reducing its tonus.As a result, these antagonists may be useful for improving the stone freeing rate and inhibiting pain attacks (8) .
Several studies have demonstrated that lower tract ureteral stones can be treated efficiently with different types of alpha1blockers with a low incidence of side effects (9) .Of the available alpha1-blockers, we chose tamsulosin because it is a combined alpha1A and alpha1D-selective adrenergic antagonist and the existence of alpha1A and alpha1D-adrenoceptor subtypes have been demonstrated in the smooth muscle cells of the human ureter (10) .
Rowatinex is a special terpenes combination and is considered to have diuretic, antiinflammatory and analgesic properties.In a randomized clinical trial, Rowatinex improved stone-free rates and reduced symptoms during stone passage (11) .Rowatinex is considered to be a traditional therapy for ureteral stones, and selected to be used in this study as comparative drug.This study was conducted to evaluate the efficacy and safety rowatinex and tamsulosin in the treatment of patients with ureteric stone.

Patients and Methods
This study was conducted prospectively at Al-Basra General Hospital from October 2011 till the end of April 2012.Forty Patients with ureteric stone ranged from 4mm to12mm (mean 8 ± 2.3), were randomized into 2 groups.patients age ranged from 18 to 65 year (mean 35.27 ± 14.7), of which 31 patients (77.5%) were males and 9 patients (22.5%) were females.The first group (Group 1) was treated with rowatinex three times daily for 3 weeks, and the second group (Group 2) was treated with tamsulosin 0.4 mg once daily for 3 weeks.In the first group the percentage of the proximal, middle, and distal ureteric stones were found to be 45%,30%, and 25% respectively, while, in the second group they were found to be 55%, 30%, and 15% respectively.
Both groups were given an antibiotic as prophylaxis during the medical expulsive therapy period and an injectable nonsteroidal anti-inflammatory drug used on demand.At the outpatient clinic all subjects were assessed by CT-scan at baseline and evaluated every 7 days by physical examination, plane abdominal X-ray (KUB), and abdominal ultrasonography.Data were analyzed by using Student t-test method used to compare the results and these data were represented as mean ± standard error of the mean (SE), differences in the success rate between treatments were compared with the chi-square test for 2× 2 tables .

Results
The data in table (1) showed that expulsion rate in patients treated with tamsulosin ( group 2) was significantly higher (p<0.05)than that of patients treated with rowatinex (group1) for the same course time.Significant reduction (p<0.05) in expulsion time was obtained from treatment with tamsulosin when compared with results of treatment with rowatinex as shown in table (2).

Table 2: The effects of rowatinex and tamsulosin on expulsion time of ureteric stone.
Values expressed as mean + standard error of mean.* Significantly different at (p<0.05).
As shown in table (3), the percent of patient experience colic episode was significantly lower (p<0.05) in patients treated with tamsulosin when compared to the percent of patient experience colic episode in patients treated with rowatinex.At the same time, the total number of colic episodes in the group of patients treated with tamsulosin was significantly lower (p<0.05)than that of patients treated with rowatinex.

Table 3: The effects of rowatinex and tamsulosin on the incidence of colic episodes in patients with ureteric stone.
* Significantly different at (p<0.05).* Significantly different at (p<0.05).Table (4) represents the total number of ureteroscopic (URS) procedures performed to remove the stone, the data showed that the total number of ureteroscopy in the group treated with rowatinex was significantly higher (p<0.05) as compared to those of group treated with tamsulosin.

Discussion
Tamsulosin, a selective α-1A-, α -1D adrenergic antagonist, which has been recently used to treat ureteral stones, achieving unexpected and startling results.The rationale for its use for this pathological condition was taken from several studies.Sympathetic nerve fibers seem to be distributed throughout the entire ureter, and therefore, α-1-blockers would seem to be effective for elimination of ureteral stones irrespective to their locations (7,12,13) .
In this study, tamsulosin 0.4mg/d shows a significant advantage on the expulsion rate of ureteric stone over rowatinex.The data in table (1) showed that expulsion rate in patients treated with tamsulosin was significantly higher (p<0.05)than that of patients treated with rowatinex for the same course time.
The results also demonstrated that patients treated with tamsulosin were associated with a greater tendency to reduce the expulsion time when compared with rowatinex.
These results were consistence with those obtained by M. Dellabella et.al. (14)who found that , the use of tamsulosin in treatment regimen produced stone expulsion in almost all cases in a short time, allowing complete home patient treatment.Tables (3,4), represent that patients treated with tamsulosin showed better control of renal colic pain as well as demonstrated by the fact that less patients in this group was urgently hospitalized during the study period.The causes of pain related to ureteral colic are the strain on muscular nerve endings and mucosa, which is caused by the increase in ureteral intraluminal pressure resulting from lithic obstruction and the production of lactic acid due to smooth muscle spasm.The stimulus is transferred to the spinal cord through type A slow fibers and type C fast fibers, and then to the cerebral centers.α-1 receptor blockade results in the reduction of visceral pain and it has been assumed that this αadrenergic blockade occurs in C-fibers (15,16) .
Therefore, according to our clinical results it would be possible to suppose a double action of tamsulosin on the control of pain associated with ureteral colic, that is a first action on smooth muscles, preventing spasm, and a second action on C-fibers or sympathetic postganglionic neurons, which also blocks pain conduction to the central nervous system.
Our results clinically supporting the validity of the hypothesis of the role of α-adrenergic receptors in the physiology of ureteral motility and the pathophysiology of renal colic . (17,18).

Table 1 : The effects of rowatinex and tamsulosin on the expulsion rate of ureteric stone.
* Significantly different at (p<0.05)

Table 4 : Effect of treatment with rowatinex and tamsulosin on the total number of ureteroscopic procedures performed to remove the ureteral stone.
Significantly different at (p<0.05). *