EFFICACY OF TAMSULOSIN AND ALFUZOSIN IN MANAGEMENT OF DISTAL URETERAL STONES

Introduction: Urinary tract calculi are the most frequent condition in urology clinics worldwide. The overall prevalence is about 5 % and lower urinary tract stones account for 70% among them. Medical expulsive therapy has been used to treat distal ureteric stone as it reduces symptoms and facilitates stone expulsion. The aim of this study is to evaluate and compare the efficacy of tamsulosin and alfuzosin as medical therapy in ureteric stones.


INTRODUCTION
Urinary tract calculi are the most frequent condition in urology clinics worldwide. The overall prevalence is about 7-13% in North America, 5-9% in Europe and 1-5% in Asia and the incidence of the disease seems to be increasing. 1 For small stone, observation and medical therapy is also one of the treatment options for management whereas, failure of the medical therapy and for larger stones requires either minimal invasive approach or open surgery. 2 The 2016 Guideline for Surgical Management of stones of The American Urological Association (AUA) recommend observation with medical therapy (alpha blockers) for distal ureteric stone size <10 mm in diameter and symptoms that are well controlled. 3 Medical expulsive therapy (MET) has been used as an adjunct to watchful waiting which is often unpredictable. Pharmacological measures are directed to reduce the edema of the ureter and ureteric spasm. 4 Blocking of these receptors (α1-blockers) which are dispersed along the entire course of the ureter with the highest density in the distal ureter, causes relaxation of the ureteric musculature, decreases the basal tone, and inhibits the rate of peristalsis and colic, thus facilitating the passage of stones. 4,5 The main objective of this study was to analyze the effectiveness of tamsulosin and alfuzosin in the conservative management of uncomplicated, symptomatic distal ureteric stones. were included in the study. Patients with urinary tract infection, single kidney, deranged kidney function tests at presentation, severe hydronephrosis, bilateral ureteric calculi, lactation or pregnancy, current use of α-blockers, calcium channel blockers or steroids, age less than 18 years, and any allergic reaction to the drugs were excluded from the study.

This
At the initial visit, a detailed history was taken, physical examination was done and urinalysis and serum creatinine levels were sent. All patients were evaluated with an ultrasound of the abdomen and pelvis and x-ray KUB and the size of the stone was calculated based on ultrasound abdomen and pelvis. CT abdomen was done in case of failure of medical therapy and if the pain did not resolve with the usual dose of medication or development of any complications.
Patients were divided into three groups. All the patients in three groups received diclofenac sodium (50 mg, tablet) two times a day for 7 days and then injection diclofenac sodium 50 mg as needed up to twice daily. Patients in Group A received 0.4 mg of Tamsulosin per day, patients in Group B received 10 mg of Alfuzosin per day and patients in Group C received 75 mg of Diclofenac sodium daily for 28 days or clinical and radiological evidence of spontaneous stone expulsion whichever is shorter. Failure of the spontaneous expulsion of the stone by the end of 28 days was regarded as treatment failure and patients were advised for surgical intervention.
All patients were followed on days 7, 14, 21, and 28. During each follow-up visit, patients were evaluated with serum creatinine level, urine analysis, a plain x-ray KUB and ultrasonography of the abdomen. Time to the spontaneous passage of stones and any side effects of the drugs were also noted.
Statistical analysis was performed by using Statistical Package for Social Sciences (SPSS) for Windows version 19. ANOVA was used for continuous variables and the chi-square test was used for categorical variables. p-value <0.05 was considered clinically significant.

RESULTS
The study consisted of 87 patients. No significant differences were found in baseline characteristics of the 3 groups (Table 1).
The rate of spontaneous stone expulsion was highest in group A (83.3%) and lowest in group C (50%). Group A and group B had a statistically significant stone expulsion rate as compared to the control group (group C), p-value 0.006 and 0.02 respectively and there was no significant difference between Group A and Group B (p=0.69) in terms of rate of stone expulsion. Similarly, a significant statistical difference was observed in terms of stone expulsion time between Group A and B as compared to Group C (p=0.01) ( Table 2) Four patients in group A and two patients in group B developed retrograde ejaculation while postural hypotension was seen in two and one patients in Group A and Group B respectively. Two patients in group B also had nasal congestion as side effects, during the study period.

DISCUSSION
There are different methods for the treatment of the ureteral stones including ureterorenoscopy, percutaneous approaches, extracorporeal shockwave lithotripsy and open ureterolithotomy. Some believe that uncomplicated ureteral stones with maximum diameter less than 10 mm should be observed if they pass without treatment.
Size of the stone is directly proportional to the rate of spontaneous expulsion. Coll DM et al reported that the spontaneous stone expulsion rate was 87% for stones 1 mm in diameter, whereas it was 25% for stones more than 9mm. 6 Ahmed et al in their study found that spontaneous stone passage rate was 88.6% for stones less than 5 mm and 67.9% for stones 5-10 mm. They also noticed that stone passage rate was 33.3%, 81.6% and 91.6% for stones located at upper, middle and lower ureter respectively and concluded that the stone passage rate is highly variable and depends on the size, site of the stone. 7 On our study, the rate of spontaneous stone expulsion for distal ureteric stone with only observation was 50% over a period of 4 weeks.
Tamsulosin and alfuzosin are the most commonly used for MET with majority of the studies showing statistically significant differences between the patients who use the drugs when compared to control group.
In a study by Sun, Yi et al, tamsulosin significantly increased the passage of distal ureteral stones and the stone passage rate was greater in those with stones greater than 6 mm in diameter. 8 Similarly, Nuraj et al in their study found a significant difference between stone expulsion rate for patients using tamsulosin and placebo which were 90.4% and 71.2% respectively in distal ureteric calculi. 9 Singal et al in their study observed stone expulsion rate of 72% in patients using tamsulosin, 68% with alfuzosin. 10 These results were comparable to present study which showed the stone passage rate of 83.3% and 79.3% with tamsulosin and alfuzosin respectively compared to analgesic only which had stone passage rate of 50% only.

CONCLUSION
Tamsulosin and alfuzosin are safe and equally effective options for medical expulsive therapy of ureteric stone in distal part of the ureter because both increase the stone passage rate, taking less time to stone expulsion.