The Use of Alpha-Blockers for the treatment of Nephrolithiasis


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The Use of Alpha-Blockers for the treatment of Nephrolithiasis

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The Use of Alpha-Blockers for the treatment of Nephrolithiasis

  1. 1. ALPHA-BLOCKER THERAPY FOR UROLOGICAL DISORDERSThe Use of Alpha-Blockers for theTreatment of NephrolithiasisMichael Lipkin, MD, Ojas Shah, MDDepartment of Urology, New York University School of Medicine, New York, NYMedical expulsion therapy has been shown to be a useful adjunct to observa-tion in the management of ureteral stones. Alpha-1-adrenergic receptor an-tagonists have been studied in this role. Alpha-1 receptors are located in thehuman ureter, especially the distal ureter. Alpha-blockers have been demon-strated to increase expulsion rates of distal ureteral stones, decrease time toexpulsion, and decrease need for analgesia during stone passage. Alpha-blockers promote stone passage in patients receiving shock wave lithotripsy,and may be able to relieve ureteral stent–related symptoms. In the appropri-ate clinical scenario, the use of -blockers is recommended in the conserva-tive management of distal ureteral stones.[Rev Urol. 2006;8(suppl 4):S35-S42]© 2006 MedReviews, LLCKey words: Alpha-blockers • Ureteral stones • Kidney stones R ecent advances in endoscopic stone management have allowed kidney stones to be treated using minimally invasive techniques, which have increased success rates and decreased treatment-related morbidity. These advances include shock wave lithotripsy (SWL), ureteroscopy, and percutaneous nephrostolithotomy. Although these approaches are less invasive than traditional VOL. 8 SUPPL. 4 2006 REVIEWS IN UROLOGY S35
  2. 2. Alpha-Blockers for Nephrolithiasis continuedopen surgical approaches, they are ex- Physiology ureters were exposed to different com-pensive and have inherent risks. Con- The human ureter contains -adrener- pounds, including agonists and an-sequently, observation has been advo- gic receptors along its entire length, tagonists, phentolamine caused a 67%cated for small ureteral stones with a with the highest concentration in the prolongation of ureteral peristaltichigh probability to pass that do not distal ureter.3,4 Stimulation of the re- discharge intervals, an 84% increasehave absolute indications for surgical ceptors increases the force of ureteral in ureteral fluid bolus volume, and anintervention. The rate of spontaneous contraction and the frequency of 18% increase in the rate of fluidpassage with no medical intervention ureteral peristalsis, whereas antago- transportation.6for a stone of 5 mm or smaller in the nism of the receptors has the opposite More recently, Sigala and col-proximal ureter is estimated to be 29% effects. Malin and colleagues first leagues4 studied 1-adrenergic recep-to 98%, and in the distal ureter, 71% demonstrated the presence of - tor gene and protein expression into 98%. The most important factors in adrenergic receptors in the human the proximal, middle, and distalpredicting the likelihood of sponta- ureter in 1970.3 These investigators ob- ureter. They demonstrated that theneous stone passage are stone location tained specimens containing all levels distal ureter expressed the greatestand stone size.1 of the human ureter. In the lower third quantity of 1 messenger ribonucleic acid (mRNA). The 1d mRNA was ex- pressed in all portions of the ureter,The most important factors in predicting the likelihood of spontaneous stone and it was expressed in significantlypassage are stone location and stone size. greater amounts than the 1a or 1b receptor subtype in both the proxi- Recently, medical expulsion therapy of the ureter, exposure to adrenaline or mal and distal ureter. Using ligand(MET) has been investigated as a sup- noradrenaline increased the tone and binding, they were able to show thatplement to observation in an effort to frequency of contractions, whereas ex- the distal ureter had the highest den-improve spontaneous stone passage posure to isoproterenol decreased the sity of receptors, and 1d was therates, which can be unpredictable. amplitude and frequency of contrac- most common receptor present in allBecause ureteral edema and ureteral tions. Similar results were seen when portions of the ureter (Figure 1). Anspasm have been postulated to affect the entire length of the ureter was ex-stone passage, these effects have been posed to adrenaline and noradrenaline. Figure 1. Representation of the kidney and ureter withtargeted for pharmacologic interven- This demonstrated the presence of - density of receptors as studied by Sigala et al.4tion. Therefore, the primary agents adrenergic receptors along the entire Alpha-1d receptor is the most common in all segments of the ureter. The highest overall density of 1 recep-that have been evaluated for MET are length of the ureter, as well as the tors is in the distal ureter.calcium channel blockers, steroids, physiologic response of increasednonsteroidal anti-inflammatory drugs tone and frequency of contractions in(NSAIDs), and 1-adrenergic receptor the ureter when exposed to -antagonists. A recent meta-analysis adrenergic agonists.3was performed, looking at studies that In a study using dog and rabbitcompared stone passage rates in pa- ureters, Weiss and associates demon-tients who were given calcium chan- strated that -adrenergic agonistsnel blockers or 1-adrenergic receptor have a stimulatory effect on theantagonists versus controls who did ureteral smooth muscle, whereas -not receive these medications. The adrenergic agonists have an inhibitory 1d 1b 1aanalysis demonstrated a 65% greater affect. Phenylephrine was found tochance of passing a ureteral stone in significantly increase the contractilepatients who received either medica- force of ureteral segments. This effecttion.2 The use of these drugs for the was blocked by pretreatment of the 1d 1a 1bpurposes of facilitating stone passage, segment with phentolamine, an -however, is investigational and off adrenergic antagonist. Additionally,label. This article will focus on the use when rabbit ureters were exposed toof -blockers in the management of electrical stimuli in the presence of 1d 1a 1bstone disease and other stone-related phentolamine, there was a decrease inprocesses. maximum force generated.5 When dogS36 VOL. 8 SUPPL. 4 2006 REVIEWS IN UROLOGY
  3. 3. Alpha-Blockers for Nephrolithiasisin vitro study comparing the effects has been to reduce ureteral spasm, in- Tamsulosin has been the most com-of nifedipine, a calcium channel crease pressure proximal to the stone, monly studied 1-blocker in the treat-blocker; diclofenac, an NSAID; and and relax the ureter in the region of ment of ureteral stones; however, the5-methylurapidil (5-MU), an 1a an- and distal to the stone.14 The rationale data have been extrapolated and clin-tagonist, demonstrated that both in using 1 antagonists in MET has ically tested on other -blockers asnifedipine and 5-MU decreased the been that they are capable of decreas- well. Tamsulosin has equal affinityforce of contraction in ureteral seg- ing the force of ureteral contraction, for 1a and 1d receptors.16 The 1dments. The predominant affect of 5- decreasing the frequency of peristaltic receptor is the most common receptorMU was found to be in the distal contractions, and increasing the fluid in the ureter and is most concentratedureter.7 bolus volume transported down the in the distal ureter.4 Cervenakov and ureter.5-7 associates17 performed one of the firstTreatment of Distal In 1972, Kubacz and Catchpole15 double-blind, randomized studiesUreteral Stones compared the effectiveness of treating comparing their standard MET withMET has been aimed at modifiable ureteral colic with meperidine, phen- and without tamsulosin (Table 1).factors that can affect stone passage. tolamine, and propanolol. They found Their standard therapy included anThese factors are mucosal edema/ that 85.5% of patients receiving injection of a narcotic and diazepaminflammation, infection, and ureteral meperidine, 63.5% of patients receiv- on presentation, followed by a dailyspasm. Several agents have been ing phentolamine, and only 6% of NSAID. They found that the sponta-studied as potential MET. Steroids patients receiving propanolol had sig- neous passage rates with and withouthave been used to reduce mucosal nificant relief of pain. Interestingly, tamsulosin were 80.4% versus 62.8%,edema and aid in stone passage. A re- they found that in 4 patients receiv- respectively. The majority of patientscent study by Porpiglia and associ- ing phentolamine, their renal obstruc- receiving tamsulosin passed theirates8 failed to demonstrate that tion was corrected, as depicted by stone within 3 days. There were fewersteroids alone promote stone passage. intravenous pyelography, as was their instances of recurrent colic with tam-However, Dellabella and colleagues9 pain. The investigators concluded that sulosin, and the tamsulosin was welldid show that steroids are a useful ad- -adrenergic blockade may have the tolerated.junct to induce more rapid stone ex- advantage of relieving obstruction as Tamsulosin increases rates of spon-pulsion. They found similar expulsion well as pain. taneous stone expulsion and decreasesrates when tamsulosin was used aloneor with deflazacort (90% vs 96.7%),but found significantly reduced timeto expulsion in the group of patients Table 1who also received steroids (120 hours Rates of Stone Expulsion for Distal Ureteral Stones in Patients Treatedvs 72 hours; P .036). NSAIDs also With Alpha-1-Blocker Versus Patients Treated With Standard Medicalhave the potential to decrease inflam- Expulsion Therapy Without Alpha-1-Blockermation and mucosal edema and areuseful for analgesia during stone pas- Distal Ureteral Stone Expulsion Rates (%)sage, but have not been proven to be With Alpha-1- Without Alpha-1-successful in stone passage when used Study Blocker Blocker P Valuealone.10 Nifedipine is the most studied 17calcium channel blocker used to treat Cervenakov I et al 80.4 62.8 N/Aureteral spasm and promotes stone Dellabella M et al18 100 70 .001passage.11-13 Resim S et al 19 86.6 73.3 .196 Alpha-1-adrenergic receptor antag- De Sio M et al20 90 58.7 .01onists have some degree of selectivity Yilmaz E et al21 79.31 (tamsulosin) 53.57 .03for the detrusor and the distal ureter 78.57 (terazosin) 53.57 .03and have therefore been the next 75.86 (doxazosin) 53.57 .04agents investigated for their potential Porpiglia F et al22 85 43 .001to promote stone expulsion and de-crease pain. The likely mechanism Dellabella M et al23 97.1 64.3 .0001that -blockers use in stone passage VOL. 8 SUPPL. 4 2006 REVIEWS IN UROLOGY S37
  4. 4. Alpha-Blockers for Nephrolithiasis continued and another group that received Table 2 tamsulosin in addition to tenoxicam. Time to Stone Expulsion for Distal Ureteral Stones in Patients Treated The stones ranged in size from 5 to With Alpha-1-Blocker Versus Patients Treated With Standard Medical 12 mm in the group without tamsu- Expulsion Therapy Without Alpha-1-Blocker losin and from 5 to 13 mm in the group receiving tamsulosin. Patients receiving tamsulosin reported signifi- Distal Ureteral Stone Expulsion Times cantly less pain using a VAS scoring Study With Alpha-1 Blocker Without Alpha-1 Blocker P Value from 1 to 10 (5.70 vs 8.30; P .0001). Dellabella M et al18 65.7 h 111.1 h .02 Patients receiving tamsulosin reported De Sio M et al 20 4.4 d 7.5 d .005 fewer instances of colic. The sponta- Yilmaz E et al21 6.31 d (tamsulosin) 10.54 d .04 neous passage rates were 86.6% for 5.75 d (terazosin) 10.54 d .03 patients receiving tamsulosin, com- 5.93 d (doxazosin) 10.54 d .03 pared with 73.3% for those who did Porpiglia F et al22 7.9 d 12 d .02 not. There were minimal side effects 23 reported from the tamsulosin, and Dellabella M et al 72 h 120 h .0001 none of the patients had to stop taking tamsulosin secondary to a side effect. In a more recent prospective study,the time to stone expulsion (Tables 1 trimetossibenzene, a spasmolytic De Sio and associates20 showed simi-and 2). Importantly, it decreases the used in Italy. All patients received an lar results. They enrolled 96 patientsamount of pain patients suffer while oral steroid (deflazacort) for 10 days, with distal ureteral stones smallerpassing their stones (Table 3). Della- clotrimoxazole for 8 days, and di- than 10 mm. The patients were ran-bella and colleagues18 evaluated clofenac as needed. The expulsion domized into 2 groups: 1 group re-60 patients with symptomatic rate was 100% for patients receiving ceiving diclofenac and aescin, anureterovesical junction stones. They tamsulosin, compared with 70% in anti-edema extract from horse chest-compared 2 groups of 30 patients the other group. The time to expul- nuts, and the second group receivingeach: 1 group received tamsulosin sion was significantly less in the tamsulosin in addition to diclofenacand the other received floroglucine- tamsulosin group, 65.7 hours com- and aescin. The stone expulsion rate pared with 111.1 hours in the group was 90.0% with tamsulosin and not using tamsulosin. Patients receiv- 58.7% without tamsulosin. The time Table 3 ing tamsulosin required significantly to expulsion was significantly less Diminished Pain During Stone fewer injections of diclofenac, 0.13 with tamsulosin: 4.4 days versus 7.5 Passage With Alpha-1 Blocker compared with 2.83. One third of the days. Patients receiving tamsulosin patients who did not receive tamsu- required significantly less analgesia. Pain Measure losin needed to be hospitalized, 3 for The rate for rehospitalization for pa- Significantly uncontrollable pain and 7 for failure tients receiving tamsulosin was 10%, Improved With to pass their stone in 28 days. Mean and none of the patients required Study Alpha-1-Blocker* stone size was significantly greater in an endoscopic procedure, whereas in Dellabella M et al18 Yes the group receiving tamsulosin, 6.7 the group who did not receive tamsu- 19 mm versus 5.8 mm in those who re- losin, 27.5% were rehospitalized Resim S et al Yes ceived floroglucine, which further and 13% underwent an endoscopic De Sio M et al20 Yes points to the effectiveness of - procedure. 21 Yilmaz E et al Yes blockers. Although tamsulosin has been the Porpiglia F et al22 Yes Patients with distal ureteral stones most commonly studied 1-blocker in Dellabella M et al 23 Yes given tamsulosin reported decreased the treatment of ureteral stones, other pain using a visual analogue scale 1 antagonists have been shown to be *Various measures were used to quantify pain in the above studies, including visual (VAS). Resim and colleagues19 studied equally effective. In a prospective analogue scale, dose of diclofenac in mil- 60 patients with lower ureteral stones randomized study, tamsulosin was ligrams, number of injections of diclofenac used, and number of episodes of colic. who were divided into 2 groups, 1 of compared with terazosin and doxa- which received tenoxicam, an NSAID, zosin. A total of 114 patients withS38 VOL. 8 SUPPL. 4 2006 REVIEWS IN UROLOGY
  5. 5. Alpha-Blockers for Nephrolithiasisdistal ureteral stones of 10 mm or In a study of 86 patients with distal losin (97.1%) when compared withsmaller were divided into 4 treatment ureteral stones smaller than 1 cm, both the group receiving nifedipinegroups: those who received either no Porpiglia and associates22 compared (77.1%) and the group receiving 1-blocker (control group), tamsu- the effectiveness of nifedipine and phloroglucinol (64.3%). The medianlosin 0.4 mg, terazosin 5 mg, or dox- tamsulosin. All 86 patients received time in hours to stone passage wasazosin 4 mg. All the patients were 10 days of deflazacort. The 86 pa- 72 hours for the group receiving tam-given diclofenac to take as needed for tients were broken down into 3 sulosin, and this was significantly lesspain. In the control group, only groups: 1 group received only de- than the 120 hours for the groups re-53.57% passed their stones, whereas flazacort (control group), 1 group re- ceiving nifedipine or phloroglucinol.the rates for the groups receiving ceived tamsulosin 0.4 mg daily, and None of the patients receiving tamsu-tamsulosin, terazosin, and doxazosin the third group received 30 mg losin required hospitalization duringwere 79.31%, 78.57%, and 75.86%, nifedipine slow release daily. All pa- the study, whereas 15.7% of the pa-respectively. The patients treated with tients received diclofenac as needed tients receiving phloroglucinol and 1-blockers also reported significantly for pain. The expulsion rates for the 4.3% of the patients receivingdecreased pain and need for analgesia control group, tamsulosin group, and nifedipine required hospitalizationwhen compared with the control nifedipine group were 43%, 85%, and during the study. The group receivinggroup. Finally, the mean times to pas- 80%, respectively. Both tamsulosin tamsulosin required significantlysage for the control group, and the and nifedipine significantly increased fewer endoscopic procedures, requiredgroups receiving tamsulosin, tera- stone passage rates. Only tamsulosin less analgesia, and lost fewer work-zosin, and doxazosin were 10.54 days, had a significantly shorter time to days when compared with the groups6.31 days, 5.75 days, and 5.93 days, stone passage when compared with receiving nifedipine or phlorogluci-respectively. The mean time to pas- the control group. The mean time to nol. At the conclusion of the study,sage was significantly lower in the passage for the control group, tamsu- patients filled out a EuroQuol ques-groups receiving 1-blockers com- losin group, and nifedipine group was tionnaire to evaluate quality of life,pared with the control group. Of note, 12 days, 7.9 days, and 9.3 days, re- and tamsulosin was shown to havethere were no instances of hypoten- spectively. Both tamsulosin and significantly improved quality of lifesion in any of the patients receiving nifedipine significantly reduced the variables such as mobility, capacity to 1-blockers, and the patients receiv- need for diclofenac when compared perform usual activities, pain and dis-ing terazosin and doxazosin were with the control group. The investiga- comfort, and anxiety. Of note, thestarted on their therapeutic doses tors concluded that tamsulosin was median stone size in the tamsulosinupon entrance into the study rather superior to nifedipine because of the group was significantly larger, 7 mmthan being titrated to those doses.21 decreased time to expulsion and compared with 6 mm in the other slightly higher rate of expulsion, even 2 groups.Alpha-1-Blockers Compared though the stone size in the tamsu-With Calcium Channel Blockers losin group was larger, although not Alpha-1-Blockers and SWLIn 1994, Borghi and colleagues statistically significantly so (5.42 mm SWL has been established as an effec-demonstrated the efficacy of the cal- vs 4.7 mm). tive therapy for the treatment ofcium channel blocker nifedipine in Dellabella and colleagues also re- ureteral and renal stones. Tamsulosinthe treatment of ureteral stones in a cently compared tamsulosin, nifedip- has been studied as an adjunct ther-randomized, double-blind, placebo- ine, and phloroglucinol, a spasmolytic apy along with SWL. One study com-controlled study.11 They enrolled agent, in 210 patients with distal pared the stone-free rate in 48 pa-86 patients to receive methylpred- ureteral stones larger than 4 mm.23 tients who received SWL for distalnisolone with placebo or nifedipine. The patients were randomly assigned ureteral stones of 6 mm to 15 mm.24The patients receiving nifedipine had to receive either tamsulosin 0.4 mg, After the patients underwent SWL,a significantly higher rate of stone nifedipine slow release 30 mg, or they were randomized to receive ei-passage compared with the placebo phloroglucinol. All patients received ther oral hydration and diclofenac, orgroup, 87% versus 65%. Studies com- 10 days of deflazacort 30 mg and oral hydration and diclofenac withparing nifedipine with tamsulosin 8 days of cotrimoxazole, as well as tamsulosin 0.4 mg. The mean stonehave shown that both are effective in diclofenac as needed. The percentage size for those receiving tamsulosinaiding in stone passage, but that tam- of stones passed was significantly was 8.6 mm, compared with 8.2 mmsulosin may be more efficacious.22,23 greater in the group receiving tamsu- for those not receiving tamsulosin. VOL. 8 SUPPL. 4 2006 REVIEWS IN UROLOGY S39
  6. 6. Alpha-Blockers for Nephrolithiasis continuedPatients were evaluated 15 days after those who did not receive tamsulosin, toward improved resolution of thereceiving SWL with abdominal radi- but the difference was not statistically steinstrasse and there is the potentialography to evaluate for residual stone significant. The mechanism of action benefit of improved analgesia.burden. The stone-free rate was 70.8% of how -blockers help clear renalfor patients who received tamsulosin, stone burden has yet to be elucidated Alpha-1-Blockerscompared with 33.3% for those who and requires further investigation; and Ureteral Stentsdid not (P .019). Only 1 patient re- however, their ability to assist in the Ureteral stents are often used in theceiving tamsulosin experienced slight passage of stone fragments when they treatment of renal and ureteral stones.dizziness. The investigators concluded pass through the ureter is intuitive, The stents can be associated withthat tamsulosin could improve stone- based on previous work as reported. some morbidity, including pain andfree rates after SWL of distal ureteral Steinstrasse is an accumulation of urinary symptoms. Deliveliotis andstones with minimal side effects. stone fragments in the ureter typi- colleagues studied whether these Gravina and colleagues studied the cally after SWL, which can lead to symptoms could be improved usingefficacy of tamsulosin as an adjunc- obstruction. It is estimated to occur the 1-blocker alfuzosin.28 Double-Jtive therapy after SWL for renal in 2% to 10% of cases, and there is stents were placed in 100 patients forstones.25 They included 130 patients increased risk with increasing stone the treatment of ureteral stoneswho underwent renal stone SWL, ex- burden.26 Resim and colleagues27 smaller than 10 mm. Patients werecluding patients with lower pole studied the effect of tamsulosin on randomized after stent placement tostones. The stones ranged in size from the resolution of steinstrasse. Patients receive either alfuzosin 10 mg daily or4 mm to 20 mm. After SWL, patients were included in the study if they had placebo for 4 weeks. At the end of thewere randomized to either receive steinstrasse in the lower ureter and if 4-week study, all patients were as-standard medical therapy, which was the column of stone fragments was sessed for stone-free status and filledmethylprednisolone, 16 mg twice obstructing the ureter, as determined out the validated Ureteral Stentdaily for 15 days and diclofenac as with radiography and renal ultra- Symptom Questionnaire (USSQ). Theneeded, or standard therapy plus tam- sound. A total of 67 patients were mean urinary symptom score, as as-sulosin 0.4 mg. Patients were evalu- included and were randomized to sessed by the USSQ, was significantlyated with renal ultrasound, radiogra- receive hydration and tenoxicam, an lower in the group receiving alfu-phy, and/or intravenous urography at NSAID, with or without tamsulosin zosin, 21.6 versus 28.1 (P .001). Pa-4, 8, and 12 weeks. Clinical success 0.4 mg. Patients were followed for 6 tients receiving alfuzosin reportedwas defined as stone-free status or the weeks. The stone passage rates were less stent related pain, 66% versuspresence of clinically insignificant determined by patient report and by 44% (P .027) and also reported astone fragments, which were defined imaging with radiography and renal lower mean pain index score, 8 versusas asymptomatic fragments 3 mm or ultrasound. The passage rates were 11.4 (P .001). Both the mean gen-less. At 12 weeks, clinical success was 75% with tamsulosin and 65.7% eral health index score and mean sex-achieved in 78.5% of patients receiv- without, which did not reach statisti- ual matters score were significantlying tamsulosin and 60% of patients cal significance. The time to passage better in patients taking alfuzosin.not receiving tamsulosin (P .037). was also not significantly different. Spontaneous stone passage was simi-Tamsulosin had a greater effect when However, patients receiving tamsu- lar between the 2 groups. Albeit acompared with the control group for losin did have significantly fewer single small study, the potential ben-larger stones. In stones 4 mm to episodes of colic and had signifi- efits of -blockers is demonstrated in10 mm, the clinical success rates with cantly lower pain scores on a VAS. reducing stent-related symptoms andand without tamsulosin were 75% Approximately 40% of patients re- should be investigated further.versus 68% (P .05), and for stones ceiving tamsulosin experienced11 mm to 20 mm the success rates minor side effects from the medica- Current Recommendationswere 81% versus 55% (P .009). tion, but none were significant When conservative management of aTamsulosin significantly reduced the enough for the patient to stop taking ureteral stone is being considered andamount of diclofenac used and re- the tamsulosin. Although -blockers the patient has no associated signs ofduced the occurrence of flank pain did not reach statistical significance infection, uncontrollable pain, orafter SWL. Patients receiving tamsu- in the previous study, they may be a renal failure, adjuvant pharmacologiclosin required ureteroscopy or a sec- useful adjunct in the management of intervention has proven efficaciousond SWL less often compared with steinstrasse because there is a trend in improving spontaneous stone pas-S40 VOL. 8 SUPPL. 4 2006 REVIEWS IN UROLOGY
  7. 7. Alpha-Blockers for Nephrolithiasissage rate and time interval, and in sage. Alpha-blockers, specifically 1 passage: a meta-analysis. Lancet. 2006;368: 1171-1179.reducing analgesic requirements. antagonists, are highly effective in in- 3. Malin JM, Deane RF, Boyarsky S. Characterisa-Many of the studies have adminis- creasing the expulsion rate of distal tion of adrenergic receptors in human ureter. Brtered the drugs in conjunction with ureteral stones, reducing the time to J Urol. 1970;42:171-174. 4. Sigala S, Dellabella M, Milanese G, et al. Evi-steroids and/or NSAIDs, which may stone passage, and decreasing the dence for the presence of alpha1 adrenoceptorreduce ureteral edema and improve amount of pain medication needed subtypes in the human ureter. Neurourol Urody-the ability for a patient to sponta- during passage stones (see Tables 1–3). namics. 2005;24:142-148. 5. Weiss RM, Bassett AL, Hoffman BF. Adrenergicneously pass a ureteral stone. How- Alpha blockers may also be a useful innervation of the ureter. Invest Urol. 1978;ever, several of the more recent adjunct in the treatment of both 16:123-127.studies have shown benefit to both - ureteral and renal stones with SWL. 6. Morita T, Wada I, Saeki H, et al. Ureteral urine transport: changes in bolus volume, peristalticblockers and calcium channel block- They may also reduce the urinary frequency, intraluminal pressure and volume ofers without the adjunctive use of symptoms and pain associated with flow resulting from autonomic drugs. J Urol.steroids; furthermore, tamsulosin, in a double-J ureteral stents. Further in- 1987;137:132-135. 7. Davenport K, Timoney AG, Keeley FX. A com-randomized trial, has been shown to vestigation is necessary to define the parative in vitro study to determine thebe more efficient than nifedipine with role of -blockers in the treatment of beneficial effect of calcium-channel and alpha(1)-a decreased time to expulsion and proximal ureteral and renal stones, adrenoceptor antagonism on human ureteric activity. BJU Int. 2006;98:651-655.slightly higher rate of expulsion.17-23 and to elucidate the potential mecha- 8. Porpiglia F, Vaccino D, Billia M, et al. Cortico- Our current treatment regimen for nisms of renal stone clearance after steroids and tamsulosin in the medical expulsiveconservative management of ureteral surgical stone intervention. therapy for symptomatic distal ureter stones: single drug or association? Eur Urol. 2006;stones, particularly distal ureteral Although success has been shown 50:339-344.stones, is to start an -adrenergic with calcium channel blockers with 9. Dellabella M, Milanes G, Muzzonigro G. Medical-receptor antagonist, prescribe anal- or without steroids and/or NSAIDs, expulsive therapy for distal ureterolithiasis: randomized prospective study on role of corti-gesics as needed, and follow the pa- -blockers, with their high success costeroids used in combination with tamsulosin-tient clinically with serial imaging rates, excellent safety profile, low side simplified treatment regimen and health-relatedand laboratory studies if needed. effect profile, and ease of use, have be- quality of life. Urology. 2005;66:712-715. 10. Laerum E, Ommundsen OE, Gronseth JE, et al.However, the combination of corti- come the leading candidate in MET Oral diclofenac in the prophylactic treatment ofcosteroids with a calcium channel and should be used as first-line ther- recurrent renal colic. A double-blind comparisonblocker or an -blocker can also be apy in any appropriate candidate on with placebo. Eur Urol. 1995;28:108-111. 11. Borghi L, Meschi T, Amato F, et al. Nifedipineused with precautions to prevent an observation protocol during the and methylprednisolone in facilitating ureteralsteroid-related complications. passage of a distal ureteral stone. stone passage: a randomized, double-blind, Additionally, -adrenergic receptor placebo-controlled study. J Urol. 1994;152: 1095-1098.Summary antagonists may be considered during 12. Porpiglia F, Destefanis P, Fiori C, Fontanta D. Ef-Alpha-1-adrenergic receptors are lo- the conservative treatment of proximal fectiveness of nifedipine and deflazacort in the and mid-ureteral stones, and after sur- management of distal ureter stones. Urology.cated throughout the human ureter. 2000;56:579-582.The physiologic response to antago- gical intervention of renal stones. 13. Porpiglia F, Destefanis P, Fiori C, et al. Role ofnism of these receptors is decreased adjunctive medical therapy with nifedipine and References deflazacort after extracorporeal shock waveforce of contraction, decreased peri- 1. Segura JW, Preminger GM, Assimos DG, et al. lithotripsy of ureteral stones. Urology. 2002;59:staltic frequency, and increased fluid Ureteral stones clinical guidelines panel sum- 835-838.bolus volume transported down the mary report on the management of ureteral cal- 14. Weiss, RM. Physiology and pharmacology of the culi. J Urol. 1997;158:1915-1921. renal pelvis and ureter. In: Walsh PC, Retik AB,ureter. These responses are likely how 2. Hollingsworth, JM, Rogers MAM, Kaufman SR, Vaughan ED Jr, Wein AJ, eds. Campbell’s Urology. -blockers assist in ureteral stone pas- et al. Medical therapy to facilitate urinary stone 8th ed. Philadelphia: Saunders; 2002:399-400. Main Points • Medical expulsion therapy is a useful adjunct to observation in the conservative management of ureteral stones. • Alpha-1 receptors are located in the human ureter, especially the distal ureter; -blockers increase expulsion rates of distal ureteral stones, decrease time to expulsion, and decrease need for analgesia during stone passage. • In the appropriate clinical scenario, the use of -blockers is recommended in the conservative management of distal ureteral stones. VOL. 8 SUPPL. 4 2006 REVIEWS IN UROLOGY S41
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