Alfa Bloker, Urolitiasis

VOL. 8 SUPPL. 4 2006 REVIEWS IN UROLOGY S35

ALPHA-BLOCKER THERAPY FOR UROLOGICAL DISORDERS

The Use of Alpha-Blockers for theTreatment of NephrolithiasisMichael Lipkin, MD, Ojas Shah, MD

Department of Urology, New York University School of Medicine, New York, NY

Medical 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, LLC

Key words: Alpha-blockers • Ureteral stones • Kidney stones

Recent advances in endoscopic stone management have allowed kidneystones to be treated using minimally invasive techniques, which haveincreased success rates and decreased treatment-related morbidity. These

advances include shock wave lithotripsy (SWL), ureteroscopy, and percutaneousnephrostolithotomy. Although these approaches are less invasive than traditional

RIUS0005(Sanofi)_12-05.qxd 12/5/06 6:20 PM Page S35

Alpha-Blockers for Nephrolithiasis continued

S36 VOL. 8 SUPPL. 4 2006 REVIEWS IN UROLOGY

open surgical approaches, they are ex-pensive and have inherent risks. Con-sequently, observation has been advo-cated for small ureteral stones with ahigh probability to pass that do nothave absolute indications for surgicalintervention. The rate of spontaneouspassage with no medical interventionfor a stone of 5 mm or smaller in theproximal ureter is estimated to be 29%to 98%, and in the distal ureter, 71%to 98%. The most important factors inpredicting the likelihood of sponta-neous stone passage are stone locationand stone size.1

Recently, medical expulsion therapy(MET) has been investigated as a sup-plement to observation in an effort toimprove spontaneous stone passagerates, which can be unpredictable.Because ureteral edema and ureteralspasm have been postulated to affectstone passage, these effects have beentargeted for pharmacologic interven-tion. Therefore, the primary agentsthat have been evaluated for MET arecalcium channel blockers, steroids,nonsteroidal anti-inflammatory drugs(NSAIDs), and �1-adrenergic receptorantagonists. A recent meta-analysiswas performed, looking at studies thatcompared stone passage rates in pa-tients who were given calcium chan-nel blockers or �1-adrenergic receptorantagonists versus controls who didnot receive these medications. Theanalysis demonstrated a 65% greaterchance of passing a ureteral stone inpatients who received either medica-tion.2 The use of these drugs for thepurposes of facilitating stone passage,however, is investigational and offlabel. This article will focus on the useof �-blockers in the management ofstone disease and other stone-relatedprocesses.

PhysiologyThe human ureter contains �-adrener-gic receptors along its entire length,with the highest concentration in thedistal ureter.3,4 Stimulation of the � re-ceptors increases the force of ureteralcontraction and the frequency ofureteral peristalsis, whereas antago-nism of the receptors has the oppositeeffects. Malin and colleagues firstdemonstrated the presence of �-adrenergic receptors in the humanureter in 1970.3 These investigators ob-tained specimens containing all levelsof the human ureter. In the lower third

of the ureter, exposure to adrenaline ornoradrenaline increased the tone andfrequency of contractions, whereas ex-posure to isoproterenol decreased theamplitude and frequency of contrac-tions. Similar results were seen whenthe entire length of the ureter was ex-posed to adrenaline and noradrenaline.This demonstrated the presence of �-adrenergic receptors along the entirelength of the ureter, as well as thephysiologic response of increasedtone and frequency of contractions inthe ureter when exposed to �-adrenergic agonists.3

In a study using dog and rabbitureters, Weiss and associates demon-strated that �-adrenergic agonistshave a stimulatory effect on theureteral smooth muscle, whereas �-adrenergic agonists have an inhibitoryaffect. Phenylephrine was found tosignificantly increase the contractileforce of ureteral segments. This effectwas blocked by pretreatment of thesegment with phentolamine, an �-adrenergic antagonist. Additionally,when rabbit ureters were exposed toelectrical stimuli in the presence ofphentolamine, there was a decrease inmaximum force generated.5 When dog

ureters were exposed to different com-pounds, including � agonists and an-tagonists, phentolamine caused a 67%prolongation of ureteral peristalticdischarge intervals, an 84% increasein ureteral fluid bolus volume, and an18% increase in the rate of fluidtransportation.6

More recently, Sigala and col-leagues4 studied �1-adrenergic recep-tor gene and protein expression inthe proximal, middle, and distalureter. They demonstrated that thedistal ureter expressed the greatestquantity of �1 messenger ribonucleicacid (mRNA). The �1d mRNA was ex-pressed in all portions of the ureter,and it was expressed in significantlygreater amounts than the �1a or �1breceptor subtype in both the proxi-mal and distal ureter. Using ligandbinding, they were able to show thatthe distal ureter had the highest den-sity of � receptors, and �1d was themost common receptor present in allportions of the ureter (Figure 1). An

The most important factors in predicting the likelihood of spontaneous stonepassage are stone location and stone size.

�1d��1b��1a

�1d��1a��1b

�1d��1a��1b

Figure 1. Representation of the kidney and ureter withdensity of � receptors as studied by Sigala et al.4

Alpha-1d receptor is the most common in all segmentsof the ureter. The highest overall density of �1 recep-tors is in the distal ureter.


Alpha-Blockers for Nephrolithiasis


in vitro study comparing the effectsof nifedipine, a calcium channelblocker; diclofenac, an NSAID; and5-methylurapidil (5-MU), an �1a an-tagonist, demonstrated that bothnifedipine and 5-MU decreased theforce of contraction in ureteral seg-ments. The predominant affect of 5-MU was found to be in the distalureter.7

Treatment of Distal Ureteral StonesMET has been aimed at modifiablefactors that can affect stone passage.These factors are mucosal edema/inflammation, infection, and ureteralspasm. Several agents have beenstudied as potential MET. Steroidshave been used to reduce mucosaledema and aid in stone passage. A re-cent study by Porpiglia and associ-ates8 failed to demonstrate thatsteroids alone promote stone passage.However, Dellabella and colleagues9

did show that steroids are a useful ad-junct to induce more rapid stone ex-pulsion. They found similar expulsionrates when tamsulosin was used aloneor with deflazacort (90% vs 96.7%),but found significantly reduced timeto expulsion in the group of patientswho also received steroids (120 hoursvs 72 hours; P � .036). NSAIDs alsohave the potential to decrease inflam-mation and mucosal edema and areuseful for analgesia during stone pas-sage, but have not been proven to besuccessful in stone passage when usedalone.10 Nifedipine is the most studiedcalcium channel blocker used to treatureteral spasm and promotes stonepassage.11-13

Alpha-1-adrenergic receptor antag-onists have some degree of selectivityfor the detrusor and the distal ureterand have therefore been the nextagents investigated for their potentialto promote stone expulsion and de-crease pain. The likely mechanismthat �-blockers use in stone passage

Tamsulosin has been the most com-monly studied �1-blocker in the treat-ment of ureteral stones; however, thedata have been extrapolated and clin-ically tested on other �-blockers aswell. Tamsulosin has equal affinityfor �1a and �1d receptors.16 The �1dreceptor is the most common receptorin the ureter and is most concentratedin the distal ureter.4 Cervenakov andassociates17 performed one of the firstdouble-blind, randomized studiescomparing their standard MET withand without tamsulosin (Table 1).Their standard therapy included aninjection of a narcotic and diazepamon presentation, followed by a dailyNSAID. They found that the sponta-neous passage rates with and withouttamsulosin were 80.4% versus 62.8%,respectively. The majority of patientsreceiving tamsulosin passed theirstone within 3 days. There were fewerinstances of recurrent colic with tam-sulosin, and the tamsulosin was welltolerated.

Tamsulosin increases rates of spon-taneous stone expulsion and decreases

has been to reduce ureteral spasm, in-crease pressure proximal to the stone,and relax the ureter in the region ofand distal to the stone.14 The rationalein using �1 antagonists in MET hasbeen that they are capable of decreas-ing the force of ureteral contraction,decreasing the frequency of peristalticcontractions, and increasing the fluidbolus volume transported down theureter.5-7

In 1972, Kubacz and Catchpole15

compared the effectiveness of treatingureteral colic with meperidine, phen-tolamine, and propanolol. They foundthat 85.5% of patients receivingmeperidine, 63.5% of patients receiv-ing phentolamine, and only 6% ofpatients receiving propanolol had sig-nificant relief of pain. Interestingly,they found that in 4 patients receiv-ing phentolamine, their renal obstruc-tion was corrected, as depicted byintravenous pyelography, as was theirpain. The investigators concluded that�-adrenergic blockade may have theadvantage of relieving obstruction aswell as pain.

Table 1Rates of Stone Expulsion for Distal Ureteral Stones in Patients TreatedWith Alpha-1-Blocker Versus Patients Treated With Standard Medical

Expulsion Therapy Without Alpha-1-Blocker

Distal Ureteral Stone Expulsion Rates (%)

With Alpha-1- Without Alpha-1-Study Blocker Blocker P Value

Cervenakov I et al17 80.4 62.8 N/A

Dellabella M et al18 100 70 .001

Resim S et al19 86.6 73.3 .196

De Sio M et al20 90 58.7 .01

Yilmaz E et al21 79.31 (tamsulosin) 53.57 .0378.57 (terazosin) 53.57 .0375.86 (doxazosin) 53.57 .04

Porpiglia F et al22 85 43 �.001

Dellabella M et al23 97.1 64.3 �.0001




the time to stone expulsion (Tables 1and 2). Importantly, it decreases theamount of pain patients suffer whilepassing their stones (Table 3). Della-bella and colleagues18 evaluated 60 patients with symptomaticureterovesical junction stones. Theycompared 2 groups of 30 patientseach: 1 group received tamsulosinand the other received floroglucine-

trimetossibenzene, a spasmolyticused in Italy. All patients received anoral steroid (deflazacort) for 10 days,clotrimoxazole for 8 days, and di-clofenac as needed. The expulsionrate was 100% for patients receivingtamsulosin, compared with 70% inthe other group. The time to expul-sion was significantly less in thetamsulosin group, 65.7 hours com-pared with 111.1 hours in the groupnot using tamsulosin. Patients receiv-ing tamsulosin required significantlyfewer injections of diclofenac, 0.13compared with 2.83. One third of thepatients who did not receive tamsu-losin needed to be hospitalized, 3 foruncontrollable pain and 7 for failureto pass their stone in 28 days. Meanstone size was significantly greater inthe group receiving tamsulosin, 6.7mm versus 5.8 mm in those who re-ceived floroglucine, which furtherpoints to the effectiveness of �-blockers.

Patients with distal ureteral stonesgiven tamsulosin reported decreasedpain using a visual analogue scale(VAS). Resim and colleagues19 studied60 patients with lower ureteral stoneswho were divided into 2 groups, 1 ofwhich received tenoxicam, an NSAID,

and another group that receivedtamsulosin in addition to tenoxicam.The stones ranged in size from 5 to12 mm in the group without tamsu-losin and from 5 to 13 mm in thegroup receiving tamsulosin. Patientsreceiving tamsulosin reported signifi-cantly less pain using a VAS scoringfrom 1 to 10 (5.70 vs 8.30; P � .0001).Patients receiving tamsulosin reportedfewer instances of colic. The sponta-neous passage rates were 86.6% forpatients receiving tamsulosin, com-pared with 73.3% for those who didnot. There were minimal side effectsreported from the tamsulosin, andnone of the patients had to stop takingtamsulosin secondary to a side effect.

In a more recent prospective study,De Sio and associates20 showed simi-lar results. They enrolled 96 patientswith distal ureteral stones smallerthan 10 mm. The patients were ran-domized into 2 groups: 1 group re-ceiving diclofenac and aescin, ananti-edema extract from horse chest-nuts, and the second group receivingtamsulosin in addition to diclofenacand aescin. The stone expulsion ratewas 90.0% with tamsulosin and58.7% without tamsulosin. The timeto expulsion was significantly lesswith tamsulosin: 4.4 days versus 7.5days. Patients receiving tamsulosinrequired significantly less analgesia.The rate for rehospitalization for pa-tients receiving tamsulosin was 10%,and none of the patients requiredan endoscopic procedure, whereas inthe group who did not receive tamsu-losin, 27.5% were rehospitalizedand 13% underwent an endoscopicprocedure.

Although tamsulosin has been themost commonly studied �1-blocker inthe treatment of ureteral stones, other�1 antagonists have been shown to beequally effective. In a prospectiverandomized study, tamsulosin wascompared with terazosin and doxa-zosin. A total of 114 patients with

Table 2Time to Stone Expulsion for Distal Ureteral Stones in Patients TreatedWith Alpha-1-Blocker Versus Patients Treated With Standard Medical

Expulsion Therapy Without Alpha-1-Blocker

Distal Ureteral Stone Expulsion Times

Study With Alpha-1 Blocker Without Alpha-1 Blocker P Value

Dellabella M et al18 65.7 h 111.1 h .02

De Sio M et al20 4.4 d 7.5 d .005

Yilmaz E et al21 6.31 d (tamsulosin) 10.54 d .045.75 d (terazosin) 10.54 d .035.93 d (doxazosin) 10.54 d .03

Porpiglia F et al22 7.9 d 12 d .02

Dellabella M et al23 72 h 120 h �.0001

Table 3Diminished Pain During StonePassage With Alpha-1 Blocker

Pain Measure Significantly

Improved With Study Alpha-1-Blocker*

Dellabella M et al18 Yes

Resim S et al19 Yes

De Sio M et al20 Yes

Yilmaz E et al21 Yes

Porpiglia F et al22 Yes

Dellabella M et al23 Yes

*Various measures were used to quantifypain in the above studies, including visualanalogue scale, dose of diclofenac in mil-ligrams, number of injections of diclofenacused, and number of episodes of colic.




distal ureteral stones of 10 mm orsmaller were divided into 4 treatmentgroups: those who received either no�1-blocker (control group), tamsu-losin 0.4 mg, terazosin 5 mg, or dox-azosin 4 mg. All the patients weregiven diclofenac to take as needed forpain. In the control group, only53.57% passed their stones, whereasthe rates for the groups receivingtamsulosin, terazosin, and doxazosinwere 79.31%, 78.57%, and 75.86%,respectively. The patients treated with�1-blockers also reported significantlydecreased pain and need for analgesiawhen compared with the controlgroup. Finally, the mean times to pas-sage for the control group, and thegroups receiving tamsulosin, tera-zosin, and doxazosin were 10.54 days,6.31 days, 5.75 days, and 5.93 days,respectively. The mean time to pas-sage was significantly lower in thegroups receiving �1-blockers com-pared with the control group. Of note,there were no instances of hypoten-sion in any of the patients receiving�1-blockers, and the patients receiv-ing terazosin and doxazosin werestarted on their therapeutic dosesupon entrance into the study ratherthan being titrated to those doses.21

Alpha-1-Blockers ComparedWith Calcium Channel BlockersIn 1994, Borghi and colleaguesdemonstrated the efficacy of the cal-cium channel blocker nifedipine inthe treatment of ureteral stones in arandomized, double-blind, placebo-controlled study.11 They enrolled86 patients to receive methylpred-nisolone with placebo or nifedipine.The patients receiving nifedipine hada significantly higher rate of stonepassage compared with the placebogroup, 87% versus 65%. Studies com-paring nifedipine with tamsulosinhave shown that both are effective inaiding in stone passage, but that tam-sulosin may be more efficacious.22,23

In a study of 86 patients with distalureteral stones smaller than 1 cm,Porpiglia and associates22 comparedthe effectiveness of nifedipine andtamsulosin. All 86 patients received10 days of deflazacort. The 86 pa-tients were broken down into 3groups: 1 group received only de-flazacort (control group), 1 group re-ceived tamsulosin 0.4 mg daily, andthe third group received 30 mgnifedipine slow release daily. All pa-tients received diclofenac as neededfor pain. The expulsion rates for thecontrol group, tamsulosin group, andnifedipine group were 43%, 85%, and80%, respectively. Both tamsulosinand nifedipine significantly increasedstone passage rates. Only tamsulosinhad a significantly shorter time tostone passage when compared withthe control group. The mean time topassage for the control group, tamsu-losin group, and nifedipine group was12 days, 7.9 days, and 9.3 days, re-spectively. Both tamsulosin andnifedipine significantly reduced theneed for diclofenac when comparedwith the control group. The investiga-tors concluded that tamsulosin wassuperior to nifedipine because of thedecreased time to expulsion andslightly higher rate of expulsion, eventhough the stone size in the tamsu-losin group was larger, although notstatistically significantly so (5.42 mmvs 4.7 mm).

Dellabella and colleagues also re-cently compared tamsulosin, nifedip-ine, and phloroglucinol, a spasmolyticagent, in 210 patients with distalureteral stones larger than 4 mm.23

The patients were randomly assignedto receive either tamsulosin 0.4 mg,nifedipine slow release 30 mg, orphloroglucinol. All patients received10 days of deflazacort 30 mg and8 days of cotrimoxazole, as well asdiclofenac as needed. The percentageof stones passed was significantlygreater in the group receiving tamsu-

losin (97.1%) when compared withboth the group receiving nifedipine(77.1%) and the group receivingphloroglucinol (64.3%). The mediantime in hours to stone passage was72 hours for the group receiving tam-sulosin, and this was significantly lessthan the 120 hours for the groups re-ceiving nifedipine or phloroglucinol.None of the patients receiving tamsu-losin required hospitalization duringthe study, whereas 15.7% of the pa-tients receiving phloroglucinol and4.3% of the patients receivingnifedipine required hospitalizationduring the study. The group receivingtamsulosin required significantlyfewer endoscopic procedures, requiredless analgesia, and lost fewer work-days when compared with the groupsreceiving nifedipine or phlorogluci-nol. At the conclusion of the study,patients filled out a EuroQuol ques-tionnaire to evaluate quality of life,and tamsulosin was shown to havesignificantly improved quality of lifevariables such as mobility, capacity toperform usual activities, pain and dis-comfort, and anxiety. Of note, themedian stone size in the tamsulosingroup was significantly larger, 7 mmcompared with 6 mm in the other2 groups.

Alpha-1-Blockers and SWLSWL has been established as an effec-tive therapy for the treatment ofureteral and renal stones. Tamsulosinhas been studied as an adjunct ther-apy along with SWL. One study com-pared the stone-free rate in 48 pa-tients who received SWL for distalureteral stones of 6 mm to 15 mm.24

After the patients underwent SWL,they were randomized to receive ei-ther oral hydration and diclofenac, ororal hydration and diclofenac withtamsulosin 0.4 mg. The mean stonesize for those receiving tamsulosinwas 8.6 mm, compared with 8.2 mmfor those not receiving tamsulosin.




Patients were evaluated 15 days afterreceiving SWL with abdominal radi-ography to evaluate for residual stoneburden. The stone-free rate was 70.8%for patients who received tamsulosin,compared with 33.3% for those whodid not (P � .019). Only 1 patient re-ceiving tamsulosin experienced slightdizziness. The investigators concludedthat tamsulosin could improve stone-free rates after SWL of distal ureteralstones with minimal side effects.

Gravina and colleagues studied theefficacy of tamsulosin as an adjunc-tive therapy after SWL for renalstones.25 They included 130 patientswho underwent renal stone SWL, ex-cluding patients with lower polestones. The stones ranged in size from4 mm to 20 mm. After SWL, patientswere randomized to either receivestandard medical therapy, which wasmethylprednisolone, 16 mg twicedaily for 15 days and diclofenac asneeded, or standard therapy plus tam-sulosin 0.4 mg. Patients were evalu-ated with renal ultrasound, radiogra-phy, and/or intravenous urography at4, 8, and 12 weeks. Clinical successwas defined as stone-free status or thepresence of clinically insignificantstone fragments, which were definedas asymptomatic fragments 3 mm orless. At 12 weeks, clinical success wasachieved in 78.5% of patients receiv-ing tamsulosin and 60% of patientsnot receiving tamsulosin (P � .037).Tamsulosin had a greater effect whencompared with the control group forlarger stones. In stones 4 mm to 10 mm, the clinical success rates withand without tamsulosin were 75%versus 68% (P � .05), and for stones11 mm to 20 mm the success rateswere 81% versus 55% (P � .009).Tamsulosin significantly reduced theamount of diclofenac used and re-duced the occurrence of flank painafter SWL. Patients receiving tamsu-losin required ureteroscopy or a sec-ond SWL less often compared with

those who did not receive tamsulosin,but the difference was not statisticallysignificant. The mechanism of actionof how �-blockers help clear renalstone burden has yet to be elucidatedand requires further investigation;however, their ability to assist in thepassage of stone fragments when theypass through the ureter is intuitive,based on previous work as reported.

Steinstrasse is an accumulation ofstone fragments in the ureter typi-cally after SWL, which can lead toobstruction. It is estimated to occurin 2% to 10% of cases, and there isincreased risk with increasing stoneburden.26 Resim and colleagues27

studied the effect of tamsulosin onthe resolution of steinstrasse. Patientswere included in the study if they hadsteinstrasse in the lower ureter and ifthe column of stone fragments wasobstructing the ureter, as determinedwith radiography and renal ultra-sound. A total of 67 patients wereincluded and were randomized toreceive hydration and tenoxicam, anNSAID, with or without tamsulosin0.4 mg. Patients were followed for 6weeks. The stone passage rates weredetermined by patient report and byimaging with radiography and renalultrasound. The passage rates were75% with tamsulosin and 65.7%without, which did not reach statisti-cal significance. The time to passagewas also not significantly different.However, patients receiving tamsu-losin did have significantly fewerepisodes of colic and had signifi-cantly lower pain scores on a VAS.Approximately 40% of patients re-ceiving tamsulosin experiencedminor side effects from the medica-tion, but none were significantenough for the patient to stop takingthe tamsulosin. Although �-blockersdid not reach statistical significancein the previous study, they may be auseful adjunct in the management ofsteinstrasse because there is a trend

toward improved resolution of thesteinstrasse and there is the potentialbenefit of improved analgesia.

Alpha-1-Blockers and Ureteral StentsUreteral stents are often used in thetreatment of renal and ureteral stones.The stents can be associated withsome morbidity, including pain andurinary symptoms. Deliveliotis andcolleagues studied whether thesesymptoms could be improved usingthe �1-blocker alfuzosin.28 Double-Jstents were placed in 100 patients forthe treatment of ureteral stonessmaller than 10 mm. Patients wererandomized after stent placement toreceive either alfuzosin 10 mg daily orplacebo for 4 weeks. At the end of the4-week study, all patients were as-sessed for stone-free status and filledout the validated Ureteral StentSymptom Questionnaire (USSQ). Themean urinary symptom score, as as-sessed by the USSQ, was significantlylower in the group receiving alfu-zosin, 21.6 versus 28.1 (P � .001). Pa-tients receiving alfuzosin reportedless stent related pain, 66% versus44% (P � .027) and also reported alower mean pain index score, 8 versus11.4 (P � .001). Both the mean gen-eral health index score and mean sex-ual matters score were significantlybetter in patients taking alfuzosin.Spontaneous stone passage was simi-lar between the 2 groups. Albeit asingle small study, the potential ben-efits of �-blockers is demonstrated inreducing stent-related symptoms andshould be investigated further.

Current RecommendationsWhen conservative management of aureteral stone is being considered andthe patient has no associated signs ofinfection, uncontrollable pain, orrenal failure, adjuvant pharmacologicintervention has proven efficaciousin improving spontaneous stone pas-




sage rate and time interval, and inreducing analgesic requirements.Many of the studies have adminis-tered the drugs in conjunction withsteroids and/or NSAIDs, which mayreduce ureteral edema and improvethe ability for a patient to sponta-neously pass a ureteral stone. How-ever, several of the more recentstudies have shown benefit to both �-blockers and calcium channel block-ers without the adjunctive use ofsteroids; furthermore, tamsulosin, in arandomized trial, has been shown tobe more efficient than nifedipine witha decreased time to expulsion andslightly higher rate of expulsion.17-23

Our current treatment regimen forconservative management of ureteralstones, particularly distal ureteralstones, is to start an �-adrenergicreceptor antagonist, prescribe anal-gesics as needed, and follow the pa-tient clinically with serial imagingand laboratory studies if needed.However, the combination of corti-costeroids with a calcium channelblocker or an �-blocker can also beused with precautions to preventsteroid-related complications.

SummaryAlpha-1-adrenergic receptors are lo-cated throughout the human ureter.The physiologic response to antago-nism of these receptors is decreasedforce of contraction, decreased peri-staltic frequency, and increased fluidbolus volume transported down theureter. These responses are likely how�-blockers assist in ureteral stone pas-

sage. Alpha-blockers, specifically �1antagonists, are highly effective in in-creasing the expulsion rate of distalureteral stones, reducing the time tostone passage, and decreasing theamount of pain medication neededduring passage stones (see Tables 1–3).Alpha blockers may also be a usefuladjunct in the treatment of bothureteral and renal stones with SWL.They may also reduce the urinarysymptoms and pain associated withdouble-J ureteral stents. Further in-vestigation is necessary to define therole of �-blockers in the treatment ofproximal ureteral and renal stones,and to elucidate the potential mecha-nisms of renal stone clearance aftersurgical stone intervention.

Although success has been shownwith calcium channel blockers withor without steroids and/or NSAIDs,�-blockers, with their high successrates, excellent safety profile, low sideeffect profile, and ease of use, have be-come the leading candidate in METand should be used as first-line ther-apy in any appropriate candidate onan observation protocol during thepassage of a distal ureteral stone.Additionally, �-adrenergic receptorantagonists may be considered duringthe conservative treatment of proximaland mid-ureteral stones, and after sur-gical intervention of renal stones.

References1. Segura JW, Preminger GM, Assimos DG, et al.

Ureteral stones clinical guidelines panel sum-mary report on the management of ureteral cal-culi. J Urol. 1997;158:1915-1921.

2. Hollingsworth, JM, Rogers MAM, Kaufman SR,et al. Medical therapy to facilitate urinary stone

passage: a meta-analysis. Lancet. 2006;368:1171-1179.

3. Malin JM, Deane RF, Boyarsky S. Characterisa-tion of adrenergic receptors in human ureter. BrJ Urol. 1970;42:171-174.

4. Sigala S, Dellabella M, Milanese G, et al. Evi-dence for the presence of alpha1 adrenoceptorsubtypes in the human ureter. Neurourol Urody-namics. 2005;24:142-148.

5. Weiss RM, Bassett AL, Hoffman BF. Adrenergicinnervation of the ureter. Invest Urol. 1978;16:123-127.

6. Morita T, Wada I, Saeki H, et al. Ureteral urinetransport: changes in bolus volume, peristalticfrequency, intraluminal pressure and volume offlow resulting from autonomic drugs. J Urol.1987;137:132-135.

7. Davenport K, Timoney AG, Keeley FX. A com-parative in vitro study to determine thebeneficial effect of calcium-channel and alpha(1)-adrenoceptor antagonism on human uretericactivity. BJU Int. 2006;98:651-655.

8. Porpiglia F, Vaccino D, Billia M, et al. Cortico-steroids and tamsulosin in the medical expulsivetherapy for symptomatic distal ureter stones:single drug or association? Eur Urol. 2006;50:339-344.

9. Dellabella M, Milanes G, Muzzonigro G. Medical-expulsive therapy for distal ureterolithiasis:randomized prospective study on role of corti-costeroids used in combination with tamsulosin-simplified treatment regimen and health-relatedquality of life. Urology. 2005;66:712-715.

10. Laerum E, Ommundsen OE, Gronseth JE, et al.Oral diclofenac in the prophylactic treatment ofrecurrent renal colic. A double-blind comparisonwith placebo. Eur Urol. 1995;28:108-111.

11. Borghi L, Meschi T, Amato F, et al. Nifedipineand methylprednisolone in facilitating ureteralstone passage: a randomized, double-blind,placebo-controlled study. J Urol. 1994;152:1095-1098.

12. Porpiglia F, Destefanis P, Fiori C, Fontanta D. Ef-fectiveness of nifedipine and deflazacort in themanagement of distal ureter stones. Urology.2000;56:579-582.

13. Porpiglia F, Destefanis P, Fiori C, et al. Role ofadjunctive medical therapy with nifedipine anddeflazacort after extracorporeal shock wavelithotripsy of ureteral stones. Urology. 2002;59:835-838.

14. Weiss, RM. Physiology and pharmacology of therenal pelvis and ureter. In: Walsh PC, Retik AB,Vaughan ED Jr, Wein AJ, eds. Campbell’s Urology.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 ureteralstones, 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.




15. Kubacz GJ, Catchpole BN. The role of adrenergicblockade in the treatment of ureteral colic. JUrol. 1972;107:949-951.

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Alfa Bloker, Urolitiasis

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