Management of renal colic

Acute renal colic is one of the most anguishing forms of pain in humans which needs quick diagnosis and timely and suitable management approach. The primary reason for this excruciating pain is presence of renal stones.

Global scenario: prevalence of renal calculi

Kidney stone and urinary stone is a worldwide problem, sparing no geographical, cultural, or racial groups. Kidney stone or nephrolithiasis is a common disease with increasing incidence and prevalence worldwide. The lifetime risk of kidney stones is of about 12% in men and 6% in women.¹Bultitude M, Rees J. Management of renal colic. BMJ 2012; 345:e5499.   Previously, the increased incidence was observed among men, but recent studies have demonstrated narrowing male to female ratio.²Scales CD Jr, Curtis LH, Norris RD, Springhart WP, Sur RL, Schulman KA, Preminger GM. Changing gender prevalence of stone disease. J Urol. 2007 Mar; 177(3):979-82.   Global prevalence of nephrolithiasis was evaluated in a study, which demonstrated increasing prevalence of the disease in recent decades in US.³Romero V, Akpinar H, Assimos DG. Kidney Stones: A Global Picture of Prevalence, Incidence, and Associated Risk Factors. Rev Urol. 2010; 12(2/3):e86-e96.  

In India, approximately 5-7 million patients suffer from stone disease and at least 1/1000 of Indian population needs hospitalization due to kidney stone disease. In India, the “stones belt” occupies parts of Maharashtra, Gujarat, Punjab, Haryana, Delhi and Rajasthan. In these regions, the disease is so prevalent that most of the members of a family will suffer from kidney stones sometime in their lives.⁴Vyas Amit S, Patel Mandev B, Patel Ajay I, Joshi Namrata R. Epidemiology of renal stone ailment in few district of Gujarat state. Pharma Science Monitor.2012;3(2):232-239.  

Who is at risk?

Decreased fluid intake and consequent urine concentration are among the most important factors influencing stone formation. Increased incidence of kidney stones is also associated with warmer climates, owing to a combination of dehydration and sun exposure. Obesity and genetic predisposition are also considered as risk factors of kidney stones. Any anatomical abnormality of the urinary tract (such as a horseshoe kidney) indicates a higher risk of stone formation, as well as several medical disorders, such as primary hyperparathyroidism, renal tubular acidosis, myeloproliferative disorders, all chronic diarrhea conditions (for example, Crohn’s disease), and gout.

Certain medications, such as triamterene, indinavir and acetazolamide, are also associated with urolithiasis. Dietary oxalate is another possible cause, but the role of dietary calcium is less clear, and calcium restriction is no longer universally recommended.⁵Portis AJ, Sundaram CP. Diagnosis and Initial Management of Kidney Stones. Am Fam Physician 2001; 63:1329-38.  

What are the symptoms of renal calculi?

Small intra-renal stones are often asymptomatic, detected incidentally on imaging for other disorders. Stones become symptomatic when they either move or have reached sufficient size to cause loin pain or hematuria.

The classic presentation of renal colic is excruciating unilateral flank or lower abdominal pain of sudden onset that is not related to any precipitating event and is not relieved by postural changes or nonnarcotic medications. Flank pain radiating to the groin, building to a maximum in half an hour and extreme in severity, is typical.

Along with this flank pain, patient may also present with gross or microscopic hematuria, dysuria or frequency, vomiting, nausea, etc. With the exception of nausea and vomiting secondary to stimulation of the celiac plexus, gastrointestinal symptoms are usually absent.

Stones in the distal ureter manifest with bladder instability like dysuria, or frequency and/or pain radiating to the tip of the penis or the labia or vulva.

Other medical conditions, such as appendicitis, cholecystitis, diverticulitis, colitis, constipation, hernias or even arterial aneurysms, other causes of urethral obstruction, etc, also present with abdominal

pain or discomfort and these should be considered for the differential diagnosis of renal colic.

What is the reason for renal colic?

The pain is caused by spasm of the ureter around the stone, causing obstruction and distension of the ureter, pelvicalyceal system, and renal capsule. Although the most common cause is a stone, the term “renal colic” actually refers to a collection of symptoms attributed to the kidney and ureter. There are other intrinsic or occasionally extrinsic causes, such as lymphadenopathy, although extrinsic causes tend to present with milder and more chronic discomfort.

The pain of renal colic is thought to be related to ureteric smooth muscle spasm, edema and inflammation at the level of the calculus, and increased peristalsis and pressure proximal to the calculus. Persistent obstruction of the urinary tract may lead to renal impairment secondary to prostaglandin release as part of the inflammatory response. Within hours, the pressure gradient across the glomerulus equalizes as pelvic pressure increases. In response, glomerular filtration and renal blood flow reduce. Unless the obstruction is relieved, renal impairment ensues.⁶Davenport K, Timoney AG, Keeley FX. Conventional and alternative methods for providing analgesia in renal colic. BJU International Volume 95, Issue 3, pages 297-300, February 2005  

Diagnosing renal colic

A detailed case history, including the past and family history of renal stones, duration, evolution of symptoms, signs or symptoms of sepsis, should be taken. Physical examination helps to rule out the

non-urologic conditions, urinalysis helps to identify microscopic hematuria, and the stone composition.

Because of the various presentations of renal colic and its broad differential diagnosis, an organized diagnostic approach is useful (Figure 1). Symptomatic stones essentially present as abdominal pain. Renal colic may be suspected based on the history and physical examination, but diagnostic imaging is essential to confirm or exclude the presence of urinary calculi. Several imaging modalities are available, and each has advantages and limitations.

During recent years, helical computed tomography has been introduced as a quick and contrastfree alternative to urography. An alternative and commonly applied method for evaluating patients with flank pain is a plain film of kidneys, ureter and bladder combined with ultrasonography.⁷Osorio L, Lima E, Autorino R, et al. Emergency management of ureteral stones: Recent advances. Indian Journal of Urology 2008;24:461-466.  

Does patient with renal colic needs hospitalization?

The severity of patient’s condition dictates the need of hospitalization. For patients in whom diagnosis is clear, adequate pain relief can be achieved, and there are no complicating factors, it may be possible to manage them in the outpatient department without any hospitalization. Inability to control pain and provide adequate analgesia are the criteria for hospitalization. Presence of sepsis and complicating risk factors in patient with renal colic needs urgent intervention or hospitalization.¹Bultitude M, Rees J. Management of renal colic. BMJ 2012; 345:e5499.  

How to manage patient with renal colic?

Management of patient with renal calculi needs a well-planned approach after the diagnosis of the condition. As the final diagnosis of renal calculi needs various lab investigations as well as imaging studies, the patient should be given the primary care for his emergency complaint, which is mainly renal colic. Pain management is the primary goal as patient of renal colic complains of unbearable pain.

Role of NSAIDs in renal colic

Even though non-steroidal anti-inflammatory drugs (NSAIDs) provide excellent analgesia in renal colic, but should be used with care in patients at risk of renal impairment, cardiac failure and gastric ulceration. They are highly effective in reducing the number of new colic episodes and readmissions to

hospital; however, they do not appear to have any effect on the time to stone passage or the likelihood of stone passage in renal colic. Hence, the decision and selection of an NSAID would entirely depend upon the Doctor, looking at the existing situation and condition of the patient.⁸Davenport K, Waine E. The Role of Non-Steroidal Anti-Inflammatory Drugs in Renal Colic. Pharmaceuticals. 2010;3(5):1304-1310.  

Antispasmodics – safer alternative

The adverse effects associated with NSAIDs invariably depict the need of having safe and effective agent. Hence, antispasmodics have been tried in the management of renal colic. Drotaverine hydrochloride, an isoquinoline derivative, is a potent spasmolytic, which acts directly on the smooth muscles by inhibiting phosphodiesterase (PDE) activity. Because of this antispasmodic action, it is widely used in biliary and renal colic, for augmentation of labor, dysmenorrhea and before instrumental diagnostic procedures.

Drotaverine has significant inhibitory effect on PDE enzyme; it inhibits PDE IV enzyme in vitro without inhibiting PDE III and PDE V. This selective inhibition may be important since PDE IV appears, functionally, to be very important in reducing contractile activity of the smooth muscles. Drotaverine has been shown to possess dose-dependent analgesic effect.

Drotaverine in renal colic vs. placebo

The efficacy of drotaverine in reducing the colicky pain in patients with renal and ureteric stones was evaluated in a placebo-controlled, multicentre, randomized, double-blind study conducted by Romics I and colleagues.⁹Romics I, Molnár DL, Timberg G, Mrklic B, Jelakovic B, Köszegi G, Blaskó G. The effect of drotaverine hydrochloride in acute colicky pain caused by renal and ureteric stones. BJU Int. 2003 Jul;92(1):92-6.   In this study, 102 patients with colicky pain were included. Among them, 48 patients were administered drotaverine and 54 patients were administered placebo. The primary endpoint was the evaluation of the antispasmodic effect of drotaverine during a 3-h study period, to confirm that drotaverine abolished or significantly decreased the intensity of pain in renal colic. The painkilling effect was defined as a decrease by at least half in the PI scale, and/or a ≥40% decrease in the visual analog scale (VAS) 40 min after either the first or the second injection of 80 mg drotaverine or placebo. Drotaverine was effective in 79% and placebo in only 46% (Figure 2). Only minor side effects were reported which subsided without any treatment. This study demonstrates that intravenous drotaverine provides effective pain relief in more than two-thirds of patients with renal colic, with no serious side-effects.⁹Romics I, Molnár DL, Timberg G, Mrklic B, Jelakovic B, Köszegi G, Blaskó G. The effect of drotaverine hydrochloride in acute colicky pain caused by renal and ureteric stones. BJU Int. 2003 Jul;92(1):92-6.  

Drotaverine vs. diclofenac in renal colic

Dash A and colleagues¹⁰Dash A, Maiti R, Akantappa Bandakkanavar TK, Arora P. Intramuscular drotaverine and diclofenac in acute renal colic: a comparative study of analgesic efficacy and safety. Pain Med. 2012 Mar;13(3):466-71.   conducted a randomized, single-blind study to evaluate the analgesic efficacy and safety of intramuscular doses of drotaverine hydrochloride (80 mg) vs. diclofenac sodium (75 mg) in treatment of acute renal colic. In this study, 100 patients with renal colic were included, 50 patients were administered droatverine and 50 patients diclofenac. Pain intensity was recorded using a VAS, which was the primary outcome measure of this study,

before drug administration and 30 and 60 minutes afterwards. The drug effectiveness was defined as ≥50% decrease in pain intensity 60 minutes after intramuscular administration, without exacerbation during the following 2 hours. After 30 minutes of drug administration, VAS decreased significantly in both the groups. Reduction of VAS at 60 minutes was 61.3% with drotaverine in comparison to 60.4% with diclofenac (Figure 3). Forty-five patients (90%) in the drotaverine group and 44 (88%) in the diclofenac group found the therapy effective (Figure 4). The need for rescue medication was in five patients of the drotaverine group and six patients in the diclofenac group. There was no significant difference in safety profile in the study groups. Thus, in patients with colicky pain drotaverine is as effective as diclofenac.¹⁰Dash A, Maiti R, Akantappa Bandakkanavar TK, Arora P. Intramuscular drotaverine and diclofenac in acute renal colic: a comparative study of analgesic efficacy and safety. Pain Med. 2012 Mar;13(3):466-71.  

Drotaverine in fixed dose combination

Spasmolytics are traditionally used in renal colic, biliary colic or dysmenorrhoea for relief of smooth muscle spasm. As spasmolytics relieve the pain associated with smooth muscle spasm, the combination of NSAIDs with spasmolytics is likely to be synergistic. Fixed dose combinations (FDC) of mefenamic acid, aceclofenac with spasmolytics such as drotaverine have been demonstrated to be highly effective in relief of acute spasmodic pain.¹¹A. Porwal, A. D. Mahajan, D. S. Oswal, et al. “Efficacy and Tolerability of Fixed-Dose Combination of Dexketoprofen and Dicyclomine Injection in Acute Renal Colic”. Pain Research and Treatment, vol. 2012, Article ID 295926, 5 pages, 2012. doi:10.1155/2012/295926.  

In the study performed by Pareek et al., addition of spasmolytic such as drotaverine to aceclofenac was found to provide significant therapeutic benefit as compared to monotherapy with aceclofenac.¹²Pareek A, Chandurkar NB, Patil RT, Agrawal SN, Uday RB, Tambe SG. Efficacy and safety of aceclofenac and drotaverine fixed-dose combination in the treatment of primary dysmenorrhoea: a double-blind, double-dummy, randomized comparative study with aceclofenac. Eur J Obstet Gynecol Reprod Biol. 2010;152(1):86-90.  

Drotaverine is also available in combination with paracetamol or mefenamic acid, synergistic effect of these combination results in better outcome.

What is the role of medical expulsive therapy?

Medical expulsive therapy has emerged as an appealing option for the management of renal calculi. Several pharmacological approaches have been proposed to act on possible causes of stone retention. Drugs like α-adrenergic blockers, calcium channel blockers, corticosteroids have been tried in patients with renal calculi.

European and US guidelines recommend MET as an option when following conditions are met:

• Newly diagnosed uretral stone<10 mm
• Well controlled pain
• Good renal function
• Periodic imaging to monitor stone position and asses hydronephrosis

Role of tamsulosin in stone expulsion

Although ureteral smooth muscle lacks direct innervation, its contractile activity is modulated by the autonomic nervous system. Stimulation of α-1 adrenergic receptors enhances contractile frequency and amplitude. A pharmacologic agent that antagonizes α-1 receptor activity should therefore decrease contractile activity associated with ureteral spasm induced by stones, thus facilitating stones passage. α-1 adrenergic antagonists reduce ureteral contractions and spasm and may hasten the passage of retained stones.

Currently α-adrenergic blockers are the commonly used drugs in the management of renal colic. Tamsulosin, a selective α-blocker with both α-1-A and α-1-D antagonist action, has been studied by various authors.

A study was conducted on 60 patients with unilateral, juxtavesical ureteral stones with mean stone size of 5.8 mm. These were randomized into two groups. Group 1 received 30 mg deflazacort (a corticosteroid to control edema) daily, cotrimoxazole (a prophylactic antibiotic) twice daily, 75 mg injectable diclofenac (Voltaren) on demand, and floroglucine-trimetossibenzene (a local spasmolytic drug) thrice daily. Group 2 received similar treatment with the substitution of 0.4 mg of tamsulosin as the spasmolytic drug. All patients were instructed to drink a lot of water. Although the mean stone size was statistically larger in group 2, the expulsion rate was greater than in group 1 (100% v 70%; P = 0.001). In addition, the mean hours to expulsion, the mean number of diclofenac injections, the rate of hospitalization, and the need for endoscopic stone removal were all lower in the tamsulosin group. This study demonstrated that tamsulosin is effective in hastening the passage of juxtavesical ureteral stones and decreasing both the severity and duration of renal colic.¹³Dellabella M, Milanese G, Muzzonigro G. Efficacy of tamsulosin in the medical management of juxtavesical ureteral stones. J Urology 2003;170:2202-5.  

Mode of action of tamsulosin – Tamsulosin stimulates α-adrenergic receptors that are present in the ureter. Stimulation of α-receptors increases the force of ureteral contraction and the frequency of ureteral peristalsis. This stimulation induces an increase in the intraureteral pressure gradient around the stone, that is an increase in the urine bolus above the stone (and consequently an increase intraureteral pressure above the stone) as well as decreased peristalsis below the ureter (and consequently a decrease in intraureteral pressure below the stone) in association with decrease in basal and micturition pressure even at the bladder neck. For these reasons there would be a stronger urge to expel the stone.

Tamsulosin with ADS technology – an innovative advantage – Unlike conventional tamsulosin formulations that depend on the presence of water in the gastrointestinal tract (GIT) to release the active ingredient, the innovative ADS technology ensures continuous and consistent tamsulosin release throughout the entire length of the GIT including the colon where water is poorly available. This results in a more constant exposure to tamsulosin over 24 hours with a smaller peak-to-trough fluctuation (PTF) than the conventional formulations; and, also reduces/eliminates the dependency on food. In fact, the innovation appears superior to conventional MR formulation of tamsulosin that has a variable absorption profile dependent on when it is taken in relation to food and gastrointestinal transit time. Furthermore, as not all patients comply with the dosing recommendations in the patient leaflet, the independence of food intake might considerably improve the tolerability of tamsulosin.¹⁴Speakman M. Efficacy and safety of tamsulosin OCAS. BJU international 2006;98(2): 13-17.   Consequently, the ADS advantage equates with less adverse effects on physiologic parameters.

Efficacy of tamsulosin in proximal stones

Tamsulosin is effective in the management of distal ureteral stones, but its role in managing proximal stones is unclear. A study was conducted to evaluate the efficacy of tamsulosin on spontaneous passage of proximal ureteral calculi ≤ 10 mm. This study was conducted on 92 patients, who were randomly divided into two groups. Group 1 was given classical conservative approach, Group 2 additionally received tamsulosin, 0.4 mg/day during 4 weeks follow-up. Stone expulsion rate was significantly better, and also higher spontaneous passage rate of stone was seen, with tamsulosin group. This study supported

Benefits of Tamsulosin with ADS technology

• 24 hours consistent drug release, and thus lesser C_Max related side effects
• Decreased risk of postural hypotension, especially in patients with cardiovascular comorbidities; thereby reducing the risk of cardiovascular events and falls and fractures
• Favourable efficacy/tolerability ratio
• Lower incidence of treatment emergent adverse events
• Independent of food intake: unlike conventional tamsulosin, it can be given independent of food
• Flexible dosing time: can be given anytime during the day without the risk of side effects

the use of tamsulosin in the proximal ureter stone management.¹⁵Yencilek F, Erturhan S, Canguven O, Koyuncu H, Erol B, Sarica K. Does tamsulosin change the management of proximally located ureteral stones? Urol Res. 2010 Jun;38(3):195-9.  

Is there any need of adding

corticosteroids to tamsulosin therapy?

The theory that corticosteroids were not necessary for the expulsion of ureteral stones was further tested in a comparison of tamsulosin plus deflazacort with tamsulosin monotherapy.¹⁶Dellabella M, Milanese G, Muzzonigro G. Medical expulsive therapy for distal ureterolithiasis: randomized prospective study on role of corticosteroids used in combination with tamsulosin-simplified treatment regimen and health-related quality of life. Urology 2005;66:712-5.   Expulsion rates of the tamsulosin and tamsulosin/deflazacort groups at study end were similarly high. The rates of emergency department visits, hospitalizations and lost work days were similar between the 2 groups. The authors concluded that the addition of deflazacort resulted in expulsion rates similar to those of tamsulosin alone. And tamsulosin alone as medical-expulsive therapy for distal ureteral calculi had excellent expulsive effectiveness.

Another, direct comparison of efficacy of monotherapy with tamsulosin and combination therapy of tamsulosin and deflazacort was done on 114 patients with symptomatic distal ureteral stones with ≥ 5mm diameter. These patients were divided into 4 groups based on the treatment they received. Group A (33 patients) received tamsulosin (0.4 mg daily), group B (24 patients) received deflazacort (30 mg daily), group C (33 patients) received both (0.4 mg tamsulosin+30 mg deflazacort daily), and control group D (24 patients) received only analgesics. The rates of expulsion for the four groups were 60%, 37.5%, 84.8%, and 33.3%, respectively. There was a significant difference between group C and the other groups (p<0.001) (Figure 5). The mean analgesic

consumption was 42.5±0.4mg for group A, 50±0.3mg for group B, 27.3±0.5mg for group C, and 81±0.33mg for group D, with a significant difference between group C and the other groups (p<0.001).17 This study demonstrated that when the medical expulsive therapy for symptomatic distal ureteral stones is considered, the use of steroids (deflazacort) proves efficient only when administered together with alpha (1)-blockers (tamsulosin). However, combination therapy should be restricted to 10 days, as prolonged use of corticosteroids is associated with side effects. Hence, in longer duration of medical expulsive therapy, corticosteroid usage is not advisable.

What is the role of urinary alkalization?

Factors implicated in uric acid stone formation include a persistently acidic urine, dehydration causing low urine volumes, and hyperuricosuria. Of these, alteration in urinary pH appears to be the most important contributory mechanism.

Urinary dissolution for uric acid and cystine calculi is now a standard therapy. Patients with uric acid stones who do not require urgent surgical intervention for reasons of pain, obstruction or infection can often have their stones dissolved with alkalization of the urine. The dosage of the alkalizing agent should be adjusted to maintain the urinary pH between 6.5 and 7.0. Urinary pH of more than 7.5 should be avoided because of the potential deposition of calcium phosphate around the uric acid calculus, which would make it undissolvable. Both uric acid and cystine calculi form in acidic environments.

Potassium citrate and sodium bicarbonate are commonly used for urine alkalization. Potassium citrate is a preferred alkalizing agent, because of the avoidance of a high sodium load. Potassium citrate should be preferred because it may avoid the complication of calcium salt precipitation. Studies have proved that urinary alkalization with potassium citrate/bicarbonate is a well tolerated and highly effective treatment, resulting in dissolution of nonobstructing uric acid stones.¹⁸Trinchieri A, Esposito N, Castelnuovo C. Dissolution of radiolucent renal stones by oral alkalinization with potassium citrate/potassium bicarbonate. Arch Ital Urol Androl. 2009 Sep;81(3):188-91.   Potassium citrate helps in chemo-dissolution of uric acid and cystine stones and is useful in prevention of stone recurrence in general and in those who have undergone SWL or percutaneous nephrolithotomy.¹⁹Singh SK, Agarwal MM, Sharma S. Medical therapy for calculus disease. BJU Int. 2011 Feb;107(3):356-68.  

Results of the study of contrasting effects of potassium citrate and sodium citrate therapies on urinary chemistries and crystallization of stoneforming salts²⁰Sakhaee K, Nicar M, Hill K, Pak CY; Contrasting effects of potassium citrate and sodium citrate therapies on urinary chemistries and crystallization of stone-forming salts; Kidney Int. 1983 Sep;24(3):348-52   indicate that potassium citrate may prevent the complication of calcium nephrolithiasis in patients with uric acid stones, whereas sodium citrate may not.

Sodium-containing products are not recommended for patients in whom sodium intake should be restricted, e.g. hypertensive patients, those with heart disease and pregnant women.

In the treatment of nephrolithiasis, alkalization can be achieved with sodium bicarbonate, sodium citrate or potassium citrate.²¹Dipiro JT, Talbert RL, Yee GC, et al. Pharmacotherapy: a pathophysiologic approach. 3rd ed. Appleton and Lange;1997.   Due to better gastrointestinal tolerance, citrate salts are often preferred.²²Sinha M, Prabhu K, Venkatesh P, Krishnamoorthy V. Results of urinary dissolution therapy for radiolucent alkali. Int Braz J Urol.2013;39:103-7.   Potassium citrate may be preferable to sodium citrate, because of a reduced potential for the development of calcium stones that may arise from sodium citrate or sodium bicarbonate therapy.

Potassium citrate is preferable as potassium urate is more soluble than sodium urate and the addition of sodium results in a concomitant increase in sodium.22 Potassium-magnesium citrate also confers an alkali load, raises urinary citrate, and diminishes stone recurrence. According to a study, if this is given for up to 3 years reduces risk of recurrence by 85%.²³Ettinger B, Pak CY, Citron JT, Thomas C, Adams-Huet B, Vangessel A. Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis. J Urol. 1997 Dec;158(6):2069-73.  

Role of potassium citrate as post ESWL therapy

Clinically insignificant residual fragments (less than 5mm) are usually present in upper urinary tract as observed at the time of regular post-SWL follow-up. As these fragments can act as a nidus for recurrent stone growth, they can become acutely dislodged and cause significant obstruction with pain and infection, or they may be the source of persistent infection, their prevention or treatment plays an important role. Medical therapy, specifically alkaline citrate, reduces the rate of stone recurrence or stone growth in patients undergoing SWL for renal calculi. Consequently, adjuvant medical therapy after SWL may actually improve stone-free rates by encouraging fragment clearance. Various studies have demonstrated that administration of potassium citrate immediately after or before SWL may prove to be efficacious.²⁴Elisa Cicerello, Franco Merlo, and Luigi Maccatrozzo. “Management of Clinically Insignificant Residual Fragments following Shock Wave Lithotripsy”. Advances in Urology, vol. 2012, Article ID 320104, 5 pages, 2012. doi:10.1155/2012/320104.  

Conclusion

Renal colic represents the collection of acute symptoms, which are characterized by very intensive and antagonizing pain, so that withstanding it calls for fast diagnosis and precise and speedy treatment. For the management of renal colic, adverse effects associated with NSAIDs make antispasmodics the preferred drugs. Drotaverine used alone or in combination with aceclofenac or mefenamic acid has shown better efficacy profile in renal colic pain management, and also demonstrated to be safer compared to NSAIDs. Medical expulsive therapy for renal calculi mainly includes α-adrenergic blockers, namely tamsulosin, which is the most widely studied and used drug in renal calculi. Urinary alkalization using potassium citrate is also a good preventive as well as therapeutic approach. Various studies have supported the use of potassium citrate/potassium magnesium citrate in dissolution of renal stones, also as prophylaxis therapy post ESWL for the prevention of residual fragments.

References

1. Bultitude M, Rees J. Management of renal colic. BMJ 2012; 345:e5499.
2. Scales CD Jr, Curtis LH, Norris RD, Springhart WP, Sur RL, Schulman KA, Preminger GM. Changing gender prevalence of stone disease. J Urol. 2007 Mar; 177(3):979-82.
3. Romero V, Akpinar H, Assimos DG. Kidney Stones: A Global Picture of Prevalence, Incidence, and Associated Risk Factors. Rev Urol. 2010; 12(2/3):e86-e96.
4. Vyas Amit S, Patel Mandev B, Patel Ajay I, Joshi Namrata R. Epidemiology of renal stone ailment in few district of Gujarat state. Pharma Science Monitor.2012;3(2):232-239.
5. Portis AJ, Sundaram CP. Diagnosis and Initial Management of Kidney Stones. Am Fam Physician 2001; 63:1329-38.
6. Davenport K, Timoney AG, Keeley FX. Conventional and alternative methods for providing analgesia in renal colic. BJU International Volume 95, Issue 3, pages 297-300, February 2005
7. Osorio L, Lima E, Autorino R, et al. Emergency management of ureteral stones: Recent advances. Indian Journal of Urology 2008;24:461-466.
8. Davenport K, Waine E. The Role of Non-Steroidal Anti-Inflammatory Drugs in Renal Colic. Pharmaceuticals. 2010;3(5):1304-1310.
9. Romics I, Molnár DL, Timberg G, Mrklic B, Jelakovic B, Köszegi G, Blaskó G. The effect of drotaverine hydrochloride in acute colicky pain caused by renal and ureteric stones. BJU Int. 2003 Jul;92(1):92-6.
10. Dash A, Maiti R, Akantappa Bandakkanavar TK, Arora P. Intramuscular drotaverine and diclofenac in acute renal colic: a comparative study of analgesic efficacy and safety. Pain Med. 2012 Mar;13(3):466-71.
11. A. Porwal, A. D. Mahajan, D. S. Oswal, et al. “Efficacy and Tolerability of Fixed-Dose Combination of Dexketoprofen and Dicyclomine Injection in Acute Renal Colic”. Pain Research and Treatment, vol. 2012, Article ID 295926, 5 pages, 2012. doi:10.1155/2012/295926.
12. Pareek A, Chandurkar NB, Patil RT, Agrawal SN, Uday RB, Tambe SG. Efficacy and safety of aceclofenac and drotaverine fixed-dose combination in the treatment of primary dysmenorrhoea: a double-blind, double-dummy, randomized comparative study with aceclofenac. Eur J Obstet Gynecol Reprod Biol. 2010;152(1):86-90.
13. Dellabella M, Milanese G, Muzzonigro G. Efficacy of tamsulosin in the medical management of juxtavesical ureteral stones. J Urology 2003;170:2202-5.
14. Speakman M. Efficacy and safety of tamsulosin OCAS. BJU international 2006;98(2): 13-17.
15. Yencilek F, Erturhan S, Canguven O, Koyuncu H, Erol B, Sarica K. Does tamsulosin change the management of proximally located ureteral stones? Urol Res. 2010 Jun;38(3):195-9.
16. Dellabella M, Milanese G, Muzzonigro G. Medical expulsive therapy for distal ureterolithiasis: randomized prospective study on role of corticosteroids used in combination with tamsulosin-simplified treatment regimen and health-related quality of life. Urology 2005;66:712-5.
17. Porpiglia F, Vaccino D, Billia M, Renard J, Cracco C, Ghignone G, Scoffone C, Terrone C, Scarpa RM. Corticosteroids and tamsulosin in the medical expulsive therapy for symptomatic distal ureter stones: single drug or association? Eur Urol. 2006 Aug;50(2):339-44. Epub 2006 Mar 3.
18. Trinchieri A, Esposito N, Castelnuovo C. Dissolution of radiolucent renal stones by oral alkalinization with potassium citrate/potassium bicarbonate. Arch Ital Urol Androl. 2009 Sep;81(3):188-91.
19. Singh SK, Agarwal MM, Sharma S. Medical therapy for calculus disease. BJU Int. 2011 Feb;107(3):356-68.
20. Sakhaee K, Nicar M, Hill K, Pak CY; Contrasting effects of potassium citrate and sodium citrate therapies on urinary chemistries and crystallization of stone-forming salts; Kidney Int. 1983 Sep;24(3):348-52
21. Dipiro JT, Talbert RL, Yee GC, et al. Pharmacotherapy: a pathophysiologic approach. 3rd ed. Appleton and Lange;1997.
22. Sinha M, Prabhu K, Venkatesh P, Krishnamoorthy V. Results of urinary dissolution therapy for radiolucent alkali. Int Braz J Urol.2013;39:103-7.
23. Ettinger B, Pak CY, Citron JT, Thomas C, Adams-Huet B, Vangessel A. Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis. J Urol. 1997 Dec;158(6):2069-73.
24. Elisa Cicerello, Franco Merlo, and Luigi Maccatrozzo. “Management of Clinically Insignificant Residual Fragments following Shock Wave Lithotripsy”. Advances in Urology, vol. 2012, Article ID 320104, 5 pages, 2012. doi:10.1155/2012/320104.