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Sunday, December 25, 2016

Use of Alpha 1 blocker as a part of Medical Expulsive Therapy (MET) for Ureteric Stone

Posted by Prahallad Panda on 12:41 PM Comments

The traditional teaching has been plenty of water, control of infection and some anti-spasmodic as an expectant treatment for small ureteric stones, i.e. around 5 mm. in diameter, to pass out; more than 10 mm, requires intervention.

In the recent days, the management of ureteric stone has been revolutionalised by introduction of Extra-Corporeal Shock Wave Lithotripsy (ESWL) and ureteroscopic surgery /other minimally invasive surgeries.
However, there is always a room for conservative management of ureteric stones, where the size of stone is around 5 mm. in diameter and is located more towards the distal part of the ureter.
Migration and increase in size of stone causes excruciating pain, only known to those, who suffer from it.
An article published in Cleveland Clinic Journal of Medicine, based on the original article published in the BMJ (British Medical Journal, Alpha Blockers & Treatment of Ureteric Stones, BMJ; ePub 2016 Dec 1; Hollingsworth, et al. December 20, 2016) recommends use of Alpha 1 blocker as a part of Medical Expulsive Therapy (MET) for ureteric stone, precisely located more distally in the ureter.
Urinary stones are common, with a prevalence of about 5% in the population. Non-contrast CT scan is the diagnostic modality of choice. When calculi are smaller than 5 mm, 90% will pass spontaneously, but as stones approach 10 mm., there is less than a 10% chance that they will pass.
Since, small stones pass spontaneously almost all of the times, alpha-blockers add little to the management of these small stones. The value of alpha-blockers is for stones of 5 mm to 10 mm in size, where the use of an alpha-blocker significantly improves the rate of passage without surgical intervention.
When conservative management of a ureteral stone is being considered and the patient has no associated signs of infection, uncontrollable pain, or renal failure, adjuvant pharmacologic intervention has proven efficacious in improving spontaneous stone passage rate and time interval, and in reducing analgesic requirements.
Many of the studies have administered the drugs in conjunction with steroids and/or NSAIDs, which may reduce ureteral edema and improve the ability for a patient to spontaneously pass a ureteral stone.
However, several of the more recent studies have shown benefit to both α-blockers and calcium channel blockers without the adjunctive use of steroids; furthermore, tamsulosin, in randomized trials, has been shown to be more efficient than nifedipine with a decreased time to expulsion and slightly higher rate of expulsion.
Alpha-1-adrenergic receptors are located throughout the human ureter. The physiologic response to antagonism of these receptors is decreased force of contraction, decreased peristaltic frequency, and increased fluid bolus volume transported down the ureter. These responses are likely, how α-blockers assist in ureteral stone passage.
Alpha-blockers, specifically α1 antagonists, are highly effective in increasing the expulsion rate of distal ureteral stones, reducing the time to stone passage, and decreasing the amount of pain medication needed during passage stones.
Alpha blockers may also be a useful adjunct in the treatment of both ureteral and renal stones after ESWL. They may also reduce the urinary symptoms and pain associated with double-J ureteral stents. 

  • 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; α-blockers increase expulsion rates of distal ureteral stones, decrease time to expulsion, and decrease need for analgesia during stone passage. Moderate quality evidence was observed that alpha blockers facilitate passage of ureteric stones. 
  • In the appropriate clinical scenario, the use of α-blockers is recommended in the conservative management of distal ureteral stones. 
  • The greatest benefit may be among patients with larger stones (57% higher likelihood of stone passage vs controls). 
  • Compared with controls, patients receiving alpha blockers had significantly shorter times to stone passage, fewer episodes, lower risks of surgical intervention, and lower risk of admission to hospital.
Urinary stone disease is frequently seen in the urology practice. Symptoms include flank or abdominal pain radiating to the groin or external genitalia. Although some patients with ureteral stones might remain asymptomatic, many have pain and thus commonly seek medical care. Ureteric stone and its' size are best assessed in a non-contrast CT in comparison to the ultrasound examination.

An acute episode of colic is the result of a stone entering the ureter and causing intermittent rise of pressure in the pyelocalyceal system. Spontaneous passage will occur in most of these stones. 
An review article published in Cochrane Library (2nd April, 2014, Authors: Campschroer T, Zhu Y, Duijvesz D, Grobbee DE, Lock M) identified 32 studies enrolling 5864 participants. The use of alpha-blockers in patients with ureteral stones resulted in a higher stone-free rate and a shorter time to expulsion and therefore decreased the duration of symptoms and rate of complications (UTI, hydronephrosis and impairment of kidney function).
Medical expulsive therapy includes the use of oral/intravenous hydration, analgesics, and medications that promote stone passage, including alpha-1 blockers.
The most common alpha-1 blocker used to aid in the passage of ureteral stones is tamsulosin. The indicated use for tamsulosin is for treating symptoms of benign prostatic hyperplasia (BPH) (Alexander, 2010); however, off-label use has recently emerged as an efficacious and safe option for the initial management of ureteral stones (Bensalah et al., 2008)
Tamsulosin may help patients pass a kidney stone by relaxing the smooth muscle of the intramural ureters, allowing urine and stones to pass through more easily.
Tamsulosin is an antagonist of alpha1Aadrenoreceptors in smooth muscle; blocking them leads to relaxation of smooth muscle in the bladder neck causing an improvement in urine flow (Alexander, 2010).
Tamsulosin also relaxes the smooth muscle of veins and arteries, which can cause patients to feel dizzy when getting up from a sitting or lying position (orthostatic hypotension). Patients who take tamsulosin should be careful not to move too quickly when changing positions to avoid dizziness or syncopy.
Other documented side or adverse effects include blurred vision, cough, decreased sexual function, diarrhea, dizziness, drowsiness, lightheadedness, runny or stuffy nose, sinus in flam mation, trouble sleeping, and weakness (Lexi-Comp, Inc., 2011). Overdose symptoms include clammy or cold skin, rapid heartbeat, lightheadedness, extreme headache, and passing out.
Because of its sustained release formulation, the manufacturer does not recommend opening, crushing, or chewing the capsule/tablet because this can increase the medication's potential side effects (Alexander, 2010). Patients with a sulfa allergy should not use tamsulosin as a cross reactivity has been noted (Lexi-Comp, Inc., 2011)
Most adverse effects were mild of origin and did not lead to cessation of therapy, and several studies reported no adverse events in either the treatment or control group.

Alpha-blockers could be considered as first-line treatment for patients presenting with urinary stones.

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