|Year : 2009 | Volume
| Issue : 4 | Page : 558-559
A study on the usefulness of diuretics combined with alpha blockers in the treatment of nocturia
Ankush Gupta, Vishwajeet Singh, Bhupendra P Singh
Department of Urology, King George Medical University, Lucknow - 226 003, Uttar Pradesh, India
|Date of Web Publication||30-Nov-2009|
Department of Urology, King George Medical University, Lucknow - 226 003, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Gupta A, Singh V, Singh BP. A study on the usefulness of diuretics combined with alpha blockers in the treatment of nocturia. Indian J Urol 2009;25:558-9
|How to cite this URL:|
Gupta A, Singh V, Singh BP. A study on the usefulness of diuretics combined with alpha blockers in the treatment of nocturia. Indian J Urol [serial online] 2009 [cited 2020 Jul 14];25:558-9. Available from: http://www.indianjurol.com/text.asp?2009/25/4/558/57896
Cho MC, Ku JH, and Paick JS. a-Blocker plus Diuretic Combination Therapy as Second-line Treatment for Nocturia in Men with LUTS: A Pilot Study. Urology 2009;73:549-53.
| Summary|| |
Nocturia is a significant bother symptom in majority of men with lower urinary tract symptoms (LUTS). The authors have prospectively tried to assess whether the addition of hydrochlorothiazide to men with LUTS and nocturia unresponsive to α-blocker monotherapy would improve the nocturnal frequency. Over a period of 34 months, 53 patients completed the study. The efficacy of treatment was assessed using the International Prostate Symptom Score (IPSS) question 7 (Q7) and a three-day frequency-volume chart (FVC) which was completed at commencement and at the termination of four-week combination therapy trial. All patients after four weeks of 4 mg terazosin therapy, who had no response, or a 25% reduction in subjective nocturia using the IPSS (Q7), or no response or a 25% reduction in objective nocturia according to the FVC, and/or nocturia ≥ 2 times per night were included. Hydrochlorothiazide was administered 8 h before bedtime. In absence of any serious side effects, a reduction of ≥50%, 25%-49%, 0%-24% and an increase in nocturia was observed in 7(13.21%), 7(13.21%), 31(58.49%), and 8(15.09%) patients, respectively using the IPSS. When the frequency-volume chart was used, 17(32.08%) patients reported reduced nocturia by more than one half, 5(9.43%) reported a reduction of 25%-49%, and 31(58.49%) reported no response to treatment (24/31) or an increase in nocturia (7/31). Assuming greater than 25% reduction as an arbitrary cut off for consideration as responders, 14 (26.4%) and 22 (41.5%) patients were considered improved on IPSS and FVC, respectively. At baseline 52 of 53(98.11%) patients had nocturnal polyuria which resolved in 6 of the 52 patients (11.5%) with the combination therapy. Further on, the quality-of-life index was improved significantly with betterment of nocturia. The authors conclude that combination therapy with 4 mg terazosin and 25 mg hydrochlorothiazide is a reasonably safe and effective treatment for treating nocturia when primary therapy with an α-blocker (terazosin) fails.
| Comment|| |
Nocturia occurs as a result of wide variety of conditions which are classified into diurnal polyuria, nocturnal polyuria and a low nocturnal bladder capacity.  The target of therapy in a reduced nocturnal bladder capacity is bladder overactivity. It has conventionally been treated with antimuscarinics. Naftopidil, a long-acting α1-blocker, which also suppresses detrusor muscle overactivity by blocking α1-D receptors in the bladder detrusor muscle and lumbosacral cord, has been effectively utilized for treating nocturia in men with BPH. 
Nocturia occurring as a result of nocturnal polyuria is associated with abnormalities of the secretion of arginine vasopressin, lifestyle or dietary factors, and other medical conditions (e.g., congestive heart failure, venous stasis disease, sleep apnea). Management involves lifestyle and behavioral modifications, and medical therapy was limited to the use of antidiuretic agents, for example Desmopressin and diuretics. Desmopressin is associated with a high incidence of hyponatremia which can be life threatening if undetected. Furosemide as an effective treatment for nocturnal polyuria was reported by Reynard et al.  Celecoxib, a COX-2 inhibitor, in a dose of 100 mg at night was found to be effective in treating patients with BPH complaining of refractory nocturia.  The postulated mechanism was a dual mode of action: (i) by reducing the tone of detrusor and thereby bladder overactivity, and (ii) by reducing urine production from the kidney by decreasing glomerular blood flow.
The effect of hydrochlorothiazide in this study appears to be by preventing water accumulation and by forcing fluid out of the system before the early sleeping hours. However, these results do not seem to be affected by fluid restriction as the total 24 h urinary volume did not change from the baseline after combination therapy. The hypotensive effect of hydrochlorothiazide in general and the restoration of circadian rhythm of blood pressure from a nondecrease to a decrease in patients with essential hypertension may be another target for treatment. Although the study shows modest efficacy of combination therapy in treating nocturia, it raises certain queries: Within a month of commencing treatment there has been a 25% patient dropout rate for which no reason has been specified. Among 31 of 53 patients who did not respond or had increase in nocturia with the combination of treatment, there were 24 who showed a 0-25% reduction in nocturia on FVC while only seven had an actual increase in nocturia on FVC. The cutoff of >25% reduction in nocturia for responders is arbitrary. What determines a significant outcome requires further studies or consensus panels based on patient derived measures. The study has used 4 mg terazosin for the treatment of BPH. The effects of hydrochlorothiazide added to 5 mg or 10 mg terazosin (doses used in North America and Europe) is questionable. The authors have not experienced any serious adverse events among their patients during the course of their study but lack of a standardized monitoring of blood pressure and serum electrolytes raises concern, especially when terazosin is known to cause postural hypotension. Further evaluation of hydrochlorothiazide for use in nocturia is essential before its application in a clinical setting.
| References|| |
|1.||Cho MC, Ku JH, Paick JS. a-Blocker plus Diuretic Combination Therapy as Second-line Treatment for Nocturia in Men with LUTS: A Pilot Study. Urology 2009;73:549-53. [PUBMED] [FULLTEXT] |
|2.||Rodney AA, Peter KS. Nocturia: etiology, diagnosis, and treatment. Neurourol Urodyn 2008;27:34-9. |
|3.||Oh-oka H. Effect of Naftopidil on Nocturia After Failure of Tamsulosin. Urology 2008;72:1051-5. [PUBMED] [FULLTEXT] |
|4.||Reynard JM, Cannon A, Yang Q, Abrams P. A novel therapy for nocturnal polyuria: a double-blind randomized trial of furosemide against placebo. BJU Int 1998;81:215-8. |
|5.||Falahatkar S, Mokhtari G, Pourreza F, Asgari SA, Kamran AN. Celecoxib for Treatment of Nocturia Caused by Benign Prostatic Hyperplasia: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study. Urology 2008;72:813-6. [PUBMED] [FULLTEXT] |