Effects of Terazosin and Tolterodine on Ureteral Stent Related Symptoms: A Double-Blind Placebo-Controlled Randomized Clinical Trial

Objective To evaluate the effects of terazosin and tolterodine on ureteral stent discomfort. Materials and Methods Of 163 patients assessed for eligibility, 104 patients were randomly assigned to receive placebo, 2 mg of terazosin twice daily, 2 mg of tolterodine daily, or both terazosin plus tolterodine during the stenting period. Prior to stenting and at stent removal, the International Prostate Symptom Score (IPSS), the IPSS quality of life (QoL) subscore and the Visual Analog Scale for Pain were determined. The patients also reported their analgesic use during the stenting period. Results Ninety-four patients completed the study. We noted significant decreases in the total IPSS scores (p = 0.002), irritative subscore (p = 0.039), QoL (p = 0.001), flank pain (p = 0.013), voiding pain (p = 0.01) and amount of analgesics used (p = 0.02) in the groups. However, neither the obstructive subscore nor the suprapubic pain improved significantly (p = 0.251 and p = 0.522, respectively). The patients receiving terazosin plus tolterodine experienced significant reductions in the total IPSS, irritative symptoms, QoL, flank pain, voiding pain and decreased analgesics use compared with those patients receiving placebo. However, compared with placebo, terazosin monotherapy did not affect pain levels, and tolterodine monotherapy did not improve QoL, flank pain or analgesics use. Conclusions Terazosin plus tolterodine improves ureteral stent-related complications, including irritative symptoms, the amount of analgesics used, QoL, flank pain and voiding pain but does not decrease obstructive symptoms or suprapubic pain. This trial was registered at www.clinicaltrials.gov as NCT01530243. .

Synergistic effect of iontophoresis and chemical enhancers on transdermal permeation of tolterodine tartrate for the treatment of overactive bladder

Purpose The objective of the study was to evaluate the synergistic transdermal permeation effect of chemical enhancers and iontophoresis technique on tolterodine tartrate (TT) transdermal gel and to evaluate its pharmacokinetic properties. Materials and Methods Taguchi robust design was used for optimization of formulations. Skin permeation rates were evaluated using the Keshary-chein type diffusion cells in order to optimize the gel formulation. In-vivo studies of the optimized formulation were performed in a rabbit model and histopathology studies of optimized formulation were performed on rats. Results Transdermal gels were formulated successfully using Taguchi robust design method. The type of penetration enhancer, concentration of penetration enhancer, current density and pulse on/off ratio were chosen as independent variables. Type of penetration enhancer was found to be the significant factor for all the responses. Permeation parameters were evaluated when maximum cumulative amount permeated in 24 hours (Q24) was 145.71 ± 2.00µg/cm2 by CIT4 formulation over control (91.89 ± 2.30µg/cm2). Permeation was enhanced by 1.75 fold by CIT4 formulation. Formulation CIT4 containing nerolidol (5%) and iontophoretic variables applied (0.5mA/cm2 and pulse on/off ratio 3:1) was optimized. In vivo studies with optimized formulation CIT4 showed increase in AUC and T1/2 when compared to oral suspension in rabbits. The histological studies showed changes in dermis indicating the effect of penetration enhancers and as iontophoresis was continued only for two cycles in periodic fashion so it did not cause any skin damage observed in the slides. Conclusion Results indicated that iontophoresis in combination with chemical enhancers is an effective method for transdermal administration of TT in the treatment of overactive bladder. .

Cardura monotherapy versus combination therapy of cardura and tolterodine L-tartrate tablets for II° ? benign prostatic hyperplasia with overactive bladder / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the effectiveness of the monotherapy of Cardura and the combination therapy of Cardura and Tolterodine L-Tartrate Tablets for II° ? benign prostate hyperplasia (BPH) with overactive bladder (OAB).</p><p><b>METHODS</b>This study included 87 cases of BPH with OAB, with a disease course > or = 3 months, daily urination > or = 8 times, nocturnal urination > or = 2 times, urine volume < 200 ml per time, International Prostate Symptom Score (IPSS) > or = 8, OAB symptom score (OABS) > or = 3, quality of life score (QOL) > or = 3, post-void residual (PVR) < or = 100 ml, maximum urinary flow (Qmax) > or = 5 ml/s, prostate weight 25-50 g, and PSA < 4 microg/L. We randomized the patients to a monotherapy group (n = 44) and combination group (n = 43), the former treated with Cardura 4 mg qd, and the latter with Cardura 4 mg + Tolterodine L-Tartrate Tablets 4 mg qd, both for 8 weeks. Then we recorded the IPSS, OABS, Qmax, PVR, PSA, and adverse events.</p><p><b>RESULTS</b>The baseline parameters showed no significant differences between the two groups (P > 0.05). In comparison with the baseline, both the monotherapy group and the combination therapy group showed significant decreased in the IPSS (16.50 +/- 4.27 vs 13.68 +/- 3.69 and 15.51 +/- 3.80 vs 11.49 +/- 2.75), urine storage symptom score (10.48 +/- 2.75 vs 7.98 +/- 2.34 and 9.47 +/- 2.31 vs 5.74 +/- 1.66), OABS (8.55 +/- 2.69 vs 6.32 +/- 1.97 and 8.21 +/- 2.55 vs 4.44 +/- 1.62), urgent micturition score (4.25 +/- 1.06 vs 3.23 +/- 0.99 and 4.07 +/- 0.83 vs 2.26 +/- 1.05), QOL (5.36 +/- 0.72 vs 3.43 +/- 0.66 and 5.07 +/- 0.86 vs 2.37 +/- 0.76) and PVR ([44.55 +/- 22.39] vs [38.30 +/- 20.20] ml and [36.19 +/- 21.21] vs [24.98 +/- 17.60] ml) (P < 0.01). All the six parameters were significantly more improved in the combination therapy group than in the monotherapy group (P < 0.01), but there were no remarkable differences between the groups in Qmax and voiding symptom score (P > 0.05). Neither group exhibited significant changes in the PSA level and prostate weight after treatment as compared with the baseline (P > 0.05). No acute urinary retention and other severe adverse reactions were observed during the medication.</p><p><b>CONCLUSION</b>Both Cardura monotherapy and the combination therapy of Cardura + Tolterodine L-Tartrate Tablets can improve II ? BPH with OAB, and the latter has an even better efficacy than the former.</p>

Statistically optimised ethosomes for transdermal delivery of tolterodine tartrate

The aim of the current investigation is to optimize ethosomes statistically for enhancing transdermal potential of Tolterodine Tartrate [TT]. Ethosomes bearing TT were prepared by cold method and characterized for various parameters like vesicle size, vesicle shape, surface morphology and% drug entrapment. Microscopic examinations suggest ethosomes as spherical unilamellar vesicles with a smooth surface. Optimized ethosomal vesicles were of 890 +/- 2.67nm size and showed 79.83 +/- 3.18% drug entrapment. Ex-vivo permeation studies across rat skin resulted in increased flux of 4.69 +/- 0.24 Micro g/cm[2]/hr and decreased lag time of 0.13 +/- 0.05 hr when compared with drug solution [0.546 +/- 0.05 Micro g/cm[2]/hr, 3 +/- 0.2 hr].This shows enhancement of transdermal delivery by 8.82 times. Anatomical changes in skin samples due to vesicle-skin interaction were observed on histological examination. Optimized formulation on storage at 4°C for 120 days showed insignificant growth in vesicular size revealing low aggregation of vesicles. The results collectively suggest ethosomes as carriers for accentuated transdermal delivery of TT

Characterization of Bladder Selectivity of Antimuscarinic Agents on the Basis of In Vivo Drug-Receptor Binding / 대한배뇨장애요실금학회지

The in vivo muscarinic receptor binding of antimuscarinic agents (oxybutynin, solifenacin, tolterodine, and imidafenacin) used to treat urinary dysfunction in patients with overactive bladder is reviewed. Transdermal administration of oxybutynin in rats leads to significant binding of muscarinic receptors in the bladder without long-term binding in the submaxillary gland and the abolishment of salivation evoked by oral oxybutynin. Oral solifenacin shows significant and long-lasting binding to muscarinic receptors in mouse tissues expressing the M3 subtype. Oral tolterodine binds more selectively to muscarinic receptors in the bladder than in the submaxillary gland in mice. The muscarinic receptor binding of oral imidafenacin in rats is more selective and longer-lasting in the bladder than in other tissues such as the submaxillary gland, heart, colon, lung, and brain, suggesting preferential muscarinic receptor binding in the bladder. In vivo quantitative autoradiography with (+)N-[11C]methyl-3-piperidyl benzilate in rats shows significant occupancy of brain muscarinic receptors with the intravenous injection of oxybutynin, solifenacin, and tolterodine. The estimated in vivo selectivity in brain is significantly greater for solifenacin and tolterodine than for oxybutynin. Imidafenacin occupies few brain muscarinic receptors. Similar findings for oral oxybutynin were observed with positron emission tomography in conscious rhesus monkeys with a significant disturbance of short-term memory. The newer generation of antimuscarinic agents may be advantageous in terms of bladder selectivity after systemic administration.

Overactive bladder after transurethral resection of prostate treated with electroacupuncture therapy and tolterodine / 中国针灸

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect of overactive bladder after transurethral resection of prostate (TURP) preventively treated with electroacupuncture and Tolterodine.</p><p><b>METHODS</b>One hundred and twenty cases of benign prostate hyperplasia of TURP were randomly divided into an electroacupuncture and medicine group, an electroacupuncture group, a medicine group and a control group, 30 cases in each group. All the patients were treated with TURP under the continuous epidural anesthesia, and the catheter was retained for 5-7 days. In electroacupuncture group, before the surgery of the same day, Huiyang (BL 35), Ciliao (BL 32), Qugu (CV 2) and Huiyin (CV 1) were acupunctured with electroacupuncture for 30 min, once a day, 5-7 days' treatment was applied. In medicine group, Tolterodine Tartrate tablet was taken for 2 mg in the morning of surgery day, twice a day and treatment was applied for 5-7 days. In electroacupuncture and medicine group, the comprehensive therapies above in both electroacupuncture group and medicine group were applied. In control group, Pethidine of 50 mg was given by intramuscular injection when bladder was overactive, combined with Anisodamine injection of 10 mg according to the symptoms. The frequency and lasting time of bladder overactivity were compared within 72 hours after TURP in each group.</p><p><b>RESULTS</b>After TURP, the frequency of bladder overactivity were 2-4 times a day, and lasted for 5-15 min each time in control group. The frequency and lasting time of bladder overactivity in treatment groups at different time were less than those in control group (P < 0.01, P < 0.001). There was no significant difference in comparison of frequency and lasting time of bladder overactivity between electroacupuncture and medicine group (all P > 0.05). The frequency and lasting time of bladder hyperactivity in electroacupuncture and medicine group were less than those in the electroacupuncture group and the medicine group at 24 hours, 24-48 hours, 48-72 hours after TUPR (P < 0.05, P < 0.01, P < 0.001).</p><p><b>CONCLUSION</b>After TURP, early prevention of combined therapy of electroacupuncture and Tolterodine with oral administration is superior to that of electroacupuncture therapy or Tolterodine for overactive bladder treatment, and it is the safe and effective method to treat overactive bladder.</p>

Parkinson's disease combined with overactive bladder syndrome treated with acupuncture and medication / 中国针灸

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect of Parkinson's disease combined with overactive bladder syndrome (GAB) treated with combined therapy of oral administration of Tolterodine with low dose and electroacuponcture.</p><p><b>METHODS</b>Sixty cases of Parkinson's disease combined with GAB were randomly divided into a combined acupuncture and medication group (group A) and a medication group (group B), 30 cases in each group. In both groups, Madopar basic doses were same, and anticholinergic agents such as Artane were stopped. In group A, Tolterodine was orally taken for 1 mg, twice a day; Baihui (GV 20), Sishengcong (EX-HN 1) and Yintang (EX-HN 3) were punctured with electroacupuncture, once a day. In group B, Tolterodine was orally taken for 2 mg, twice a day. After 6 weeks, the changes of urination and UPDRS III scores were observed, and the adverse reactions were recorded in both groups.</p><p><b>RESULTS</b>After treatment, the frequency of average urination of 24 hours, frequency of incontinence of 24 hours and average urine volume at a time were obviously improved (all P < 0. 01), of which, the above items in group A were superior to those in group B (all P < 0. 05) the UPDRSIII score in group A was superior to that in group B (P < 0.05). The adverse reactions in group A were less than those in group B.</p><p><b>CONCLUSION</b>The therapeutic effect of Parkinson' s disease combined with GAB treated with combined therapy of Tolterodine with low dose and electroacupuncture is superior to that of complete dose of Tolterodine with oral administration, with less adverse reactions. And it also can improve the motor symptom of Parkinson's disease patients.</p>

Comparisons of efficacy and safety of tolterodine and oxybutynin in children with idiopathic overactive bladder / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To compare the efficacy and safety of tolterodine and oxybutynin in the treatment of idiopathic overactive bladder in children.</p><p><b>METHODS</b>A total of 204 children with idiopathic overactive bladder were randomly divided into three groups (n=68 each): placebo, tolterodine-treated and oxybutynin-treated. The efficacy and safety were evaluated two weeks after treatment.</p><p><b>RESULTS</b>The effective rate was 25% in the placebo group, 89% in the tolterodine-treated group, and 92% in the oxybutynin-treated group. The effective rate in the two treatment groups was significantly higher than that in the placebo group (P<0.05). There was a similar efficacy between the two treatment groups. The incidence of adverse events in the tolterodine-treated group (28%) was significantly lower than that in the oxybutnin-treated group (57%) (P<0.05).</p><p><b>CONCLUSIONS</b>Tolterodine has a similar efficacy to oxybutynin in the treatment of idiopathic overactive bladder in children, with better safety in pharmacotherapy.</p>

Expressed sequence tag analysis of khat (Catha edulis) provides a putative molecular biochemical basis for the biosynthesis of phenylpropylamino alkaloids

Khat (Catha edulis Forsk.) is a flowering perennial shrub cultivated for its neurostimulant properties resulting mainly from the occurrence of (S)-cathinone in young leaves. The biosynthesis of (S)-cathinone and the related phenylpropylamino alkaloids (1S,2S)-cathine and (1R,2S)-norephedrine is not well characterized in plants. We prepared a cDNA library from young khat leaves and sequenced 4,896 random clones, generating an expressed sequence tag (EST) library of 3,293 unigenes. Putative functions were assigned to > 98 percent of the ESTs, providing a key resource for gene discovery. Candidates potentially involved at various stages of phenylpropylamino alkaloid biosynthesis from L-phenylalanine to (1S,2S)-cathine were identified.

Dissimilar Effects of Tolterodine on Detrusor Overactivity in Awake Rats with Chemical Cystitis and Partial Bladder Outlet Obstruction / 대한배뇨장애요실금학회지

PURPOSE: We investigated bladder function, with a special focus on nonvoiding contractions (NVCs), in awake rats with chronic chemical cystitis and bladder outlet obstruction (BOO) by use of simultaneous registrations of intravesical and intraabdominal pressures. In addition, we tested the effects of tolterodine on the NVCs in these models. METHODS: A total of 20 female Sprague-Dawley rats were used in this study. In eight rats, chemical cystitis was induced by intravesical instillation of HCl. Twelve rats were subjected to sham instillations or partial BOO. Four weeks after intravesical instillation or 2 weeks after partial BOO, cystometrograms were obtained by use of simultaneous recording of intravesical and intraabdominal pressure in all unanesthetized, unrestrained rats in metabolic cages. RESULTS: A total of 17 rats survived. In the rats with acute injury by HCl, 50% showed detrusor overactivity (DO), which was not seen in the sham group. The cystitis group had lower DO pressure without a difference in DO frequency compared with the BOO group. After the administration of tolterodine, the cystitis group showed no difference in DO frequency or pressure, whereas the BOO group showed decreased values for both parameters. CONCLUSIONS: Our study showed that toleterodine produced no effect on DO during the filling phase in rats with chronic chemical cystitisbut decreased the frequency and pressure of DO in rats with BOO. Clinically, studies are needed to improve the treatment effect of anticholinergic drugs ininterstitial cystitis patients with overactive bladder.

Tolterodine tartrate combined with alpha-receptor blocker for benign prostatic hyperplasia with detrusor overactivity / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Tolterodine Tartrate combined with the alpha-receptor blocker in the treatment of benign prostatic hyperplasia with detrusor overactivity (BPH-DO).</p><p><b>METHODS</b>A total of 113 patients with BPH-DO were randomly assigned to receive Tolterodine Tartrate combined with Cardura (Group A) and Cardura alone (Group B), both for 12 weeks. Then we recorded and compared their average 24 h urinary frequency, IPSS and QOL score, maximum urinary flow rate, residual urine volume and urinary retention times before and after the treatment.</p><p><b>RESULTS</b>After the treatment, Group A showed significantly better improvement in the average 24 h urinary frequency and scores on IPSS and QOL than Group B. No significant differences were found between the two groups in the maximum urinary flow rate and residual urine volume. No acute urinary retention occurred in either group.</p><p><b>CONCLUSION</b>The combined use of Tolterodine Tartrate and the alpha-receptor blocker can effectively relieve the symptoms of dysuria, urinary frequency and urinary urgency in patients with BPH-DO, with neither significant adverse effects on the maximum flow rate and residual urine volume nor increase in the incidence of acute urinary retention.</p>

Stent Position Is More Important than alpha-Blockers or Anticholinergics for Stent-Related Lower Urinary Tract Symptoms after Ureteroscopic Ureterolithotomy: A Prospective Randomized Study

PURPOSE: To evaluate the clinical factors that impact ureteral stent-related lower urinary tract symptoms (LUTS) after ureteroscopic ureterolithotomy, including the stent position and medication. MATERIALS AND METHODS: Fifty-three patients who underwent ureteroscopic ureterolithotomy with indwelling a stent were distributed into three groups. On demand analgesics were given to the group 1 (n=18). Daily tamsulosin 0.2 mg was added for group 2 (n=15) and daily tamsulosin 0.2 mg and tolterodine 4 mg was added for group 3 (n=20). The patients were also subclassified into appropriate or inappropriate group according to stent position. All the patients completed a visual analogue scale (VAS) and International Prostate Symptom Score (IPSS) on the 1st and 7th postoperative days. The VAS and IPSS were analyzed according to the medication groups and the stent position. RESULTS: In the appropriate stent potion group, only the storage symptom scores of groups 2 and 3 on the 1st postoperative day were significantly lower than those of the group 1 (p=0.001). This medication effect on LUTS was not observed in the inappropriate stent position group. In this group, total IPSS (p=0.015) and storage symptom scores (p=0.002) were higher than in the appropriate stent position group on the 7th postoperative day. CONCLUSIONS: Correct placement of the stent was more important than medication for lessening stent-related storage symptoms.

Combination of tamsulosin and tolterodine alleviates refractory lower urinary tract symptoms in male patients / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate and compare the clinical efficacy and safety of the highly selective alpha receptor antagonist tamsulosin and its combination with the M receptor antagonist tolterodine in the treatment of refractory lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH).</p><p><b>METHODS</b>We included in this study 184 BPH patients with refractory LUTS with the disease course of 4 weeks to 2 years, whose LUTS were not alleviated after a week's treatment with tamsulosin. The patients were randomly divided into Groups A and B, the former (n=89) treated with tamsulosin at 0.2 mg qd and the latter (n=95) given tolterodine at 2 mg bid in addition to tamsulosin medication, both for 4 weeks. Scores on IPSS, QOL and Qmax were obtained before and after the treatment, and the improvement of LUTS evaluated after the medication.</p><p><b>RESULTS</b>The tamsulosin group showed no significant differences before and after the treatment in the scores on IPSS (13.23 +/- 4.39 vs. 12.21 +/- 4.07), QOL (4.23 +/- 1.27 vs 3.53 +/- 0.95) and Qmax ([12.3 +/- 8.39] ml/s vs. [14.1 +/- 8.62] mls) (P > 0.05), while the combination group exhibited significantly higher scores on IPSS and QOL and lower score on Qmax after the medication than before it (IPSS: 14.45 +/- 5.31 vs. 6.56 +/- 2.03, P < 0.05; QOL: 4.45 +/- 0.79 vs. 2.34 +/- 0.73, P < 0.05; Qmax: [11.4 +/- 9.21] ml/s vs. [15.5 +/- 8.35] ml/s, P < 0.01). No severe complications were found in any of the cases.</p><p><b>CONCLUSION</b>Combination of tamsulosin and tolterodine can significantly alleviate refractory LUTS and improve QOL without causing serious adverse events in BPH patients.</p>

Combination of tolterodine and tamsulosin for benign prostatic hyperplasia / 中华男科学杂志

<p><b>OBJECTIVE</b>Overactive bladder may coexist with bladder outlet obstruction induced by benign prostatic hyperplasia (BPH). This study aimed to evaluate the efficacy of the combined use of tolterodine and tamsulosin in the treatment of BPH accompanied by overactive bladder.</p><p><b>METHODS</b>We selected 53 cases of clinically diagnosed BPH, and randomly assigned them to a tamsulosin group (n = 25) to receive 0.2 mg of tamsulosin once a day and a tamsulosin + tolterodine group (n = 28) to be treated with 0.2 mg of tamsulosin once a day plus 2 mg of tolterodine twice a day, both for 12 weeks. Before and after the treatment, we obtained the International Prostate Symptoms Score (IPSS), quality of life (QOL) score and Qmax, and recorded the adverse events.</p><p><b>RESULTS</b>All the patients accomplished the 12-week treatment. The tamsulosin group showed a significant decrease in IPSS and QOL from 21.50 +/- 5.42 and 4.58 +/- 0.94 before the treatment to 14.80 +/- 4.21 and 2.78 +/- 0.91 after it (P < 0.05), but a significant increase in Qmax from (12.20 +/- 6.60) ml/s to (16.40 +/- 5.13) ml/s (P < 0.05). In the tamsulosin + tolterodine group, IPSS and QOL were decreased from 20.90 +/- 5.15 and 4.61 +/- 0.86 at the baseline to 14.90 +/- 5.32 and 2.12 +/- 0.87 after the medication (P < 0.05), Qmax was increased from (13.30 +/- 7.80) ml/s to (16.70 +/- 6.32) ml/s (P < 0.05), and the score on the urinary storage phase symptoms was reduced from 10.12 +/- 3.10 to 4.77 +/- 0.75 (P < 0.05).</p><p><b>CONCLUSION</b>Tamsulosin could quickly relieve BPH-induced lower urinary tract symptoms (LUTS) , while the combined use of tolterodine and tamsulosin could even better alleviate the LUTS and improve the QOL of BPH patients.</p>

Surface degradation of composite resins by acidic medicines and ph-cycling

This study evaluated the effects of acidic medicines (Dimetapp® and Claritin®), under pH-cycling conditions, on the surface degradation of four composite resins (microhybrid: TPH, Concept, Opallis and Nanofilled: Supreme). Thirty disc-shaped specimens (Ø = 5.0 mm / thickness = 2.0 mm) of each composite were randomly assigned to 3 groups (n = 10): a control and two experimental groups, according to the acidic medicines evaluated. The specimens were finished and polished with aluminum oxide discs, and the surface roughness was measured by using a profilometer. After the specimens were submitted to a pH-cycling regimen and immersion in acidic medicines for 12 days, the surface roughness was measured again. Two specimens for each material and group were analyzed by scanning electron microscopy (SEM) before and after pH-cycling. Data were analyzed by the Student's-t test, ANOVA, Duncan's multiple range test and paired t-test (α=0.05). Significant increase in roughness was found only for TPH in the control group and TPH and Supreme immersed in Claritin® (p<0.05). SEM analyses showed that the 4 composite resins underwent erosion and surface degradation after being subjected to the experimental conditions. In conclusion, although the roughness was slightly affected, the pH-cycling and acidic medicines caused surface degradation of the composite resins evaluated. Titratable acidity seemed to play a more crucial role on surface degradation of composite resins than pH.

The Clinical Effects of Amitriptyline on the Nocturia of Patients with Benign Prostatic Hyperplasia / 대한비뇨기과학회지

PURPOSE: We evaluated the effects of amitiptyline, as one of the first-line therapies, on the nocturia of patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Between June 2005 and December 2006, 50 patients completed this study(Group I=20, Group II=14, Group III=16). Group I was treated with doxazocin 4mg, group II was treated with doxazocin 4mg and tolterodine 4mg and the third group was treated with doxazocin 4mg and amitriptyline 10mg. We measured the treatment efficacy, the clinical parameters and we examined three days of the voiding diaries at baseline and after 4 weeks of treatment, respectively. RESULTS: After 4 weeks of treatment, all the patients had significant improvement for the International Prostate Symptom Score(IPSS) and the quality of life(QoL) score among the clinical parameters and they also showed improvement of their frequency of micturition per 24 hours, per night(nocturnal frequency) among the voiding diary parameters(p0.05). Although there was 1 case of mild dry-mouth in group II and 1 case of mild dry-mouth and drowsiness in group III, none of the patient dropped out due to side effects. CONCLUSIONS: We found significant improvement in the IPSS, the QoL score and the nocturnal frequency after treatment with amitriptyline 10mg. Therefore, amitriptyline 10mg would be helpful as a first-line therapy for BPH patients with nocturia.

Efficacy and safety of combined therapy with terazosin and tolteradine for patients with lower urinary tract symptoms associated with benign prostatic hyperplasia: a prospective study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The primary objectives of the treatment for the lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are to produce rapid, sustained, and safe improvements in the symptoms that affect the quality of life in the majority of men over 50. In this study, we evaluated the efficacy and safety of the combined therapy with terazosin (apha1-adrenergic receptor antagonist) and tolterodine (anticholinergic agent) for LUTS associated with BPH.</p><p><b>METHODS</b>This combination study included 69 patients diagnosed with LUTS associated with BPH based on the International Prostate Symptom Scores (IPSS), urinary flow rate, prostate volume, urinary residual, and their serum prostate-specific antigen levels. Initially, 191 patients were treated with terazosin 2 mg once daily for one week. Those patients with continued LUTS after the initial treatment were allocated randomly into two groups: terazosin group (n = 36) in which patients were treated with terazosin 2 mg once daily for six weeks, and combination group (n = 33) in which patients were treated with both terazosin 2 mg once daily and tolterodine 2 mg twice daily for 6 weeks.</p><p><b>RESULTS</b>The IPSS were significantly improved in both groups after treatment, and the reduction of IPSS in the combination group was significantly greater than that in the terazosin group (P < 0.01). A decrease in urgency, frequency and nocturia were the main contributory factors causing the reduction of IPSS in the combination group. The differences about the peak urinary flow rate and the residual urine from the baseline values were noted in both groups after treatment, but were not significant between the two groups. The incidence of adverse effects in the combination group was higher than that in the terazosin group. As expected the most common adverse effect was mouth dryness which was associated with anticholinergic drugs such as tolterodine.</p><p><b>CONCLUSIONS</b>Patients with LUTS associated BPH appear the improved IPSS after combined therapy with terazosin and tolterodine. This study, although short term and limited numbers of patients, provides evidence that the combined therapy with terazosin plus tolterodine is a good approach for meeting the objectives of rapid, sustained, and safe improvements in the LUTS associated with BPH. And the profile of patients in this study might be used as the indication of such combined therapy for LUTS associated with BPH without urodynamic evaluation.</p>

Effectiveness of tolterodine in nonneurogenic voiding dysfunction.

The efficacy of tolterodine was analysed in children with non-neurogenic voiding dysfunction, using dysfunctional voiding symptom score (DVSS). Of 44 patients (mean age 9.3 yrs; M:F = 25:19), 36 received long acting tolterodine tartrate at a dose of 2mg OD and 8 at a dose of 4mg OD. The mean (SD) DVSS before and after the treatment was 17.1 (2.8) and 12.0 (2.4). There was a significant improvement in the mean DVSS score at the end of the treatment (Students t test P < 0.01). The dysfunctional symptoms were cured in 28(63.6 %), improved in 14(31.8 %) and failed to show improvement in 2 (4.6 %). Over all 95 % were compliant with the single daily medication. Our results demonstrate that long acting tolterodine is effective in children with voiding dysfunction. The single daily dose has good compliance and minimal side effect profile.

Effects of Bladder Training and/or Tolterodine in Female Patients with Overactive Bladder Syndrome: A Prospective, Randomized Study

We compared the effects of bladder training and/or tolterodine as first line treatment in female patients with overactive bladder (OAB). One hundred and thirty-nine female patients with OAB were randomized to treatment with bladder training (BT), tolterodine (To, 2 mg twice daily) or both (Co) for 12 weeks. Treatment efficacy was measured by micturition diary, urgency scores and patients' subjective assessment of their bladder condition. Mean frequency and nocturia significantly decreased in all treatment groups, declining 25.9% and 56.1%, respectively, in the BT group; 30.2% and 65.4%, respectively, in the To group; and 33.5% and 66.3%, respectively in the Co group (p<0.05 for each). The decrease in frequency was significantly greater in the Co group than in the BT group (p<0.05). Mean urgency score decreased by 44.8%, 62.2% and 60.2% in the BT, To, and Co groups, respectively, and the improvement was significantly greater in the To and Co groups than in the BT group (p<0.05 for each). Although BT, To and their combination were all effective in controlling OAB symptoms, combination therapy was more effective than either method alone. Tolterodine alone may be instituted as a first-line therapy, but may be more effective when combined with bladder training.

Urinary symptoms and quality of life changes in Thai women with overactive bladder after tolterodine treatment.

OBJECTIVES: To study the urinary symptoms and quality of life changes in Thai women with overactive bladder (OAB) after tolterodine treatment. MATERIAL AND METHOD: Thirty women (aged 30-77 years) diagnosed as having OAB at the Gynecology Clinic, King Chulalongkorn Memorial Hospital from January to April 2004 were included in the present study. Tolterodine 2 mg, twice daily was given. After 8 weeks treatment, changes in micturition diary variables and tolerability were determined. Short form 36 (SF36) questionaires (Thai version) were given before and after 8 weeks of treatment. RESULTS: At 8 weeks, all micturition per day decreased from 16. 7 +/- 5. 3 to 6. 7 +/- 2.4 times per day. The number of nocturia episodes decreased from 5.4 +/- 4.2 to 1.1 +/- 1.0 times per night. The most common side effect was dry month in 5 cases (16.7%) with 2 cases reporting a moderate degree and 1 case with severe degree. Only one case (3.3%) withdrew from the present study due to a severe dry mouth. The SF-36 scores changed significantly in the domains of physical functioning, role function emotional, social function and mental heath. CONCLUSION: Tolterodine was well tolerated and its effects improved the quality of life in Thai women with OAB.