Objective: To study the dosage regimen of oral M-receptor blocker following transurethral resection of the prostate (TURP) for severe benign prostate hyperplasia (BPH) with predominant urine storage period symptoms (USPSs) and its clinical effect. METHODS: Severe BPH patients with predominant USPSs received oral tolterodine (2 mg q12d or 4 mg qd) 6 hours after TURP for 4 weeks. The medication continued for another 2 weeks in case of recurrence of USPSs or until the 12th week in case of repeated recurrence. Before and at 1, 4, 8 and 12 weeks after TURP, we analyzed the International Prostate Symptoms Score (IPSS), quality of life (QoL) score, maximum urinary flow rate (Qmax), and postvoid residual volume (PVR) of the patients. RESULTS: Complete clinical data were collected from 106 cases, of which 33 achieved successful drug withdrawal with no aggravation of USPSs at 4 weeks after TURP, 51 at 6－8 weeks, 13 at 10－12 weeks, and 9 needed medication after 12 weeks. Before and at 1, 4, 8 and 12 weeks after TURP, the total IPSSs were 25.33 ± 3.45, 19.33 ± 3.62, 11.56 ± 2.45, 8.38 ± 2.0 and 7.74 ± 1.87, those in the urine storage period were 11.97 ± 1.53, 10.76 ± 1.82, 6.16 ± 1.22, 4.08 ± 1.19 and 3.91 ± 1.15, those at urine voiding were 9.80 ± 1.60, 5.59 ± 1.45, 3.40 ± 0.92, 2.85 ± 0.71, and 2.61 ± 0.67, and the QoL scores were 4.70 ± 0.78, 3.92 ± 0.75, 2.55 ± 0.74, 1.83 ± 0.72 and 1.66 ± 0.75, respectively, with statistically significant differences between the baseline and the scores at 1 and 4 weeks (P <0.01) but not at 8 or 12 weeks (P >0.05). Qmax and PVR were improved progressively and significantly at 1 and 4 weeks (P <0.01) but not at 8 or 12 weeks (P >0.05). CONCLUSIONS Four to eight weeks of oral administration of M-receptor blocker may be an effective dosage regimen for severe BPH with predominant USPSs after TURP.
Administration, Oral ; Clinical Protocols ; Drug Administration Schedule ; Humans ; Male ; Muscarinic Antagonists ; administration & dosage ; Postoperative Care ; Prostatic Hyperplasia ; drug therapy ; surgery ; Quality of Life ; Recurrence ; Tolterodine Tartrate ; administration & dosage ; Transurethral Resection of Prostate ; Treatment Outcome ; Urination ; Urological Agents ; administration & dosage

Overactive bladder (OAB) is a symptom-driven condition characterized by urinary urgency with or without urinary incontinence and a common problem that can significantly affect quality of life. Drugs that prevent acetylcholine-mediated involuntary detrusor contractions are the mainstay of OAB treatment, but several alternative therapeutic options have become established treatments for OAB. Mirabegron (a β3-adrenoceptor agonist) has a different mechanism of action from antimuscarinic agents. Recently published randomized controlled trials have shown that mirabegron is an effective and safe drug for the symptomatic treatment of OAB patients. Mirabegron represents a valid option both for patients with OAB who are antimuscarinics treatment-naïve, as well as for those who are unresponsive or intolerant to antimuscarinics. Intravesical injection of botulinum toxin A is an effective treatment for OAB that is refractory to antimuscarinics. Treatment with botulinum toxin A showed clinically relevant improvement in all OAB symptoms and health-related quality of life. It was generally well tolerated by most patients, and most treatment-related complications were acceptable. However, increased risk of a larger volume of post-void residual urine was noted in several patients and the possibility of chronic catheterization requires careful evaluation before treatment. In sum, recent options for management of OAB, mirabegron and intravesical injection of botulinum toxin A, expand the treatment options for the optimal treatment of each patient.
Administration, Intravesical ; Botulinum Toxins* ; Catheterization ; Catheters ; Drug Therapy* ; Humans ; Muscarinic Antagonists ; Quality of Life ; Urinary Bladder, Overactive* ; Urinary Incontinence

Urinary incontinence (UI) has been a serious health problem which can significantly affect quality of life. UI may occur at any age but more common in the elderly population. Many conditions may leak to UI and differential diagnosis is critical to guide appropriate manage strategy. After a brief description of the pathophysiology, classification, and diagnostic evaluation of UI, this review highlights oral pharmacological therapy mainly in clinical point of view. For urge UI, antimuscarinic are the most commonly used medication supported with high level of evidence. Antimuscarinics competitively block muscarinic receptors with variations in selectivity for the different subtypes. Common adverse effects are dry mouth, constipation, and blurred vision. High caution for cognitive function should be applied in the use of antimuscarinics in the elderly. Mirabegron, a beta3-agonist, is a new class of drug targeting urge UI, which reported similar efficacy with antimuscarinics and favorable adverse effect profile. For stress UI, various type of medications have been clinically investigated but so far none showed satisfactory resolution of stress UI. Duloxetine is the only medication approved for stress UI in European countries but not in US Food and Drug Administration and Korean Food and Drug Administration due to low benefit-risk profile for UI. Conclusively, pharmacological therapy should be tailored to the type of UI. Recent options of medications may give further treatment possibilities for the optimal treatment for each patient.
Aged ; Classification ; Constipation ; Diagnosis, Differential ; Drug Delivery Systems ; Duloxetine Hydrochloride ; Humans ; Medication Therapy Management ; Mouth ; Muscarinic Antagonists ; Quality of Life ; Receptors, Muscarinic ; United States Food and Drug Administration ; Urinary Incontinence* ; Urinary Incontinence, Stress ; Urinary Incontinence, Urge

Administration, Inhalation ; Adrenal Cortex Hormones ; therapeutic use ; Adrenergic beta-Agonists ; therapeutic use ; Anti-Asthmatic Agents ; therapeutic use ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Asthma ; prevention & control ; therapy ; Guideline Adherence ; Humans ; Molecular Targeted Therapy ; Muscarinic Antagonists ; therapeutic use ; Omalizumab ; therapeutic use ; Practice Guidelines as Topic ; Primary Prevention ; Quality Improvement ; Sublingual Immunotherapy

Intravesical onabotulinumtoxinA (BoNT-A) injection is an effective treatment for overactive bladder syndrome (OAB) that is refractory to antimuscarinics. An injectable dose of 100 U has been suggested to achieve the optimal balance of benefit and safety in patients with OAB. BoNT-A (total volume of 10 mL) was administered as evenly distributed intradetrusor injections (5 U) across 20 sites approximately 1 cm apart (0.5 mL per site) using a flexible or rigid cystoscope. Treatment with BoNT-A was generally well tolerated by most patients, and most treatment-related adverse events were localized to the urinary tract. The prevalence of OAB increases with age, and elderly patients are more vulnerable to complications. The short-term efficacy of intravesical BoNT-A injection for refractory OAB with no treatment-related complications in the elderly population has been documented. Frail elderly patients can experience the same treatment results, such as significantly improved urgent urinary incontinence and quality of life, as young and nonfrail elderly patients with 100-U BoNT-A injections. However, increased risk of larger postvoid residual (PVR) urine and lower long-term success rates were noted in frail elderly patients; around 11% had acute urinary retention, while 60% had PVR urine volume >150 mL after treatment. In addition, intravesical injection of BoNT-A effectively decreased urgency symptoms in elderly patients with OAB and central nervous system lesions. The adverse effects were acceptable, while the long-term effects were comparable to those in patients with OAB without central nervous system lesions. Nonetheless, the possibility of longstanding urinary retention and chronic catheterization in this vulnerable population requires careful evaluation before treatment with intravesical BoNT-A. In conclusion, the current findings indicate that intravesical BoNT-A is an effective and safe treatment for OAB in elderly patients.
Administration, Intravesical ; Aged ; Botulinum Toxins, Type A ; Catheterization ; Catheters ; Central Nervous System ; Cystoscopes ; Frail Elderly ; Humans ; Muscarinic Antagonists ; Prevalence ; Quality of Life ; Urinary Bladder, Overactive* ; Urinary Incontinence ; Urinary Retention ; Urinary Tract ; Vulnerable Populations

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.
Administration, Cutaneous ; Animals ; Autoradiography ; Benzhydryl Compounds ; Brain ; Colon ; Cresols ; Heart ; Humans ; Imidazoles ; Injections, Intravenous ; Lung ; Macaca mulatta ; Mandelic Acids ; Memory, Short-Term ; Mice ; Muscarinic Antagonists ; Phenylpropanolamine ; Positron-Emission Tomography ; Quinuclidines ; Rats ; Receptors, Muscarinic ; Salivation ; Solifenacin Succinate ; Submandibular Gland ; Tetrahydroisoquinolines ; Tolterodine Tartrate ; Urinary Bladder ; Urinary Bladder, Overactive

The study aims to elucidate the characteristics of pharmacokinetics of scopolamine hydrobromide oral disintegrative microencapsule tablets in healthy Beagle dogs. Chromatographic separation was performed on a C18 column (100 mm x 3.0 mm, 3.5 microm) with methanol - 2 mmol x L(-1) ammonium formate (25 : 75) as the mobile phase. A trip-quadrupole tandem mass spectrum with the electrospray ionization (ESI) source was applied and positive ion multiple reaction monitoring mode was operated. Six Beagle dogs were randomly devided into two groups. They received oral single dose of scopolamine hydrobromide oral disintegrative microencapsule tablets 0.6 mg (test tablet) or scopolamine hydrobromide normal tablets (reference tablet). Plasma samples were collected at designed time. Plasma concentration of scopolamine hydrobromide was determined by LC-MS/MS and pharmacokinetic parameters were calculated. The pharmacokinetic parameters of test tablet vs reference tablet were as follows: C(max): (8.16 +/- 0.67) ng x mL(-1) vs (3.54 +/- 0.64) ng x mL(-1); t1/2: (2.83 +/- 0.45) h vs (3.85 +/- 0.82) h; t(max): (1.25 +/- 0.27) h vs (0.42 +/- 0.09) h; AUC(0-12h): (25.06 +/- 3.75) h x ng x mL(-1) vs (9.59 +/- 1.02) h x ng x mL(-1); AUC(0-infinity): (26.30 +/- 3.92) h x ng x mL(-1) vs (10.80 +/- 1.45) h x ng x mL(-1); MRT(0-12h): (3.38 +/- 0.34) h vs (3.86 +/- 0.26) h; MRT(0-infinity): (3.98 +/- 0.63) h vs (5.37 +/- 1.00) h. The absorption rate and AUC of test tablet is different from that of reference tablet. The bioavailability of test tablet is better than those of reference tablet.
Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Capsules ; Chromatography, Liquid ; Dogs ; Drug Stability ; Female ; Male ; Muscarinic Antagonists ; administration & dosage ; blood ; pharmacokinetics ; Random Allocation ; Scopolamine Hydrobromide ; administration & dosage ; blood ; pharmacokinetics ; Spectrometry, Mass, Electrospray Ionization ; Tablets ; Tandem Mass Spectrometry

OBJECTIVETo observe the therapeutic effect of tiotropium bromide powder inhalation on stable bronchiectasis.

METHODSTwenty-two patients with stable bronchiectasis received inhalation of totropium bromide powder at the daily dose of 18 microg, and on days 1 and 28, the patients were examined for forced expiratory volume in one second (FEVl), predicted value [FEVl(%)], forced expiratory volume (FEV), and FEVl/FVC. The symptom score and BODE index were also recorded.

RESULTSAfter 1 month of inhalation therapy, the FEV1% of the patients showed a moderate increase but the increment was not statistically significant (t=-1.875, P>0.05); the symptom score and BODE index decreased significantly after the therapy (t=7.091, P<0.001; t=2.982, P<0.05).

CONCLUSIONLong-term inhalation of tiotropium bromide powder can improve the clinical symptoms and BODE index and enhance the exercise tolerance and quality of life of the patients with bronchiectasis.

Administration, Inhalation ; Adult ; Aged ; Bronchiectasis ; drug therapy ; Female ; Forced Expiratory Volume ; Humans ; Male ; Middle Aged ; Powders ; Receptor, Muscarinic M3 ; antagonists & inhibitors ; Scopolamine Derivatives ; administration & dosage ; Tiotropium Bromide

PURPOSE: Adenosine triphosphate (ATP) from the urothelium acts as a sensory neurotransmitter and is augmented in many diseases, such as overactive bladder. We investigated the effects of intravesical instillation of oxybutynin on ATP-induced bladder overactivity to determine whether this effect is mediated by effects on urothelial muscarinic receptors. MATERIALS AND METHODS: Cystometry (at rate of 0.04 ml/min) was performed in female Sprague-Dawley rats (body weight 250 g) under urethane anesthesia (1.2 g/kg). After a 2-hour baseline period, protamine sulfate (10 mg/ml) was instilled for 1 hour, and then ATP (60 mM, pH 6.0) or a mixture of oxybutynin (10(-6) M) and ATP (60 mM, pH 6.0) was instilled intravesically. We performed experiments with 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP) and methoctramine by the same methods. Cystometric parameters, such as the intercontraction interval (ICI), pressure threshold (PT), and maximal voiding pressure (MVP), were compared. RESULTS: With intravesical instillation of ATP after protamine sulfate treatment, the ICI was decreased compared with baseline (ICI: baseline, 487.1+/-64.8 s; protamine, 450.6+/-56.1 s; ATP, 229.7+/-35.3 s; p<0.05). Addition of oxybutynin, 4-DAMP, or methoctramine in the ATP solution did not significantly change the ICI compared with ATP solution alone (ICI: oxybutynin, 189.1+/-32.3 s; 4-DAMP, 161.1+/-22.8 s; methoctramine, 341.0+/-113.3 s; p>0.05). Intravesical instillation of ATP decreased MVP and PT significantly compared with baseline, but MVP and PT were not changed significantly with oxybutynin, 4-DAMP, or methoctramine compared with ATP. CONCLUSIONS: Bladder overactivity induced by intravesical instillation of ATP was not suppressed by intravesical instillation of antimuscarinics. Suppression of ATP-induced bladder overactivity by intravenous oxybutynin is not mediated by urothelial muscarinic receptors.
Adenosine ; Adenosine Triphosphate ; Administration, Intravesical ; Anesthesia ; Animals ; Diamines ; Female ; Humans ; Hydrogen-Ion Concentration ; Mandelic Acids ; Muscarinic Antagonists ; Neurotransmitter Agents ; Piperidines ; Polyphosphates ; Protamines ; Rats ; Rats, Sprague-Dawley ; Receptors, Muscarinic ; Urethane ; Urinary Bladder ; Urinary Bladder, Overactive ; Urothelium

PURPOSE: To maximize effective use of mydriatic drugs through comparing the pupillary dilation effects between 1% tropicamide and 2.5% phenylephrine. METHODS: Fifty people requiring pupillary dilation were divided into 3 groups. Group 1 was treated with one drop of 1% tropicamide in the right eye and one drop of 2.5% phenylephrine in the left eye. Group 2 was treated twice during a 5-minute interval with 1% tropicamide in the right eye. Group 3 was treated twice during a 5-minute interval with 2.5% phenylephrine in the right eye. Groups 2 and 3 were treated with 2.5% phenylephrine and 1% tropicamide in the left eye, administered during a 5-minute interval. The pupillary size was measured in all groups for 40 minutes following eye drops administration. RESULTS: The mean patient age was 15.7 years. Group 1 included 10 patients, and groups 2 and 3 included 20 patients each. Eight patients in group 1 and 16 patients in group 2 developed a larger right pupil. Fourteen patients in group 3 developed a larger left pupil. CONCLUSIONS: Our study showed that 1% tropicamide, with its parasympathetic antagonistic mechanism of action, was more effective at inducing pupillary dilation than 2.5% phenylephrine, and the combination of 1% tropicamide and 2.5% phenylephrine was more effective than multiple drops of single eye drops.
Adolescent ; Adult ; Child ; Child, Preschool ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Humans ; Male ; Muscarinic Antagonists/*administration & dosage ; Mydriatics/*administration & dosage ; Ophthalmic Solutions ; Phenylephrine/*administration & dosage ; Pupil/*drug effects ; Refractive Errors/diagnosis/physiopathology ; Retrospective Studies ; Tropicamide/*administration & dosage ; Young Adult