Combination Of Anticholinergics Research Articles

Treatment of urge incontinence in postmenopausal women: A systematic review.

Urinary incontinence and other urinary symptoms tend to be frequent at menopause because of hormonal modifications and aging. Urinary symptoms are associated with the genitourinary syndrome of menopause which is characterized by physical changes of the vulva, vagina and lower urinary tract. The treatment strategies for postmenopausal urinary incontinence are various and may include estrogens, anticholinergics, and pelvic floor muscle training. A comparison of these treatments is difficult due to the heterogeneity of adopted protocols. We systematically reviewed the evidence from randomized controlled trials (RCTs) focusing on treatment of postmenopausal women with urge incontinence. We conducted a systematic review and meta-analysis by searching PubMed and EMBASE databases for randomized controlled trials (RCTs) reporting results of treatments for postmenopausal urinary urge incontinence. Odds ratios for improvement of urinary incontinence were calculated using random effect Mantel-Haenszel statistics. Out of 248 records retrieved, 35 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared with placebo, systemic estrogens were associated with decreased odds of improving urinary incontinence in postmenopausal women (OR = 0.74, 95% CI: 0.61-0.91, 7 series, 17132 participants, Z = 2.89, P = 0.004, I2 = 72%). In most studies, no significant improvement in urinary symptoms was observed in patients treated with local estrogens, although they showed to be helpful in improving vaginal symptoms. Vitamin D, phytoestrogens and estrogen modulators were not effective in improving symptoms of incontinence and other symptoms of genitourinary menopause syndrome or yielded contradictory results. A randomized controlled trial demonstrated that oxybutynin was significantly better than placebo at improving postmenopausal urgency and urge incontinence. The combination of anticholinergics with local estrogens has not been shown to be more effective than anticholinergics alone in improving urinary incontinence symptoms in postmenopausal women. Physical therapy showed an overall positive outcome on postmenopausal urinary incontinence symptoms, although such evidence should be further validated in the frame of quality RCTs. The evidence for effective treatment of postmenopausal urinary incontinence is still lacking. Welldesigned large studies having subjective and objective improvement primary endpoints in postmenopausal urinary incontinence are needed. At present, a combination of different treatments tailored to the characteristics of the individual patient can be suggested.

Kajian DRPs dan pola peresepan pada pasien rawat inap anak dengan asma

The incidence of drug-related problems (DRPs) is very common occur in pediatric inpatients where treatment must be prioritized because their physiological conditions are not yet perfect so metabolism and drug absorption cannot be equated. The risk of developing DRPs results in a decrease in the patient's quality of life, increases the rate of death and disability and increases costs. Asthma is a chronic disease, the prevalence of asthma in children is high enough that it requires serious attention. In Indonesia, the prevalence of asthma in elementary school children (0-14 years) is 9.6%. This study aims to identify drug related problems and determine treatment patterns in pediatric patients with asthma at X Hospital. This research was a non-experimental study conducted with a descriptive design through retrospective data retrieval of the medical records of children with asthma who were hospitalized in January-July 2017 at X hospital. DRPs and treatment patterns were assessed from the patient's medical record data and then analyzed using percentages. DRPs were entered in bullet points while treatment patterns were in the table. The results of this study were the class of drugs used. Corticosteroids, beta-2 agonists, beta-2 agonists and anticholinergic combinations, beta-2 agonist combinations with corticosteroids, antihistamines, antihistamine and decongestant combinations and methylxanthine. Types of drugs used are salbutamol, procaterol, dexamethasone, methylprednisolone, triamcinolone, budesonide, aminophylline, and a combination of albuterol and ipratropium bromide. The results of the DRPs study were, that there was no indication that there was no treatment, drugs with inappropriate indications in 50%, the wrong drug was 66.6%, the dose was too high at 61.1%, drug interactions amounted to 22.2%, and non-compliance does not exist.Â

Current use of anticholinergic medications in a large naturalistic sample of psychiatric patients.

Due to the high number of psychotropic drugs with anticholinergic potential, patients taking psychotropic drugs are at high risk for anticholinergic adverse drug reactions (ADRs). The aim of this study was to analyze the prevalence and type of pharmacodynamic anticholinergic drug-drug interactions in psychiatric patients. The retrospective longitudinal analysis used data from a large pharmacovigilance study conducted in ten German psychiatric hospitals. Anticholinergic burden of drugs was defined as "strong" or "moderate" based on current literature. Number and type of anticholinergic drugs were assessed. In total, 27,396 patient cases (45.6% female) with a mean age of 47.3 ± 18.3years were included. 17.4% (n = 4760) of patients were ≥ 64years. 35.4% of the patients received between one and four anticholinergic drugs simultaneously. A combination of drugs with anticholinergic potential was detected in 1738 cases (6.3%). Most prescribed drugs were promethazine (n = 2996), olanzapine (n = 2561), biperiden (n = 1074), and doxepin (n = 963). Patients receiving anticholinergic combinations were younger (45.7 vs. 47.4years, p < 0.01) and had a longer inpatient stay (median 18 vs. 26.5days, p < 0.001). The prevalence of anticholinergic drug use in psychiatry is high. Further efforts need to focus on reducing the rate of anticholinergics and inappropriate medication especially in the elderly. Anticholinergic ADRs can be prevented by avoiding high-risk drug combinations. Replacing tricyclic antidepressants and first-generation antihistamines with drugs with lower anticholinergic potential and avoiding biperiden could reduce 59.3% of anticholinergic drug application.

Effect of desmopressin lyophilisate (MELT) plus anticholinergics combination on functional bladder capacity and therapeutic outcome as the first-line treatment for primary monosymptomatic nocturnal enuresis: A randomized clinical trial.

PurposeTo assess the efficacy of desmopressin plus anticholinergic combination therapy as first-line treatment for children with primary monosymptomatic nocturnal enuresis (PMNE) and to analyze this combination's effect on functional bladder capacity (FBC).Materials and MethodsA total of 99 children with PMNE were prospectively enrolled from 2015 to 2019 and randomly allocated to a monotherapy group (n=49), with oral desmopressin lyophilisate (MELT) only; and a combination group (n=50), with desmopressin plus an anticholinergic (propiverine 5 mg). Efficacy and FBC were evaluated at 1 and 3 months after treatment initiation; the relapse rate was assessed at 6 months after treatment cessation.ResultsThe combination therapy group showed a higher rate of complete response than the monotherapy group after 3 months of treatment (44.0% vs. 22.4%, p=0.002). A significant increase in mean FBC was observed only in the combination group, from 88.72±26.34 mL at baseline to 115.52±42.23 mL at 3 months of treatment (p=0.024). Combination therapy was significantly associated with treatment success at 3 months after treatment initiation (odds ratio [OR], 3.527; 95% confidence interval [CI], 1.203–6.983; p=0.011) and decreased risk of relapse at 6 months after treatment cessation (OR, 0.306; 95% CI, 0.213–0.894; p=0.021), by multivariable analysis.ConclusionsThis study represents the first prospective, randomized controlled trial showing higher response rates and lower relapse rates with desmopressin plus anticholinergic combination therapy compared with desmopressin monotherapy as first-line treatment for children with PMNE.

Gabapentin add-on therapy for patients with spinal cord injury associated neurogenic overactive detrusors that are unresponsive to combined anticholinergic and beta-3 adrenergic therapy.

IntroductionSpinal cord injury is a major cause of lifelong morbidity and functional micturition problems. Some patients are refractory to the available therapeutics, even when used in combination. In this paper we report our results of using gabapentin as an add-on treatment in refractory overactive detrusor cases secondary to spinal cord injury.Material and methodsA total of 27 patients who had a spinal cord injury between the levels of the second thoracic and fourth lumbar vertebrae and had an overactive detrusor in urodynamic studies were included in this retrospective study. The patients were selected due to the fact that they also had not responded to a combination of an anticholinergic and mirabegron and had neuropathic pain. Gabapentin treatment was added to the previous therapy. Demographics, previous treatments, chronic conditions, urodynamic findings, clinical and urodynamic responses are reported in this paper.ResultsWe observed a response to treatment in the urodynamic studies of 11 patients (40.17%), in terms of decreased detrusor contractions, maximal detrusor pressure, and the number of incontinence episodes. Sixteen patients did not respond to the gabapentin add-on therapy and were referred for Botulinum toxin injections to the bladder.ConclusionsGabapentin add-on therapy can be considered as a third or further option, before Botulinum toxin injection, for patients with neurogenic overactive detrusor who did not respond to the combination of anticholinergics and mirabegron. The approved usage of gabapentin for neurogenic pain justifies its usage in this area. In our selected patient group, who had not responded to the combination therapy, we observed a clinical benefit in one-third of the patients.

Drugs used in wheeze associated respiratory infection among children in tertiary care teaching hospital

Background: This study was done to study the drugs used in wheeze associated lower respiratory infected paediatric patients in tertiary care teaching hospital.Methods: Sample size was calculated as 78 and patients were selected based on the inclusion and exclusion criteria. The study was a prospective observational study and conducted in Department of Pediatrics, Rajah Muthiah Medical College and Hospital (RMMCH), Annamalai University.Results: Our study shows that male children (63%) are affected with more than female children (37%). The most frequently prescribed drugs are antibiotics (96%), antipyretics (63%), expectorants and antitussives (54%) followed by beta adrenergic agonist (46%), beta adrenergic agonist with anticholinergic combination (14%) corticosteroids (18%). Our study also shows wheeze associated lower respiratory infection (WALRI) in children were significantly associated with bacterial infections (72%).Conclusions: Our study concluded that antibiotics and antipyretics are the most commonly prescribed drugs for WALRI followed by expectorants and antitussives, beta adrenergic agonist, corticosteroids, beta adrenergic agonist with anticholinergic combination. Most of the treatment strategies are adopted from Standard Treatment Guidelines (STG) and World Health Organisation (WHO). The average number of prescribed drugs per encounter was more than that of WHO standards. The percentage of encounters in which an antibiotics and injections was higher than the ideal WHO standards it leads to anti-microbial resistance and costly forms of drug therapy.

Kas İnvaziv Olmayan Mesane Kanserinde BCG Verilmesi Sırasında İrritatif Semptomların Azaltılmasının Önemi: Bir Pilot Çalışma

INTRODUCTION: We evaluated use of anticholinergics, mirabegron, and combination of anticholinergics with mirabegron during Bacillus Calmette-Guérin (BCG) instillation for reducing irritative symptoms in patients with non-muscle invasive bladder cancer (NMIBC). METHODS: Prospectively recorded data of NMIBC patients receiving BCG were retrospectively evaluated between August 2015 and April 2019. Patients with low-grade T1 solitary papillary lesions &lt;4 cm were included in the study. Validated questionnaires (OAB-V8) for irritative symptoms adapted to Turkish language, and QoL index forms were filled out by the study participants. OAB-V8 scores of ≥8 were considered as an indication to start medical treatment for irritative symptoms. Groups were formed according to daily used anticholinergic drugs and combinations as follows: Group 1, tolterodine; Group 2, solifenacin 5mg; Group 3, mirabegron, and Group 4, mirabegron with solifenacin 5 mg. RESULTS: Mean follow- up period was 20.4±6.8 months. There were 132 patients [110 men (83%) and 22 (17%) women] with irritative symptoms and NMIBC. Mean age of the study population was 59.7±12.4 years. The OAB-V8 scores and QoL indexes significantly improved with all drugs. However, in subgroup analyses, Group 4 provided the most dramatic improvement in OAB-V8 and QoL index scores (P=0.02 for both). The longest in time to micturition was recorded in Group 4 (P=0.04). Tumour recurrence was similar for groups 12 months after BCG instillation (P=0.9), however the least recurrence was observed in Group 4. DISCUSSION AND CONCLUSION: Combination of solifecacin and mirabegron can reduce irritative symptoms, improve QoL, and prolong time to micturition, during BCG instillation in selected NMIBC patients. This combination may also decrease recurrence rates in this patient population.

Time Course of Treatment for Primary Enuresis With Overactive Bladder.

PurposeTo characterize the course of treatment for nonmonosymptomatic enuresis with overactive bladder (OAB) in a real clinical setting.MethodsData from 111 OAB patients with moderate to severe enuresis were analyzed. The baseline analysis included a questionnaire, voiding diary, uroflowmetry with postvoid residual urine measurement, and plain abdominal radiography of the kidneys, ureters, and bladder (KUB). Following standard urotherapy for 1 month, anticholinergic medication was administered with or without laxatives. Desmopressin was added if there was a partial response to OAB. Patients were followed every 3 months to evaluate the status of OAB and enuresis. Multivariate analysis was performed to identify predictors associated with the lack of complete response (CR) in enuresis at 12 months.ResultsFollowing 12 months of treatment, 64% and 88% of patients experienced at least partial response in enuresis and OAB, respectively. Urgency improved more quickly than enuresis, supporting the need to address daytime symptoms before enuresis. Seventy-nine patients (71%) had fecal impaction on KUB and/or subjective constipation. The combination of anticholinergics with either laxatives or desmopressin fared better than anticholinergics alone. Daytime incontinence and anticholinergics-only treatment were associated with a lack of CR during 12 months of treatment.ConclusionsThe data confirmed the validity of addressing OAB before treating enuresis. The results of this study also highlight the need to address fecal impaction. Patients should be counseled about the need for a prolonged course of treatment before starting treatment. Anticholinergics should be accompanied with either desmopressin or laxatives for better control of enuresis.

Комбинированная терапия расстройств мочеиспускания после трансуретральной резекции предстательной железы

Surgery in patients with large prostates due to benign prostatic hyperplasia (BPH) results in severe dysuria manifesting as frequent or urgent need to urinate and urinary incontinence. Traditionally, these conditions are treated with alpha blockers. Recently, alpha-blockers and the anticholinergic combination have been used showing additional advantages. This study aimed to investigate the comparative effectiveness of monotherapy versus combination therapy in the treatment of postoperative dysuria in BPH patients with large prostates undergoing transurethral surgery. From September 2016 to March 2017, 94 BPH patients with prostates greater than 100 cc underwent transurethral surgery at the Department of Urology of D.D. Pletnev Clinical Hospital; 22 patients had exclusion criteria. In the postoperative period, 36 patients received 0.4 mg of modified release tamsulosin (Omnik) for a month, and 36 patients were administered controlled release tablets tamsulosin 0.4 mg + solifenacin 6 mg (Vezomni) as fixed-dose combination therapy. At one month postoperatively, patients were asked to rate their symptoms on a visual analogue scale and fill out I-PSS and QoL questionnaires. Preoperative parameters of the groups were: visual analogue scale scores were 5.1 and 5.2, I-PSS scores were 24 and 24.2, QoL scores were 4.5 in both groups. Prostate volumes were 114 and 118 cc; maximum urinary flow rates were 7.7 vs. 7.5 ml/sec, residual urine volumes were 110 vs. 105 ml, respectively. Visual analogue scale scores were 6.5 versus 9.2 points, I-PSS scores were 16.3 versus 12.1. The patients of the second group had greater mean micturition volume (150 versus 240 ml); other variables did not differ statistically significantly between the groups. Adverse reactions were mild, and drugs were not discontinued in any case. In BPH patients with dysuria after transurethral resection of large prostates, Vezomni administration results in a better quality of life due to an improvement in urgency and nocturia.

Triple fixed inhaled therapy in frequent chronic obstructive pulmonary disease exacerbators: potential advantages for various degrees of airways obstruction

ABSTRACTIntroduction: Inhaled therapies are the therapeutic mainstay in stable chronic obstructive pulmonary disease (COPD). They are represented by long-acting bronchodilators (anticholinergics or beta2-agonists) and by inhaled corticosteroids, currently available as a monotherapy or as combination therapies in one inhaler. Combinations of anticholinergics and beta2 agonists or beta2 agonists and inhaled corticosteroids are widely used per the prescription guidelines. The advantage of them are related with higher adherence and better acceptability by the patients as compared to both components dosed with individual inhalers. Bronchodilator combinations have also been demonstrated to exhibit a superior efficacy due to their synergistic mechanism of action when compared to either monotherapy. Triple therapies with anticholinergic-beta2 agonist-inhaled corticosteroid have been under investigation over the last few years and recently one such product became available in the EU for the treatment of stable COPD.Areas covered: The the FULFIL trial (Lung FUnction and quality of LiFe assessment in COPD with closed trIpLe therapy) investigated the efficacy and safety of fluticasone/vilanterol/umeclidinium once daily therapy in COPD patients.Expert opinion: The results discussed in this paper support the use of this combination in advanced COPD but also in earlier stages in patients with frequent exacerbation. However further and more long-term assessments are required.

GOLD 2017: what change were made in global strategy of treatment of chronic obstructive pulmonary disease and why?

In 1997, the International Expert group on chronic obstructive pulmonary disease (COPD) has come to decision to initiate the Global Initiative for COPD (GOLD). The first GOLD report was published in 2001 and provided the basis for many national programs for COPD diagnosis and management. Research data accumulated in the next decade allowed to perform complete revision of global strategy in 2011 (updated 2013), considering personalized approach to prognosis and treatment selection in an individual patient. At the end of2016, anew comprehensive reassessment of GOLD report was released. The ABCD assessment tool has been refined; the role of spirometry in COPD management has been updated. Regular assessment of inhaler technique to improve the disease control has been emphasized. New data on therapy with long-acting β2-agonists/long acting anticholinergic combinations and «triple therapy» have been added. Classification of severity of COPD exacerbations was provided and impact of concomitant diseases was stressed. The section on pulmonary rehabilitation has been amplified.

Oculogyric crisis with atypical antipsychotics: A case series.

Oculogyric crisis (OGC) is an acute dystonic reaction, commonly seen with the administration of typical antipsychotics, and rarely reported with atypical antipsychotics. Here, we report five cases of oculogyric crisis, developed after administration of atypical antipsychotics. The first case developed OGC on quetiapine 800 mg/day and the second case on olanzapine 20 mg/day. Both the patients did not improve on adding anticholinergic agents and finally stabilized by switching to clozapine. The third case developed OGC on amisulpride 400 mg and lurasidone 40 mg/day and improved by reducing amisulpride dose to 200 mg and stopping lurasidone. The fourth case developed OGC on aripiprazole 30 mg/day and improved by dose reduction. The fifth case developed OGC on amisulpride 400 mg/day and improved by switching to risperidone and anticholinergic combination. Oculogyric crisis is a potential side effect of antipsychotic medications (mostly with typical and rarely with atypical) and generally respond to oral anticholinergics, but in some cases, dose reduction or discontinuation of antipsychotic agent and switching to safer alternatives or clozapine is required.

Immediate 1-month efficacy of desmopressin and anticholinergic combination therapy versus desmopressin monotherapy in the treatment of pediatric enuresis: A meta-analysis

Several studies have proposed the combination of desmopressin and anticholinergic as a treatment regimen to address the pathophysiology of polyuria and bladder dysfunction in pediatric enuresis. However, the available literature is inconsistent with regards to the immediate 1-month efficiency of the combination therapy in the treatment for pediatric enuresis. The aim was to assess the immediate 1-month efficacy and safety of desmopressin and anticholinergic agent combination therapy versus desmopressin monotherapy in the treatment of pediatric enuresis using meta-analysis of randomized controlled trials (RCTs). Systematic literature acquisition was carried out on electronic medical databases up to April 2015. RCTs relevant to the topic were critically appraised. Dichotomous data of the 1-month post-treatment response rate (defined as ≥90% reduction of wet nights) were extracted for calculation of the risk ratio (RR) and 95% confidence interval (CI). The Mantel-Haenszel method with the random effects model was used to pool effect estimates. Inter-study heterogeneity and publication bias were assessed. Subgroup analysis was done for the desmopressin treatment-naive versus treatment-resistant groups: PROSPERO (CRD42015017922). Four RCTs of good methodological quality without heterogeneity were included for meta-analysis. The pooled effect estimates showed that combination therapy was associated with a significantly better immediate 1-month response rate than desmopressin monotherapy. Subgroup analysis showed a greater immediate 1-month response rate among desmopressin-resistant patients than treatment-naive patients. No severe adverse events were noted among combination therapy treated groups. The limitation of the current meta-analyses is the small sample size, albeit with high-quality studies pooled for effect estimation. Despite the limitation, the study results were able to consistently illustrate a large treatment effect of combination therapy among desmopressin treatment-resistant patients. It was consistent with the literature review of retrospective and non-comparative studies by Alloussi etal. (2011), who summarized a similar impressive treatment outcome. However, due to the low level of evidence available at the time of their study, only a grade B-C recommendation was given to combination therapy as an approach for second-line treatment. This study also summarized that combination therapy was well tolerated and similar to desmopressin monotherapy. This study was able to summarize the immediate 1-month efficacy of combination therapy compared with desmopressin monotherapy in the treatment of pediatric enuresis. For both treatment-naive and desmopressin-resistant pediatric enuresis, combination therapy of desmopressin with an anticholinergic agent is well tolerated and resulted in a significantly better immediate 1-month response rate than desmopressin monotherapy.

Prescribing Pattern in an Intensive Car Unit in a Tertiary Care Teaching Hospital, Bangalore, South India

INTRODUCTION: Critical care presents with a major patient safety challenges and requires fast-paced, complex and urgent high-risk decisionmaking, by physicians with varying levels of critical care training. In Intensive Care Unit (ICU) settings, the rate of preventable and potential Adverse Drug Events (ADEs) is even higher, being almost twice as high as in non-ICUs.Many studies states that, the presence of clinical pharmacists in ICUs has reduced the number of adverse events, improved cost savings and medications, stay, and shortened the duration of ICU admission. AIM : To study the prescribing pattern in an Intensive Care Unit (ICU). METHOD : A prospective - observational study on prescription pattern was done in the ICU Department of a tertiary care teaching hospital in Bangalore for a period of 6 months. All patients admitted in the ICU above 18 years were included in the study and patients who were admitted in ICU for less than 24 hours were excluded. Patients satisfying Inclusion criteria were enrolled after obtaining Informed Consent (IC) and their medication orders were observed for Prescription Pattern and analysed. RESULTS and DISCUSSION : A total of 120 cases were observed and analysed in which 45% were females and 55% were males. Majority of the patients belong to the age category of above 50 years. A total of 1165 drugs were prescribed out of which 20% were antibiotics followed by broncho dilators (9.2%), anti-hypertensives (9.4%), corticosteroids and analgesics (7.4%) each, anti-diabetics (5.6%), antidotes (1.6 %) and others (38.8%). Antibiotics were the uppermost class prescribed, among which Ceftriaxone or Cefaperazone -Sulbactum combination was widely found. Atropine (52.6%) was the most commonly prescribed antidote. Among bronchodilators, combination of anti-cholinergics and beta blockers was prescribed more (49%). Short acting glucocorticoid and para- aminophenol derivatives with 81.6% and 85% respectively, were the most prescribed corticosteroid and analgesics. CONCLUSION : The results of the study highlights areas that need improvement among which most importantly, there is a need to implement local antibiotic management program or infectious disease specialist consultation which could lead to marked reductions in antibiotic consumption. There are considerable variations in the practice of emergency medications by various professionals in the ICU, hence preparation and implementation of emergency medication practice guidelines may bridge the variations among practitioners and continually improve the quality of care to the patients.

Impact of anaesthetic drugs and adjuvants on ECG markers of torsadogenicity

Drug-induced prolongation of cardiac repolarization may trigger malignant ventricular arrhythmias, such as torsade de pointes. The duration of QT interval, QT corrected for heart rate (QTc), JT interval, QT dispersion (QTd), QT variability index, and transmular dispersion of repolarization (TDR) are ECG markers of torsadogenicity. All volatiles, especially isoflurane and desflurane, have been found to prolong QTc and QTcd, while sevoflurane has probably no effects on TDR. Among i.v. anaesthetics, propofol seems superior due to its minimal effects on QTc and TDR; moreover, a decrease in QTc and QTcd has been demonstrated in many studies. Regarding opioids, fentanyl, alfentanil, and remifentanil produce no effects on QTc, while sufentanil, at high doses, may induce QT prolongation. Succinylcholine, but not the non-depolarizing neuromuscular blockers, produces QTc prolongation which can be attenuated by opioids and β-blockers. Reversal of neuromuscular block with anticholinesterase–anticholinergic combinations has been associated with significant QTc prolongation, while such an effect has not been demonstrated for sugammadex, even at high doses. Local anaesthetics have probably no intrinsic action on duration of repolarization; nevertheless, an extensive subarachnoid sympathetic block may increase the duration of QTc. On the contrary, thoracic epidural anaesthesia has been associated with a decrease in both QTc and TDR. Among adjuvants, midazolam seems to have no effect on QTc and TDR, while commonly used antiemetics, such as droperidol, domperidone, and most 5-HT3 antagonists, produce significant QT prolongation. The effects of anaesthetic drugs and techniques on electrocardiographic torsadogenic markers should be considered in the perioperative management of patients with preexisting repolarization abnormalities.

MECHANISMS OF ANTICHOLINERGIC EFFECTS AND PROBABLE MECHANISMS OF THEIR POTENTIATION USING BETA-2-AGONISTS

Current basic therapy of chronic obstructive pulmonary disease includes inhaled long-acting bronchodilators. This article reviews mechanisms of action of anticholinergic drugs and their potentiation with beta-2-agonists. There are several upcoming fixed combinations of anticholinergics and beta-2-agonists. In 2013, the first fixed combination of anticholinergic glycopyrronium and beta-2-agonist indacaterol has been registered. A beta-2-agonist decreases acetylcholine release due to changes in the cholinergic neuronal transmission via presynaptic beta-2-adrenoreceptors that leads to better smooth muscle relaxation in bronchi caused by anticholinergics. Moreover, anticholinergic drug could reduce acetylcholineinduced constriction and amplify bronchodilation caused by beta-2-agonist. The combination of anticholinergic glycopyrronium and beta-2-agonist indacaterol is to be effective.

Long-term alpha-blockers and anticholinergic combination treatment for men with lower urinary tract symptoms in real-life practice

To analyze the treatment outcomes and clinical courses for men with lower urinary tract symptoms, after long-term treatment of alpha-blocker and anticholinergic combination in real-life practice. A total of 210 men, with lower urinary tract symptoms, had combination therapy for 3 months. Patients were reevaluated and were decided on an alpha-blocker single treatment or a combination therapy, according to the patient-reported outcome for 2 years. The patient responses in 2-year treatment were divided into 3 groups, which depended on clinical courses: 56 patients had an alpha-blocker single therapy after 3-month combination therapy (group I); 106 patients had a continuous alpha-blocker therapy with intermittent 3-month anticholinergic therapy (group II); 48 patients with continuous storage symptoms maintained a combination therapy (group III). Endpoints included 2-year changes in International Prostate Symptom Score (IPSS), Qmax, and residual volume. Group III had significantly increased IPSS total and subscores compared to that of the other groups in the baseline characteristics. IPSS total and subscores significantly decreased at 3 months and were maintained for 2 years in all groups. Increase in Qmax was significant in all the groups at 3 months, and its increase was still significant after 2 years. Residual urine volume increased in all the groups at 3 months, but changes at 2 years were not statistically significant. After 3 months of alpha-blocker and anticholinergic combination treatment, 73.4 % of the patients still needed a combination therapy. Although only one patient developed acute urinary retention, voiding difficulty was common (13.3 %), after a combination treatment in the real-life practice.

Low-Dose Anticholinergic Combination Therapy in Male Benign Prostatic Hyperplasia Patients with Overactive Bladder Symptoms.

Most men with lower urinary tract symptoms have both storage and voiding symptoms. Overactive bladder symptoms occur in 50-75% of men with benign prostatic obstruction. Alpha-blockers are usually the first option in medical therapy. Even though voiding symptoms are alleviated by the use of medicines or transurethral resection of the prostate, storage symptoms continue in 30-65% of patients. Combination therapy with an alpha1-receptor antagonist and an anticholinergic agent in benign prostatic hyperplasia patients with overactive bladder symptoms significantly alleviates symptoms and improves quality of life. In clinical practice, the efficacy and safety of anticholinergic combination therapy may not be comparable with well-controlled studies. Overactive bladder symptoms usually require long-term treatment, and benign prostatic hyperplasia tends to progress with time. When male LUTS patients are treated with anticholinergic combination therapy, there are still some concerns about the development of acute urinary retention, voiding difficulty, and other anticholinergic side-effects. If the drug is prescribed in a relatively low dosage, however, this approach could be appealing regarding adverse effects. There is a relatively small number of clinical reports about low-dose combination therapy, which is in its early stages. Promising results are being reported, though the level of evidence is low. We await the final results.

İşeme ve Depolama Semptomları Olan Erkeklerde Trospium Klorid Eklenmesinin Rolü

Objective: In patients who suffer from Lower Urinary Tract Symptom (LUTS) and overactive bladder (OAB), the quality of life is affected negatively. The aim of this study was to assess the efficacy and safety of trospium chloride, which is here used for the first time in an alpha-blocker and anticholinergic combination therapy for older men who suffer from benign prostate hypertrophy (BPH)-related LUTS with OAB. Material and Methods: This prospective, randomized, placebo controlled, double-blind trial included men aged ?45 years with LUTS and OAB. Subjects were randomized into trospium chloride 45 mg with terazosin 5 mg or placebo with terazosin 5mg for 12 weeks. At baseline and week 12, subjects were evaluated using total prostate serum antigen, uroflowmetry, and post voiding residual urine (PVRU) and completed the International Prostate Symptom Score (IPSS), Overactive Bladder Questionnaire (OAB-q), 3-day bladder diaries, BPH impact index, and Urolife quality of life questionnaire form. The patients were monitored for side effects and safety at 4, 8 and 12 weeks. Results: While the improvement in maximum and average urination streams, PVRU, bladder capacity, IPSS, OAB, BPH impact index scores was not significant, ther was significant improvement in Urolife quality of life questionnaire score and voiding frequency in favour of the trospium chloride group (0.0009 and 0.0216 respectively). There was no statistically significant difference in side effect profile between the groups. Conclusion: In men with BPH-related OAB trospium chloride and alpha-blocker combination treatment is effective and safe. The improvement in quality of life is remarkable.

Editorial Comment

This small, but well-designed, nonrandomized cross-over study of oxybutynin combined with alarm therapy showed no improvement in monosymptomatic nocturnal enuresis (MNE) after the institution of anticholinergics to those without a response to alarm therapy. The families were initially allowed to choose oxybutynin or alarm therapy as monotherapy. Their results showed that 10% of those taking oxybutynin alone had a full response compared with 56% of those using alarm therapy alone. None of the patients without a response to alarm therapy became dry after initiating an appropriate dose of oxybutynin. In contrast, 33% of those without a response to oxybutynin monotherapy had a full response after the addition of alarm therapy. No differences were noted in the mean functional bladder capacity between the 2 groups. Anticholinergics Do Not Improve Cure Rate of Alarm Treatment of Monosymptomatic Nocturnal EnuresisUrologyVol. 77Issue 3PreviewTo determine whether previous anticholinergic therapy or a combination of anticholinergics and alarm treatment could increase the success rates for monosymptomatic nocturnal enuresis. Alarm treatment of monosymptomatic nocturnal enuresis is the treatment of choice, with the greatest lasting success. It has been proposed that failures are related to a patient's small bladder volume. Full-Text PDF