Reduction of Overactive Bladder Medications in Spinal Cord Injury With Self-Administered Neuromodulation; a Randomized Trial.

PURPOSE: To evaluate if self-administered bladder neuromodulation with transcutaneous tibial nerve stimulation can safely replace overactive bladder medications in people with spinal cord injury. MATERIALS AND METHODS: We performed a 3-month, randomized, investigator-blinded, tibial nerve stimulation vs sham-control trial in adults with spinal cord injury and neurogenic bladder performing intermittent catheterization and taking overactive bladder medications. The primary outcome was a reduction in bladder medications while maintaining stable bladder symptoms and quality of life based on pre-post Neurogenic Bladder Symptom Score and the Incontinence-QOL questionnaire, respectively. Secondary outcomes included changes in pre-post cystometrogram, 2-day voiding diaries, and an anticholinergic medication side effect survey. RESULTS: Fifty people consented to the study, with 42 completing the trial. No dropouts were due to stimulation issues. All baseline demographics and surveys were comparable at baseline. Cystometrogram parameters were also comparable at baseline, except the stimulation group had a higher proportion of loss of bladder compliance compared to the control group. At the end of the trial, a significantly greater percentage of the tibial nerve stimulation group were able to reduce medications (95% v 68%), by a 26.2% difference in medication reduction (95% confidence interval 1.17%-51.2%). Function and quality of life surveys and cystometrograms at the end of the trial were alike between groups. Transcutaneous tibial nerve stimulation satisfaction surveys and adherence to protocol were high. CONCLUSIONS: In people with chronic spinal cord injury performing intermittent catheterization, transcutaneous tibial nerve stimulation can be an option to reduce or replace overactive bladder medications.

Management of overactive bladder: consensus statements from the Hong Kong Urological Association and the Hong Kong Geriatrics Society.

Overactive bladder (OAB) is a common urological disease with a high prevalence in older adult populations. Antimuscarinic drugs have been the most common treatment for OAB for more than a decade, but their anticholinergic side-effects and potential impact on cognitive function among older patients are usually underestimated. This consensus aimed to provide practical recommendations concerning OAB management, with a particular emphasis on older patients. A joint consensus panel was formed by representatives of the Hong Kong Urological Association and the Hong Kong Geriatrics Society. Literature searches regarding OAB and its management were performed in PubMed and Ovid. Several working meetings were held to present and discuss available evidence, develop consensus statements, and vote for the statements. A modified Delphi method was used in this consensus process. To address questions regarding various aspects of OAB, 29 consensus statements were proposed covering the following areas: diagnosis, initial assessment, non-pharmacological treatments, considerations before administration of pharmacological treatments, various pharmacological treatments, combination therapy, and surgical treatment. Twenty-five consensus statements were accepted.

Health-related quality of life and use of medication with anticholinergic activity in patients with multiple myeloma.

PURPOSE: Verify the association between anticholinergic burden and health-related quality of life of patients with multiple myeloma. METHODS: Cross-sectional study with multiple myeloma outpatient from a state capital city in southeastern Brazil. Sociodemographic, clinical, and pharmacotherapeutic variables were collected by interview. Clinical data were complemented by medical records. Drugs with anticholinergic activity were identified with Brazilian Anticholinergic Activity Drug Scale. Health-related quality of life scores were obtained using QLQ-C30 and QLQ-MY20 instruments. Mann-Whitney was used to compare the median of the health-related quality of life scale scores and the independent variables. Multivariate linear regression was performed to verify the association between independent variables and health-related quality of life scores. RESULTS: Two hundred thirteen patients were included, 56.3% had multi-morbidities, and 71.8% used polypharmacy. In all health-related quality of life domains, there were differences between the medians of the polypharmacy variable. A significant difference was identified between the ACh burden and QLQ-C30 and QLQ-MY20 scores. Linear regression identified an association between the use of drugs with anticholinergic activity and the reduction of global status scores (QLQ-C30), functional scale (QLQ-C30), body image (QLQ-MY20), and future perspective (QLQ-MY20). Drugs with anticholinergic activity were associated with increased symptom scores (QLQ-C30 and QLQ-MY20). Polypharmacy was associated with reduction of functioning score and increase of symptom score (QLQ-C30). CONCLUSION: Anticholinergic burden in MM patients is associated with lower scores in quality of life domains: global health and symptoms (QLQ-C30) and functional (QLQ-C30 and QLQ-MY20). The presence of polypharmacy is also associated with lower scores for functional scales and symptom scales (QLQ-C30).

Development of the Swedish anticholinergic burden scale (Swe-ABS).

BACKGROUND: Drugs with anticholinergic properties are associated with cognitive adverse effects, especially in patients vulnerable to central muscarinic antagonism. A variety of drugs show weak, moderate or strong anticholinergic effects. Therefore, the cumulative anticholinergic burden should be considered in patients with cognitive impairment. This study aimed to develop a Swedish Anticholinergic Burden Scale (Swe-ABS) to be used in health care and research. METHODS: A systematic literature review was conducted in PubMed and Ovid Embase to identify previously published tools quantifying anticholinergic drug burden (i.e., exposure). Drugs and grading scores (0-3, no to high anticholinergic activity) were extracted from identified lists. Enteral and parenteral drugs authorized in Sweden were included. Drugs with conflicting scores in the existing lists were assessed by an expert group. Two drugs that were not previously assessed were also added to the evaluation process. RESULTS: The systematic literature search identified the following nine anticholinergic burden scales: Anticholinergic Activity Scale, Anticholinergic Burden Classification, updated Anticholinergic Cognitive Burden scale, Anticholinergic Drug Scale, Anticholinergic Load Scale, Anticholinergic Risk Scale, updated Clinician-rated Anticholinergic Scale, German Anticholinergic Burden Scale and Korean Anticholinergic Burden Scale. A list of drugs with significant anticholinergic effects provided by The Swedish National Board of Health and Welfare was included in the process. The suggested Swe-ABS consists of 104 drugs scored as having weak, moderate or strong anticholinergic effects. Two hundred and fifty-six drugs were listed as having no anticholinergic effects based on evaluation in previous scales. In total, 62 drugs were assessed by the expert group. CONCLUSIONS: Swe-ABS is a simplified method to quantify the anticholinergic burden and is easy to use in clinical practice. Publication of this scale might make clinicians more aware of drugs with anticholinergic properties and patients' total anticholinergic burden. Further research is needed to validate the Swe-ABS and evaluate anticholinergic exposure versus clinically significant outcomes.

A Retrospective Study of Anticholinergic Use and Later Mobilization as Risk Factors for Urinary Retention After Major Lower Extremity Joint Arthroplasty.

BACKGROUND: Postoperative urinary retention (POUR) is a common surgical complication of major joint arthroplasty and is associated with increased lengths of stay and urinary tract infections. Studies have found that certain anticholinergic medications and reduced mobility are associated with POUR. This study assessed the effect of anticholinergic burden and later postoperative ambulation on POUR. METHODS: In this retrospective cohort study, we included subjects who had undergone elective primary or revision hip or knee arthroplasty (total hip arthroplasty [THA] or total knee arthroplasty [TKA]) between March 2015 and December 2017 in a single health system. Anticholinergic burden was measured using the Anticholinergic Drug Scale (ADS). We performed bivariate and multivariable logistic regression with POUR as the dependent variable. Of the 1,397 study subjects, 622 (45%) underwent THA and 775 (55%) underwent TKA. Their mean age was 65 years (range, 21 to 98), and 841 (60%) were women. POUR developed in 183 (13%) subjects. RESULTS: In multivariable analyses, ADS was associated with POUR after THA (P < .05), but not TKA (P = .08), while later ambulation was not associated with POUR after either procedure (P > .3 for both). CONCLUSION: Anticholinergic burden after THA was independently associated with POUR. Strategies to reduce anticholinergic burden may help reduce POUR after THA.

Cholinergic Antagonists and Behavioral Disturbances in Neurodegenerative Diseases.

Cholinergic antagonists interfere with synaptic transmission in the central nervous system and are involved in pathological processes in patients with neurocognitive disorders (NCD), such as behavioral and psychological symptoms of dementia (BPSD). In this commentary, we will briefly review the current knowledge on the impact of cholinergic burden on BPSD in persons with NCD, including the main pathophysiological mechanisms. Given the lack of clear consensus regarding symptomatic management of BPSD, special attention must be paid to this preventable, iatrogenic condition in patients with NCD, and de-prescription of cholinergic antagonists should be considered in patients with BPSD.

Dementia Associated with Anticholinergic Drugs Used for Overactive Bladder: A Nested Case-Control Study Using the French National Medical-Administrative Database.

PURPOSE: We analyzed the relationship between use of anticholinergic drugs to treat overactive bladder (OAB) and risk of incident dementia in older patients, overall and for each drug separately. MATERIALS AND METHODS: We conducted a nested case-control study using the French National Medical-Administrative Database. We identified incident dementia cases and controls from January 1, 2013 to December 31, 2018 in individuals aged ≥60 years. Controls were matched 5:1 to cases by date of case diagnosis (index date), age, sex, and income. We set a 5-year exposure period ending 2 years before the index date (lag-time period to avoid protopathic bias). We quantified cumulative exposure to flavoxate, oxybutynin, solifenacin, trospium, and fesoterodine using defined daily doses (DDDs). We performed conditional logistic regression analyses adjusted for factors known to be associated with OAB and/or dementia including obesity, diabetes, stroke, coronary heart disease, and psychotic disorders. RESULTS: We analyzed 4,810 cases and 24,050 matched controls with a median age of 82 years. OAB anticholinergic use was associated with an increased risk of dementia (adjusted OR [aOR]=1.23, 95% CI 1.10-1.37) with a cumulative dose-response: aOR=1.07 (95% CI 0.91-1.25) for 1-90 DDDs, aOR=1.29 (1.05-1.58) for 91-365 DDDs and aOR=1.48 (1.22-1.80) for >365 DDDs. Considering each OAB anticholinergic separately showed a particularly marked increased risk of dementia for oxybutynin and solifenacin, but no increased risk for trospium. CONCLUSIONS: When treating OAB in older patients, OAB anticholinergics should be used with caution, taking into account the patient's cognitive status, the anticholinergic load, and the different therapeutic options.

Transcutaneous electrical nerve stimulation as add-on therapy in children receiving anticholinergics and/or mirabegron for refractory daytime urinary incontinence: A retrospective cohort study.

AIMS: To investigate if children with daytime urinary incontinence (DUI) and overactive bladder (OAB) refractory to standard urotherapy and medicinal treatment, would experience improvement in symptoms after add-on treatment with transcutaneous electrical nerve stimulation (TENS). METHODS: Children were retrospectively enrolled from tertiary referral centers at Aarhus and Aalborg University Hospitals. All data were retrieved from the patients' journals. All children were prescribed TENS as an add-on treatment to the highest-tolerable dose of medicinal treatment in a standardized regime of 2 h a day for around 3 months. Primary endpoints were the number of wet days per week (WDPW) and incontinence episodes per day. Effect of treatment was defined as greater or equal to 50% reduction in the frequency of DUI episodes. Secondary endpoints were to establish predictive factors for the effect of treatment using logistic regression. RESULTS: Seventy-six children diagnosed with DUI and OAB refractory to treatment with standard urotherapy and pharmacological treatment, at the age of 5-16 years were included from February 2017 to February 2020. A reduction in WDPW (from 6.31 [5.86-6.61] to 4.27 [3.45-4.90], p < 0.05) and incontinence episodes per day (from 2.45 [1.98-2.91] to 1.43 [1.07-1.80], p < 0.05) was observed. Twelve patients became completely dry. At 6 months follow-up, seven of the 12 complete responders had relapsed while five remained dry. A history of constipation before TENS was a predictor of poor treatment response (p = 0.016). CONCLUSIONS: TENS as add-on to anticholinergic treatment seems effective in a number of children with treatment-refractory DUI.

Use of tricyclic antidepressants and other anticholinergic medicines by older Aboriginal Australians: association with negative health outcomes.

BACKGROUND: Aboriginal and Torres Strait Islander Australians have a relatively high prevalence of multimorbidity requiring treatment with medications. This study examines medication use and anticholinergic burden (ACB) among a cohort of older Aboriginal and Torres Strait Island people. METHOD: This cross-sectional study involving five Aboriginal communities (two in metropolitan Sydney and three on the mid-north coast of New South Wales) used a structured interview process to assess cognition, depression, and activities of daily living for a cohort of older adults (aged 60 years and over). Participants also reported on their health status, medical history, and prescription medications during the interview. ACB was calculated, and its association with adverse health outcomes including cognitive impairment, falls, hospitalization, and depressive symptoms were examined. RESULTS: Most participants (95%) were taking at least one regular medication with polypharmacy (≥5 medications) observed in 43% of participants; 12.2% had a significant ACB (≥3) with antidepressants being a major contributor. Anticholinergic medication use was associated with cognitive impairment, recent hospitalization (past 12 months), and depressive symptoms. After controlling for age, sex, and comorbidity, only the presence of depressive symptoms remained significantly associated with the use of anticholinergic medication (odds ratio 2.86; 95% confidence interval 1.48-5.51). CONCLUSIONS: Clinically significant ACB was common in older Aboriginal Australians and was largely attributable to inappropriate use of tricyclic antidepressants. Greater awareness of medication-related risk factors among both health care professionals and Aboriginal communities can play an important role in improving health and quality of life outcomes.

[Use of central anticholinergics in 2022]. / Utilisation des anticholinergiques centraux en 2022.

Cholinergic antagonists have been used for 60 years in the treatment of movement disorders. Their effect arises from a modulating activity within basal ganglia motor circuitry. Due to diffuse distribution among many organs, anticholinergic medications have numerous adverse effects. Nowadays, the indication of these molecules in the treatment of Parkinson disease is reduced, due to more effective and better tolerated alternatives. Iatrogenic parkinsonism is hardly alleviated by anticholinergics. These medications allow to prevent acute dystonic reactions induced by highly-dosed first generation antipsychotic agents. Once acute dystonia has appeared, parenteral treatment is to be preferred, but oral cholinergic antagonists may be used after the acute phase to prevent relapse. Botulinum toxin is preferred to anticholinergics for focal dystonia. In generalized dystonia, anticholinergic moderately alleviate symptoms.

Les anticholinergiques sont utilisés depuis plus de 60 ans pour traiter les mouvements anormaux. Leur effet thérapeutique provient d'une modulation, via des récepteurs muscariniques, des boucles motrices des noyaux gris centraux. Ce type de traitement a aussi de nombreux effets indésirables en lien avec la large distribution de récepteurs muscariniques dans plusieurs organes. Actuellement, la place de ces molécules est marginale dans le traitement de la maladie de Parkinson en raison d'alternatives plus efficaces et mieux tolérées. Leur efficacité est limitée en cas de parkinsonisme iatrogène. Ils contribuent à la prévention de la dystonie aiguë liée à l'utilisation de neuroleptiques de première génération à fortes doses. Lorsque la dystonie aiguë est présente, une solution parentérale est à privilégier, avec un relais possible par les anticholinergiques par voie orale. En cas de dystonie focale, les injections de toxine botulique sont plus efficaces. En cas de dystonie généralisée, les anticholinergiques ont une efficacité modérée.

Persistence and Adherence of Anticholinergics and Beta-3 Agonist for the Treatment of Overactive Bladder: Systematic Review and Meta-Analysis, and Network Meta-Analysis.

PURPOSE: We aimed to investigate the persistence and adherence rate of overactive bladder medications and factors that affect these rates. MATERIALS AND METHODS: We conducted electronic English-language literature searches of the PubMed®, Cochrane Library, and EMBASE® databases from the earliest available date of indexing through May 21, 2019 using the Medical Subject Headings (MeSH) terms and EMBASE subject headings (Emtree). Primary measurement outcomes were overall persistence and adherence rate at 6, 12, 24, and 36 months in anticholinergics and mirabegron. Secondary outcomes were individual effect of each medication on persistence and adherence rate at 12 months, and moderating factors affecting the overall persistence and adherence rate at 12 months. RESULTS: Pooled overall persistence rate at 12 months of overactive bladder medications of anticholinergics and mirabegron was 0.218 (95% CI: 0.197-0.240). The pooled overall persistence rate at 12 months was 0.402 (95% CI: 0.277-0.528) in mirabegron, 0.249 (95% CI: 0.182-0.316) in solifenacin, and 0.220 (95% CI: 0.078-0.361) in fesoterodine. Overall adherence rate of overactive bladder medications of anticholinergics and mirabegron was 0.589 (95% CI: 0.507-0.670). The pooled overall adherence rate at 12 months was 0.654 (95% CI: 0.528-0.781) in mirabegron, 0.784 (95% CI: 0.588-0.980) in solifenacin, 0.782 (95% CI: 0.652-0.911) in fesoterodine, and 0.679 (95% CI: 0.651-0.707) in imidafenacin. Persistence and adherence rates were associated with age, gender, anticholinergic exposure history, type of medication, study type, and study year. CONCLUSIONS: Persistence and adherence rates were lower than previously reported and were associated with certain clinical and demographic factors.

Association between anticholinergic burden and anticholinergic adverse outcomes in the elderly: Pharmacological basis of their predictive value for adverse outcomes.

The use of anticholinergic drugs and other drugs with anticholinergic activity is highly prevalent in older people. Cumulative anticholinergic effects, known as anticholinergic burden, are associated with important peripheral and central adverse effects and outcomes. Several methods have been developed to quantify anticholinergic burden and to estimate the risk of adverse anticholinergic effects. Serum anticholinergic activity (SAA) and anticholinergic burden scoring systems are the most commonly used methods to predict the occurrence of important negative outcomes. These tools could guide clinicians in making more rational prescriptions to enhance patient safety, especially in older people. However, the literature has reported conflicting results about the predictive ability of these tools. The majority of these instruments ignore relevant pharmacologic aspects such as the doses used, differential muscarinic receptor subtype affinities, and blood-brain barrier permeability. To increase the clinical relevance of these tools, mechanistic and clinical pharmacology should collaborate. This narrative review describes the rational and pharmacological basis of anticholinergic burden tools and provides insight about their predictive value for adverse outcomes.

Quantifying cumulative anticholinergic and sedative drug load among US Medicare Beneficiaries.

PURPOSE: Medications with anticholinergic and sedative properties are widely used among older adults despite strong evidence of harm. The drug burden index (DBI), a pharmacological screening tool, measures these properties across drug classes, and higher DBI drug exposure (DBI > 1) has been associated with certain physical function-related adverse events. Our aim was to quantify mean daily DBI drug exposure among older adults in the United States (US). METHODS: We screened medications for DBI properties and operationalized the DBI for US Medicare claims. We then conducted a retrospective cohort study of a 20% random, nationwide sample of 4 137 384 fee-for-service Medicare beneficiaries aged 66+ years (134 757 039 person-months) from January 2013 to December 2016. We measured the monthly distribution based on mean daily DBI, categorized as (a) >0 vs 0 (any use) and (b) 0, 0 < DBI ≤ 1, 1 < DBI ≤ 2, and DBI > 2, and examined temporal trends. We described patient-level factors (eg, demographics, healthcare use) associated with high (>2) vs low (0 < DBI≤1) DBI drug exposure. RESULTS: The distribution of the mean daily DBI, aggregated at the month-level, was: 58.1% DBI = 0, 29.0% 0 < DBI≤1, 9.3% 1 < DBI≤2, and 3.7% DBI > 2. Predictors of high monthly DBI drug exposure (DBI > 2) included certain indicators of increased healthcare use (eg, high number of drug claims), white race, younger age, frailty, and a psychosis diagnosis code. CONCLUSIONS: The predictors of high DBI drug exposure can inform discussions between patients and providers about medication appropriateness and potential de-prescribing. Future Medicare-based studies should assess the association between the DBI and adverse events.

Otorhinolaryngological adverse effects of urological drugs.

PURPOSE: To describe the otorhinolaryngological adverse effects of the main drugs used in urological practice. MATERIALS AND METHODS: A review of the scientific literature was performed using a combination of specific descriptors (side effect, adverse effect, scopolamine, sildenafil, tadalafil, vardenafil, oxybutynin, tolterodine, spironolactone, furosemide, hydrochlorothiazide, doxazosin, alfuzosin, terazosin, prazosin, tamsulosin, desmopressin) contained in publications until April 2020. Manuscripts written in English, Portuguese, and Spanish were manually selected from the title and abstract. The main drugs used in Urology were divided into five groups to describe their possible adverse effects: alpha-blockers, anticholinergics, diuretics, hormones, and phosphodiesterase inhibitors. RESULTS: The main drugs used in Urology may cause several otorhinolaryngological adverse effects. Dizziness was most common, but dry mouth, rhinitis, nasal congestion, epistaxis, hearing loss, tinnitus, and rhinorrhea were also reported and varies among drug classes. CONCLUSIONS: Most of the drugs used in urological practice have otorhinolaryngological adverse effects. Dizziness was most common, but dry mouth, rhinitis, nasal congestion, epistaxis, hearing loss, tinnitus, and rhinorrhea were also reported. Therefore, doctors must be aware of these adverse effects to improve adherence to the treatment and to minimize damage to the health of patients.

Effect of Early Oxybutynin Treatment on Posterior Urethral Valve Outcomes in Infants: A Randomized Controlled Trial.

PURPOSE: We studied the effect of oxybutynin on bladder and upper urinary tract outcomes in infants following posterior urethral valve ablation. MATERIALS AND METHODS: Patients younger than 12 months old who had undergone primary endoscopic valve ablation for posterior urethral valves were screened for eligibility. Patients who had undergone urinary diversion or had other conditions that could affect lower urinary tract function were excluded. Study patients were randomized to either oxybutynin (0.2 mg/kg 3 times daily) until toilet training or active observation. The study end points were serum creatinine, estimated glomerular filtration rate, hydronephrosis improvement, vesicoureteral reflux resolution, febrile urinary tract infection and toilet training. RESULTS: A total of 49 infants (24 receiving oxybutynin and 25 undergoing observation) were enrolled between December 2013 and September 2015 and completed at least 1 year of followup. Oxybutynin was discontinued before toilet training in 5 patients due to facial flushing in 2, bladder and upper tract dilatation in 2, and cognitive changes in 1. After a median followup of 44.2 months (range 12 to 57.6) median serum creatinine and estimated glomerular filtration rate were not significantly different between the groups (p=0.823 and p=0.722, respectively). Renal units in the oxybutynin group had a greater likelihood of hydronephrosis improvement (61.9% vs 34.8%, p=0.011) and resolution of vesicoureteral reflux (62.5% vs 25%, p=0.023). Febrile urinary tract infection (29.2% vs 40%, p=0.404), completion of toilet training (70.8% vs 76%, p=0.748) and age at toilet training (p=0.247) did not differ significantly between the oxybutynin and observation groups. CONCLUSIONS: Oxybutynin enhances hydronephrosis improvement and vesicoureteral reflux resolution following primary endoscopic valve ablation in infants but periodic monitoring is warranted.

Potentially inappropriate prescriptions of anticholinergic drugs in patients with benign prostatic hyperplasia.

BACKGROUND: Prostatic hyperplasia is frequent in the elderly, and it can be associated with urinary retention in patients who use cholinergic antagonists. The objective was to estimate the anticholinergic burden of drugs prescribed to patients diagnosed with benign prostatic hyperplasia. METHODS: A cross-sectional study using a population database to identify prescriptions of cholinergic antagonists drugs used in the management of benign prostatic hyperplasia. The anticholinergic burden was evaluated using the Anticholinergic Drug Scale. RESULTS: Three thousand seven hundred and sixty patients with benign prostatic hyperplasia were identified, with a mean age of 68.26 ± 10.46 years. Of these patients, 2961 (78.8%) received pharmacological treatment mainly with tamsulosin monotherapy (34.7%, n = 1026). Overall, 34.7% (n = 1303) of all patients were taking cholinergic antagonists. Patients aged 75-84 years (OR: 1.985, 95%CI: 1.063-3.709) and those 85 or older (OR: 2.52, 95%CI: 1.287-4.948) had a greater probability of having an anticholinergic burden score ≥3 points. Of the patients not receiving pharmacological treatment for benign prostatic hyperplasia, 35% (n = 280) were taking medications with anticholinergic properties. CONCLUSIONS: A high proportion of patients with benign prostatic hyperplasia were receiving medical management for the relief of symptoms, mostly via monotherapy. However, one-third of patients received some type of medication with anticholinergic properties, being much more frequent after 75 years.

Potentially Inappropriate Prescriptions for Anticholinergic Medications for Patients with Constipation.

INTRODUCTION: Constipation is a very common functional gastrointestinal disorder in the general population and can be primary or secondary. OBJECTIVE: The aim of this study was to estimate the anticholinergic burden of prescribed drugs in a population diagnosed with constipation in Colombia. METHODS: This was a cross-sectional study that used a population database of 6.5 million people to identify the prescription of cholinergic antagonists and drugs for the management of constipation in outpatient services. The anticholinergic burden was evaluated using the Anticholinergic Drug Scale. Potentially inappropriate prescriptions that increased the risk of constipation were identified. RESULTS: A total of 3,887 patients with constipation were identified; the identified patients had a mean age of 54.4 ± 21.9 years, and 69.4% were women. Eighty percent received at least one laxative, and the most prescribed laxative was bisacodyl (50.5%). Forty-one percent (n = 1,586) of all patients received drugs with cholinergic antagonist activity, in particular codeine (6.5%) and valproic acid (6.5%). Being over 30 years of age (odds ratio [OR]: 1.79; 95% confidence interval [CI]: 1.24-2.57), being treated in the cities of Manizales (OR: 2.20; 95% CI: 1.50-3.21) and Pereira (OR: 1.49; 95% CI: 1.07-2.09), and having hypothyroidism as a comorbidity (OR: 1.37; 95% CI: 1.08-1.73) were associated with a greater probability of receiving medications with an anticholinergic burden of 3 or more points. CONCLUSIONS: The majority of patients with constipation were women and were using laxatives to manage constipation. A large proportion of patients were prescribed at least one cholinergic antagonist drug, with an increased probability of use after 30 years of age.

Functional basis for dose-dependent antagonism of rat and rabbit neuromuscular transmission by the bis-pyridinium oxime MMB4.

Organophosphorus (OP) compounds inhibit central and peripheral acetylcholinesterase (AChE) activity, overstimulating cholinergic receptors and causing autonomic dysfunction (e.g., bronchoconstriction, excess secretions), respiratory impairment, seizure and death at high doses. Current treatment for OP poisoning in the United States includes reactivation of OP-inhibited AChE by the pyridinium oxime 2-pyridine aldoxime (2-PAM). However, 2-PAM has a narrow therapeutic index and its efficacy is confined to a limited number of OP agents. The bis-pyridinium oxime MMB4, which is a more potent reactivator than 2-PAM with improved pharmaceutical properties and therapeutic range, is under consideration as a potential replacement for 2-PAM. Similar to other pyridinium oximes, high doses of MMB4 lead to off-target effects culminating in respiratory depression and death. To understand the toxic mechanisms contributing to respiratory depression, we evaluated the effects of MMB4 (0.25-16 mM) on functional and neurophysiological parameters of diaphragm and limb muscle function in rabbits and rats. In both species, MMB4 depressed nerve-elicited muscle contraction by blocking muscle endplate nicotinic receptor currents while simultaneously prolonging endplate potentials by inhibiting AChE. MMB4 increased quantal content, endplate potential rundown and tetanic fade during high frequency stimulation in rat but not rabbit muscles, suggesting species-specific effects on feedback mechanisms involved in sustaining neurotransmission. These data reveal multifactorial effects of MMB4 on cholinergic neurotransmission, with the primary toxic modality being reduced muscle nicotinic endplate currents. Evidence of species-specific effects on neuromuscular function illustrates the importance of comparative toxicology when studying pyridinium oximes and, by inference, other quaternary ammonium compounds.

Bencycloquidium bromide nasal spray is effective and safe for persistent allergic rhinitis: a phase III, multicenter, randomized, double-blinded, placebo-controlled clinical trial.

PURPOSE: To investigate the efficacy and safety of bencycloquidium bromide nasal spray (BCQB) in patients with persistent allergic rhinitis (PAR). METHODS: We enrolled 720 patients from 15 hospitals across China and randomly assigned them into BCQB group or placebo group (90 µg per nostril qid) to receive a 4-week treatment. Visual analog scale (VAS) for rhinorrhea, sneezing, nasal congestion, itching and overall symptoms were recorded by patients every day. Anterior rhinoscopy scoring was completed by doctors on every visit. Adverse events were recorded in detail. RESULTS: A total of 354 and 351 patients were included in BCQB group and in placebo group. Baseline information was comparable. At the end of the trial, the decrease of VAS for rhinorrhea from baseline was 4.83 ± 2.35 and 2.46 ± 2.34 in BCQB group and placebo group, respectively (P < 0.001). The change ratio from baseline of VAS for rhinorrhea in BCQB group was 72.32%, higher than 31.03% in placebo group (P < 0.001). VAS for other symptoms and overall symptoms also improved significantly in the BCQB group, while no inter-group difference was found in anterior rhinoscopy scoring. The incidence of adverse reaction was similar between the two groups. Most reactions were mild and no severe reactions happened. CONCLUSION: 90 µg BCQB per nostril four times daily is effective and safe in the treatment of rhinorrhea as well as sneezing, nasal congestion and itching for patients with PAR. RETROSPECTIVELY REGISTERED: ChiCTR2000030924, 2020/3/17.

Potentially inappropriate prescriptions of anticholinergic medications in patients with closed-angle glaucoma.

PURPOSE: Glaucoma is the leading cause for blindness after cataracts worldwide. The aim was to identify anticholinergic drugs prescribed to patients diagnosed with closed-angle glaucoma in Colombia. METHODS: This cross-sectional study identified the prescribing patterns of cholinergic antagonists related to the increased intraocular pressure in patients diagnosed with closed-angle glaucoma from a Colombian database. The Anticholinergic Drug Scale was used to quantify the anticholinergic burden. RESULTS: We identified 1958 patients with closed-angle glaucoma, with a mean age of 70.5 ± 10.3 years, 72.9% of whom were women. Cholinergic antagonists were prescribed in at least 32.4% of cases. An age range between 75 and 84 years (odds ratio (OR) 2.35, 95% confidence interval (CI) 1.366-4.059) and being aged 85 years or older (OR 3.40, 95% CI 1.809-6.425) were associated with a greater probability of receiving an anticholinergic burden between 1 and 2 points. Females (OR 1.54, 95% CI 1.096-2.181) had a higher probability of receiving an anticholinergic burden ≥ 3 points. Interactions between antiglaucoma medications and anticholinergic treatments were identified in 32.1% of the patients. CONCLUSIONS: Most patients were prescribed multiple antiglaucoma medications, reflecting a large number of potentially inappropriate prescriptions, with anticholinergic drugs, related to the increased intraocular pressure.