Anticholinergic Side Effects Research Articles

Increasing prevalence of anticholinergic medication use in older people in England over 20\u2009years: cognitive function and ageing study I and II

BackgroundAnticholinergic medication use is linked with increased cognitive decline, dementia, falls and mortality, and their use should be limited in older people. Here we estimate the prevalence of anticholinergic use in England’s older population in 1991 and 2011, and describe changes in use by participant’s age, sex, cognition and disability.MethodsWe compared data from participants aged 65+ years from the Cognitive Function and Ageing Studies (CFAS I and II), collected during 1990–1993 (N = 7635) and 2008–2011 (N = 7762). We estimated the prevalence of potent anticholinergic use (Anticholinergic Cognitive Burden [ACB] score = 3) and average anticholinergic burden (sum of ACB scores), using inverse probability weights standardised to the 2011 UK population. These were stratified by age, sex, Mini-Mental State Examination score, and activities of daily living (ADL) or instrumental ADL (IADL) disability.ResultsPrevalence of potent anticholinergic use increased from 5.7% (95% Confidence Interval [CI] 5.2–6.3%) of the older population in 1990–93 to 9.9% (9.3–10.7%) in 2008–11, adjusted odds ratio of 1.90 (95% CI 1.67–2.16). People with clinically significant cognitive impairment (MMSE [Mini Mental State Examination] 21 or less) were the heaviest users of potent anticholinergics in CFAS II (16.5% [95% CI 12.0–22.3%]). Large increases in the prevalence of the use medication with ‘any’ anticholinergic activity were seen in older people with clinically significant cognitive impairment (53.3% in CFAS I to 71.5% in CFAS II).ConclusionsUse of potent anticholinergic medications nearly doubled in England’s older population over 20 years with some of the greatest increases amongst those particularly vulnerable to anticholinergic side-effects.

Maintenance Electroconvulsive Therapy Meeting Unmet Needs of Antipsychotics in Older Patients: A Case Report

This case report highlights problems encountered by psychiatrists when treating a 68-year-old female patient who presented with a first episode of psychosis. She suffered from constipation, an anticholinergic side effect of quetiapine and both anticholinergic and extrapyramidal side effects of olanzapine. Finally, she was able to tolerate a combination of two pharmacologically different antipsychotics namely olanzapine and aripiprazole combined with a course of ECT followed by maintenance ECT. The authors would like to highlight maintenance ECT as part of the solution to patients who find it difficult to tolerate antipsychotics. Especially when only low doses of antipsychotics can be tolerated by the patient.

Obsessive-Compulsive Disorder in Older Adults: A Comprehensive Literature Review.

We reviewed English-language articles concerning obsessive-compulsive disorder (OCD) in older adults. PubMed was searched using key words that included obsessive-compulsive disorder, geriatric, elderly, aging, and older. Of the 644 articles identified, we included 78 that were relevant to the topic. Articles that were excluded as irrelevant included studies that were not focused on OCD in older adults, animal studies, and older case reports if we identified similar more recent case reports. The literature contains very little information about the epidemiology, diagnosis, psychopathology, and treatment of OCD in older adults. Even though the diagnostic criteria for OCD are the same for older and younger adults, different manifestations and progression in older patients have been reported. While the domains and severity of symptoms of OCD do not change with age, pathologic doubt may worsen. The Yale-Brown Obsessive Compulsive Scale is used for diagnosing and evaluating illness severity, and the Obsessive-Compulsive Inventory-Revised is another valuable tool for use in older adults. Psychotherapy, specifically exposure and response prevention, is the first-line treatment for OCD because of minimal adverse effects and reported benefit. Although the US Food and Drug Administration has not approved any medications specifically for OCD in older adults, pharmacotherapy is a consideration if psychotherapy is not successful. Selective serotonin reuptake inhibitors have the fewest side effects, while the cardiovascular and anticholinergic side effects of tricyclic antidepressants are especially worrisome in older adults. OCD in older adults has received little attention, and further studies are needed.

Unusual Cause of Transient Unilateral Fixed Dilated Pupil in Infant with Bronchiolitis: A Case Report

Background: Unilateral anisocoria has a variety of causes, some of which could be life-threatening. Mydriasis can represent a serious neurological finding in intensive care units. Bronchiolitis is the most common cause of intensive care in the infancy period. Ipratropium bromide is anticholinergic and commonly used in the intensive care unit (ICU). Anisocoria is due to the overactivation of the sympathetic nervous system or hypoactivity of the parasympathetic nervous system. Objectives: Assessment of cases of anisocoria in infants with bronchiolitis under ipratropium bromide therapy. Patient and methods: A case report study of a 9-month-old infant with a fixed dilated pupil. He was admitted into the ICU and given ipratropium bromide. Results: Ultimately, the patient’s symptoms of pupillary dilation resolved over 24 hours with the discontinuation of ipratropium bromide, with a complete recovery. The case presented here is typical of anticholinergic side effects, and the evidence of this benefit is even more limited, which might lead to frustrating observations among patients and health care providers. Conclusion: Anisocoria is not an uncommon finding in patients receiving ipratropium bromide. Paediatricians should follow the Saudi Bronchiolitis Guideline recently published in 2018, in which no indication of ipratropium bromide in bronchiolitis was clearly stated.

Development and clinical success of novel soft drugs

Retrometabolic drug design combines the structure-activity and structure-metabolism relationships, allowing the effective separation of drug action and side effects. This combination results in significant improvement of the therapeutic index. The main aim is not only to study the metabolism but to build into the drug molecule the desired metabolic route, in addition to the therapeutic activity. There are two basically different approaches to achieve this aim. Both use designed-in metabolism. The 1. chemical drug-targeting systems (CDS) and 2. soft drug, both control the drug targeting and action by strategically designed metabolism. In the case of the soft drugs, we want to rely on hydrolytic enzymes, avoiding the oxidative processes. In the present work, we focus on the clinical successes of the soft drugs designed in our laboratories. In order to show the difference, we briefly present a brain-targeted delivery system, where the originally inactive molecular construct undergoes sequential metabolism to allow specific concentration of the active drug in the brain. Among the soft drugs first we present the highly successful soft corticosteroids. Loteprednol etabonate has been used worldwide for over twenty years, and its use is constantly growing. In addition to the dramatically improved therapeutic index, the specific, serious ophthalmic side effects (elevation of intraocular pressure; glaucoma and cataract formation) were completely eliminated. Similarly designed second generation of soft corticosteroids are also presented, where the soft pharmacophore is structurally unexpected. The most recent soft drug design involves anticholinergics. Sofpironium bromide, a highly effective molecule but without the typical anticholinergic side effects, was first developed to treat hyperhidrosis, an unmet need. Phase III clinical studies were successfully completed and its marketing approval is pending. Since the soft drug design principles, methods and rules are general and specific in nature, a computerized expert system was also developed. Orv Hetil. 2020; 161(10): 363-373.

The effects of botulinum toxin injection on urodynamic changes in pediatric population with neurospastic bladder: First trial in Iran

BackgroundNeurogenic bladder is one of the serious, disturbing problems referred to pediatric urologic clinics. The increase in bladder pressure may damage the upper urinary tract. Anticholinergic medications have been used as the first line of complementary treatment. Regardless can be omitted, botulinum toxin (BT) was introduced as an alternative method for increasing bladder compliance. BT is a neurotoxic poison that can interfere with acetylcholine release, leading to reduced external sphincter pressure and detrusor activity. This study was established to assess urodynamic changes following BT injection among Iranian pediatric population, for the first time. MethodsThis clinical trial was conducted at Shahid Beheshti University of Medical Sciences (SBUM), Tehran, Iran, from November 2018 to January 2019 as a medical graduation dissertation. Twenty patients, previously as followings with a neurogenic bladder who met the eligibility criteria, underwent BT injection with general anesthesia using a rigid cystoscope and an endoscopic needle. Demographic data, history of anticholinergic consumption, side effects or intolerance, and the dosage of the injected BT were all recorded. The urodynamic variables during our study included: flow rate in second two, the flow time of diuresis, time of peak flow, average flow, discharged volume, maximum detrusor muscle filling pressure, maximum flow, acceleration, post-void residual volume, compliance, and cystometric bladder capacity. SPSS software version 22 was used to analyze data. The significance level was considered less than 0.05. ResultsTwenty patients who did not respond to anticholinergic medications or could not tolerate the side effects were entered the study. The mean age was 7.7 ± 2.02 years (range 5–13), and 13 (65%) of them were male. All patients received anticholinergic medications before BT injection. Discharge volume and maximum detrusor muscle filling pressure showed the most significant changes after injection (p < 0.005). However, there was no significant effect of the baseline characteristics on post-injection improvement in urodynamic results (p > 0.05). ConclusionIn this study, maximum detrusor filling pressure and discharge volume were both significantly improved. These findings motivate additional studies towards selecting better indexes for defining the clinical improvement and its relation with specific urodynamic results. Level of EvidenceTreatment study, level III.

Relationship between Lower Urinary Tract Dysfunction and Dementia.

Lower urinary tract dysfunction (LUTD) is a common health challenge in dementia patients with significant morbidity and socioeconomic burden. It often causes lower urinary tract (LUT) symptoms, restricts activities of daily life, and impairs quality of life. Among several LUT symptoms, urinary incontinence (UI) is the most prominent storage symptom in the later stages of dementia. UI in patients with dementia results not only from cognitive impairment, but also from urological defects such as detrusor overactivity. Management of LUTD in patients with dementia is based on multiple factors, including cognitive state, functional impairment, concurrent comorbidities, polypharmacy and urologic condition. Behavioral therapy under caregiver support represents appropriate treatment strategy for UI in these patients. Pharmacological treatment can be considered in patients refractory to behavioral therapy, but it is more effective when combined with behavioral therapy. Antimuscarinics and mirabegron, a beta-3 receptor agonist, are effective for managing storage symptoms involving the LUT. However, anticholinergic side effects in elderly subjects are a concern, particularly when there is a risk of exacerbating cognitive impairment with prolonged use of antimuscarinics. Proper recognition and treatment of LUTD in dementia can improve quality of life in these patients.

310 IV Cetirizine Versus IV Diphenhydramine in Treatment of Acute Urticaria

Acute urticaria, the most common symptom of acute allergic reactions, is a frequent presentation in the emergency department (ED). Diphenhydramine injection, the only available antihistamine injection, is sedating, short in duration with anticholinergic side effects. Cetirizine injection 10 mg/mL, a recent innovation in antihistamine pharmacology, may minimize these problems. A multicenter phase III randomized trial was conducted, in which a newly developed IV cetirizine was compared to IV diphenhydramine in treatment of acute urticaria. Adult subjects who presented to 19 EDs and urgent care centers (UCCs) with acute urticaria requiring IV antihistamine injections were randomized to either IV cetirizine 10 mg or IV diphenhydramine 50 mg. Primary endpoint was the 2-h pruritus score change from baseline, using a previously validated scoring scale. Key secondary endpoints were time spent in treatment center and need to return to ED/clinic. Patient sedation was scored at 1 h, 2 h, and discharge. Other secondary endpoints (rescue drugs, symptom recurrence, etc) were also measured. Adult subjects (n=262) were enrolled from March 2017 to April 2018. The 2-hour pruritus score change from baseline from IV cetirizine was demonstrated to be statistically non-inferior to IV diphenhydramine (change from baseline in diphenhydramine group, -1.50 (SD 0.984); change from baseline in cetirizine group, -1.61 (SD 0.944); p=NS). Time spent in treatment center was 2.1 h in the diphenhydramine group vs 1.7 h in the cetirizine group (p=0.0024). Return to ED/Clinic was 14.0% in the diphenhydramine group and 5.5% in the cetirizine group (p=0.0232). There was significantly less sedation in the cetirizine group at 1h (p=0.0034), 2 h (p=0.0292), and at discharge (p=0.0443) compared to diphenhydramine. There were significantly fewer adverse events (p=0.0083) and fewer rescue drug usages (p=0.0159) reported in subjects treated with cetirizine compared to diphenhydramine. This study demonstrates IV cetirizine as an effective alternative to IV diphenhydramine in the treatment of acute urticaria with less sedation, fewer adverse events, less symptom recurrence, less rescue drug use, shorter time to discharge and lower readmission to EDs and UCCs.

3116 Dilated Rectum in Psychotic Patient—Stercoral Colitis Causing Complications

INTRODUCTION: Constipation is common finding in hospitalized patient from nursing home, psychiatry unit or hospice facility. Assessment of abdominal symptoms in patient with psychiatric illness is challenging. Their medication compliance and lifestyle modification are not optimal due to limited insight. We present such case with constipation ended up with complicated hospital stay. CASE DESCRIPTION/METHODS: 71-year-old male who is sent from inpatient psychiatry hospital for abdominal distention and an episode of bilious vomiting. His caregiver has notified patient has inadequate oral intake from last 2 weeks. His past medical history includes schizophrenia, hypothyroidism, gastroesophageal reflux disease, status post cholecystectomy, benign prostate hyperplasia and chronic constipation. Prior to admission he is on laxatives polyethylene glycol, senna and docusate but he is not taking regularly. Abdominal CT scan with IV without oral contrast revealed extensive stool burden with severely distended rectum 9.4 cm diameter (Figure 1), stercoral colitis, small intestinal focalization, esophageal thickening suspected esophagitis. Patient is required nasogastric tube placement, manual fecal disimpection, frequent enemas, multiple laxatives to improve constipation. His hospital stay is prolonged and further complicated with acute blood loss anemia due to upper gastrointestinal bleeding. EGD revealed reflux esophagitis, erosive gastropathy likely caused by vomiting, urinary retention secondary to constipation and concern of aspiration. Psychiatry evaluation is sought to adjust antipsychotic medication to help lessen constipation as side effect. DISCUSSION: There is substantial risk of gastrointestinal hypomotility in patient receiving first generation or atypical antipsychotics. Most of the antipsychotic medications have anticholinergic side effect leading to constipation. Other psychosocial factors that can contribute are limited water consumption, lack of physical activity, inexpressive to thirst or abdominal symptoms, labile mood hampering medication compliance. Such patients are likely to have higher rate of hospitalization and complications like reflux esophagitis, urinary retention, aspiration, risk of perforation or gastrointestinal bleeding like in this patient. Vigilant bowel movement record and early initiation of constipation treatment at living facility is important in such patients.

Feasibility of Self-administered Neuromodulation for Neurogenic Bladder in Spinal Cord Injury.

PurposeTo determine if self-administered transcutaneous tibial nerve stimulation (TTNS) is a feasible treatment option for neurogenic bladder among people with spinal cord injury (SCI) who utilize intermittent catheterization for bladder management.MethodsFour-week observational trial in chronic SCI subjects performing intermittent catheterization with incontinence episodes using TTNS at home daily for 30 minutes. Those using anticholinergic bladder medications were given a weaning schedule to begin at week 2. Primary outcomes were compliance and satisfaction. Secondary outcomes included change in bladder medications, efficacy based on bladder diary, adverse events, and incontinence quality of life (I-QoL) survey.ResultsAll 16 subjects who started the study completed the 4-week trial rating TTNS with high satisfaction and easy to use, without discomfort. Twelve of 14 patients (86%) using anticholinergic bladder medications reduced their dosage and maintained similar frequency and volumes of bladder catheterization and incontinence episodes. Bladder medication reduced by approximately 3.2 mg weekly (95% confidence interval, -5.9 to -0.4) and anticholinergic side effects of dry mouth and drowsiness decreased more than 1 level of severity from baseline (P=0.027, P=0.015, respectively). At 4 weeks, total I-QoL score improved by an average of 3.2 points compared to baseline in all domains.ConclusionsThis pilot trial suggests TTNS is feasible to be performed at home in people with chronic SCI. Participants were able to reduce anticholinergic medication dosage and anticholinergic side effects while maintaining continence, subsequently improving QoL scores. These results advocate for further randomized, controlled trials with longer duration and urodynamic evaluation to assess long-term efficacy.

Systemic infection and microglia activation: a prospective postmortem study in sepsis patients

BackgroundSystemic infection is associated with long-term cognitive deficits and functional decline. In this study we hypothesized that severe systemic inflammation leads to a neuroinflammatory response that is characterized by microglial activation, and that these effects might be more pronounced in patients using medication with anticholinergic side-effects.MethodsBased on the results of a pilot study in 8 patients, we assessed the number of MHC-II and CD-68 positive cells by immunohistochemistry and compared the number of microglia in specific brain regions of 16 well-characterized patients with septic shock and 15 controls.ResultsIn the pilot study, patients with sepsis tended to have higher density of MHC-II and CD-68 positive microglia in the basal ganglia (putamen, caudate nucleus and globus pallidus) and of MHC-II positive microglia in the hippocampus. In the validation study, patients with sepsis had a significantly higher number of CD-68 positive cells in hippocampus (1.5 fold; p = 0.012), putamen (2.2 fold; p = 0.008) and cerebellum (2.5 fold; p = 0.011) than control patients. The density of MHC-II positive microglia was similar between sepsis and control groups. There was no consistent correlation between microglia counts and anti-cholinergic activity drugs score.ConclusionIn patients who die during septic shock, severe systemic inflammation is accompanied by localized and strong upregulation of CD-68 positive microglia, but not of MHC-II positive microglia. We identified regional differences in the brain with increased microglial activation in putamen, hippocampus and cerebellum.

Claims Data Analysis on the Dispensing of Tricyclic Antidepressants Among Patients With Dementia in Germany.

Objective: A restrictive use of tricyclic antidepressants (TCA) in patients with dementia (PwD) is recommended due to the hazard of anticholinergic side effects. We evaluated the frequency of TCA dispensing in PwD over a period of 1 year and the use of TCA before and after the incident diagnosis of dementia. Methods: This analysis was based on administrative data from a German statutory health insurance for a period of 2 years. Totally, 20,357 patients with an incident diagnosis of dementia in 2014 were included. We evaluated the dispensing of TCA in 2015. Subgroup analyses were conducted to evaluate associations between the incident diagnosis of dementia and modifications in TCA dispensing. Results: In 2015, 1,125 dementia patients (5.5%) were treated with TCA and 31% were medicated with TCA in all four quarters of 2015. Most dispensings were conducted by general practitioners (67.9%). On average, patients received 3.7 ± 2.6 dispensings per year. Amitriptyline (56.3%), doxepin (26.8%), and trimipramine (16.8%) were dispensed most often. Subgroup analyses revealed that the dispensing of TCA remained mainly unchanged following the incident diagnosis. Conclusion: A relevant number of PwD were treated with TCA. To maintain the patients’ safety, an improved implementation of guidelines for the pharmaceutical treatment of PwD in healthcare institutions might be required. Since 68% of the patients suffered from depression, future studies should further evaluate the indications for TCA.

Doxepin in difficult-to-treat chronic urticaria: A retrospective, cross-sectional study from Turkey.

Doxepin is an old tricyclic antidepressant, whose efficacy in chronic urticaria had been well documented until 1990. However, over the past three decades, there has been limited data on its use. We aimed to assess the efficacy and safety of doxepin in the treatment of patients with chronic urticaria who were poorly responsive to antihistamines. In this retrospective, cross-sectional, single-center study from Turkey, data were examined from patients with chronic urticaria who had poor antihistamine responses and received doxepin therapy from 1998 to 2017. Patient data were analyzed with regard to the duration of the disease, age, sex, treatment outcomes using a weekly urticaria activity score (UAS7), and adverse effects of doxepin therapy. A reduction of ≥90% in UAS7 was defined as "complete response," 30-89% as "partial response" and <30% as "no significant response." Thirty-six patients were included in this study. Doxepin was effective in a majority (n = 27, 75%) of the patients with a short onset time. Sixteen patients (44.4%) showed a complete response. Mild sedative and anticholinergic side effects were well tolerated. Doxepin seems to be a reasonable, efficient, and affordable alternative for the treatment of chronic urticaria in patients who respond poorly to antihistamine therapy.

Treatment efficacy of tolterodine versus belladonna mixture in children with idiopathic overactive bladder

ObjectivesChildren with symptoms of urinary urgency, frequency and incontinence are common in the clinic. The aim of the present study was to compare the tolerability and efficacy of tolterodine, a...

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Developing an Appetite

SUCCESSFUL USE OF ELECTROCONVULSIVE THERAPY FOR THE TREATMENT OF NEUROPSYCHIATRIC MANIFESTATIONS OF DEMENTIA WITH LEWY BODIES

Introduction Dementia with Lewy bodies (DLB) is one of the most common neurodegenerative disorders. DLB is characterized by progressive cognitive decline, executive dysfunction, visual hallucinations, fluctuating cognition, and Parkinsonism. Up to 65% of patients with Lewy Body Dementia have depression. Psychiatrists frequently treat individuals with DLB given prominent neuropsychiatric manifestations, including depression, hallucinations, delusions, agitation, and fluctuating cognition. Individuals with DLB require a comprehensive but specific treatment approach given sensitivity to both antipsychotic medications and anticholinergic side effects of other medications. Electroconvulsive therapy (ECT) is often omitted from the treatment model for DLB because of limited evidence. We highlight the use of electroconvulsive therapy (ECT) in a case of DLB. Methods We provide a case report and literature review on the use of ECT for the treatment of DLB. A 67-year-old male veteran with depression, 10-year history of REM sleep behavior disorder, bradykinesia, three-year history of cognitive impairment, and visual hallucinations was admitted for depressed mood and disturbing visual hallucinations featuring a saw blade swinging around his head and somatic delusion of a water hose traversing his body. At night he moved to avoid being hit by the blade. His wife reported word-finding difficulty, memory problems, and having to manage their finances. Four years prior to presentation, he stopped working as a pastor due to inability to write sermons. On admission, his MOCA was 19/30 and QIDS was 22. Medication trials including paroxetine, sertraline, escitalopram, vilazodone, bupropion, mirtazapine, venlafaxine, quetiapine, aripiprazole, alprazolam, buspirone, and lorazepam failed to address his depression and hallucinations. Results Brain MRI was unremarkable, with mild microvascular ischemic changes in periventricular white matter. Iodine-123 dopamine transporter SPECT (DAT-scan) imaging showed abnormal uptake consistent with a Parkinsonian syndrome (supporting the diagnosis of DLB). Considering past medication failures, patient consented for an acute course of ECT. He received eight right unilateral (RUL) ultra-brief pulse treatments utilizing Mecta Spectrum over the course of three weeks without any major side effects. For muscle relaxation he received succinylcholine; methohexital and remifentanil were given for anesthesia. Over his acute course of treatment, charge was progressively increased from six, to eight, to ten times the seizure threshold. At the end of his acute course of eight ECT treatments, his MOCA improved from 19/30 to 23/30 and QIDS improved from 22 to 12. Following the course of ECT, his visual hallucinations disappeared, and he was more interactive, engaged, and less depressed. The patient's improvement is congruent with other case reports in the literature showing clinical improvement following ECT for symptoms related to DLB. A table with a literature review describing the use of ECT for DLB will be presented. Conclusions DLB presents frequently to psychiatrists secondary to prominent psychiatric manifestations of the illness such as mood and behavioral disturbances. The treatment of psychiatric symptoms in DLB is often challenging due to the sensitivity of antidopaminergic medications on motor symptoms. ECT is a feasible alternative to treat neuropsychiatric manifestations of DLB; however, infrequently considered due to fear of complications and stigma. Modifications to the treatment such us holding dopamine agonists the morning of ECT to avoid delirium, decreasing the frequency of ECT to twice per week to minimize cognitive effects, and close monitoring of the patient's cognitive function are measures that can be implemented to optimize ECT in this population. No double-blinded randomized control trials exist in this area; comparing standard treatment to ECT would help further delineate the role of ECT in treating patients with DLB. This research was funded by None.

Clinical guidance for the use of trazodone in major depressive disorder and concomitant conditions: pharmacology and clinical practice.

To provide a review of the clinically relevant evidence pertaining to the use of trazodone in major depressive disorder. Medline and Cochrane Library searches were searched using the keywords 'trazodone' AND 'depression', to identify the most relevant literature pertinent to the pharmacological properties of trazodone and its use in clinical practice. Articles that were selected included basic pharmacology papers, clinical trials, clinical practice guidelines, and reviews. Related references were cross checked. European and United States prescribing information was reviewed as well. An effort was made to give weight to the information that was most relevant for daily clinical practice. Trazodone is an antidepressant with a mechanism of action that remains innovative and with a favorable profile for the treatment of depression. The appropriate antidepressant doses are usually 150-300 mg/day and are often higher than the doses that are used when trazodone is prescribed to augment the antidepressant effect of another medication, for instance when trazodone is prescribed to address insomnia in a patient treated with an SSRI. Trazodone is usually well tolerated and has a low risk of anticholinergic side effects, weight gain and sexual side effects. Trazodone is an established medication that is efficacious for the treatment of a broad array of depressive symptoms, including symptoms that are less likely to respond to other antidepressants (e.g. SSRI), such as insomnia. As an antidepressant, trazodone has proven as efficacious as the tricyclic and second-generation antidepressants and is tolerated relatively well. Trazodone may be helpful for patients with major depression and comorbid insomnia, anxiety or psychomotor agitation. Trazodone is efficacious antidepressants with a relatively low risks of side effects such as weight gain, sexual or anticholinergic effects (such as constipation, urinary retention, dry mouth). In addition to being able to control a wide range of depressive symptoms, trazodone may improve sleep and be particularly helpful for patients whose symptoms of depression include insomnia.

Chapter 27 - Urological function and dysfunction in aging: Diagnosis and treatment

Urinary symptoms worsen further the quality of life of persons already burdened by neurologic disease. Urinary symptoms frequently occur in the setting of neurologic diseases such as Parkinson disease and Parkinson-plus syndromes, multiple sclerosis, and stroke. Urinary incontinence is associated with increased caregiver burden and enhances the risk of institutionalization among those living with dementia. Nocturia is associated with impaired sleep and work productivity. Providing patient-centered care for urinary symptoms involves assessing patient and family goals for care and incorporating a multicomponent assessment and treatment plan to align treatment options with the goals for care. Lifestyle and behavioral therapies are available as first-line treatment for most urinary symptoms. Consideration of drug therapy should aim to minimize the potential for adverse drug events such as orthostatic hypotension when using α blockers for men with concomitant prostate enlargement or anticholinergic side effects with anticholinergic bladder relaxant therapy. Interventional therapies such as percutaneous nerve stimulation, cystoscopic botulinum toxin injection, and sacral neuromodulation are available for patients who do not have significant urinary retention at baseline. Containment strategies aim to prevent skin irritation and provide support. With a patient-centered approach, providers empower patients to control and contain urinary symptoms and, thus, maintain confidence and social engagement.

Pharmacological characterization of DA-8010, a novel muscarinic receptor antagonist selective for urinary bladder over salivary gland

Several antimuscarinics have been commonly used for overactive bladder patients, but dry mouth as a major anticholinergic side effect remains a shortcoming to limit long-term use. The aim of this study was to elucidate the pharmacological properties of DA-8010, a novel muscarinic receptor antagonist selective for urinary bladder over salivary gland. DA-8010 exhibited a high binding affinity for human muscarinic M3 receptor with pKi of 8.81 ± 0.05 and great potencies for human M3 receptor and rat bladder preparation. The potency of DA-8010 for bladder smooth muscle cells was 3.6-fold higher than that for salivary gland cells isolated from mice. Intravenous administration of DA-8010 dose-dependently inhibited rhythmic urinary bladder contractions induced by distension in rats, indicating the most potent activity (ID30 = 0.08 mg/kg) among the antimuscarinics tested. Taken together with the inhibitory effects of DA-8010 and other antimuscarinics on carbachol-induced salivary secretion in rats, the in vivo functional selectivity of DA-8010 for urinary bladder over salivary gland was 3.1-fold, 3.2-fold and 5.2-fold greater than those observed for solifenacin, oxybutynin and darifenacin, respectively. Furthermore, oral administration of DA-8010 in mice resulted in more selective and persistent binding for muscarinic receptors in the bladder rather than in the submaxillary gland, in comparison with other antimuscarinics. These findings suggest that DA-8010 is a potent muscarinic M3 receptor antagonist to be highly selective for bladder over salivary gland, which might be a promising agent with greater efficacy and less dry mouth in the treatment of overactive bladder.

An anticholinergic burden score for German prescribers: score development

BackgroundAnticholinergic drugs put elderly patients at a higher risk for falls, cognitive decline, and delirium as well as peripheral adverse reactions like dry mouth or constipation. Prescribers are often unaware of the drug-based anticholinergic burden (ACB) of their patients. This study aimed to develop an anticholinergic burden score for drugs licensed in Germany to be used by clinicians at prescribing level.MethodsA systematic literature search in pubmed assessed previously published ACB tools. Quantitative grading scores were extracted, reduced to drugs available in Germany, and reevaluated by expert discussion. Drugs were scored as having no, weak, moderate, or strong anticholinergic effects. Further drugs were identified in clinical routine and included as well.ResultsThe literature search identified 692 different drugs, with 548 drugs available in Germany. After exclusion of drugs due to no systemic effect or scoring of drug combinations (n = 67) and evaluation of 26 additional identified drugs in clinical routine, 504 drugs were scored. Of those, 356 drugs were categorised as having no, 104 drugs were scored as weak, 18 as moderate and 29 as having strong anticholinergic effects.ConclusionsThe newly created ACB score for drugs authorized in Germany can be used in daily clinical practice to reduce potentially inappropriate medications for elderly patients. Further clinical studies investigating its effect on reducing anticholinergic side effects are necessary for validation.