[The Effect of Patient Age on Anticholinergic Use in the Elderly Japanese Population -Differences between Four Anticholinergic Scales].

We previously reported that anticholinergic (AC) drug use increases with age in the elderly Japanese population. In this analysis, we investigated attribution for each AC drug type to total AC burden using different elderly age groups. Prescription records (from 09/23/2015 to 12/31/2016) for outpatients using any AC were extracted from pharmacy claims (primary source) and hospital-based databases. AC burden (number of AC drugs and AC score) and AC type were assessed using the Anticholinergic Cognitive Burden (ACB) scale, Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and Beers criteria. Age was categorized using three subgroups (65-74, 75-84, and ≥85 years). Overall, 125426, 140634, 35628, and 23149 of the pharmacy outpatients received ≥1 AC drug from the ACB scale, ADS, ARS, or Beers criteria, respectively. The number of AC drugs increased with age for the ACB scale and ADS groups; but decreased for the ARS and Beers criteria. Antihypertensives provided the biggest contribution to AC score using the ACB scale and ADS, and antihistamines for the ARS. Proportional attribution to AC score typically increased with age for antihypertensives (ADS highest proportion: 34.6% for ≥85 years) and cardiac agents, but decreased for antihistamines (ARS lowest proportion: 15.3% for ≥85 years), corticosteroids, and antiepileptics. Similar findings were typically observed for the hospital database. In conclusion, antihypertensives were the principal type of AC drugs using the ACB scale and ADS and their attribution to AC score increased with age. Antihistamines were the principal drug type for the ARS.

How do cognitive and functional impairment relate to the use of anticholinergic medications in hospitalised patients aged 65 years and over?

BACKGROUND: Anticholinergic medications are commonly prescribed to older adults despite their unfavourable pharmacological profile. There are no specific systems in place to alert prescribers about the wide range of medications with anticholinergic properties and their cumulative potential. AIMS: To examine associations between medications with anticholinergic properties and cognitive and functional impairment in hospitalised patients aged 65 years and older. METHODS: This descriptive, cross-sectional study included 94 patients admitted to a rehabilitation ward and a geriatric evaluation and management unit. Anticholinergic burden was calculated using the Anticholinergic Risk Scale. The Addenbrooke's Cognitive Examination and the Elderly Symptom Assessment Scale tools were utilised to assess cognitive function and burden of anticholinergic symptoms, respectively. RESULTS: Medications with anticholinergic properties were taken by 72.3% of patients with level 1 being the most commonly consumed (median 1, IQR = 0-2) medications. There was no association between anticholinergic medication use and cognitive function or anticholinergic symptoms. Increasing age and the hospital length of stay were associated with fewer anticholinergic symptoms (p < 0.001 and p = 0.021, respectively), whereas the total number of medications consumed was linked to a greater burden of anticholinergic symptoms (p < 0.001). CONCLUSION: A lack of association between anticholinergic medications and cognitive function could be related to duration of exposure to this group of medications and the age sensitivity. Additionally, the total number of medications consumed by patients was linked to a greater burden of anticholinergic symptoms. These findings highlight the need for improved knowledge and attentiveness when prescribing medications in general in this vulnerable population.

Development of a Brazilian anticholinergic activity drug scale.

OBJECTIVE: To develop a scale of anticholinergic activity drugs used in Brazil, to be applied in health care and pharmacoepidemiology research. METHODS: We performed a literature review on PubMed/MEDLINE® to identify previously published scales of anticholinergic drugs. This scale started with anticholinergic drugs, and those with known anticholinergic activity as per the 4th level, chemical-therapeutic subgroup, of the Anatomical Therapeutic Chemical classification. We also included drugs with high anticholinergic activity, as described in a list of potentially inappropriate medications for use in older adults, according to the 2015 American Geriatrics Society Beers Criteria. Drugs listed in at least two anticholinergic scales were added. Then we verified which drugs in the previous steps were marketed in Brazil. We assigned a score of 1, 2 and 3, based on their anticholinergic action. RESULTS: A total of 273 anticholinergic drugs were identified, of which 125 were included in the scale. We identified 45 (36.0%) drugs with a score of 3, 13 (10.4%) with a score of 2, and 67 (53.6%) with a score of 1. Drugs for the nervous and respiratory systems were the most frequent in the scale. Eight drugs were not present in previous scales. CONCLUSION: The methodology used for development of the Brazilian anticholinergic activity scale is simple, systematized, reproducible and easy to update. The scale allows evaluating the impact of anticholinergic burden on health outcomes, and can potentially contribute to pharmacoepidemiology research, leading to more accurate measurements of anticholinergic activity.

Development of an Anticholinergic Burden Scale specific for Korean older adults.

AIM: The aim of this study was to develop the Korean Anticholinergic Burden Scale through assessment of previously developed tools, a literature review and a modified Delphi process. METHODS: We carried out a systematic review to identify previously published anticholinergic burden tools. A composite medication list was made by extracting medications and their quantitative grading from the existing tools, after excluding the medications not distributed in Korea and topical agents. We also added medications available in Korea that had not been rated. For medications with conflicting anticholinergic scores or no anticholinergic score, we determined the final score from 0 ("no anticholinergic effect") to 3 ("strong anticholinergic effect") with a literature review and expert consensus through a two-round Delphi process. RESULTS: A composite list of 655 medications with anticholinergic scores was extracted from 10 existing tools. A total of 38 medications available in Korea were added to the list. A total of 494 medications were deemed suitable for a Korean-specific scale. We confirmed the anticholinergic scores of 352 medications from existing scales, and 142 underwent the Delphi process. The final scores graded by experts showed high reliability among experts with an intra-class correlation of 0.98 (95% confidence interval 0.97-0.98). Finally, 56 medications were categorized as strong anticholinergics, 23 as moderate, 59 as weak and 356 as having no anticholinergic activity. CONCLUSIONS: This newly created consensus-driven anticholinergic burden scale designed specifically for the Korean healthcare system might be a practical tool for assessing anticholinergic burden in older adults with polypharmacy in routine medication reviews and in research. Geriatr Gerontol Int 2019; 19: 628-634.

The effect of overactive bladder treatment with anticholinergics on female sexual function in women: a prospective observational study.

PURPOSE: The aim of the study was to determine the effect of anticholinergics used for overactive bladder treatment on the sexual function of women. METHODS: Between January 2016 and August 2018, over 18 years old, 216 sexual active women with OAB and 165 healthy women as control group were prospectively enrolled in the study. Five different anticholinergics were used for the treatment. Female Sexual Function Index (FSFI), eight-item overactive bladder awareness tool (OAB-V8), and Beck Depression Inventory form were completed before and after 3 months. Baseline and post-treatment scores were compared with a control group of age-matched healthy women. RESULTS: Patients with OAB reported at baseline significantly worse sexual function in all FSFI domains compared to healthy control group (21.47 ± 3.22 vs. 26.79 ± 5.56, p < 0.01). Three months after treatment, over 85% of participants reported clinically relevant improvements in sexual function, with statistically significant changes in mean FSFI scores. CONCLUSIONS: Treatment of OAB with anticholinergics can improve sexual function of sexual active women with OAB. Patients may be informed about this potential benefit of anticholinergic treatment, to improve their sexual function.

Development of a Brazilian anticholinergic activity drug scale / Desenvolvimento de uma escala brasileira de medicamentos com atividade anticolinérgica

ABSTRACT Objective To develop a scale of anticholinergic activity drugs used in Brazil, to be applied in health care and pharmacoepidemiology research. Methods We performed a literature review on PubMed/MEDLINE® to identify previously published scales of anticholinergic drugs. This scale started with anticholinergic drugs, and those with known anticholinergic activity as per the 4th level, chemical-therapeutic subgroup, of the Anatomical Therapeutic Chemical classification. We also included drugs with high anticholinergic activity, as described in a list of potentially inappropriate medications for use in older adults, according to the 2015 American Geriatrics Society Beers Criteria. Drugs listed in at least two anticholinergic scales were added. Then we verified which drugs in the previous steps were marketed in Brazil. We assigned a score of 1, 2 and 3, based on their anticholinergic action. Results A total of 273 anticholinergic drugs were identified, of which 125 were included in the scale. We identified 45 (36.0%) drugs with a score of 3, 13 (10.4%) with a score of 2, and 67 (53.6%) with a score of 1. Drugs for the nervous and respiratory systems were the most frequent in the scale. Eight drugs were not present in previous scales. Conclusion The methodology used for development of the Brazilian anticholinergic activity scale is simple, systematized, reproducible and easy to update. The scale allows evaluating the impact of anticholinergic burden on health outcomes, and can potentially contribute to pharmacoepidemiology research, leading to more accurate measurements of anticholinergic activity.

RESUMO Objetivo Desenvolver uma escala de atividade anticolinérgica abrangendo os medicamentos utilizados no Brasil, para aplicação no cuidado em saúde e em pesquisas farmacoepidemiológicas. Métodos Realizou-se revisão da literatura no PubMed/MEDLINE®para identificação das escalas de mensuração da atividade anticolinérgica. Iniciou-se a escala com os fármacos anticolinérgicos e aqueles com atividade anticolinérgica conhecida, relacionados segundo o nível 4, subgrupo químico, na classificação da Anatomical Therapeutic Chemical . Incluíram-se os fármacos com atividade anticolinérgica alta, descritos na lista de medicamentos potencialmente inapropriados para idosos, segundo o 2015 American Geriatrics Society Beers Criteria . Adicionaram-se os medicamentos que constavam em, no mínimo, duas escalas anticolinérgicas. Em seguida, verificaram-se os medicamentos constantes nas etapas anteriores comercializados no Brasil. A magnitude da atividade anticolinérgica foi estabelecida em escores com os valores de 1, 2 e 3. Resultados Foram identificados 273 medicamentos com atividade anticolinérgica, sendo 125 incluídos na escala. Destes, 45 (36,0%) receberam pontuação 3, 13 (10,4%) tiveram pontuação 2, e 67 (53,6%) pontuação 1. A maioria dos medicamentos da escala atuava nos sistemas nervoso e respiratório. Oito fármacos não constavam em escalas prévias. Conclusão A metodologia de desenvolvimento da escala brasileira de atividade anticolinérgica é simples, sistematizada, reprodutível e de fácil atualização. A escala permite avaliar o impacto da carga anticolinérgica nos resultados em saúde e pode contribuir com as pesquisas farmacoepidemiológicas, propiciando mensurações mais exatas da atividade anticolinérgica.

Hyperhidrosis: Management Options.

Hyperhidrosis is excessive sweating that affects patients' quality of life, resulting in social and work impairment and emotional distress. Primary hyperhidrosis is bilaterally symmetric, focal, excessive sweating of the axillae, palms, soles, or craniofacial region not caused by other underlying conditions. Secondary hyperhidrosis may be focal or generalized, and is caused by an underlying medical condition or medication use. The Hyperhidrosis Disease Severity Scale is a validated survey used to grade the tolerability of sweating and its impact on quality of life. The score can be used to guide treatment. Topical aluminum chloride solution is the initial treatment in most cases of primary focal hyperhidrosis. Topical glycopyrrolate is first-line treatment for craniofacial sweating. Botulinum toxin injection (onabotulinumtoxinA) is considered first- or second-line treatment for axillary, palmar, plantar, or craniofacial hyperhidrosis. Iontophoresis should be considered for treating hyperhidrosis of the palms and soles. Oral anticholinergics are useful adjuncts in severe cases of hyperhidrosis when other treatments fail. Local microwave therapy is a newer treatment option for axillary hyperhidrosis. Local surgery and endoscopic thoracic sympathectomy should be considered in severe cases of hyperhidrosis that have not responded to topical or medical therapies.

Deprescribing anticholinergic and sedative medicines: protocol for a Feasibility Trial (DEFEAT-polypharmacy) in residential aged care facilities.

INTRODUCTION: Targeted deprescribing of anticholinergic and sedative medicines can lead to positive health outcomes in older people; as they have been associated with cognitive and physical functioning decline. This study will examine whether the proposed intervention is feasible at reducing the prescription of anticholinergic and sedative medicines in older people. METHODS AND ANALYSIS: The Standard Protocol Items: Recommendations for Interventional trials (SPIRIT checklist) was used to develop and report the protocol. Single group (precomparison and postcomparison) feasibility study design. STUDY POPULATION: 3 residential care homes have been recruited. INTERVENTION: This will involve a New Zealand registered pharmacist using peer-reviewed deprescribing guidelines, to recommend to general practitioners (GPs), sedative and anticholinergic medicines that can be deprescribed. The cumulative use of anticholinergic and sedative medicines for each participant will be quantified, using the Drug Burden Index (DBI). OUTCOMES: The primary outcome will be the change in the participants' DBI total and DBI PRN 3 and 6 months after implementing the deprescribing intervention. Secondary outcomes will include the number of recommendations taken up by the GP, participants' cognitive functioning, depression, quality of life, activities of daily living and number of falls. DATA COLLECTION POINTS: Participants' demographic and clinical data will be collected at the time of enrolment, along with the DBI. Outcome measures will be collected at the time of enrolment, 3 and 6 months' postenrolment. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Human Disability and Ethics Committee. Ethical approval number (16/NTA/61). TRIAL REGISTRATION NUMBER: Pre-results; ACTRN12616000721404.

Anticholinergic drugs and negative outcomes in the older population: from biological plausibility to clinical evidence.

The use of medication with anticholinergic properties is widespread among older subjects. Many drugs of common use such as antispasmodics, bronchodilators, antiarrhythmics, antihistamines, anti-hypertensive drugs, antiparkinson agents, skeletal muscle relaxants, and psychotropic drugs have been demonstrated to have an anticholinergic activity. The most frequent adverse effects are dry mouth, nausea, vomiting, constipation, abdominal pain, urinary retention, blurred vision, tachycardia and neurologic impairment such as confusion, agitation and coma. A growing evidence from experimental studies and clinical observations suggests that drugs with anticholinergic properties can cause physical and mental impairment in the elderly population. However, the morbidity and management issues associated with unwanted anticholinergic activity are underestimated and frequently overlooked. Moreover, their possible relation with specific negative outcome in the elderly population is still not firmly established. The aim of the present review was to evaluate the relationship between the use of drugs with anticholinergic activity and negative outcomes in older persons. We searched PubMed and Cochrane combining the search terms "anticholinergic", "delirium", "cognitive impairment", "falls", "mortality" and "discontinuation". Medicines with anticholinergic properties may increase the risks of functional and cognitive decline, morbidity, institutionalization and mortality in older people. However, such evidences are still not conclusive probably due to possible confounding factors. In particular, more studies are needed to investigate the effects of discontinuation of drug with anticholinergic properties. Overall, minimizing anticholinergic burden should always be encouraged in clinical practice to improve short-term memory, confusion and delirium, quality of life and daily functioning.

Systematic review of anticholinergic risk scales in older adults.

BACKGROUND: Anticholinergic drugs are often involved in explicit criteria for inappropriate prescribing in older adults. Several scales were developed for screening of anticholinergic drugs and estimation of the anticholinergic burden. However, variation exists in scale development, in the selection of anticholinergic drugs, and the evaluation of their anticholinergic load. This study aims to systematically review existing anticholinergic risk scales, and to develop a uniform list of anticholinergic drugs differentiating for anticholinergic potency. METHODS: We performed a systematic search in MEDLINE. Studies were included if provided (1) a finite list of anticholinergic drugs; (2) a grading score of anticholinergic potency and, (3) a validation in a clinical or experimental setting. We listed anticholinergic drugs for which there was agreement in the different scales. In case of discrepancies between scores we used a reputed reference source (Martindale: The Complete Drug Reference®) to take a final decision about the anticholinergic activity of the drug. RESULTS: We included seven risk scales, and evaluated 225 different drugs. Hundred drugs were listed as having clinically relevant anticholinergic properties (47 high potency and 53 low potency), to be included in screening software for anticholinergic burden. CONCLUSION: Considerable variation exists among anticholinergic risk scales, in terms of selection of specific drugs, as well as of grading of anticholinergic potency. Our selection of 100 drugs with clinically relevant anticholinergic properties needs to be supplemented with validated information on dosing and route of administration for a full estimation of the anticholinergic burden in poly-medicated older adults.

Effects of anticholinergic drugs on cognitive function in older Australians: results from the AIBL study.

BACKGROUND/AIMS: The nature and extent of adverse cognitive effects due to the prescription of anticholinergic drugs in older people with and without dementia is unclear. METHODS: We calculated the anticholinergic load (ACL) of medications taken by participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing, a cohort of 211 Alzheimer's disease (AD) patients, 133 mild cognitive impairment (MCI) patients and 768 healthy controls (HC) all aged over 60 years. The association between ACL and cognitive function was examined for each diagnostic group (HC, MCI, AD). RESULTS: A high ACL within the HC group was associated with significantly slower response speeds for the Stroop color and incongruent trials. No other significant relationships between ACL and cognition were noted. CONCLUSION: In this large cohort, prescribed anticholinergic drugs appeared to have modest effects upon psychomotor speed and executive function, but not on other areas of cognition in healthy older adults.

[Oral anticholinergics in overactive bladder]. / Orale Anticholinergika bei überaktiver Blase.

Behavioural therapy and anticholinergics are the mainstays in the treatment of symptoms of overactive bladder in patients with idiopathic and neurogenic detrusor overactivity; they are the first-line treatment. Oxybutynin, propiverine, tolterodine and trospium chloride as well as the "newcomers" solifenacin and darifenacin are comparable in regards to their efficacy. However, based on different pharmacokinetics and pharmacodynamics with different resorption velocity, different metabolisation and different CNS penetration, the profile of adverse events is different, qualitatively and quantitatively. Substances that are resorbed slowly or available as slow-release formulations are tolerated better. Lipophilic anticholinergics which pass the blood-brain barrier may compromise cognitive functions, especially in geriatric patients, who are already on cholinesterase inhibitors due to memory disorders. The following article gives an overview of the anticholinergics currently prescribed in patients with symptoms of overactive bladder with special attention to the influence of pharmacokinetics/pharmacodynamics on the adverse events profile including possible CNS side effects.

G-protein coupled receptors: SAR analyses of neurotransmitters and antagonists.

BACKGROUND: From the deductive point of view, neurotransmitter receptors can be divided into categories such as cholinergic (muscarinic, nicotinic), adrenergic (alpha- and beta-), dopaminergic, serotoninergic (5-HT1 approximately 5-HT5), and histaminergic (H1 and H2). Selective agonists and antagonists of each receptor subtype can have specific useful therapeutic applications. For understanding the molecular mechanisms of action, an inductive method of analysis is useful. OBJECTIVE: The aim of the present study is to examine the structure-activity relationships of agents acting on G-protein coupled receptors. METHOD: Representative sets of G-PCR agonists and antagonists were identified from the literature and Medline [P.M. Walsh (2003) Physicians' Desk Reference; M.J. O'Neil (2001) The Merck Index]. The molecular weight (MW), calculated logarithm of octanol/water partition coefficient (C log P) and molar refraction (CMR), dipole moment (DM), E(lumo) (the energy of the lowest unoccupied molecular orbital, a measure of the electron affinity of a molecule and its reactivity as an electrophile), E(homo) (the energy of the highest occupied molecular orbital, related to the ionization potential of a molecule, and its reactivity as a nucleophile), and the total number of hydrogen bonds (H(b)) (donors and receptors), were chosen as molecular descriptors for SAR analyses. RESULTS: The data suggest that not only do neurotransmitters share common structural features but their receptors belong to the same ensemble of G-protein coupled receptor with seven to eight transmembrane domains with their resultant dipoles in an antiparallel configuration. Moreover, the analysis indicates that the receptor exists in a dynamic equilibrium between the closed state and the open state. The energy needed to open the closed state is provided by the hydrolysis of GTP. A composite 3-D parameter frame setting of all the neurotransmitter agonists and antagonists are presented using MW, Hb and mu as independent variables. CONCLUSION: It appears that all neurotransmitters examined in this study operate by a similar mechanism with the G-protein coupled receptors.

Cold, cough, allergy, bronchodilator, and antiasthmatic drug products for over-the-counter human use; final monograph for combination drug products. Final rule.

The Food and Drug Administration (FDA) is issuing a final rule in the form of a final monograph that establishes conditions under which over-the-counter (OTC) cold, cough, allergy, bronchodilator, and antiasthmatic (cough-cold) combination drug products are generally recognized as safe and effective and not misbranded as part of its ongoing review of OTC drug products. FDA is issuing this final rule after considering public comments on the agency's proposed regulation (tentative final monograph) and new data and information on OTC cough- cold combination drug products that have come to the agency's attention.