The cumulative effect of taking multiple medicines with anticholinergic properties termed as anticholinergic burden can adversely impact cognition, physical function and increase the risk of mortality. Expert opinion derived risk scales are routinely used in research and clinical practice to quantify anticholinergic burden. These scales rank the anticholinergic activity of medicines into four categories, ranging from no anticholinergic activity (= 0) to definite/high anticholinergic activity (= 3). The aim of this systematic review was to compare anticholinergic burden quantified by the anticholinergic risk scales and evaluate associations with adverse outcomes in older people. We conducted a literature search in Ovid MEDLINE, EMBASE and PsycINFO from 1984-2014 to identify expert opinion derived anticholinergic risk scales. In addition to this, a citation analysis was performed in Web of Science and Google Scholar to track prospective citing of references of selected articles for assessment of individual scales for adverse anticholinergic outcomes. The primary outcomes of interest were functional and cognitive outcomes associated with anticholinergic burden in older people. The critical appraisals of the included studies were performed by two independent reviewers and the data were extracted onto standardised forms. The primary electronic literature search identified a total of 1250 records in the 3 different databases. On the basis of full-text analysis, we identified 7 expert-based anticholinergic rating scales that met the inclusion criteria. The rating of anticholinergic activity for medicines among these rating scales was inconsistent. For example, quetiapine was rated as having high anticholinergic activity in one scale (n = 1), moderate in another scale (n = 1) and low in two other scales (n = 2). Citation analysis of the individual scales showed that the Anticholinergic Cognitive Burden (ACB) scale was the most frequently validated expert based anticholinergic scale for adverse outcomes (N = 13). In conclusion, there is not one standardised tool for measuring anticholinergic burden. Cohort studies have shown that higher anticholinergic burden is associated with negative brain effects, poorer cognitive and functional outcomes.

The study of the magnitude and variation of drug response is defined as pharmacodynamics (PDs). PD models examine plasma concentration and effect relationship. It can predict the archetypal effect ([Formula: see text]) of a drug as a function of the drug concentration ([Formula: see text]) and estimate an unknown PD parameter ([Formula: see text]). The PD models have been described as fixed, linear, log-linear, [Formula: see text], sigmoid [Formula: see text], and indirect PD response. Ligand binding model is an example of a PD model that works on the underpinning PD principle of a drug, eliciting its pharmacological effect at the receptor site. The pharmacological effect is produced by the drug binding to the receptor to either activate or antagonise the receptor. Ligand binding models describe a system of interacting components, i.e. the interaction of one or more ligands with one or more binding sites. The [Formula: see text] model is the central method that provides an empirical justification for the concentration/dose-effect relationship. However, for ligand binding models justification is provided by theory of receptor occupancy. In essence, for ligand binding models, the term [Formula: see text] is best used to describe the fraction of receptors occupied at a particular ligand concentration. It is stated that the [Formula: see text], which means the effect of a drug should depend on the fraction of receptors that are occupied. In the future, network-based systems pharmacology models using ligand binding principles could be an effective way of understanding drug-related adverse effects. This will facilitate and strengthen the development of rational drug therapy in clinical practice.

Introduction: Anticholinergics are a class of medicines that block the neurotransmitter, acetylcholine, in the brain and peripheral tissues. Medicines with anticholinergic activity are widely prescribed for and used by older people for various medical conditions. One-third to one-half of the medicines commonly prescribed for older people have anticholinergic activity. Several studies have reported anticholinergic burden to be a predictor of cognitive and functional impairments in older people.Areas covered: This article exemplifies the theoretical and clinical aspects of medicines with anticholinergic activity, including pharmacology (definition of medicines that possess anticholinergic activity, antimuscarinic receptors, therapeutic and adverse effects), epidemiology, measures and effects of cumulative anticholinergic burden in older adults, and clinical recommendations. In addition, the gaps in the literature have been identified for future research.Expert opinion: Many medicines that are common...

Background: Polypharmacy and hyperpolypharmacy are proxy indicators for inappropriate medicine use. Inappropriate medicine use in older people leads to adverse clinical outcomes. Objective: The objectives of this study were to investigate the prevalence and trends of polypharmacy and hyperpolypharmacy in older people in New Zealand from 2005 to 2013, analyzing the pharmaceutical collections maintained by the Ministry of Health. Methods: A repeated cross-sectional analysis of population-level dispensing data was conducted from January 1, 2005 to December 31, 2013. Polypharmacy and hyperpolypharmacy in individuals were defined as the use of 5-9 medicines and ≥10 medicines, respectively, dispensed concurrently for a period of ≥90 days. Differences in polypharmacy and hyperpolypharmacy between 2005 and 2013 were examined. A multinomial regression model was used to predict sociodemographic characteristics associated with polypharmacy and hyperpolypharmacy. Results: Polypharmacy and hyperpolypharmacy were found to be higher in 2013 compared to 2005 (polypharmacy: 29.5 vs. 23.4%, p < 0.001; hyperpolypharmacy: 2.1 vs. 1.3%, p < 0.001). The risk of polypharmacy and hyperpolypharmacy was higher in females, in those aged 80-84 years, in the Māori population (for polypharmacy) and the Middle Eastern, Latin American, or African population (for hyperpolypharmacy), in people living in the Southern-district health board, and in individuals with increasing deprivation. Conclusion: The population of New Zealand is aging and the number of older people with multiple chronic conditions is increasing. The proportion of older people exposed to polypharmacy and hyperpolypharmacy has increased in 2013 compared to 2005. Our study provides important information to alert health policy makers, researchers, and clinicians about the dire need to reduce the medication burden in older New Zealanders.

This narrative review aims to provide an overview of the current literature on the pharmacology, safety, efficacy and tolerability of intranasal esketamine, the S-enantiomer of ketamine, for the treatment of treatment-resistant depression (TRD). A literature search using Medline, Embase, PsycINFO and Cochrane Central was conducted (January 2000 to July 2019). Product information and www.clinicaltrials.gov were also reviewed. The literature search was limited to human studies published in English. Phase I, II, and III studies of intranasal esketamine for TRD were reviewed. About a third of patients with major depressive disorder fail to achieve remission despite treatment with multiple antidepressants. This article examines the trials that led to the approval of esketamine in the United States, as well as other recent studies of esketamine for TRD. The findings from limited phase III trials illustrate that intranasal esketamine is effective and safe in reducing depressive symptoms and achieving clinical response in patients with TRD. The optimum duration and frequency of use are not fully understood. Although the nasal spray is a convenient dosage form, its use in practice may be limited by cost and administrative regulation. While it may prove beneficial to many patients who suffer from TRD, further long-term data are required, along with comparative trials with the R-isomer (arketamine). In the interim, care and monitoring should be exercised in its use in clinical practice. Plain language summary: Esketamine: new therapy for severe depression Intranasal esketamine, the S-enantiomer of ketamine, was recently approved in the United States for the treatment of treatment-resistant depression (TRD). The findings from limited clinical trials indicate that intranasal esketamine is effective and safe in patients with TRD, although the optimum dose, duration and frequency of use are not fully understood. Its use in practice may be limited by cost and administrative regulation, and further long-term data are required.