Drugs with anticholinergic properties: a current perspective on use and safety

Introduction: Many commonly used drugs have primary or secondary anticholinergic effects contributing to adverse outcomes ranging from mild-to-severe to potentially lethal. Anticholinergic adverse effects frequently occur with medications prescribed with other intended mechanisms of action, including antihistamines, antidepressants, and antipsychotics. Anticholinergic drugs are also the principal treatments of clinical conditions, such as urinary incontinence, that tend to occur in the elderly. Older patients and those with mental illness are particularly vulnerable to the adverse neuropsychiatric effects of anticholinergics as they may already have cognitive impairment.

Areas covered: Medline and Pubmed literature searches (1966 – the present) were performed using ‘anticholinergic’ and ‘drug safety’. Abstracts were assessed and references scanned for appropriate articles. Here, the authors i) describe the neural pathways of the cholinergic system; ii) outline the main clinical uses and adverse effects of anticholinergic agents with a focus on cognitive impairment; and iii) discuss anticholinergic safety monitoring.

Expert opinion: Prescribers need to be vigilant for adverse anticholinergic effects, particularly in older patients. The symptoms may range from subtle cognitive impairment to delirium and may be due to the cumulative effect of multiple medications of modest antimuscarinic activity. The Anticholinergic Drug Scale and tables listing drugs with known anticholinergic properties may help in guiding clinical decision-making to reduce anticholinergic burden.     

Nonsteroidal Anti-inflammatory Drugs Utilization Patterns and Risk of Adverse Events due to Drug-Drug Interactions among Elderly Patients: A Study from Jordan

BackgroundWorldwide, the prescribing pattern of the Nonsteroidal Anti-inflammatory Drugs (NSAIDs) has increased. They are considered highly effective medications in controlling various conditions including inflammatory diseases. They are associated with various adverse effects including gastrointestinal bleeding and ulcer and renal toxicity though. These adverse effects are generally potentiated when NSAIDs are co-prescribed with other drugs that share similar adverse effects and toxicities. Developing severe side effects from NSAIDs is more prone among elderly patients. Hence, it is crucial to evaluate prescribing pattern of these agents to prevent/decrease the number of unwanted side effects caused by NSAIDs.AimThe aim of this study is to assess the prescribing pattern of NSAIDs among elderly and the co-prescribing of NSAIDs and different interacting drugs, which could lead to more incidences of NSAIDs-induced toxicities among Jordanian elderly patients.Settings and MethodologyA multicenter retrospective study was performed during a three months period in Jordan. The study involves a total number of (n = 5916) elderly patient’s records obtained from Four governmental hospitals in Jordan.ResultsA total number of (n = 20450) drugs were prescribed and dispensed for patient. NSAIDs drugs prescribing percentage was 10.3% of total medications number. Aspirin was the most commonly prescribed NSAIDs among patients (70.4%), followed by Diclofenac sodium in all dosage forms (25.1%) and oral Ibuprofen (3.1%. In addition, Aspirin was the highest NSAIDs co-prescribed with ACEI (e.g., Enalapril), ARBs (e.g. Candesartan and Losartan), Diuretics (Furosemide, Indapamide, Hydrochlorothiazide, Amiloride, and Spironolactone), Warfarin and antiplatelets (Clopidogreal and Ticagrelor) followed by Diclofenac and other NSAIDs.ConclusionNSAIDs prescribing rate among elderly patients was high. Additionally the co-prescribing of NSAIDs especially Aspirin with other agents, which contributes to NSAIDs nephrotoxicity and gastrointestinal toxicity, were high. Strict measurements and action plans should be taken by prescribers to optimize the medical treatment in elderly through maximizing the benefits and decreasing the unwanted side effects.     

Anticholinergic burden and risk of cognitive impairment in elderly nursing home residents with depression

BackgroundAlthough the adverse cognitive effects of anticholinergic medications in the elderly are well-documented, little is known regarding the cognitive impact of anticholinergics among nursing home residents with depression.ObjectiveThis study examined the risk of mild-to-moderate cognitive impairment due to anticholinergic burden among elderly nursing home residents with depression.MethodsA population-based nested case-control study was conducted using Minimum Data Set (MDS)-linked Medicare data where the base cohort included patients ≥ 65 years with depression who had intact cognition (MDS Cognition score of 0 or 1) and no dementia. Cases were identified as those who had mild-to-moderate cognition (MDS Cognition score of 2–4). Each case was matched on age and sex to one control using incidence density sampling. The study evaluated cumulative anticholinergic burden (defined as score of 3 or more) within 30, 60 and 90 days preceding the event date based on the Anticholinergic Drug Scale (ADS). Conditional logistic regression model stratified on matched case-control sets was performed to evalaute cognitive impairment due to cumulative anticholinergic burden after controlling for other risk factors.ResultsThe study sample included 3707 cases with mild-to-moderate cognition and 3707 matched controls with intact cognition. Bivariate analysis showed significant association between cumulative anticholinergic exposure and cognitive impairment (Odds Ratio [OR], 1.15; 95% Confidence Interval [CI],1.04–1.30); after controlling for potential risk factors, cumulative anticholinergic exposure 30 days preceding the event was no longer associated with cognitive impairment, (aOR, 1.07; 95% CI, 0.95–1.21). However, the odds of cognitive impairment increased with cumulative anticholinergic exposure 60 days (aOR 1.16; 1.04–1.30) and 90 days (aOR 1.28; 1.14–1.44) before the event date.ConclusionCumulative anticholinergic use for prolonged exposure periods was associated with modestly increased risk of cognitive impairment in elderly residents with depression who had intact cognition. The findings suggest the need to be cautious when prescribing multiple anticholinergic drugs in residents, including those with intact cognition.     

Medication utilization pattern among outpatients during the Hajj mass gathering

BackgroundThe Kingdom of Saudi Arabia (KSA) provides free healthcare, including medications, for the over 2 million Muslim pilgrims who attend Hajj every year. Information on drug utilization patterns at the Hajj is important to strengthen the supply chain for medicines, avert stock-outs, identify inappropriate use, and support public health planning for the event.MethodWe investigated drug utilization pattern among outpatients in eight seasonal Holy sites hospitals in Makkah, KSA, during the 2018 Hajj. Data on medication prescribed and dispensed were retrieved from the hospitals' electronic records. Data were also used to calculate six of the WHO indicators for drug use at these facilities.ResultsA total of 99,117 medications were prescribed for 37,367 outpatients during 37,933 encounters. Outpatients were mainly older males and originated from 134 countries. Twenty medications accounted for 72.8% of the 323 different medications prescribed. These were mainly nonsteroidal anti-inflammatory drugs, analgesics and antipyretics, and antibacterial medicines for systemic use. Outpatients were prescribed an average of 2.6 (SD = 1.2) drugs per consultation and polypharmacy (≥5 medications) was observed in 4.8% of the encounters. Antibiotics and an injection were prescribed in 46.9% and 6.5% of encounters, respectively. Nearly 90% of the prescribed drugs were actually dispensed. On average, medications were dispensed 16.4 (SD = 119.8) minutes from the time they were prescribed for the patient. All hospitals had a copy of the essential drugs list available and all of the prescribed drugs appeared on that list.ConclusionNonsteroidal anti-inflammatory drugs, analgesics and antibiotics are the most common medications prescribed to outpatient during Hajj. Our results, including the calculated WHO drug use indicators, can form a basis for further investigations into appropriate drug use at the Hajj and for planning purposes. These results could also guide the development of reference values for medications prescribing and use indicators at mass gatherings.     

Drugs with anticholinergic properties: a current perspective on use and safety

INTRODUCTION: Many commonly used drugs have primary or secondary anticholinergic effects contributing to adverse outcomes ranging from mild-to-severe to potentially lethal. Anticholinergic adverse effects frequently occur with medications prescribed with other intended mechanisms of action, including antihistamines, antidepressants, and antipsychotics. Anticholinergic drugs are also the principal treatments of clinical conditions, such as urinary incontinence, that tend to occur in the elderly. Older patients and those with mental illness are particularly vulnerable to the adverse neuropsychiatric effects of anticholinergics as they may already have cognitive impairment. AREAS COVERED: Medline and Pubmed literature searches (1966 - the present) were performed using 'anticholinergic' and 'drug safety'. Abstracts were assessed and references scanned for appropriate articles. Here, the authors i) describe the neural pathways of the cholinergic system; ii) outline the main clinical uses and adverse effects of anticholinergic agents with a focus on cognitive impairment; and iii) discuss anticholinergic safety monitoring. EXPERT OPINION: Prescribers need to be vigilant for adverse anticholinergic effects, particularly in older patients. The symptoms may range from subtle cognitive impairment to delirium and may be due to the cumulative effect of multiple medications of modest antimuscarinic activity. The Anticholinergic Drug Scale and tables listing drugs with known anticholinergic properties may help in guiding clinical decision-making to reduce anticholinergic burden.     

Impact of residential medication management reviews on anticholinergic burden in aged care residents

Objectives:

The primary objective of this study was to investigate the impact of Residential Medication Management Reviews (RMMRs) on anticholinergic burden quantified by seven anticholinergic risk scales.

Design:

Retrospective analysis.

Setting:

Accredited pharmacists conducted RMMRs in aged-care facilities (ACFs) in Sydney, Australia.

Participants:

RMMRs pertained to 814 residents aged 65 years or older.

Measurements:

Anticholinergic burden was quantified using seven scales at baseline, after pharmacists’ recommendations and after the actual GP uptake of pharmacists’ recommendations. Change in the anticholinergic burden was measured using the Wilcoxon sign rank test.

Results:

At baseline, depending on the scale used to estimate the anticholinergic burden, between 36% and 67% of patients were prescribed at least one regular anticholinergic medication (ACM). Anticholinergic burden scores were significantly (p?<?0.001) lower after pharmacists’ recommendations as determined by each of the seven scales. The reduction in anticholinergic burden was also significant (p?<?0.001) after GPs’ acceptance of the pharmacists’ recommendations according to all scales with the exception of one scale which reached borderline significance (p?=?0.052).

Conclusion:

Despite the limitations of the retrospective design and differences in the estimation of anticholinergic burden, this is the first study to demonstrate that RMMRs are effective in reducing ACM prescribing in ACF residents, using a range of measures of anticholinergic burden. Future studies should focus on whether a decrease in anticholinergic burden will translate into improvement in clinical outcomes.     

Anticholinergics: theoretical and clinical overview

ABSTRACT

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 commonly prescribed to older people have a degree of anticholinergic activity that can contribute to anticholinergic burden. Anticholinergic burden, measured in several ways that consider number, dose and/or degree of anticholinergic activity of medicines, has shown to be a predictor of adverse health and functional outcomes. The anticholinergic burden on older people should be minimised by avoiding, reducing dose and deprescribing medicines with anticholinergic activity where clinically possible.     

Use of PRN medications in skilled nursing facilities

Many elderly individuals in skilled nursing facilities (SNFs), afflicted with an array of acute and chronic diseases, may have as many as 20 different prescribed medications administered on a pro re nata (PRN) basis. In this study, 20 SNFs in Indiana were inspected. Data on PRN medications were taken from medical charts to determine the extent of PRN medication use by the patients. From one to 10 PRN medication were prescribed per patient; 47% of the patients had not used any of their PRN medications. Further data are needed to justify PRN medication prescribing and usage and to decrease the potential for hidden medical costs, adverse drug effects, and drug interactions.     

Off-label use of anti-cancer drugs between clinical practice and research: the Italian experience

Background  

Off-label use is the practice of prescribing a drug outside the terms of its official labeling. Worldwide, about 20% of the commonly prescribed medications are off-label, and the percentage increases in specific patient populations, such as children, pregnant women, and cancer patients. Off-label use is particularly widespread in oncology for many reasons, including the wide variety of cancer subtypes, the difficulties involved in performing clinical trials, the rapid diffusion of preliminary results, and delays in the approval of new drugs by regulatory organizations/agencies.     

Anticholinergic Drug Burden in Older People's Brain – How well is it Measured?

Concurrent use of several drugs with potential anticholinergic properties is highly prevalent in the elderly. Methods to determine the overall anticholinergic drug burden have been developed to estimate the risk of central anticholinergic adverse effects. The objective of this MiniReview was to critically appraise the clinical utility of the methods used to assess the anticholinergic drug burden in older people's brain. We evaluated the in vitro method used to measure the anticholinergic activity in a patient's serum and the four anticholinergic drug scales: Anticholinergic Risk Scale, Anticholinergic Cognitive Burden, Drug Burden Index and Anticholinergic Drug Scale. Medline searches of the literature from January 1988 to January 2013 were performed. Studies that related anticholinergic drug burden to central adverse outcomes in elderly people were included, while case reports and studies of single substances were excluded. Despite the consistently reported association between a high anticholinergic drug burden and negative cognitive and psychomotor outcomes in older patients, there are discrepancies in the literature. Furthermore, no significant cognitive improvements after the anticholinergic drug burden was reduced have been shown in randomized controlled trials. It is reasonable to question whether the estimated anticholinergic drug burden can predict the overall brain effects of multiple anticholinergic agents in older people.     

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.