Anticholinergic burden in the elderly

INTRODUCTION

Anticholinergic burden is a term that refers to a cumulative effect of taking several drugs with the capacity to develop anticholinergic adverse effects. These drugs block the effect of acetylcholine both centrally and peripherally, thus causing quite characteristic side effects in patients (1).

Although Henry Dale discovered acetylcholine in 1914, it was not until 1921 when Otto Loewi demonstrated in an experiment with frogs that acetylcholine was involved in signal neurotransmission (2). Today, it is known that acetylcholine is a neurotransmitter involved in processes such as neuronal excitability or synaptic connection, among others, and that cholinergic modulation is an essential mechanism for coordinating the response of neuronal networks (3).

Acetylcholine sends signals through two types of receptors: nicotinic and muscarinic.

Nicotinic receptors are subdivided into N1 receptors (peripheral muscle receptor present in skeletal muscle) and N2 (central or neuronal receptor present in the central and peripheral nervous system).

Muscarinic receptors are subdivided into 5 types: M1 (found in the cerebral cortex, salivary glands and gastric glands), M2 (found in smooth muscle and cardiac tissue), M3 (found in smooth muscle, gastric and salivary glands), M4 and M5 (located in the hippocampus and substantia nigra) (4).

Due to this great variety of cholinergic receptors that play an important role in the neuronal transmission of the somatic and autonomic nervous systems, the administration of drugs with anticholinergic activity gives rise to numerous adverse effects. At the peripheral level, the most common are decreased secretions, slowing of intestinal motility, dry mouth, constipation, increased heart rate, blurred vision or urinary retention, among others. At the central level we find other effects such as cognitive and physical deterioration, the appearance of delirium, lack of concentration, falls, agitation, memory loss and confusion.

As the years progress, drug metabolism and excretion decreases, blood-brain barrier permeability increases, and the brain has less cholinergic activity, so it is common for many of these anticholinergic adverse effects to occur in the elderly. In addition, polymedication (a term that refers to treatment with 5 or more drugs in a patient with 2 or more diagnosed chronic diseases) is common in these patients, so it is likely that an elderly person is prescribed more than one drug with anticholinergic activity. This has led some researchers to consider the option that the occurrence of anticholinergic effects such as cognitive and functional impairment in many cases leads to a false diagnosis of dementia, when in fact they may be side effects of the prescribed drugs (6,7).

This hypothesis has been evaluated and numerous studies have correlated the use of anticholinergic drugs with cognitive alterations, falls, fractures, delirium or dementia in elderly people.

OBJECTIVES

• To study hypotheses on the possible association between cognitive and physical deterioration in elderly people and the anticholinergic load of the treatment they take
• To determine the prevalence of high anticholinergic load in elderly patients by means of a cross-sectional study in which the medication of a sample of polymedicated patients over 70 years of age will be reviewed and to establish which drugs have a higher anticholinergic load and are prescribed more frequently in the elderly population.

 

MATERIAL AND METHODS

The methodology consists of two parts:

• Firstly, to review the possible association between cognitive and physical deterioration in elderly people with the anticholinergic load of their medication, a literature review was carried out in which articles from the PubMed database were selected. The search terms “anticholinergic burden”, “anticholinergic older” and “anticholinergic effects” were used, obtaining a wide variety of results and selecting the most recent, within the last 20 years, and excluding reviews and those which, due to their publication date, are already obsolete, there being articles with more complete information at a later date.
• Second, to study the possible relationship between physical and cognitive deterioration and a high anticholinergic load, a cross-sectional study was designed to review the treatment and estimate the anticholinergic load of medication in polymedicated elderly people.

 

Type of design: Cross-sectional study.

Scope: Community pharmacy.

Study period: from May 2021 to September 2021.

Sample: 34 patients.

Selection criteria: 34 anonymous patients (18 women and 16 men) over 70 years old and with more than 5 prescribed drugs (including all routes of administration), who were part of the Multi-Compartment Aids program (MCA) in the study period, were randomly selected.

Method of analysis: The ACB scale was used to calculate the anticholinergic burden. This scale, as indicated above, classifies drugs by assigning them a score of 1 (possible anticholinergic burden), 2 (demonstrated anticholinergic burden) and 3 (strong anticholinergic burden). Regarding the cumulative anticholinergic load, when the score is between 0 and 2 points, it is considered that there is no risk, however when the score is 3 or higher, it is considered that there is a risk of cognitive and physical deterioration of the patient, and it is recommended to replace the drugs with high anticholinergic load by others.

Data sources and ethical aspects: the patients included at discharge from the MCA program signed a consent form to treat all their medical and pharmacological data.

 

OUTCOMES

In the literature review, among one of the possible hypotheses, it was noted that the most prescribed anticholinergic drugs were tricyclic antidepressants, first-generation antihistamines and bladder antimuscarinics and that a cumulative use of these was associated with an increased risk of dementia.

This was described in 2015 when a cohort study was published in which patients older than 65 years were followed for 10 years (8).

In another case-control study involving patients over 55 years of age, it was observed that the drugs with the highest anticholinergic load were antidepressants, antiparkinsonian drugs, antipsychotics, antimuscarinic drugs and antiepileptic drugs, and that a cumulative use of these drugs led to highlight the importance of reducing exposure to anticholinergic drugs in middle-aged and elderly patients due to the risk of dementia (9).

In these studies the investigators discuss different ways of measuring anticholinergic burden: using scales and measuring serum anticholinergic activity (SAA). Some trials that have evaluated the relationship between SAA and increased cognitive impairment have observed that there are drugs that are not normally considered anticholinergic but nevertheless at high doses do have measurable anticholinergic effects, such as digoxin, fentanyl or metformin. This may be because the pharmacologically active metabolites of these drugs have anticholinergic effects. Therefore, measuring SAA seems a good way to know the anticholinergic burden of each drug and its metabolites. However, this technique is not accessible to most practitioners, is expensive and has low acceptance. That is why the most common way of measuring the anticholinergic burden is by means of different scales: Anticholinergic Drug Scale (ADS), Anticholinergic Burden Scale (ABS), Drug Burden Index (DBI), Anticholinergic Risk Scale (ARS) and Anticholinergic Cognitive Burden (ACB), the last two being the most commonly used (6,10).

These scales were created in 2008 and assign an anticholinergic load to each drug, with differences between them, but all with the aim of being a useful tool for optimizing prescriptions in elderly patients. In the case of drugs with a high anticholinergic load, it is recommended that alternative treatments be sought whenever possible. The most common pharmacological groups with high anticholinergic load are: urinary antimuscarinics, first generation antihistamines, antipsychotics, tricyclic antidepressants and antiparkinsonians.

The following table (Table 1) lists the most prescribed drugs of these pharmacological groups and they have been classified according to the CBA scale. This scale assigns a score of 3 to those drugs with a strong anticholinergic load, a score of 2 to those with a proven anticholinergic load and a score of 1 to drugs with a possible anticholinergic load.

 

Table 1. Characteristics of pharmacological groups according to cholinergic load.

 

In all the studies published (8,9,10), the researchers tried to show that there was a relationship between a high anticholinergic load and increased cognitive and physical impairment in elderly people. Although the results supported this increasingly growing hypothesis, they were not conclusive in establishing a direct relationship, but nevertheless this has important implications for the benefit-risk of many drugs commonly used in the elderly.

In the cross-sectional study, after calculating the anticholinergic load using the CBA scale (11) of the 34 polymedicated patients over 70 years of age who were part of the sample, the following results were obtained: Figure 1 shows that of the total 34 patients analyzed, 16 of them (44%) had a score between 0 and 2, 11 of them (31%) a score of 3 and 9 of them (25%) a score higher than 3. This means that more than half of the patients analyzed (56%) have an increased risk of suffering both physical and cognitive deterioration due to the anticholinergic load of their treatment, being in 25% of them this risk higher (anticholinergic load score higher than 3).

Figure 1. Representation of the total sample as a function of anticholinergic load score.

 

Table 2 shows the data for men and women separately. Of the 18 women analyzed, 8 of them (44%) have a score between 0 and 2, 5 of them (28%) a score of 3 and 5 of them (28%) a score higher than 3. That is, more than half (56%) of the women analyzed obtained a high anticholinergic load, implying a higher risk of cognitive and physical deterioration. As for the sample of the 16 men analyzed, 8 of them (50%) obtained an anticholinergic load score between 0 and 2, 6 of them (37%) a score of 3 and 2 of them (13%) a score higher than 3. In this case, half (50%) of the men analyzed obtained an anticholinergic load score of 3 or higher, i.e., at higher risk of physical and cognitive impairment. There is, therefore, no statistically significant difference between the two groups (p=0,53).

 

Table 2. Representación de la muestra de mujeres y hombres analizada

All drugs prescribed to the 34 patients analyzed were classified according to the score assigned by the ACB scale for anticholinergic burden. Table 3 represents the drugs with score 1, 2 (with demonstrated anticholinergic load) and 3 (with strong anticholinergic load) and the number of patients belonging to the sample who are prescribed these drugs leaving out those drugs that were only prescribed to 1 or 2 patients in the sample.

 

Table 3. Number of patients prescribed drugs with score 1, 2, and 3 according to the CBA scale.

 

DISCUSSION

Anticholinergic drugs block the effect of acetylcholine both centrally and peripherally, thus causing characteristic adverse effects. At the central level we speak of disorientation, cognitive impairment and falls, and at the peripheral level of dry mouth, blurred vision or urinary retention, among others. Anticholinergic drugs have different activities, i.e. the greater the anticholinergic load, the greater the risk of these adverse effects appearing.

When we talk about elderly people, in whom drug metabolism is reduced, these adverse effects increase and appear more frequently. In addition, in this age group, it is more common for patients to have more than one chronic disease diagnosed and, therefore, to be polymedicated patients, so the probability of an elderly person being prescribed a drug with anticholinergic properties increases.

For this reason, it is important to know the anticholinergic load of drugs when prescribing them, and for this purpose scales are used, such as the ACB scale used in this project.

In the results of the study carried out in a sample of 34 elderly patients over 70 years old who were polymedicated, it was observed that 56% of the patients had a cumulative anticholinergic load of 3 or higher, that is, in more than half of the patients there was an elevated risk of cognitive and physical deterioration. In addition, it was also observed that this risk was higher in women than in men: 56% of women had cumulative anticholinergic load scores of 3 or higher compared to 50% of men, however this is not a significant value.

The results of our study reflect the same information as that described by other authors (12), in the sense that the prevalence of prescriptions of anticholinergic drugs in the polymedicated elderly is high and this may entail a risk of greater cognitive and physical deterioration, greater risk of falls and hospital admissions. In addition to being detrimental to the quality of life of the patient and their caregivers, this also entails greater expenditure for the healthcare system. It would be interesting, therefore, to provide this information to prescribing physicians and to make them aware of the importance of the anticholinergic load of drugs in elderly patients. In this way they could take this information into account when prescribing and many of the problems associated with a high anticholinergic load could be avoided.

Regarding the limitations of this study, we found a small sample size, which is not representative enough to draw firm conclusions about the prevalence of a high anticholinergic burden in the elderly population and a short study time period.

In relation to the proposed objectives, in this project we have obtained data from elderly patients by means of a cross-sectional study, in which we can observe that more than half of the analyzed sample presents a high anticholinergic load, being higher in women than in men. In other words, these data support the hypothesis of the articles reviewed on the frequency with which drugs with a high anticholinergic load are prescribed to elderly patients, who, due to the conditions of their organism, are more vulnerable to the appearance of adverse effects, the most common being falls, confusion or different symptoms that sometimes lead to false diagnoses of dementia.

The most frequently prescribed drugs in the sample of elderly patients analyzed were antidepressants, anxiolytics, diuretics, opioid analgesics and antiparkinsonian drugs. This is of interest to physicians when prescribing, since considering that certain drugs can cause symptoms such as cognitive deterioration, they can avoid prescribing certain drugs and try to replace them with others with a lower anticholinergic load.

 

CONCLUSIONS

Therefore, although the data obtained are not sufficient to establish an association between cognitive impairment in elderly patients and the anticholinergic load of their treatment, a high prevalence has been established in a sample of patients, which makes us reflect on the medication of the elderly population and the need to take into account the anticholinergic load when prescribing to avoid the associated symptomatology that can be very harmful in this population group.

 

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