Spring 2011

Anticholinergic Burden — Tracking Adverse Effects

By Kevin T. Bain, PharmD, MPH, BCPS, CGP, CPH, FASCP, CCA
Aging Well
Vol. 4 No. 2 P. 8

Medications with anticholinergic (ACh) properties are ones that block the effects of acetylcholine in the body. The term “anticholinergic burden” refers to the cumulative effect of using multiple medications with ACh properties concomitantly. The purpose of this article is to provide an overview of medications with ACh properties that are commonly used in aging patients and the adverse effects of these medications. This article also provides guidance on assessing and reducing ACh burden.

Medications With ACh Properties
Medications with ACh properties are commonly used in the elder population.1,2 Some medications such as atropine, benztropine, and oxybutynin are used specifically for their ACh properties, and others such as diphenhydramine, cyclobenzaprine, and olanzapine have ACh properties unrelated to their primary use. Furthermore, some medications such as amitriptyline, chlorpromazine, and hyoscyamine have strong ACh properties compared with others such as methocarbamol, paroxetine, and quetiapine. Table 1 provides examples of medications with ACh properties commonly used in the elder population.

Adverse Effects of Medications With ACh Properties
Numerous studies and clinical experiences have shown that medications with ACh properties are associated with clinically significant adverse effects.3,4 Among these effects are blurred vision, dry eyes, constipation, dry mouth, urinary retention, decreased sweating, heat intolerance, cognitive impairment, confusion, delirium, dizziness, drowsiness, and increased heart rate. By no means is this list exhaustive of the adverse effects of medications with ACh properties on all organ systems nor the severity of such effects.

The risk of these adverse effects increases with the use of medications with strong ACh properties, higher doses of medications with ACh properties, and the greater total number of medications with ACh properties. Moreover, older patients, as a result of normal age-related physiological changes (eg, decreased renal function) and preexisting clinical conditions (eg, dementia), are much more sensitive to the adverse effects of medications with ACh properties.2-4

In the elder population, adverse effects of medications with ACh properties may be misattributed to advancing age or worsening clinical condition.2,3 Failure to recognize these adverse effects as attributable to medications with ACh properties not only predisposes aged patients to physiological, psychological, and physical risks but can also lead to use of other medications to treat these adverse effects, increased medication costs and healthcare expenditures, decreased quality of life, and increased caregiver burden.2,3 Because aged patients are likely to use medications with ACh properties and are particularly sensitive to their adverse effects, assessing ACh burden is crucial in this population.

Assessing ACh Burden
There are two primary methods used for assessing ACh burden: assessment using ACh rating scales and measurement using radioreceptor assays. A detailed review of each of these methods is beyond the scope of this article but has been published elsewhere.4 Currently the only method useful for assessing ACh burden in routine clinical practice is the use of ACh rating scales.4 Several such scales have been published.5-8 Using these scales, clinicians can rate the ACh properties of medications to determine ACh burden and subsequently develop interventions to reduce it. An example of how to use one of the ACh rating scales to assess ACh burden for an older patient is provided in the sidebar.

Reducing ACh Burden
Medications with ACh properties should be avoided in aged patients whenever possible. If deemed clinically necessary, they should be used at the lowest dose and shortest duration possible. The ACh burden can be further reduced by replacing medications having strong ACh properties with alternatives, including medications with no or weak ACh properties or with nonpharmacologic interventions. The best alternative for many medications with ACh properties is to use nonpharmacologic interventions; however, this is not always possible. Table 2 provides alternatives for several medications with strong ACh properties. An example of how to use two of the alternatives to reduce ACh burden for an older patient is provided in the sidebar.

Final Thoughts
Many medications commonly used by older patients have ACh properties that can be cumulative and unsafe. Medications with ACh properties are best avoided in the older population; however, some medications are used specifically for their ACh properties, making avoidance even more challenging. Clinicians need to be vigilant in reducing exposure to medications with ACh properties in this population. Using ACh rating scales to assess the magnitude of ACh burden can help clinicians achieve this goal and ultimately enhance safety in aged patients.

— Kevin T. Bain, PharmD, MPH, BCPS, CGP, CPH, FASCP, CCA, is vice president of clinical support at excelleRx, Inc, an Omnicare company in Philadelphia.

Anticholinergic Risk Scale Illustration
J. B. is a 70-year-old man with a medical history of hypertension, diabetes with neuropathy, and depression. He is using the following medications:

• ramipril 5 mg orally once daily;

• amlodipine 5 mg orally once daily;

• metformin 500 mg orally twice daily;

• lidocaine 5% transdermal patch applied once daily for 18 hours;

• amitriptyline 50 mg orally once daily; and

• vitamin E 400 IU orally once daily.

He comes to your office complaining of difficulty urinating and dry mouth that affects his appetite and speech. Your review of his medication regimen reveals that J. B. has also been taking diphenhydramine 25 mg orally at bedtime, three to four times per week, for the past three weeks due to difficulty falling asleep, and he has been taking his amitriptyline in the morning rather than at bedtime.

The Anticholinergic Risk Scale (ARS) is an anticholinergic (ACh) rating scale that rates medications according to ACh properties (0, none or weak; 1, moderate; 2, strong; and 3, very strong).

Higher ARS scores are associated with an increased risk of ACh adverse effects in the elder population. When the total ARS score is 3 or higher, for instance, 70% or more aged patients report at least two ACh adverse effects.5

• Using the ARS, how could you measure the ACh burden for J. B.? Add the ARS ratings assigned to each of the medications J. B. is using as follows: 0 (ramipril) + 0 (amlodipine) + 0 (metformin) + 0 (lidocaine) + 3 (amitriptyline) + 0 (vitamin E) + 3 (diphenhydramine). Based on the ARS ratings, the ACh burden for J. B. is 6.

• How could you reduce the ACh burden for J. B.? Use an alternative antidepressant such as a selective serotonin reuptake inhibitor(SSRI) or a serotonin and norepinephrine reuptake inhibitor (SNRI) to treat his depression. You could switch amitriptyline to an SNRI such as duloxetine, which is effective for both depression and diabetic neuropathy.

To further reduce the ACh burden, use an alternative to treat his insomnia. You could switch diphenhydramine to a nonpharmacologic intervention, a nonbenzodiazepine sedative-hypnotic such as zolpidem, or a combination thereof. You could also stop diphenhydramine and reassess his insomnia after switching amitriptyline to duloxetine to determine whether an alternative to diphenhydramine is still necessary.

— KTB

References
1. Chatterjee S, Mehta S, Sherer JT, Aparasu RR. Prevalence and predictors of anticholinergic medication use in elderly nursing home residents with dementia: Analysis of data from the 2004 National Nursing Home Survey. Drugs Aging. 2010;27(12):987-997.

2. Mintzer J, Burns A. Anticholinergic side-effects of drugs in elderly people. J R Soc Med. 2000;93(9):457-462.

3. Feinberg M. The problems of anticholinergic adverse effects in older patients. Drugs Aging. 1993;3(4):335-348.

4. Rudd KM, Raehl CL, Bond CA, Abbruscato TJ, Stenhouse AC. Methods for assessing drug-related anticholinergic activity. Pharmacotherapy. 2005;25(11):1592-1601.

5. Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med. 2008;168(5):508-513.

6. Carnahan RM, Lund BC, Perry PJ, Culp KR, Pollock BG. The relationship of an anticholinergic rating scale with serum anticholinergic activity in elderly nursing home residents. Psychopharmacol Bull. 2002;36(4):14-19.

7. Carnahan RM, Lund BC, Perry PJ, Pollock BG, Culp KR. The Anticholinergic Drug Scale as a measure of drug-related anticholinergic burden: Associations with serum anticholinergic activity. J Clin Pharmacol. 2006;46(12):1481-1486.

8. Hilmer SN, Mager DE, Simonsick EM, et al. A drug burden index to define the functional burden of medications in older people. Arch Intern Med. 2007;167(8):781-787.

Table 1: Medications With Anticholinergic (ACh) Properties Commonly Used in the Elder Population*

GI = gastrointestinal, N/V = nausea/vomiting
*Primary indications for use are provided in parentheses.
† Medications with strong ACh properties compared with other medications in the table. Table adapted from reference 5

Table 2: Alternatives for Several Medications With Strong Anticholinergic (ACh) Properties

SNRI = serotonin-norepinephrine reuptake inhibitor, SSRI = selective serotonin reuptake inhibitor, TCAs = tricyclic antidepressants