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A Strategy to Decrease the Use of Risky Drugs in the Elderly

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A Strategy to Decrease the Use of Risky Drugs in the Elderly REVIEW SUSAN M. FOSNIGHT, RPH, CGP, BCPS KYLE R. ALLEN, DO CME Clinical Staff Pharmacist, Department of Pharmacy, Summa Health Chief, Division of Geriatric Medicine, Medical Director, Post Acute CREDIT System, Akron, OH and Senior Services, Summa Health System; Associate Professor of Clinical Internal and Family Medicine, Northeastern Ohio Universities College of Medicine, Akron, OH CAROLYN M. HOLDER, MSN, RN, CNS SUSAN HAZELETT, MSN, RN Geriatrics Coordinator, Post Acute and Senior Services, Summa Research Associate, Summa Health System, Akron, OH Health System, Akron, OH A strategy to decrease the use of risky drugs in the elderly ■ ABSTRACT OME MEDICATIONS that are safe in most S patients are best avoided in elderly Many medications that are safe in most patients pose patients—and pharmacists can help physicians serious risks in older patients, including functional avoid them. decline, delirium, falls, and poorer outcomes. We describe In this paper we discuss three medications, our institution’s program of “academic detailing,” chosen on the basis of scientific evidence and designed to reduce the use of three high-risk drugs in our personal experience, that are associated elderly patients. with unacceptable risk in elderly patients and for which reasonable alternatives exist: ■ KEY POINTS meperidine, diphenhydramine, and amitripty- line. Meperidine, diphenhydramine, and amitriptyline all pose We also describe our institution’s program a high risk of adverse reactions in older adults. Safer of “academic detailing” to reduce their use. alternatives are available. Whenever a physician prescribes one of these high-risk drugs to an elderly patient at our In our program, the pharmacy computer system generates institution, a computer alerts the pharmacist, a daily report of elderly patients who are prescribed any who contacts the prescribing physician to explain the problems patients often have with of these three agents. A pharmacist contacts the these agents and to suggest alternatives. Under prescribing physician directly or leaves a preprinted note this program, use of these three drugs has fall- on the patient’s chart, explaining the problems older en by one third to one half. patients often have with these medications and suggesting alternatives. ■ SCOPE OF THE PROBLEM Although medications may contribute to delirium, Adverse drug reactions are a huge problem, dementia, constipation, or urinary retention, the especially in the elderly. Each year, at least contribution may be subtle or occur slowly, making it 100,000 people are estimated to die of medica- difficult to detect. tion-related problems.1 Adverse drug reactions are some of the most common complications Meperidine has a long-acting, renally excreted metabolite in hospitalized elders and often lead to poorer outcomes.2,3 An estimated $4 billion is spent that is toxic to the central nervous system; morphine is on medication-related problems in acute care preferred. facilities each year.4 Medications have been documented to be a significant factor in both Diphenhydramine and amitriptyline have powerful delirium and falls.5–7 anticholinergic effects; alternatives depend on the This is an important quality-improvement indication. issue, since half of all adverse drug effects in This paper discusses therapies that are experimental or are not approved by the US Food and older patients have been reported to be avoid- Drug Administration for the use under discussion. able.3 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 71 • NUMBER 7 JULY 2004 561 Downloaded from www.ccjm.org on September 27, 2021. For personal use only. All other uses require permission. HIGH-RISK MEDICATIONS FOSNIGHT AND COLLEAGUES ■ MEPERIDINE: than 600 mg/24 hours.10 Neither the RISK OF TOXICITY, DELIRIUM American Geriatrics Society’s Panel on Persistent Pain nor its Panel for Assessing Meperidine poses well-defined risks in older Care of Vulnerable Elders recommends patients.8 meperidine use in the elderly.16,17 Meperidine is metabolized by two hepatic Meperidine is generally reserved for severe pathways, one of which causes N-demethyla- pain for which a parenteral narcotic is needed. tion and the formation of the only active The alternative agent in this situation is mor- metabolite, normeperidine. Normeperidine is phine. excreted renally and has a longer half-life than Morphine, like meperidine, has an active meperidine (15–40 hours vs 3–6 hours, respec- metabolite. Although this metabolite may tively)9; it accumulates in patients who also become elevated in patients with renal receive repeated high doses and in patients insufficiency, it has a much shorter half-life with renal dysfunction. Since renal function (2.4–6.7 hours); therefore, it is less likely to declines with age, normeperidine often accu- accumulate. This metabolite is not associated mulates in older adult patients, placing them with excitatory effects on the central nervous at risk of toxicity.10 system.15 Kaiko et al11 correlated high normeperi- dine levels with central nervous system toxic- ■ DIPHENHYDRAMINE: ity, including anxiety, tremors, twitches, ANTICHOLINERGIC EFFECTS myoclonus, and seizures. Meperidine has also been reported to Diphenhydramine poses a risk in older adults cause delirium.12,13 In a retrospective analy- owing to its powerful anticholinergic effects. sis of 92 elderly patients with hip fractures, With age, acetylcholine production Adunsky et al14 found that patients receiv- decreases, leading to increased sensitivity of ing meperidine had a significantly higher cholinergic receptors and eventual destruction incidence of delirium than did those receiv- of cholinergic neurons. In demented patients, Meperidine’s ing morphine. the rate and extent of this process is accelerat- active ed.18 This places older adults, and especially Theoretical advantage of meperidine demented patients, at a greater risk of adverse metabolite in gall bladder or pancreas disease reactions from anticholinergic agents. accumulates in Despite its risks, meperidine is often pre- The anticholinergic actions of medica- scribed to hospitalized older patients, perhaps tions can cause or worsen confusion, sedation, patients who because of its proposed advantage over mor- blurred vision, urinary retention, and constipa- have renal phine in patients with cholecystitis and pan- tion.3 These drugs also oppose the action of the failure creatitis. acetylcholinesterase inhibitors (ie, donepezil, Compared with morphine, meperidine galantamine, and rivastigmine) in patients has less effect on the motility of the sphinc- being treated for dementia. ter of Oddi. However, no studies have been Many studies have documented the dele- done to see if there is any difference in clini- terious effects of medications with anticholin- cal outcome or pain control due to this ergic effects. effect.15 Without these data, it is difficult to Han et al,19 in a prospective observation- justify meperidine’s use in patients at high al study, found that the greater the anticholin- risk of normeperidine accumulation and tox- ergic “load” (defined as the sum of the anti- icity. cholinergic activity of medications that a patient received), the greater the severity of Instead of meperidine, use morphine delirium symptoms. Many organizations no longer recommend the Gustafson et al,20 in a prospective study of use of meperidine. The American Pain 111 patients treated for femoral neck fractures, Society recommends it only for brief courses found that the incidence of an acute confu- (< 48 hours) in patients without renal or cen- sional state was significantly greater in tral nervous system disease, at doses lower patients receiving drugs with anticholinergic 562 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 71 • NUMBER 7 JULY 2004 Downloaded from www.ccjm.org on September 27, 2021. For personal use only. All other uses require permission. properties than in patients not receiving and loratadine to chlorpheniramine and them. diphenhydramine. Although they concluded Agostini et al,21 in a prospective cohort that cetirizine and loratadine were less likely study of 426 patients, found that diphenhy- to cause central nervous system effects than dramine use in patients older than 70 years diphenhydramine and chlorpheniramine, was associated with an increased risk of delir- variances in measurements did not allow para- ium. metric statistical tests in this study. Older patients face a significantly higher Studies in younger patients have demon- risk of illness and death if they develop deliri- strated a lower incidence of central nervous um in the hospital. Moreover, delirium is system effects with the second-generation often not recognized or treated appropriately antihistamines, although cetirizine has been and is often associated with a prolonged hos- associated with a higher incidence of somno- pital stay, functional decline, and postdis- lence than the other second-generation charge institutionalization. agents.27–29 Loratadine or fexofenadine are Other cognitive adverse reactions have preferred for this reason. been associated with anticholinergic agents. For insomnia, sleep hygiene protocols Lu and Tune22 found that in 69 patients with are preferred to medications.21,30 If sleep Alzheimer disease receiving donepezil 10 hygiene protocols fail or cannot be used, low mg/day, Mini-Mental State Exam scores at 2 doses of trazodone (25–50 mg) may be an years were significantly worse for those who option, although trazodone is not approved by received anticholinergic medications com- the
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