Article, Emergency Medicine

Prescribing to older ED patients

Review

Prescribing to older ED patients

Kevin M. Terrell DO, MSa,*,1, Kennon Heard MDb,1, Douglas K. Miller MDc

aDepartment of Emergency Medicine, Indiana University Center for Aging Research, Regenstrief Institute, Inc,

Indiana University School of Medicine, Indianapolis, IN, USA

bDivision of Emergency Medicine, Colorado Emergency Medicine Research Center, Rocky Mountain Poison and Drug Center,

University of Colorado School of Medicine, Denver, CO, USA

cDivision of General Internal Medicine and Geriatrics, Indiana University Center for Aging Research, Regenstrief Institute, Inc, Indiana University School of Medicine, Indianapolis, IN, USA

Received 10 November 2005; accepted 15 January 2006

Abstract The purpose of this article is to assist emergency physicians in selecting safe and effective drug therapy for seniors. Because safer alternatives exist, medications on the Beers list of potentially inappropriate medications should generally be avoided. We also review risks associated with several classes of medications: nonsteroidal anti-inflammatory drugs, benzodiazepines, and anticholinergic medications. They are associated with adverse outcomes when taken by older adults and should be used with caution. We also address the use of opioid medications in seniors. Although they are not without risk, opioids are generally safe with slow titration, precautions, and a bowel regimen to prevent constipation. Prescribers should also consider the need for estimating creatinine clearance when prescribing medications that require dosage adjustment in the setting of renal insufficiency. Two areas in need of research are identifying the proper dosing and safety of medications in seniors and prescribing with electronic decision support to assist in prescribing decisions.

D 2006

Introduction

adverse drug events are common among older adults and often lead to additional health services use [1-3]. They account for 7% to 11% of all ED visits by patients aged 65 years and older [4,5] and contribute to 12% of hospital admissions by older adults [6]. Adverse drug events are not

* Corresponding author. Department of Emergency Medicine, Room R2200, Indianapolis, Indiana 46202, USA. Tel.: +1 317 630 7276; fax: +1

317 656 4216.

E-mail address: [email protected] (K.M. Terrell).

1 Drs Terrell and Heard are supported by a Dennis W. Jahnigen Career Development Scholars Award, which are funded by the American Geriatrics Society, the John A. Hartford Foundation, and Atlantic Philanthropies, Inc.

only a common serious problem among the elderly, but they are also costly; drug-related morbidity and mortality have an estimated annual cost of $76.6 billion to the US health care system [7].

Balanced against the potential for adverse events, medications can increase survival and improve quality of life. Drug therapy is among the most widely used and highly valued interventions for acute and chronic diseases of older adults [8]. Seniors, as a group, have a greater burden of disease and receive a larger number of medications than younger persons [9,10]. People aged 65 years and older comprise 12.4% of the US population [11] but consume more than 30% of all prescription drugs [12]. More than 90% of elderly patients presenting to the ED are already taking 1 or more medications [5], and these seniors take an

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physiological changes with agin”>average of 4 to 8 medications [5,13,14]. Upon release from the ED, 30% to 50% are prescribed 1 or more new medications [15-17].

When prescribing to older adults, there are additional factors that providers should bear in mind. Emergency physicians should consider (1) the physiological changes associated with aging, (2) a medication’s risk specifically in the elderly population, and (3) the number and type of medications that the older patient is already taking. The purpose of this review is to provide an overview of these issues and to guide emergency physicians in selecting the safest and most effective drug therapy for seniors.

Relevant physiological changes with aging

The effect of drug therapy in an individual is the net result of pharmacokinetics and pharmacodynamics [9]. Pharmacokinetics refers to how an individual’s body handles a medication, that is, how it is absorbed into the body, distributed into the tissues and organs, and eventually eliminated [9,18]. Pharmacodynamics refers to the relation- ship between drug concentration and the drug’s effects, that is, what the drug does to the body [18]. Aging results in changes in pharmacokinetics and pharmacodynamics and is characterized by the progressive loss of organ system functional reserve that begins after 20 to 30 years of age [19].

Pharmacokinetic factors include drug bioavailability, volume of distribution, clearance, and half-life [18]. Most studies suggest little clinically significant age-related change in the rate or extent of drug absorption or bioavailability from the gastrointestinal tract with administration of a single medication [9,19]. However, simultaneous administration of several medications increases the probability that there will be competition for the same absorptive or first-pass metabolic processes that can affect drug bioavailability [9]. Because aging adults, as a whole, have an increase in body fat percentage and decreases in both total body water and muscle mass, the volume of distribution of medications is affected by aging [9,18,20]. In particular, water-soluble drugs become more concentrated and, therefore, have higher initial concentrations [9,20], and fat-soluble drugs have longer half-lives because of the slow release of drug from

fatty tissue [20].

Drug clearance or elimination occurs through hepatic metabolism, renal excretion, or a combination of the two [18]. The efficacy of hepatic metabolism may be influenced by blood flow to the liver, functional hepatocyte number, and the activity of the Cytochrome P450 mixed-function oxidase system [19]. A decline in hepatic blood flow is nor- mally associated with aging [9,18-21]. In addition, liver size decreases with aging, which is associated with a decline in functional hepatocyte number and enzyme content [18-21]. Unfortunately, these age-related changes in hepatic drug clearance, half-life, bioavailability, and volume of distribu-

tion are unpredictable and difficult to estimate, which adds complexity to prescribing drugs that are metabolized by the liver to seniors [9]. Changes in renal clearance are compa- ratively more predictable [9]. Glomerular filtration rate decreases by approximately 10% per decade after 20 years of age [9,19]. Even in the absence of kidney disease, renal clearance is generally reduced by as much as 50% in elderly patients [21].

Although pharmacodynamic changes associated with aging may be even more important than pharmacokinetic changes, the pharmacodynamic alterations have been less extensively studied [9]. With aging, the response to a drug on its target organ may be increased, decreased, or unchanged [18]. Consequently, older adults are generally more sensitive to some drugs and less sensitive to others [20]. Even if the pharmacokinetics of a drug are not altered, an elderly patient may require a smaller dosage because of a change in pharmacodynamic sensitivity [21].

Potentially inappropriate medications

In the attempt to reduce the frequency of adverse drug events among older adults, several methods have been developed to assess the appropriateness of individual medications for seniors [22]. The Beers criteria for determining potentially Inappropriate medication use [23-25] is a method that is well-suited to application in the ED setting. Little physiological information is required about the patient, and the use of these criteria is rapid, unlike most other methods [22]. Furthermore, an accurate list of medications is not required when using the Beers criteria. This is particularly advantageous in the ED setting where less than half of patients bring a medication list or know their current medications [13,26,27]. The latest version of the Beers criteria [25] includes 2 categories of potentially Inappropriate prescribing. First, to prevent potential drug- disease interactions, the authors list 20 medications that should be avoided in older adults if a patient has certain medical conditions. Considering the medications most commonly prescribed or administered to ED patients [28], drug-disease interactions that emergency physicians should keep in mind are Nonsteroidal anti-inflammatory drugs Peptic ulcer disease interactions, anticholinergics/ antihistamines-bladder outflow obstruction interactions, and anticholinergics/antihistamines-cognitive impairment interactions. Second, the authors listed 48 individual med- ications or classes of medications that, as a rule, should be avoided in older adults. Of the 48, 6 are potentially inap- propriate only above certain doses or durations of therapy. The remaining 42 medications and Medication classes, commonly referred to as the Beers list of potentially inap- propriate medications, are considered unsafe for older adults regardless of dose or duration of therapy. The left column of Table 1 lists the potentially inappropriate medications most commonly prescribed to older adults upon release from the

ED [14,29]. The table also includes promethazine, which was more recently added to the Beers list of medications to avoid in older adults [25]. When discharged from the ED, 6% to 10% of visits by older adults result in 1 or more prescriptions for a potentially inappropriate medication [14,29] with no evidence of improvement over time [43]. This amounts to 1 or more potentially inappropriate med- ications being prescribed at as many as 1 million ED visits by older adults each year [28,44].

The Beers criteria have been used extensively to examine medication use in older adults. These criteria or modifications of the criteria have been used to study prescribing in nursing homes [45-48], assisted living and board and care facilities [49,50], homebound older adults [51], community-dwelling elderly patients [52-56], office prescribing [57-60], and ED medication administration [61] and prescribing [14,29,62].

The use of the Beers list has been met with some controversy. The primary objection to the use of this and similar lists of inappropriate drugs for the elderly is the lack of consideration of the clinical circumstances for an individual patient [63]. However, the criteria are not intended to supersede the clinical judgment of the physician or practitioner [25]. In addition, published data indicate an association between the use of drugs on the Beers list and adverse outcomes. The use of potentially inappropriate

medications is associated with higher costs and more outpatient and inpatient visits [64]. Their use by nursing home residents is associated with increased ED visits [65], hospitalizations [65,66], and deaths [65,66]. Conversely, studies of largely community-dwelling older adults have not identified a significant association between potentially inappropriate medication use and mortality [14,67] or ED visits [14,64]. However, in a recent review article, the literature was found to support the Beers selection of potentially inappropriate medications for the elderly popula- tion [68]. These medications are generally considered inappropriate because safer or more effective alternatives exist. Table 1 lists suggested Alternative therapies for the most common potentially inappropriate medications prescribed to older ED patients. The substitute therapies are sorted by common indications for prescribing the medications.

Many observational studies have shown an association between prescribing potentially inappropriate medications and adverse outcomes in older patients. However, is this relationship causal, or are confounding factors responsible for the identified associations? The extant literature is inadequate to answer this question. There is a need for clinical trials to measure the effect of inappropriate medi- cations. Nevertheless, there is little to lose and much potential gain by attempting to reduce potentially inappropriate

Table 1 Potentially inappropriate medications [25] most commonly prescribed to older ED patients [14,29], diagnoses for which they may be prescribed, and suggested alternatives

PIM Diagnosisa Notes Suggested alternatives

Cyclobenzaprine Muscle spasm or pain No proven benefit; side effects

common in older adults [30,31]

Diazepam BPPV Side effects common; safer therapy available

Ice or heat; pain medications

Particle repositioning [32,33]; meclizine

Dicyclomine Abdominal cramps Side effects common Treat underlying condition; pain medications

Diphenhydramine Allergic symptoms, seasonal

allergies, Contact dermatitis Hydroxyzine See diphenhydramine above

More sedating than second generation H1 antagonists

Steroids (nasal, topical, or oralb); second generation H1 antagonist [34]

Indomethacin Acute gout No advantage over other NSAIDs and carries a higher risk of adverse effects [35]

Promethazine Nausea/vomiting More effective agents with

fewer side effects available

Ibuprofen [36]c, steroids [37]b, ACTH [38], colchicined, opioids

Prochlorperazine [39], 5HT3 antagonists, metoclopramide

Insomnia Side effects common Behavioral therapy; treatment of underlying conditions [40];

Trazodone [41]

BPPV See diazepam above Propoxyphene Pain Other medications are more

effective and have fewer side effects [42]

Muscle spasm or pain See cyclobenzaprine above Insomnia See diphenhydramine above

Acetaminophen, Ibuprofenc, hydrocodone/acetaminophen

PIM, potentially inappropriate medication; BPPV, benign paroxysmal peripheral vertigo; ACTH, adrenocorticotropic hormone.

a Diagnosis or symptom for which a potentially inappropriate medication may be prescribed.

b If low risk for gastrointestinal bleeding.

c If low risk for gastrointestinal bleeding and estimated creatinine clearance is greater than 50 mL/min.

d If estimated creatinine clearance is greater than 50 mL/min.

prescribing to older adults, especially when safer and more effective alternative therapies are available. As a result, interventional trials of methods to reduce the prescribing of potentially inappropriate medications, such as educational sessions or computer-assisted decision support systems integrated into discharge instructions, have been recommen- ded and have been judged to be among the highest priority research in Geriatric EMergency medicine [69].

High-risk medications and suggested alternatives

Emergency physicians prescribe several categories of medications that have potential to be hazardous to older adults. The objective of this section is to review the risks that these classes of medication entail.

Nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs are often effective for mild to moderate pain when used alone or in combination with opioids or other analgesics [70]. However, NSAIDs, generally, are no better than acetaminophen for mild to moderate pain, and when used for severe pain, they have a ceiling effect [70]. Once the ceiling is reached, increasing the NSAID’s dose increases the risk of adverse effects without intensifying the pain-relieving effects.

Age is an independent risk factor for peptic ulcer disease complications, and use of NSAIDs by seniors adds greatly to that risk [71]. In older adults, NSAID use is associated not only with increased risk for peptic ulcer disease [72] and ulcer complications [71] but also with increased costs for gastroprotective drugs and hospitalizations for gastrointesti- nal hemorrhage [73]. In addition, there is a clear dose- response relationship, such that the risk for the development of peptic ulcer disease [72] and ulcer complications [71,74] significantly grows with increasing dose of NSAID. Even a brief course of NSAID therapy may not be without risk to older adults. Less than 1 month of NSAID therapy is associated with the development of peptic ulcer disease [72] and peptic ulcer disease complications [71,73,74]. Although the risk of adverse gastrointestinal events varies by NSAID, there is no risk-free NSAID. Thus, although the risk is lowest with ibuprofen [71,72,74], even ibuprofen is associated with an increased risk of peptic ulcer disease and its complications [71,74]. Persons who use NSAIDs and have a history of previous peptic ulcer disease [75] or its complications [71] are at particularly high risk for recurrent disease and complications. The concomitant use of misoprostol, hista- mine-2 receptor antagonists, proton pump inhibitors, and antacids is only partially successful in reducing the risk of gastrointestinal bleeding associated with NSAID use [70].

Nonsteroidal anti-inflammatory drugs are associated not only with peptic ulcer disease and its complications but also with renal complications. Use of NSAIDs decreases the

production of vasodilating renal prostaglandins [9]. This can lead to a reduction in renal perfusion, particularly in seniors, a group whose renal blood flow may be more dependent on prostaglandin regulation than that of younger individuals [9]. As a result, there is an association between use of NSAIDs by older adults and acute renal failure [76]. Similar to the relationship between NSAIDs and Gastrointestinal complications, a dose-response relationship between NSAIDs and acute renal failure is evident [76], and even short-term use of NSAIDs is associated with acute Renal impairment [76].

Because of the high risk of gastrointestinal and renal complications, NSAIDs should be used with caution in older adults. In particular, they should be avoided in patients who are on other medications that can have deleterious effects on the gastrointestinal tract or renal system and in patients with a history of peptic ulcer disease or renal insufficiency. If used in an older adult, we recommend ibuprofen at a low dose and a limited number of tablets, keeping in mind that even a short course can lead to gastrointestinal and renal complications. For many patients, opioid therapy, low-dose Corticosteroid therapy (for those with Inflammatory conditions), or other nonopioid analgesic strategies may be associated with fewer risks than NSAID therapy [70].

Research is needed to define older patients at low risk of NSAID-induced complications and to evaluate therapies to prevent peptic ulcer disease and renal complications [77].

Benzodiazepines

Although benzodiazepines may be prescribed by emer- gency physicians for a variety of conditions, such as benign paroxysmal peripheral vertigo, Acute back pain, and alcohol withdrawal, the question of benzodiazepine safety in older adults is an important consideration. The safety of benzo- diazepines has been studied by means of cohort and case- control studies with numerous outcome measures. Because benzodiazepines have a wide margin of safety, adverse outcomes are uncommon in the general population; how- ever, they have substantial risks in older patients.

Benzodiazepines are associated with an increased risk of falls [78], hospitalizations for falls [79], and Hip fractures [80,81] in older adults. A brief course of benzodiazepines prescribed to an older adult is no safer than long-term use. The rates of falls [79] and hip fracture [80,81] are substantially higher in the first 2 weeks of therapy, and the fall risk may be highest in the first 7 days of benzo- diazepine therapy [78].

Both long and short half-life benzodiazepines are associated with increased risk of adverse outcomes in older adults. Most published studies have identified increased risks of falls [78] and Hip fractures [81-83] among older adult users of long half-life benzodiazepines. Studies of complications with use of short half-life benzodiazepines have produced varied results. Some studies have reported no

significant association with falls [84] or hip fractures [83], whereas others have reported increased rates of falls during the night [78] and hip fractures [81]. One group has suggested that the half-life of the benzodiazepine may not be the critical factor in determining the risk to older adults, and instead, the risk of injury varies by benzodiazepine, independent of half-life or category (eg, anxiolytic) [85].

As with all therapeutic decisions, the clinician must determine if the individual patient’s potential benefits outweigh these potential risks. However, based on the above considerations, benzodiazepines should be pres- cribed with caution, if at all, to older ED patients. If a benzo- diazepine is felt to be necessary, then prescribe a low-dose, short-acting benzodiazepine in very limited supply. There are other effective and safer treatments for acute musculo- drug-Drug interactions“>skeletal pain, such as analgesic medications combined with physical modalities such as heat, cold, and Physical therapy. The older adult with benign paroxysmal peripheral vertigo is more challenging to treat without prescribing a potentially hazardous medication. Because medications are not as effective in treating vertigo [33,86,87], particle repositioning maneuvers should be the first-line therapy [32,33]. Potential medical therapy, other than benzodiaze- pines, includes meclizine, diphenhydramine, and prometha- zine [88]. We favor meclizine as second-line therapy, but it isn’t clear which of the options is most effective and safest for older adults. Although numerous drugs have been recommended for acute alcohol withdrawal, benzodia- zepines are the mainstay of treatment [89]. If the older patient with mild alcohol withdrawal improves with a low dose of lorazepam after a period of observation and does not develop side effects, then use of lorazepam for out- patient treatment is recommended (along with appropriate ED and outpatient counseling for detoxification). If the ED trial of lorazepam fails, then we recommend hos- pital admission.

Anticholinergic medications

Several medications commonly prescribed in the ED, including diphenhydramine, promethazine, cyclobenza- prine, and hydroxyzine, have anticholinergic properties. Adverse effects of anticholinergic medications include delirium, Urinary retention, constipation, and fecal impac- tion and occur more frequently in older patients [9]. These adverse effects can occur in older adults even with use of drugs with only weak anticholinergic activity [9].

Diphenhydramine causes cognitive decrements in older adults [90] and is associated with symptoms of delirium [91] and constipation [92] among elderly patients. Similarly, cyclobenzaprine, hydroxyzine, and promethazine may cause adverse central nervous system effects in older adults [93]. Medications with anticholinergic properties should be avoided when possible in older adults. Occasionally, one of these medications should be administered, such as diphen- hydramine in anaphylaxis. In most circumstances in which

an antihistamine is necessary, second-generation H1 antag- onists are less likely to cause adverse effects in older adults [93]. Promethazine is less effective than prochlorperazine in the treatment of acute nausea and vomiting and is accompanied by fewer side effects [39]. In the treat- ment of acute back and neck pain, cyclobenzaprine and other centrally acting Muscle relaxants are of marginal value at best [30,31], and their use should be avoided in older adults.

Opioids

Studies designed to identify an association between opioid use and falls or fractures have been mixed. In a 1999 systematic review [94], no significant association between opioid use and falling in older adults was identified. We identified 3 studies since the systematic review was published. One concurred that there is no association between opioid use in older adults and falls [84]. Two others examined the impact of opioids on fall-related adverse events and found opioids to be more harmful. One reported that opioid use by older adults is associated with injurious falls leading to ED visits [95]. In the other, taking opioids by older women was found to be associated with all nonvertebral fractures combined but not with hip fractures considered separately [96].

Three prescription analgesics generally should be avoided in older adults: propoxyphene, codeine, and meperidine. Annual prevalence of propoxyphene use is 6.8% by community-dwelling elderly Medicare beneficia- ries and 15.5% by institutionalized elderly Medicare beneficiaries [97]. However, propoxyphene has never been shown to be superior to acetaminophen, and its use entails significant risk [70]. The use of propoxyphene by older adults has been associated with hip fracture [98] and an increased risk of a Composite outcome that included hospitalization, ED visit, or death [65]. Similarly, the risk of hip fracture in older adult users of codeine is also significantly elevated compared with nonusers [98]. Finally, meperidine may cause delirium, impaired mental perfor- mance, and confusion in older adults [93].

We discuss the appropriate use of opioid medications in the Underuse of indicated medications section below.

Drug-drug interactions

Older adults released from the ED are prescribed medications with potential drug interactions more frequently than are younger adults (18% vs 4%) [17]. However, age is not the predictor of whether a potential drug interaction will be introduced [17]. The number of medications that the patient is taking is the critical factor [17,99].

When prescribing to patients who are on warfarin or digoxin, emergency physicians should be particularly concerned about the possibility of introducing drug inter- actions. Warfarin and digoxin are 2 of the most common

medications that are associated with considerable morbidity or fatal outcomes in studies of drug interactions [100]. Antibiotics that are commonly prescribed in the ED may lead to serious and even fatal interactions with warfarin and digoxin. Ciprofloxacin and trimethoprim-sulfamethoxazole may enhance the anticoagulant effect of warfarin [100]. Clarithromycin, erythromycin, and tetracycline have been shown to increase digoxin levels by altering the gut flora that is important in digoxin metabolism [100].

Other important Drug-drug interactions include the following combinations: (1) 2 anticholinergic medications,

(2) NSAIDs plus oral steroids, (3) NSAIDs plus sulfonyl- urea medications, and (4) QT interval-prolonging anti- biotics plus class IA or class III antiarrhythmics. As we described in the Anticholinergic medications section, older adults are sensitive to medications with anticholinergic properties [9]. Older adults are at even greater risk when a second anticholinergic medication is added to a patient’s regimen, such as adding an antihistamine for a patient already on an antidepressant with anticholinergic properties. Prescribers should also avoid prescribing NSAIDs for patients taking oral steroids or sulfonylurea medications. Nonsteroidal anti-inflammatory drugs and steroids each in- crease the risk of peptic ulcer disease and its compli- cations in older adults, and the combination of NSAIDs and steroids should be avoided [101]. Nonsteroidal anti- inflammatory drugs should also be avoided in patients taking sulfonylureas because this combination of medica- tions may increase the risk of hypoglycemia [102-104]. The evidence is strongest for aspirin; however, when prescribing any NSAID to a patient on a sulfonylurea medication, the physician should advise the patient of the possibility of serious drops in blood glucose. Commonly prescribed antibiotics, including macrolides (erythromycin, azithromy- cin, and clarithromycin) and quinolones (ciprofloxacin and levofloxacin), may be associated with QT prolongation [105,106]. These antibiotics should be used with particular caution in patients on other medications that may prolong the QT interval, such as class IA antiarrhythmics (quinidine, disopyramide, and procainamide) and class III antiarrhyth- mics (sotalol and amiodarone).

Prescribing in renal insufficiency

To avoid excessively dosing these medications, emer- gency physicians must not only recognize which medica- tions require dosage adjustment in the setting of renal insufficiency but also identify which patients have renal insufficiency. Significant renal impairment may remain

Fig. 1 Cockcroft-Gault equation [111] to estimate creati- nine clearance.

Table 2 Reduction in dosage is recommended [114] for the following medications commonly prescribed in the ED [28]

Amoxicillin Hydrochlorothiazide

Amoxicillin/clavulanate Cephalexin Trimethoprim/sulfamethoxazole Levofloxacin Ciprofloxacin Metformin

Colchicine Ranitidine

unrecognized by physicians who rely on serum creatinine to identify renal insufficiency [19,107]. Serum creatinine remains normal until the glomerular filtration rate has fallen by at least 50% [108]. Nearly half of older patients have a normal serum creatinine level but a reduced creatinine clearance estimate [109,110]. The Cockcroft-Gault equation (Fig. 1) [111], a formula used to estimate creatinine clearance, provides a better approximation of renal function than using serum creatinine alone [18,112] and is the most frequently used method to approximate renal function [18,107]. Using this equation, an 80-year-old, 50-kg woman with a bnormalQ serum creatinine of 1.0 mg/dL has an estimated creatinine clearance of 38 mL/min. This estimate of creatinine clearance would require dosage adjustment for several commonly used medicines, such as levofloxacin and ranitidine.

The Cockcroft-Gault equation should be used with some precautions in mind. To improve accuracy, the use of ideal body weight is advised [111]. It may be inaccurate in patients with muscle-wasting disease and requires that the patient’s serum creatinine is at a steady state [111]. In addition, creatinine is not only filtered by the glomerulus but is also secreted by the proximal tubule [107]. As a result, creatinine clearance systematically overestimates glomerular filtration rate [108,113]. Despite these limitations, the Cockcroft-Gault equation is accurate enough to be useful under most clinical circumstances in the ED, and it is clearly more revealing than relying on serum creatinine alone.

Renal adjustment is recommended for many medications commonly prescribed in the ED (see Table 2). The clinical implications of failing to adjust for decreased drug clearance estimates are unknown for many of these medications. For some medications, such as metformin, failing to adjust for renal insufficiency puts the patient at significant risk for life- threatening adverse events. However, renal dose adjustment is recommended for many medications that have a large therapeutic window. For example, failing to adjust the dose of cephalexin, amoxicillin/clavulanate, or metronidazole for renal insufficiency may or may not result in serious effects. Additional studies are needed to determine whether dosage adjustment is necessary for these and other medications.

Underuse of indicated medications

The central issue in considering drug misuse in the elderly is no longer just a concern about potentially inappropriate

medications or drug-induced side effects [115]. The under- use of medications with proven efficacy is a topic that must be addressed as well [115,116]. Underuse of beneficial drug therapy by seniors has been associated with increased morbidity, mortality, and reduced quality of life [116], and thus, underuse has joined overuse and misuse as indi- cators for assessing the quality of medication prescribing to seniors [115]. Examples include the underuse of neces- sary medications to treat conditions such as depression, isolated systolic hypertension, and hyperlipidemia in older adults [115].

The most apparent underuse of medication in emergency medicine is the need to more effectively treat acute pain in older patients. Balanced against the potentially negative impact of adding medications in the ED is the possibility of oligoanalgesia in older patients [117]. Age is unfortunately a risk factor for receiving inadequate analgesia in the ED. For example, younger adults with isolated Long-bone fractures are more likely to receive an analgesic medication, receive them more quickly, and receive an opioid analgesic when a pain medication is provided, compared with older patients with similar injuries [118].

Older adults perceive pain differently compared with younger adults. The pain of intravenous catheter place- ment has been shown to be significantly lower in elderly patients, compared with their younger counterparts [119]. Similarly, younger patients report more postoperative pain than do older patients [120]. Younger postoperative patients also obtain less pain relief after the administration of morphine than do older patients [120]. Older adults may therefore achieve pain relief from smaller doses of opioids than younger people. However, the pain of intravenous catheter insertion and postoperative pain may be different from the assorted types of pain experienced by ED patients.

When treating pain in older adults, acetaminophen should be used initially for mild or moderate pain, and NSAIDs should only be used with the precautions described in the High-Risk Medications and Suggested Alternatives section above. However, if acetaminophen or NSAIDs fail or if a patient has more than mild or moderate pain, then opioid analgesics should be considered. They are generally safe for older adults when understood and used correctly [70]. Begin with low doses and slowly titrate up as needed for adequate analgesia. Tolerance to side effects usually develops within just a few days, at which time, patients usually return to a fully alert status and baseline Cognitive function [70]. Constipation is a side effect of opioid medications to which older adults characteristically do not develop tolerance [70]. Opiate-induced constipation may lead to severe discomfort and can contribute to inadequate pain treatment because patients may then minimize analge- sic use [75]. The prevention and management of constipa- tion can be important for adequate analgesia and may include increasing fluid intake and use of stool softeners and motility agents [70].

Strategies to improve prescribing to older adults

Computerized physician Order entry by emergency physicians can reduce errors and interruptions. When comparing handwritten and computer-assisted prescriptions for ED patients, computer-assisted prescriptions are more than one third less likely to contain errors and 80% less likely to require pharmacist clarification than handwritten prescriptions [121].

Computer-assisted decision support use has been shown in multiple settings to augment the capabilities of computerized physician order entry. In the inpatient setting, physician order entry with electronic decision support decreases the rate of Medication errors [122]; increases the rate of delivery of preventive measures (pneumococcal vaccination, influenza vaccination, prophylactic heparin, and prophylactic aspirin at discharge) [123]; increases adherence with practice guide- lines, reduce Errors of omission, and result in fewer interventions initiated by pharmacists [124]; and results in an increases the use of the less expensive drugs, reduces orders exceeding the maximum recommended dose, and increases the use of subcutaneous heparin to prevent thrombosis [125]. Inpatient order entry programs with decision support that estimates creatinine clearance and suggests an appropriate alteration in dosing for specific medications significantly reduce the number of excessively dosed medications [126-128], significantly reduce hospital length of stay [127,128], and reduce costs [127,128].

In the outpatient clinic setting, order entry with elec- tronic decision support increases the rates of discussion of Advance directives and completion of advance directive forms among elderly outpatients with serious illnesses [129] and reduces the prescribing of potentially inappropriate medications [130].

Medical Informatics systems that guide emergency physicians toward better decisions and improvED patient care could have substantial benefit to older ED patients [131]. Physician order entry with electronic decision support has been studied almost entirely outside the ED setting. These systems should be studied in the ED setting so that more definitive conclusions can be reached; however, they have great promise to reduce the prescribing of potentially inappropriate medication, prevent drug-drug interactions, improve proper dosing of medications to patients with renal insufficiency, and much more. At the same time, vigilance will be required to anticipate and address inherent limi- tations and new problems raised in the implementation of computerized prescribing [132,133].

Conclusions

The first tenet of prescribing to older adults should be to use drug therapy only when it is essential. Avoid adding to the list of medications taken by older patients if possible.

When drug therapy is indicated or has established efficacy, the goal must be to achieve maximal therapeutic benefit, the least possible adverse effects, and good compliance with minimal financial hardship [19]. Emergency providers should consider the normal physiological changes that are associated with aging, a medication’s risk in the older adult population, and other medications that the older patient is taking.

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