Editors: Kane, Robert L.; Ouslander, Joseph G.; Abrass, Itamar B.
Title: Essentials of Clinical Geriatrics, 5th Edition
Copyright 2004 McGraw-Hill
> Table of Contents > Part III - General Management Strategies > Chapter 14 - Drug Therapy
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Chapter 14
Drug Therapy
Geriatric patients are frequently prescribed multiple drugs in complex dosage schedules. In some instances, this is justified because of the presence of multiple chronic medical conditions, the proven efficacy of an increasing number of drugs for these conditions, and practice guidelines that recommend their use. In many instances, however, complex drug regimens are unnecessary; they are costly and predispose to noncompliance and adverse drug reactions. Many older patients are prescribed multiple drugs, take over-the-counter drugs, and are then prescribed additional drugs to treat the side effects of medications they are already taking. This scenario can result in an upward spiral in the number of drugs being taken and commonly leads to polypharmacy.
Several important considerations, some pharmacological and others nonpharmacological, influence the safety and effectiveness of drug therapy in the geriatric population. This chapter focuses on these considerations and gives practical suggestions for prescribing drugs for older patients. Drug therapy for specific geriatric conditions is discussed in several other chapters throughout this text.
NONPHARMACOLOGICAL FACTORS INFLUENCING DRUG THERAPY
Discussions of geriatric pharmacology frequently center around age-related changes in drug pharmacokinetics and pharmacodynamics. Although these changes are sometimes of clinical importance, nonpharmacological factors can play an even greater role in the safety and effectiveness of drug therapy in the geriatric population. Several steps make drug therapy safe and effective (Fig. 14-1). Many factors can interfere with this scheme in the geriatric population, and, as can be seen, most of them come into play before pharmacological considerations arise.
FIGURE 14-1 Factors that can interfere with successful drug therapy. |
Effective drug therapy can be hampered by inaccurate diagnoses. Many older patients tend to underreport symptoms; complaints of other patients may be vague and multiple. Symptoms of physical diseases frequently overlap with symptoms of psychological illness. To add to this complexity, many diseases present with atypical symptoms. Consequently, making the correct diagnoses and prescribing the appropriate drugs are often difficult tasks in the geriatric population.
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There is a tendency among health care professionals to treat symptoms with drugs rather than to evaluate the symptoms thoroughly. Because older patients tend to have multiple problems and complaints and consult several health care professionals, they often end up with prescriptions for several drugs. Moreover, older patients or their family members sometimes exert pressure on health care professionals to prescribe medication, thus adding to the tendency for polypharmacy. This pressure is increasing because of the new trend of direct-to-consumer advertising of drugs.
Frequently, neither the patients nor the health care providers have a clear picture of the total drug regimen. New patients undergoing initial geriatric assessment should be asked to empty their medicine cabinets and to bring all bottles to their first appointments. Medication records, such as the one shown in Fig. 14-2, carried by the patient and maintained as an integral part of the overall medical
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FIGURE 14-2 Example of a medication record. |
Adherence plays a central role in the success of drug therapy in all age groups (see Fig. 14-1). In addition to the tendency for polypharmacy and complex dosage schedules, older patients face other potential barriers to adherence. The chronic nature of illness in the geriatric population can play a role in nonadherence. The consequences of these illnesses are often delayed (as opposed to the more dramatic effects of acute illnesses), and chronic illnesses necessitate ongoing prophylactic or suppressive rather than relatively short and time-limited courses of therapy. Adherence tends to be poor for these types of drug regimens. Diminished hearing, impaired vision, and poor literacy, and poor short-term memory can interfere with patient education and adherence. Problems with transportation can make getting to a pharmacy difficult. Outpatient prescriptions are not covered by Medicare (as of June, 2003), thus forcing older persons to pay for their drugs from a limited income. A Medicare prescription benefit will help, but is likely to be limited and involve substantial copayments. Some older people have Medigap insurance policies that cover some medication costs, and capitated
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Several strategies might improve adherence in the geriatric population (Table 14-1). As few drugs as possible should be prescribed, and the dosage schedule should be as simple as possible. Drugs should be given on the same dosage schedules whenever possible, and the administration should correspond to a daily routine in order to enhance the consistency of taking the drugs and compliance. For many drugs, once-daily dosing is available and should be prescribed when clinically appropriate. Relatives or other caregivers should be instructed in the drug regimen, and they, as well as others (e.g., home health aides and pharmacists), should be enlisted to help the older patient comply. Specially designed pill dispensers, dosage calendars, and other innovative techniques can be useful. Geriatric patients and their health care providers should keep an updated record of the drug regimen (see Fig. 14-2). Medications should be brought to appointments, and patients and families should show all medications to their physicians, particularly on initial visits to new primary care physicians or at a consultation with a specialist. Health care professionals should regularly inquire about other medications being taken (prescribed by other physicians or purchased over the counter) and review their patients' knowledge of and compliance with the drug regimen.
TABLE 14-1 STRATEGIES TO IMPROVE COMPLIANCE IN THE GERIATRIC POPULATION | |
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ADVERSE DRUG REACTIONS AND INTERACTIONS
Primum non nocere ( first, do no harm ), a watchword phrase in the practice of medicine, is nowhere more applicable than when drugs are being prescribed for the geriatric population. Adverse drug reactions are the most common forms of iatrogenic illness (see Chap. 5). The incidence of adverse drug reactions in hospitalized patients increases from approximately 10 percent in those between 40 and 50 years of age to 25 percent in those older than age 80 (Lazarou et al., 1998). They account for between 3 and 10 percent of hospital admissions of older patients each year, and result in several billion dollars in yearly health care expenditures. Many drugs can produce distressing, and sometimes disabling or life-threatening, adverse reactions (Table 14-2). Psychotropic drugs and cardiovascular agents are common causes of serious adverse reactions in the geriatric population. In part, this is because of the narrow therapeutic:toxic ratio of many of these drugs. In some instances, age-related changes in pharmacology, such as diminished renal excretion and prolonged duration of action, predispose to adverse reactions. Some side effects can have a therapeutic benefit and may be key factors in drug selection (see below).
TABLE 14-2 EXAMPLES OF COMMON AND POTENTIALLY SERIOUS ADVERSE DRUG REACTIONS IN THE GERIATRIC POPULATION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Because symptoms can be nonspecific or may mimic other illnesses, adverse drug reactions may be ignored or unrecognized. Patients and family members should be educated to recognize and report common and potentially serious adverse reactions. In some instances, another drug is prescribed to treat these symptoms, thus contributing to polypharmacy and increasing the likelihood of an adverse drug interaction. The problem of polypharmacy is exacerbated by visits to multiple physicians who may prescribe still more drugs and the use of multiple pharmacies. Medication records kept by the patient (see Fig. 14-2), as well as the physician's medical record, should help to prevent unnecessary polypharmacy when many physicians are involved. Several drugs commonly prescribed for the geriatric population can interact, with adverse consequences (Table 14-3). The more common types of potential adverse drug interactions are drug displacement from protein-binding sites by other highly protein-bound drugs, induction or suppression of the metabolism of other drugs, and additive effects of different drugs on blood pressure and mental function (mood, level of consciousness, etc.). In addition to the potential to interact with other drugs, several drugs can interact adversely with underlying medical conditions in the geriatric population, creating drug patient interactions (Table 14-4). A good example of this problem is the increased risk of hospitalization for congestive heart failure among older patients taking diuretics who are told to take a nonsteroidal antiinflammatory drug (Heerdink et al., 1998).
TABLE 14-3 EXAMPLES OF POTENTIALLY CLINICALLY IMPORTANT DRUG DRUG INTERACTIONS | |||||||||||||||||||||||||||
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TABLE 14-4 EXAMPLES OF POTENTIALLY CLINICALLY IMPORTANT DRUG PATIENT INTERACTIONS | |||||||||||||||||||||||||||||
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Health care professionals should have a thorough knowledge of the more common drug side effects, adverse reactions to drugs, and potential drug interactions
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AGING AND PHARMACOLOGY
Several age-related biological and physiological changes are relevant to drug pharmacology (Table 14-5). With the exception of changes in renal function, however, the effects of these age-related changes on dosages of specific drugs for individual patients are variable and difficult to predict. In general, an understanding of the physiological status of each patient (taking into account factors such as state of hydration, nutrition, and cardiac output) and how that status affects the pharmacology of a particular drug is more important to clinical efficacy than are age-related changes. New technology in drug delivery systems, such as oral sustained-release preparations and skin patches, have been developed for many medications. Such technology may be useful in designing strategies to account for the effect of aging changes on pharmacology and to make many drugs safer in the geriatric population. Given these caveats, the effects of aging on each pharmacological process are briefly discussed below.
TABLE 14-5 AGE-RELATED CHANGES RELEVANT TO DRUG PHARMACOLOGY | ||||||||||||
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Absorption
Several age-related changes can affect drug absorption (see Table 14-5). Most studies, however, have failed to document any clinically meaningful alterations in drug absorption with increasing age. Absorption, therefore, appears to be the pharmacological parameter least affected by increasing age.
Distribution
In contrast to absorption, clinically meaningful changes in drug distribution can occur with increasing age. Serum albumin, the major drug-binding protein, tends to decline, especially in hospitalized patients. Although the decline is numerically small, it can substantially increase the amount of free drug available for action. This effect is of particular relevance for highly protein-bound drugs,
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Age-related changes in body composition can prominently affect pharmacology by altering the volume of distribution (Vd). The elimination half-life of a drug varies with the ratio Vd:drug clearance. Thus, even if the rate of clearance of a drug is unchanged with age, changes in Vd can affect a drug's half-life and duration of action.
Because total body water and lean body mass decline with increasing age, drugs that distribute in these body compartments, such as most antimicrobial agents, digoxin, lithium, and alcohol, may have a lower Vd and can, therefore,
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Metabolism
The effects of aging on drug metabolism are complex and difficult to predict. They depend on the precise pathway of drug metabolism in the liver and on several other factors, such as gender and amount of smoking. There is evidence that the first, or preparative, phase of drug metabolism, including oxidations, reductions, and hydrolyses, declines with increasing age, and that the decline is more prominent in men than in women. In contrast, the second phase of drug metabolism (biotransformation, including acetylation and glucuronidation) appears to be less affected by age. There is also evidence that the ability of environmental factors (most importantly smoking) to induce drug-metabolizing enzymes declines with age. Even when liver function is obviously impaired, as by intrinsic liver disease or right-sided congestive heart failure, the effects of aging on the metabolism of specific drugs cannot be precisely predicted. It is not safe to assume, however, that geriatric patients with normal liver function tests can metabolize drugs as efficiently as can younger individuals.
The cytochrome P450 system in the liver has been extensively studied. More than 30 isoenzymes have been identified and classified into families and subfamilies. Genetic mutations in some of these enzymes, while relatively uncommon, can impair metabolism of specific drugs. Although aging may affect this system, the effects of commonly used drugs are probably more important. Ketoconazole, erythromycin, and the selective serotonin reuptake inhibitors (especially fluoxetine) can inhibit the metabolism of several drugs (see Chap. 7). Potentially fatal ventricular arrhythmias have been caused by high levels of the antihistamines terfenadine and astemizole, resulting from inhibition of these enzymes.
Excretion
Unlike those of metabolism, the effects of aging on renal functions are somewhat more predictable. The tendency for renal function to decline with increasing age can affect the pharmacokinetics of several drugs (and their active metabolites) that are eliminated predominantly by the kidney (Table 14-6). These drugs are cleared from the body more slowly, their half-lives (and duration of action) are prolonged, and there is a tendency to accumulate to higher (and potentially toxic) drug concentrations in the steady state.
TABLE 14-6 IMPORTANT CONSIDERATIONS IN GERIATRIC PRESCRIBING | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Several considerations are important in determining the effects of age on renal function and drug elimination:
There is wide interindividual variation in the rate of decline of renal function with increasing age. Thus, although renal function is said to decline by 50 percent between the ages of 20 and 90 years, this is an average decline. A 90-year-old individual may not have a creatinine clearance of only 50 percent of normal. Applying average declines to individual elderly patients can result in over- or underdosing.
Muscle mass declines with age; therefore, daily endogenous creatinine production declines. Because of this decline in creatinine production, serum creatinine may be normal at a time when renal function is substantially reduced. Serum creatinine, therefore, does not reflect renal function as accurately in elderly people as it does in younger persons.
A number of factors can affect renal clearance of drugs and are often at least as important as age-related changes. State of hydration, cardiac output, and intrinsic renal disease should be considered in addition to age-related changes in renal function.
Several formulas and nomograms have been used to estimate renal function in relation to age. Table 14-7 shows the most widely used and accepted formula. This formula is useful in initial estimations of creatinine clearance for the purpose of drug dosing in the geriatric population. Clinical factors (such as state of hydration and cardiac output), which vary over time, should be considered in determining drug dosages.
TABLE 14-7 RENAL FUNCTION IN RELATION TO AGE* | ||
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When drugs with narrow therapeutic:toxic ratios are being used, actual measurements of creatinine clearance and drug blood levels (when available) should be used.
Tissue Sensitivity
A proportion of the drug or its active metabolite will eventually reach its site of action. Age-related changes at this point that is, responsiveness to given drug
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GERIATRIC PRESCRIBING
General Principles
Several considerations make the development of specific recommendations for geriatric drug prescribing very difficult. These include the following:
Multiple interacting factors influence age-related changes in drug pharmacology.
There is wide interindividual variation in the rate of age-related changes in physiological parameters that affect drug pharmacology. Thus, precise predictions for individual older persons are difficult to make.
The clinical status of each patient (including such factors as state of nutrition and hydration, cardiac output, intrinsic renal and liver disease) must be considered in addition to the effects of aging.
As more research studies with newer drugs are carried out in well-defined groups of older subjects, more specific recommendations will be possible.
Adherence to several general principles can make drug therapy in the geriatric population safer and more effective (Table 14-8). Cardiovascular drugs, which account for a substantial proportion of adverse drug reactions, are also discussed in Chap. 10. Because psychotropic drugs are so commonly used, they are discussed in greater detail below.
TABLE 14-8 GENERAL RECOMMENDATIONS FOR GERIATRIC PRESCRIBING | |
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GERIATRIC PSYCHOPHARMACOLOGY
Psychotropic drugs can be broadly categorized as antidepressants (discussed in detail in Chap. 7), antipsychotics (Table 14-9), and sedatives and hypnotics (Table 14-10). These drugs are probably the most misused class of drugs in the geriatric population. Several studies show that more than half of nursing home residents are prescribed at least one psychotropic drug and that these prescriptions are changed
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TABLE 14-9 EXAMPLES OF ANTIPSYCHOTIC DRUGS* | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Several considerations can be helpful in preventing the misuse of psychotropic drugs in the geriatric population:
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Psychological symptoms (depression, anxiety, agitation, insomnia, paranoia, disruptive behavior) are often caused or exacerbated by medical conditions in geriatric patients. A thorough medical evaluation should therefore be done before symptoms are attributed to psychiatric conditions alone and psychotropic drugs are prescribed.
Reports of psychiatric symptomatology such as agitation are often presented to physicians by family caregivers and nursing home personnel who are inexperienced in the description, interpretation, and differential diagnosis of these symptoms. Agitation or disruptive behavior may, in fact, have been a reasonable response to an inappropriate interaction or situation created by the caregiver. Psychotropic drugs should, therefore, be prescribed only after the physician has clarified what the symptoms are and what correctable factors might have precipitated them.
Psychological symptoms and signs, like physical symptoms and signs, can be nonspecific in the geriatric patient. Therefore, appropriate drug treatment often depends on an accurate psychiatric diagnosis. Psychiatrists and psychologists experienced with geriatric patients should be consulted, when available, in order to identify and help target psychotropic drug treatment to the major psychiatric problem(s).
Many nonpharmacological treatment modalities can either replace or be used in conjunction with psychotropic drugs in managing psychological symptoms. Behavioral modification, environmental manipulation, supportive psychotherapy, group therapy, recreational activities, and other related techniques can be useful in eliminating or diminishing the need for drug treatment.
Within each broad category of psychotropic drug, there are considerable differences among individual agents with regard to effects, side effects, and potential interactions with other drugs and medical conditions. Rational prescription of these drugs necessitates careful consideration of the characteristics of each drug in relation to the individual patient.
Because geriatric patients are, in general, more sensitive to the effects and side effects of psychotropic drugs, initial doses should be lower, increases should be gradual, and monitoring should be frequent.
Careful, ongoing assessment of the response of target symptoms and behaviors to psychotropic drugs is essential. In addition to reports from patients themselves, objective observations by trained and experienced professionals should be continuously evaluated in order to adjust psychotropic drug therapy.
All psychotropic drugs must be used judiciously in geriatric patients because of their potential side effects. The most common and potentially disabling side effects of psychotropic drugs fall into four general categories: changes in cognitive status (e.g., sedation, delirium, dementia) and extrapyramidal, anticholinergic, and cardiovascular effects. Research documents that psychotropic drugs can
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Anticholinergic and cardiovascular side effects are most prominent with the tricyclic antidepressants. Antipsychotic drugs with -adrenergic blocking properties, including chlorpromazine and thioridazine, also have cardiovascular side effects, most notably hypotension. Newer drugs without such effects have largely replaced these agents. Extrapyramidal side effects are most common with several antipsychotic drugs (see Table 14-9). These effects which include pseudoparkinsonism (rigidity, bradykinesia, tremor), akathisia (restlessness), and involuntary dystonic movements (such as tardive dyskinesia) can be severe and may cause substantial disability. Rigidity and bradykinesia can lead to immobility and the complications discussed in Chap. 10. Akathisia can make the patient appear more anxious and agitated, and can lead to the inappropriate prescription of more medication. Tardive dyskinesia can cause permanent disability as a consequence of continuous orolingual movements and difficulty with eating. In addition to side effects, many psychotropic drugs interact with each other and with other drug classes. Some of these interactions can be clinically important and can enhance the risk of toxicity (Steffens and Krishnan, 1998).
Optimal efficacy of psychotropic drugs necessitates considering the characteristics of the drugs in relation to several clinical factors in each patient (Table 14-11). In general, the antipsychotic agents should be reserved for treatment of psychoses (i.e., paranoid states, delusions, and hallucinations), which are common in dementia patients. These drugs may also be useful for severe physical and/or verbal agitation that does not respond to nonpharmacological interventions. Environmental and behavioral interventions should be attempted before psychotropic drugs are prescribed. There is no clear choice of one antipsychotic agent over another based on controlled clinical trials. Some of the newer agents, such as risperidone, olanzapine, and quetiapine, have less extrapyramidal side effects than older drugs. They are clearly the drugs of choice for psychosis that occurs in dementia of Parkinson's disease and dementia associated with Lewy bodies (see Chap. 6). In some situations, intermittent agitation, especially at night, is best treated by a short-acting benzodiazepine (see Table 14-10). When antipsychotics fail or cause side effects, and sedation is not desired, carbamazepine and valproic acid may be useful alternatives in some patients. Both of these drugs, however, have the potential for hematological and hepatic toxicity and must be used cautiously in the geriatric population. Periodic attempts to taper and discontinue the use of these drugs are required in nursing facilities, and can result in the successful removal of psychotropics for some patients (Cohen Mansfield et al., 1999).
TABLE 14-11 CLINICAL CONSIDERATIONS IN PRESCRIBING PSYCHOTROPIC DRUGS | |||||||||||||||||||||
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TABLE 14-10 EXAMPLES OF SEDATIVES AND HYPNOTIC AGENT* | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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A variety of nonpharmacological measures can be effective in geriatric patients with agitation or excessive anxiety. Specific behavioral and other nonpharmacological therapeutic approaches are described in detail in some of the
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Insomnia, like agitation, can be the manifestation of depression or physical illness. It is a very common complaint in geriatric patients, and causes of sleep disorders should be sought (see Chap. 7). Nonpharmacological measures (such as increasing activity during the day, diminishing nighttime noise, and ensuring cooler nighttime temperatures) are sometimes helpful. Several alternatives are available for drug treatment of insomnia (see Table 14-10). Melatonin, a naturally occurring hormone available over the counter, has gained increasing popularity as a hypnotic. Geriatric sleep disturbances are associated with changes in the melatonin cycle. Doses of 1 to 3 mg may improve the initiation and maintenance of sleep. The long-term effects of chronic hypnotic use in the geriatric population are unknown, but rebound insomnia can become a problem in patients who use hypnotics (especially benzodiazepine hypnotics and melatonin) regularly and then discontinue them. Whatever the indication, it is extremely important that after a psychotropic drug is prescribed the patient be closely monitored for the effects of the drug on the target symptoms and side effects, and that the drug regimen be adjusted accordingly.
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Beers MH: Explicit criteria for determining potentially inappropriate medication use by the elderly. Arch Intern Med 157:1531 1536, 1997.
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Carlson DL, Fleming KC, Smith GE, et al: Management of dementia-related behavioral disturbances: a nonpharmacologic approach. Mayo Clin Proc 70:1108 1115, 1995.
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Selma TP, Beizer JL, Higbee MD: Geriatric Dosage Handbook, 5th ed. Hudson, OH, American Pharmaceutical Association and Lexi-Comp, 2000 2001.