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Pharmacotherapy Problems in the Elderly
armacotherapy Pro lems in the Elderly A basic understanding of how physiologic
changes of aging affect the fate and action of drugs can help the pharmacist develop pharmaceutical care plans. Joseph F. Steiner, PharrnD
Introduction The past 20 years have seen a revolution in our knowledge of how the processes of
aging affect drug therapy. With this knowledge has come remarkable progress in caring for patients over the age of 65. Advances in medical technology have enhanced studies of the physiologic changes of aging, and we now have a much more formidable understanding of how physiologic changes affect the treatment of disease and the use of medications. This knowledge forms the basis of care. Ongoing research is constantly updating and expanding this knowledge base. Numerous diseases present and progress differently in the elderly than in younger Counseling elderly patients on the proper use of medications is an patients. Many of these differences represent increasingly crucial thrust ofpharmaceutical care. important considerations in developing pharmaceutical care plans for the ill elderly patient. Moreover, new medications have been devel- Summary oped for treating diseases primarily seen in the • As the elderly population increases, pharmacists will routinely confront elderly. aging-related problems in drug therapy. At one time new medications under Food • Drug therapy plans must take into account that diseases will present and Drug Administration (FDA) review for and progress differently in the elderly. marketing were studied primarily in younger patients; often, the elderly were specifically • Individual variations characterize the aging process, and it is physiologic-versus chronologic-aging that underlies age-related differences excluded by the study protocols. The results in pharmacokinetics and pharmacodynamics. of these studies were then inappropriately extrapolated to the elderly. FDA now requires • More than one in six elderly Americans are taking prescription drugs that medications intended for use in a certain whose adverse effects can have serious consequences in this age group. age group be studied in patients of that age VoL NS36, No.7
July 1996
journal of the American Phannaceutical Association
group to gain approval for marketing. 1 Because of this, the Physiology of Aging problems specific to the elderly now have a better chance of being known when a new drug is introduced , and The elderly population is not a homogeneous one. Rather, the patients can be monitored or interventions made. There are now physicians and nurse practitioners who are aging process is characterized by marked individual variations. board certified in the practice of geriatrics. These health care Physiologic aging does not parallel chronologic aging, and with providers understand the physiologic differences that exist in the exception of the effects produced by disease, it is physiologic the elderly and have the expertise to diagnose and treat with- aging that underlies age-related differences in the fate and action in these parameters. Often, these professionals may use a mul- of drugs.3 Therefore, effective and safe use of dnlgS in geriatric tidisciplinary geriatric assessment team for global evaluation patients is a matter of careful individualization of therapy. of an elderly patient. The composition of these teams is flexible, but usually includes a physician and a nurse practitioner, a social worker, a nutritionist, and a pharmacist. All pharma- Multiple disease states Multiple disease states are common in the elderly, and it cists have a role in the dnlg therapy of the elderly through the is the nIle rather than the exception that each disease is provision of pharmaceutical care. The major reasons for this growing interest in geriatrics treated with one or more medications. At least 80% of are the increase in the elderly population, the vast number those over the age of 75 suffer from at least one chronic of ailments seen in this group, and the subsequently consid- disease, and of those, as many as 40% suffer from two or erable use of medications . The population of the United more comorbidities. 4 In long-term care institutions, multiStates is growing older every day. Currently, 12% of the pop- ple pathology is routine for most patients. Often, multiple I ulation-32 million Americans-are 65 years of age or older. prescribers are involved, and one may be unaware of what There is currently a dip in the growth rate of this population the other has prescribed or may not detect potential probbecause of the lower number of births during the Great lems. Without intervention by a pharmacist, this situation I Depression; however, the growth rate should accelerate may lead to polypharmacy, with its inherent increased I around 2010 and peak in 2030 as the "baby boom" genera- incidence of adverse drug reactions, increased potential tion reaches age 75 to 85. By the year 2040 the elderly pop- for drug-drug and drug-disease interactions, and compliulation is expected to increase to 68 million, or 23% of the ance problems .5 Additionally, diseases may alter the projected population. 2 patient 's response to therapy, so that the anticipated In 1986 the 12% of the population over 65 represented response is not seen or other effects become more pro- I 25% of all patient visits in the United States. Today, elderly nounced. ericans spend approximately $3 billion annually on preOccasionally, one medication may have the pharmacologcription medications, little of which is reimbursed by third ic advantage of producing several beneficial effects and party payers. In the United may be used to treat multate and other develtiple problems in an indioped countries, this segvidual patient. Use of a More than one in six ment of the population single medicatio n currently accounts for reduces the potential for elderly Americans are taking about 25 % of the total polypharmacy and with prescription drugs that drug expenditures , but it the inherent risks of thi proportion is estimatadverse drug reactions, are not suitedfor older people ed to reach 40 % by the noncompliance , and year 2030. 3 drug-drug interactions. With these changes , For example , a patient the incidence of probwith depression and lems associated with insomnia may be better medication use has the treated with a sedating potential to grow expoantidepressant at bednentially, creating a great time than a serotoni n challenge for pharmacists who provide care to elderly reuptake inhibitor (SSRI) antidepressant in the morning and patients. The pharmacist must therefore have a basic under- a sedative at bedtime. The pharmacist can help the prestanding of the underlying physiologic changes of aging, scriber select appropriate alternatives for individual how these affect the pharmacokinetics and pharmacody- patients. When multiple disease states are present, care namics of medications, and medications that have the great- must be taken to ensure that no contraindications exist to est potential for problems. the use of a particular single agent. Journal of the American Pharmaceutical Association
July 1996
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Altered reserve capacity A con istent characteri tic of aging organ i the pr gr 'ive deterioration of re rve functional capacity. Each organ , tern in a young, h althy adult will not normally be working at full capacity, 0 a re erve will exist. Exce sive organ re elve allows the body to compensate for large variations in phy iologic parameters or biologic insults. This capacity may be up to 10 times that necessary to sustain life in a young, healthy adult. However, it is estimated that the re erve functional capacity of various organs declines at a rate of 0.8% to 0.9% per year after age 30. Because of the large initial capacity, this grcldual decrease should not cause signs, symptoms, or disability until a "critical threshold" for that organ system is reached. Ideally, this would occur at the end of the natural life span or not be reached at all before death. Many diseases and lifestyle habits may accelerate this decline in organ reserve capacity, so that organ failure , disability, and death occur much earlier. This partially explains the altered presentation of disease states in the elderly. For example, confusion may be the only symptom of a urinary tract infection in an elderly patient. An elderly patient who has one or more organ systenls approaching or past the critical threshold is at an increased risk for adverse drug reactions, and drugs may be the stressor that shifts the reserve to below the critical threshold. Drugs can also precipitate organ failure by antagonism of compensatory mechanisms that help to maintain function. 6
Adverse reactions and interactions More than one in six elderly Americans are taking prescription drugs that are not suited for older people and may lead to physical or mental deterioration-possibly even death.7 While the elderly are often perceived as more likely to have adverse reactions to medications, this perception is not supported by the literature. 8 The elderly do take lllore medications, which increases the risk, and adverse reactions account for 17% of the hospitalizations of the elderly at a cost of $20 billion annually.8 Several factors influence patient susceptibility to adverse drug reactions. 9 First, the incidence of adverse reactions increases exponentially with the number of medications taken. Second, multiple disease states and increased severity of disease nlay alter the pharmacokinetics of certain medications and lead to adverse reactions. Third, not properly adjusting doses to allow for normal pharmacokinetic changes in the elderly accounts for 70% to 80% of adverse reactions. Fourth, some drugs are more likely to cause adverse reactions than others, and these, unfortunately, are often prescribed for the elderly. Fifth, pharmacodynamic alteration that increase receptor sensitivity may lead to a higher incidence of adverse drug reactions. Of the 30 rnillion noninstitutionalized Medicare recipients aged 65 or older, an estimated 17.5% had been prescribed drugs inappropriate for their age group when safer drugs existJ Pharmacists can play an important role in avoidVol NS36, No. 7
July 1996
in r acti n b un lin Id rl pr p r n1 dication u , rking ith th pr th u e f th a.fi t m di ati n ~ r a rtain r vi wing pr cription rd r ~ r inappr priat
pati nt ab ut rib r t c nditi n and m di ati
Compliance Many patients, not only th elderly, hav difficulty taking medication as prescribed by their clinicians. It ha b n estimated that noncompliance rate range from 25% to 59% in the elderly, including omission of medication , lack of knowledge of the medication, use of a medication not prescribed, and errors in dosing , sequence, or timing.s The rate of noncompliance increases with an increase in the number of medications taken up to an error rate of 70% when the patient is taking six or more medications. Compliance nlay be helped by decreasing the number of doses , decreasing the frequency of administration, patient education, cue cards, calendars, and dispensing devices. However, the only plan that has been shown to consistently improve compliance is to decrease the number of doses and the frequency of administration. The prohibitive cost of the medications may lead some elderly to skip doses to stretch the medication, especially when multiple expensive medications are prescribed; hence less expensive alternatives may greatly aid compliance. lo Elderly patients are also likely to return to taking medications from discontinued prescriptions, not recognizing that an identical new medication has been prescribed. The pharmacist may aid compliance by monitoring prescriptions for timely refills, asking the patient whether the cost is a barrier to obtaining and taking the medication, and working closely with the prescriber to select less expensive alternatives or fmd other sources of funding or medication, such as pharmaceutical company indigent care program . The pharmacist should also monitor for repetitions in therapy by reviewing the medication record and by compiling a careful drug history with the patient when new medication are added.
Pharmacokinetic Problems Table 1 summarizes the direction of ag -r lat d pharmacokinetic changes in drug ab orption di tributi n metabolism, and elimination.
Absorption Absorption of medications is the pharmacokinetic parameter least affected by aging. Normal aging decreases splanchnic blood flow , slows gastric motility, and delays gastric journal of the American Pharmaceutical Association
Table 1
Age-Related Changes in Pharmacokinetics Function
Direction of Change
Absorption Rate of absorption splanchnic blood flow gastric motility gastric emptying Extent of absorption
Distribution Body fat Lean muscle mass Total body water Serum albumin u 1-acid glycoprotein
Metabolism Hepatic blood flow Hepatic function Phase I (oxidation, cytochrome P-450) Phase II (conjugation)
Elimination Renal function
emptying. These changes may decrease the rate of absorption for a few medications after oral administration. Other changes may decrease the extent of absorption-gastric acid secretion is decreased in approximately 40% of the elderly, and the intestinal surface area is decreased with aging. The implications for clinical drug therapy are few, however. Prodrugs that require an acid medium may not be activated, and the onset of effect of as-needed medications may be slowed. Most drugs that have been studied in the elderly show no significant change in the extent of absorption, and while the rate may be slower, the total amount absorbed (area under the curve) remains the same. 9
Distribution Age-related body fat increases are on the average of 18% to 36% for males and 33% to 45% for females. This may increase the volume of distribution (Vd) for those lipophilic (fat-soluble) medications that distribute to fat tissue. This larger Vd for Journal of the American Phannaceutical Association
lipid-soluble drugs, such as anesthetics, barbiturates, and ben. zodiazepines, may result in a longer half-life (tw) and pro. longed effects in the elderly. Total body water decreases 10% to 15% and muscle mass decreases 20% as humans age. This may decrease the Vd and therefore increase the concentration of medications that are hydrophilic (water-soluble) and pri. marily distributed to lean body tissue. 9 Ethanol is an example of a water-soluble medication that has increased effects as peo. pIe age because of the relative increased concentration pro. duced by the decreased Vd. Additionally, the serum plasma proteins, such as albumin, may decrease up to 25% because of decreased hepatic pro. duction. This change may result in a reduced protein-bound (inactive) form of a medication that is highly protein bound and an increase in the free (active) form, which may result in increased pharmacologic activity and risk of toxicity. Nonnal· ly, laboratories will measure total drug (both bound and unbound) when serum drug levels are requested. Therefore, this measurement may not reflect the true drug activity when serum proteins are reduced. When the prescriber or consulting pharmacist suspects this is occurring, a free drug level should be obtained whenever possible. Conversely, an acute· phase reactant, alpha I-glycoprotein, may be released in the presence of inflammation and advanced age (e.g., in rheuma- \ toid arthritis). This reaction may increase the protein binding of basic drugs, such as lidocaine and propranolol, decreasing the amount of unbound active drug and decreasing the pharmacologic effect. 2 ,3,6
Metabolism Hepatic function and blood flow determine the rate of drug metabolism. In the elderly, these two factors may vary considerably between individuals, but both decline with aging. Generally, liver mass decreases and the number of functioning hepatocytes is reduced. Liver blood flow also declines by 0.3% to 1.5% per year as a person ages, and, subsequently, may be reduced by 40% to 45% in the typical 65year-old when compared with that seen at age 25. 2 These physiologic changes may result in a marked decrease in the frrst-pass metabolism of drugs. Hepatic metabolism occurs by two mechanisms: the microsomal enzyme mixed-function oxidase system (Phase I), which includes the cytochrome P-450 systems; and conjugation of the drug molecule with a glucuronide, a sulfa, or an acetyl moiety (phase II). Phase I metabolism may produce compounds with pharmacologic activity, while Phase II metabolism usually produces inactive metabolites. Declines in Phase I metabolism are often noted in the elderly, and several enzymatic reactions of the cytochrome P-450 systems are slowed considerably with advancing age . Phase II metabolism, however, is generally unaffected by aging. Therefore , metabolism may be slowed and a prolonged duration of action seen in the elderly for those medications that are priJuly 1996
Vol. NS36, No.7
I
lllarily metabolized through Pha
I reactions, but n t tho e metabolized through Phas II.2 ,3,6,9
~
r
Table 2
Questions to Ask in Developing a Pharmaceutical Care Plan
Elimination Drug elimination i determined primarily by renal function, which declines continuously with normal aging. The degree of this decline, however, varies greatly between individuals. The glomerular ftitration rate is reduced due to age-related decreases in renal mass , loss of functional nephrons, and diminished renal arterial perfusion. Creatinine clearance (CCr) is a good indicator of renal function and correlates well with drug elimination. After the age of 25, where CCr is approximately 120 mL/minute, a decrease of 0.5 to 1 mL/minute/70 kg yearly is seen. This may increase the t ];2 of medications that are renally cleared, lead to accumulation of the medication or active metabolites, and increase the potential for toxicity, especially if the medication has a narrow therapeutic index. Muscle mass is the primary site for creatinine production and release, and the concurrent decrease in mass seen with aging renders the serum creatinine (SCr) invalid as a measure of age-related renal decline. 2 However, the SCr may be used to calculate the creatinine clearance, and the following Crokcroft-Gault formula is most commonly used for estimating age-related declines l l : CCr (mL/min)
= (140 - age) x weight(kg) x 0.85 (females only) 72
x SCr
1. When considering drug therapy: • What is the therapeutic goal? What is the appropriate duration of therapy? • Is the problem being dismissed without treatment as a symptom solely of old age when drug therapy can contribute to improved quality of life? • Is drug treatment necessary or can alternatives to medications be used? • Is this medication the best choice for initial therapy for this patient based on efficacy, cost, ease of administration, patient risk, safety, potential adverse reactions, interactions, and the possibility of treating several medical conditions with one drug? • Is this medication being added to treat the side effect of a current medication? • Is the dose appropriate ("start low and go slow")? 2. When monitoring a patient: • Has the goal of drug therapy (cure vs. increased quality of life) been met (or is it being met), and is a particular medication still considered necessary? • What specific objective parameters should be monitored for this medication and how often should these be repeated? • Are there symptoms of adverse reactions or interactions? • Can the dose be decreased while still maintaining pharmacologic effect? • Is compliance a problem? • Is there redundant drug therapy?
Dosages of many medications that are renally cleared are based on CCr. When prescribed for the elderly, doses may have to be reduced or the dosing schedule modified to prevent toxicity. The use of multiple medications increases both the likelihood of pharmacokinetic drug interactions and the difficulty of predicting serum levels of medications.
3. When dispensing the medication:
Pharmacodynamic Problems
4. When counseling and providing patient education:
Alterations in end-organ responses to medications occur with aging when receptor sensitivity to the drug at a given plasma level either increases or decreases. Thus, lower levels of some drugs may produce marked clinical effects or higher dosages may be necessary for other medications to achieve the desired therapeutic effect. 9,12 These pharmacodynamic changes may be due to changes in receptor binding, decreases in receptor number, or altered translation of a receptor-initiated cellular response into a biochemical reaction. While the pharmacokinetic changes related to aging are well documented, the pharmacodynamic changes are known only for a few medications. Vol. NS36, No.7
July 1996
• Are there any potential physical problems with the use of this medication? (e.g., can the patient open safety containers, read the label, swallow solids, etc.)? • Is a dispensing device appropriate for this patient? If so, what type of device?
• Who should be educated-the patient, the caregiver, or both? (The pharmacist may have to assess the patient's memory and cognition.) • The patient or caregiver should understand and remember: • Which medications mayor may not be taken together • The timing of doses in relation to food intake • When to return for laboratory tests to monitor drug response or adverse reactions • Condition the medication is intended to treat • What to do when doses are missed • Potential adverse reactions and their signs and symptoms
journal of the American Pharmaceutical
Specific Diseases and Pharmacotherapy Problems While an understanding of the general problems that affect drug therapy in the elderly is essential for the provision of pharmaceutical care, the pharmacist must also consider the impact of aging on specific diseases and the implications of drug therapy. It is beyond the scope of this paper to present all of the specific diseases and pharmacotherapy problems that exist, so what follows is a discussion of some of the more common ones.
I
Cardiovascular Digoxin is renally eliminated and with its narrow therapeutic index has the potential for toxicity in elderly patients. The CCr should be calculated for all elderly patients and digoxin dosed accordingly. Also, since digoxin is a water-soluble medication, its Vd will be reduced. Therefore, loading doses should be reduced. 2 Patients should be monitored for signs of toxicity (arrhythmias, anorexia, nausea, and visual disturbances), and a digoxin serum level should be obtained once steady state is reached. This may take 10 days to 2 weeks because of the prolonged tw' Digoxin serum levels may be altered by many medications that may be either added or discontinued in the elderly, such as quinidine or verapamil, without thought to the interaction. Diuretics may produce several problems in the elderly. With the loss of renal function, the thiazide-type diuretics, with the exception of metolazone, lose their efficacy when the CCr drops below 20 mL/min.2 The loop diuretics and metolazone are considered effective to a CCr of 5 mL/min. Diuretics may cause dehydration and electrolyte disorders in the frail elderly, and this may pass the critical threshold of reserve for some patients. This potential volume depletion increases the risk of nonsteroidal anti-inflammatory drug (NSAID) and angiotensin-converting enzyme (ACE) inhibitor-induced renal toxicity. Finally, diuretics have great potential for drug interactions in the elderly. For example, diureticinduced potassium loss may increase the potential for digoxin toxicity, or diuretics may induce gout in a patient with hyperuricemia. Warfarin manifests a pharmacodynamic alteration in that the elderly may be more sensitive to its inhibition of the synthesis of vitamin K-dependent clotting factors and bleeding may be a problem. 13 The international normalization ratio (lNR) should be monitored closely in elderly patients on oral anticoagulants and maintained in the therapeutic range for the condition being treated. Many medications and foods rich in vitamin K may interact with warfarin, causing fluctuations in the INR. Journal of the American Pharmaceutical Association
Hypertension Beta-blocker and beta adrenergic stimulant response are diminished in the elderly due to altered pharmacodynami . The decrease in number of beta receptors and in their sensi. tivity with aging makes these medications less effective in the elderly. 14 Also, beta-blockers have the potential for antagoniz. ing compensatory mechanisms in elderly patients with cal} gestive heart failure. To compensate for the heart failure, the sympathetic nervous system is activated and its support of the failing myocardium is negated by beta-blockade. The use of beta-blockers may also be detrimental in patients with chron· ic obstructive pulmonary disease, diabetes, and peripheral claudication. Also, ocular beta-blockers may be sufficiently absorbed to cause systemic adverse reactions. The calcium channel blockers verapamil and diltiazem require increased serum concentrations to produce their pharmacologic effect of PR-interval prolongation on an elec· trocardiogram when compared with the concentrations need· ed to produce this effect in younger adults. This is considered an age-induced pharmacodynamic alteration and suggests a decreased sensitivity to the depressant effects of these medi· cations on cardiac conduction.
Psychologic disorders Antidepressant use in the elderly presents several prob· I lems. The older tricyclic antidepressants, such as amitriptyline I or imipramine, have high anticholinergic, cardiac, sedative, and orthostatic adverse reactions, all of which may be more I severe in the elderly because of lack of reserve and the poten· I tial for additive effects with other medications. Orthostatic I hypotension is a particular problem in that it may lead to falls in susceptible elderly patients, increasing the risk of fractures. Although incidence of depression does not differ between the elderly and the younger population, elderly patients may have more symptoms of depression. 15 Depression must also be considered as an underlying cause for dementia in the elderly. The potential for suicide may exist in the depressed elderly patient, and these medications have the potential for fatalities at relatively low toxic doses. For these reasons, the selective serotonin reuptake inhibitors (SSRIs) have been touted as the drug of choice for the treatment of depression in the elderly. However, these medications are generally more expensive, and they may also produce troublesome adverse reactions in elderly patients, such as anxiety, sexual dysfunction, weight loss, and gastrointestinal distress. Depression is a common adverse reaction for many medications. The drug list should be reviewed and any medications that cause depression discontinued before antidepressant treatment is started. Benzodiazepines pharmacodynamically produce an enhanced effect in the elderly. Also, many of the benzodi· azepines are metabolized by the oxidative cytochrome p-450 system and their metabolism may be slowed in elderly patients, leading to accumulation of the drug and its active July 1996
VoL NS36, No.
roetabolit and pr I n d a dati n.2 •6 Th exceptions ar I raz pam xaz pam and t maz pam hi h are metab liz d t ina ti mp un thr ugh njugati n. e eral tudi of ld rly pati n n b nz diaz pin h w that an incre in falls is iat d with only th b nzodiazepine who half-live ar prolong d with aging.16.1 veral medication , uch as cimetidine, may ven further compromise the cytochrome P-4 50 metaboli m of the benzodiazepine and prolong their half-li e . The potential for problems exists with the liberal use of elf-medication by the elderly and the availability of cimetidine over the counter. Finally, benzodiazepines are lipid-soluble and will accumulate in the increased adipose tissue seen in the elderly, further increasing these drugs' half-lives. Antipsychotic medications have been used to control agitation, aggression, hallucinations, and paranoia, primarily in residents of long-term care institutions. Pharmacodynamically, the elderly are very sensitive to the effects of the antipsychotic agents and particularly vulnerable to their adverse reactions. The low-potency, high-dose antipsychotics (chlorpromazine and thioridazine) are more sedating and cause more postural hypotension. The high-potency, low-dose antipsychotics (haloperidol and thiothixene) cause more extrapyramidal symptoms. Either type can cause tardive dyskinesia and arrhythmias. 2 ,3 These medications should be avoided in the elderly, but when used, initial daily doses should be very low (e.g., 0.5 mg haloperidol or equivalent) and given at bedtime (see "Managirig Dementia-Related Behavior in the Community."JAmPharmAssoc. April 1996;NS36:249-56).
Arth ritis and pain NSAIDs have the p harmacologic effect of blocking the production of prostaglandins through inhibition of cyclooxygenase. Unfortunately, a compensatory mechanism to maintain renal blood flow in some elderly patients is prostaglandin-mediated renal arterial dilation. This may be blocked by NSAIDs, precipitating congestive heart failure. 2 NSAIDs may also decrease the effect of many antihypertensive medications through this mechanism. NSAIDs with long halflives, such as piroxicam (Feldene-Pratt, t1l2 = 30 to 86 hours) are particularly problematic in that this effect on the kidneys may last a week or longer, causing some geriatricians to recommend against the routine use of these drugs in geriatric patients. Older patients should be educated about this effect and have their weight and blood pressure monitored for signs of its onset. Often, topical analgesics may be used effectively in the elderly, avoiding the potential for NSAID-induced adverse reactions. Acetaminophen may also be very effective if there is no history of hepatic dysfunction or ethanol abuse and is considered the drug of choice for osteoarthritis.18 If an NSAID is necessary, sulindac, which is inactivated by the kidney, and the non-acetylated salicylate do not affect renal blood flow and may be used as alternatives to the other Vol NS36, No.7
July 1996
AID in pati n h may be at risk. 19 ar tic pr duce a gr ater effect in the elderly through pharmacodynamic alterations, and this may lead to an incr in the dativ and respiratory depressant effects of th e medication .2 Generally, initial doses of narcotics hould be decreased in the geriatric patient and then titrated to maintain pain control.
Infectious disease and inappropriate antibiotic use Exce sive use of antibiotics may lead to the development of more resistant and virulent bacterial strains and to increased antibiotic-associated colitis. 2o Many antibiotics are renally cleared, and the normal decrease in renal function seen with aging is sufficient to lead to accumulation of these antibiotics and increase the potential for toxicity. Gentamicin is an antibiotic that has a narrow therapeutic range, and renal function must be considered when dosing in the elderly.
Peptic ulcer disease Histamine-2 receptor blockers are usually fairly safe for use in the elderly. The exception is cimetidine, a potent inhibitor of cytochrome P-450, which may block the Phase I metabolism of many medications, increasing the potential for toxicity. Cimetidine may also accumulate and cause delirium in those elderly patients who have renal dysfunction greater than that seen with aging. 2 With the availability of cimetidine over the counter, the pharmacist may see this problem more often. Antibiotic treatment may offer the elderly a cure for peptic ulcer disease. This treatment should be considered with recurrent ulcers, thereby avoiding the use of a chronic medication. Misoprostol is effective prophylaxis against peptic ulcers for the elderly patient taking an NSAID.21 The drug should not be used indiscriminately for all elderly patients taking NSAIDs, but its use should be considered in patients with a history of peptic ulcer disease or those who develop ulcers on NSAID therapy and for whom there is no alternative but to continue an NSAID.
Conclusion Helping the elderly avoid medication problems should be a primary component of pharmaceutical care . Table 2 lists questions that should be asked when developing a drug therapy plan for an elderly patient. Most important, elderly patients should be assessed to determine whether the goal of drug therapy is being met. Usually, the goal is not a cure, but an Elderly continued on p. 467 journal of the American phannaceutical Association
changes of aging affect the fate and action of drugs can help the pharmacist develop pharmaceutical care plans. Joseph F. Steiner, PharrnD
Introduction The past 20 years have seen a revolution in our knowledge of how the processes of
aging affect drug therapy. With this knowledge has come remarkable progress in caring for patients over the age of 65. Advances in medical technology have enhanced studies of the physiologic changes of aging, and we now have a much more formidable understanding of how physiologic changes affect the treatment of disease and the use of medications. This knowledge forms the basis of care. Ongoing research is constantly updating and expanding this knowledge base. Numerous diseases present and progress differently in the elderly than in younger Counseling elderly patients on the proper use of medications is an patients. Many of these differences represent increasingly crucial thrust ofpharmaceutical care. important considerations in developing pharmaceutical care plans for the ill elderly patient. Moreover, new medications have been devel- Summary oped for treating diseases primarily seen in the • As the elderly population increases, pharmacists will routinely confront elderly. aging-related problems in drug therapy. At one time new medications under Food • Drug therapy plans must take into account that diseases will present and Drug Administration (FDA) review for and progress differently in the elderly. marketing were studied primarily in younger patients; often, the elderly were specifically • Individual variations characterize the aging process, and it is physiologic-versus chronologic-aging that underlies age-related differences excluded by the study protocols. The results in pharmacokinetics and pharmacodynamics. of these studies were then inappropriately extrapolated to the elderly. FDA now requires • More than one in six elderly Americans are taking prescription drugs that medications intended for use in a certain whose adverse effects can have serious consequences in this age group. age group be studied in patients of that age VoL NS36, No.7
July 1996
journal of the American Phannaceutical Association
group to gain approval for marketing. 1 Because of this, the Physiology of Aging problems specific to the elderly now have a better chance of being known when a new drug is introduced , and The elderly population is not a homogeneous one. Rather, the patients can be monitored or interventions made. There are now physicians and nurse practitioners who are aging process is characterized by marked individual variations. board certified in the practice of geriatrics. These health care Physiologic aging does not parallel chronologic aging, and with providers understand the physiologic differences that exist in the exception of the effects produced by disease, it is physiologic the elderly and have the expertise to diagnose and treat with- aging that underlies age-related differences in the fate and action in these parameters. Often, these professionals may use a mul- of drugs.3 Therefore, effective and safe use of dnlgS in geriatric tidisciplinary geriatric assessment team for global evaluation patients is a matter of careful individualization of therapy. of an elderly patient. The composition of these teams is flexible, but usually includes a physician and a nurse practitioner, a social worker, a nutritionist, and a pharmacist. All pharma- Multiple disease states Multiple disease states are common in the elderly, and it cists have a role in the dnlg therapy of the elderly through the is the nIle rather than the exception that each disease is provision of pharmaceutical care. The major reasons for this growing interest in geriatrics treated with one or more medications. At least 80% of are the increase in the elderly population, the vast number those over the age of 75 suffer from at least one chronic of ailments seen in this group, and the subsequently consid- disease, and of those, as many as 40% suffer from two or erable use of medications . The population of the United more comorbidities. 4 In long-term care institutions, multiStates is growing older every day. Currently, 12% of the pop- ple pathology is routine for most patients. Often, multiple I ulation-32 million Americans-are 65 years of age or older. prescribers are involved, and one may be unaware of what There is currently a dip in the growth rate of this population the other has prescribed or may not detect potential probbecause of the lower number of births during the Great lems. Without intervention by a pharmacist, this situation I Depression; however, the growth rate should accelerate may lead to polypharmacy, with its inherent increased I around 2010 and peak in 2030 as the "baby boom" genera- incidence of adverse drug reactions, increased potential tion reaches age 75 to 85. By the year 2040 the elderly pop- for drug-drug and drug-disease interactions, and compliulation is expected to increase to 68 million, or 23% of the ance problems .5 Additionally, diseases may alter the projected population. 2 patient 's response to therapy, so that the anticipated In 1986 the 12% of the population over 65 represented response is not seen or other effects become more pro- I 25% of all patient visits in the United States. Today, elderly nounced. ericans spend approximately $3 billion annually on preOccasionally, one medication may have the pharmacologcription medications, little of which is reimbursed by third ic advantage of producing several beneficial effects and party payers. In the United may be used to treat multate and other develtiple problems in an indioped countries, this segvidual patient. Use of a More than one in six ment of the population single medicatio n currently accounts for reduces the potential for elderly Americans are taking about 25 % of the total polypharmacy and with prescription drugs that drug expenditures , but it the inherent risks of thi proportion is estimatadverse drug reactions, are not suitedfor older people ed to reach 40 % by the noncompliance , and year 2030. 3 drug-drug interactions. With these changes , For example , a patient the incidence of probwith depression and lems associated with insomnia may be better medication use has the treated with a sedating potential to grow expoantidepressant at bednentially, creating a great time than a serotoni n challenge for pharmacists who provide care to elderly reuptake inhibitor (SSRI) antidepressant in the morning and patients. The pharmacist must therefore have a basic under- a sedative at bedtime. The pharmacist can help the prestanding of the underlying physiologic changes of aging, scriber select appropriate alternatives for individual how these affect the pharmacokinetics and pharmacody- patients. When multiple disease states are present, care namics of medications, and medications that have the great- must be taken to ensure that no contraindications exist to est potential for problems. the use of a particular single agent. Journal of the American Pharmaceutical Association
July 1996
Vol. NS36, No.
Altered reserve capacity A con istent characteri tic of aging organ i the pr gr 'ive deterioration of re rve functional capacity. Each organ , tern in a young, h althy adult will not normally be working at full capacity, 0 a re erve will exist. Exce sive organ re elve allows the body to compensate for large variations in phy iologic parameters or biologic insults. This capacity may be up to 10 times that necessary to sustain life in a young, healthy adult. However, it is estimated that the re erve functional capacity of various organs declines at a rate of 0.8% to 0.9% per year after age 30. Because of the large initial capacity, this grcldual decrease should not cause signs, symptoms, or disability until a "critical threshold" for that organ system is reached. Ideally, this would occur at the end of the natural life span or not be reached at all before death. Many diseases and lifestyle habits may accelerate this decline in organ reserve capacity, so that organ failure , disability, and death occur much earlier. This partially explains the altered presentation of disease states in the elderly. For example, confusion may be the only symptom of a urinary tract infection in an elderly patient. An elderly patient who has one or more organ systenls approaching or past the critical threshold is at an increased risk for adverse drug reactions, and drugs may be the stressor that shifts the reserve to below the critical threshold. Drugs can also precipitate organ failure by antagonism of compensatory mechanisms that help to maintain function. 6
Adverse reactions and interactions More than one in six elderly Americans are taking prescription drugs that are not suited for older people and may lead to physical or mental deterioration-possibly even death.7 While the elderly are often perceived as more likely to have adverse reactions to medications, this perception is not supported by the literature. 8 The elderly do take lllore medications, which increases the risk, and adverse reactions account for 17% of the hospitalizations of the elderly at a cost of $20 billion annually.8 Several factors influence patient susceptibility to adverse drug reactions. 9 First, the incidence of adverse reactions increases exponentially with the number of medications taken. Second, multiple disease states and increased severity of disease nlay alter the pharmacokinetics of certain medications and lead to adverse reactions. Third, not properly adjusting doses to allow for normal pharmacokinetic changes in the elderly accounts for 70% to 80% of adverse reactions. Fourth, some drugs are more likely to cause adverse reactions than others, and these, unfortunately, are often prescribed for the elderly. Fifth, pharmacodynamic alteration that increase receptor sensitivity may lead to a higher incidence of adverse drug reactions. Of the 30 rnillion noninstitutionalized Medicare recipients aged 65 or older, an estimated 17.5% had been prescribed drugs inappropriate for their age group when safer drugs existJ Pharmacists can play an important role in avoidVol NS36, No. 7
July 1996
in r acti n b un lin Id rl pr p r n1 dication u , rking ith th pr th u e f th a.fi t m di ati n ~ r a rtain r vi wing pr cription rd r ~ r inappr priat
pati nt ab ut rib r t c nditi n and m di ati
Compliance Many patients, not only th elderly, hav difficulty taking medication as prescribed by their clinicians. It ha b n estimated that noncompliance rate range from 25% to 59% in the elderly, including omission of medication , lack of knowledge of the medication, use of a medication not prescribed, and errors in dosing , sequence, or timing.s The rate of noncompliance increases with an increase in the number of medications taken up to an error rate of 70% when the patient is taking six or more medications. Compliance nlay be helped by decreasing the number of doses , decreasing the frequency of administration, patient education, cue cards, calendars, and dispensing devices. However, the only plan that has been shown to consistently improve compliance is to decrease the number of doses and the frequency of administration. The prohibitive cost of the medications may lead some elderly to skip doses to stretch the medication, especially when multiple expensive medications are prescribed; hence less expensive alternatives may greatly aid compliance. lo Elderly patients are also likely to return to taking medications from discontinued prescriptions, not recognizing that an identical new medication has been prescribed. The pharmacist may aid compliance by monitoring prescriptions for timely refills, asking the patient whether the cost is a barrier to obtaining and taking the medication, and working closely with the prescriber to select less expensive alternatives or fmd other sources of funding or medication, such as pharmaceutical company indigent care program . The pharmacist should also monitor for repetitions in therapy by reviewing the medication record and by compiling a careful drug history with the patient when new medication are added.
Pharmacokinetic Problems Table 1 summarizes the direction of ag -r lat d pharmacokinetic changes in drug ab orption di tributi n metabolism, and elimination.
Absorption Absorption of medications is the pharmacokinetic parameter least affected by aging. Normal aging decreases splanchnic blood flow , slows gastric motility, and delays gastric journal of the American Pharmaceutical Association
Table 1
Age-Related Changes in Pharmacokinetics Function
Direction of Change
Absorption Rate of absorption splanchnic blood flow gastric motility gastric emptying Extent of absorption
Distribution Body fat Lean muscle mass Total body water Serum albumin u 1-acid glycoprotein
Metabolism Hepatic blood flow Hepatic function Phase I (oxidation, cytochrome P-450) Phase II (conjugation)
Elimination Renal function
emptying. These changes may decrease the rate of absorption for a few medications after oral administration. Other changes may decrease the extent of absorption-gastric acid secretion is decreased in approximately 40% of the elderly, and the intestinal surface area is decreased with aging. The implications for clinical drug therapy are few, however. Prodrugs that require an acid medium may not be activated, and the onset of effect of as-needed medications may be slowed. Most drugs that have been studied in the elderly show no significant change in the extent of absorption, and while the rate may be slower, the total amount absorbed (area under the curve) remains the same. 9
Distribution Age-related body fat increases are on the average of 18% to 36% for males and 33% to 45% for females. This may increase the volume of distribution (Vd) for those lipophilic (fat-soluble) medications that distribute to fat tissue. This larger Vd for Journal of the American Phannaceutical Association
lipid-soluble drugs, such as anesthetics, barbiturates, and ben. zodiazepines, may result in a longer half-life (tw) and pro. longed effects in the elderly. Total body water decreases 10% to 15% and muscle mass decreases 20% as humans age. This may decrease the Vd and therefore increase the concentration of medications that are hydrophilic (water-soluble) and pri. marily distributed to lean body tissue. 9 Ethanol is an example of a water-soluble medication that has increased effects as peo. pIe age because of the relative increased concentration pro. duced by the decreased Vd. Additionally, the serum plasma proteins, such as albumin, may decrease up to 25% because of decreased hepatic pro. duction. This change may result in a reduced protein-bound (inactive) form of a medication that is highly protein bound and an increase in the free (active) form, which may result in increased pharmacologic activity and risk of toxicity. Nonnal· ly, laboratories will measure total drug (both bound and unbound) when serum drug levels are requested. Therefore, this measurement may not reflect the true drug activity when serum proteins are reduced. When the prescriber or consulting pharmacist suspects this is occurring, a free drug level should be obtained whenever possible. Conversely, an acute· phase reactant, alpha I-glycoprotein, may be released in the presence of inflammation and advanced age (e.g., in rheuma- \ toid arthritis). This reaction may increase the protein binding of basic drugs, such as lidocaine and propranolol, decreasing the amount of unbound active drug and decreasing the pharmacologic effect. 2 ,3,6
Metabolism Hepatic function and blood flow determine the rate of drug metabolism. In the elderly, these two factors may vary considerably between individuals, but both decline with aging. Generally, liver mass decreases and the number of functioning hepatocytes is reduced. Liver blood flow also declines by 0.3% to 1.5% per year as a person ages, and, subsequently, may be reduced by 40% to 45% in the typical 65year-old when compared with that seen at age 25. 2 These physiologic changes may result in a marked decrease in the frrst-pass metabolism of drugs. Hepatic metabolism occurs by two mechanisms: the microsomal enzyme mixed-function oxidase system (Phase I), which includes the cytochrome P-450 systems; and conjugation of the drug molecule with a glucuronide, a sulfa, or an acetyl moiety (phase II). Phase I metabolism may produce compounds with pharmacologic activity, while Phase II metabolism usually produces inactive metabolites. Declines in Phase I metabolism are often noted in the elderly, and several enzymatic reactions of the cytochrome P-450 systems are slowed considerably with advancing age . Phase II metabolism, however, is generally unaffected by aging. Therefore , metabolism may be slowed and a prolonged duration of action seen in the elderly for those medications that are priJuly 1996
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I
lllarily metabolized through Pha
I reactions, but n t tho e metabolized through Phas II.2 ,3,6,9
~
r
Table 2
Questions to Ask in Developing a Pharmaceutical Care Plan
Elimination Drug elimination i determined primarily by renal function, which declines continuously with normal aging. The degree of this decline, however, varies greatly between individuals. The glomerular ftitration rate is reduced due to age-related decreases in renal mass , loss of functional nephrons, and diminished renal arterial perfusion. Creatinine clearance (CCr) is a good indicator of renal function and correlates well with drug elimination. After the age of 25, where CCr is approximately 120 mL/minute, a decrease of 0.5 to 1 mL/minute/70 kg yearly is seen. This may increase the t ];2 of medications that are renally cleared, lead to accumulation of the medication or active metabolites, and increase the potential for toxicity, especially if the medication has a narrow therapeutic index. Muscle mass is the primary site for creatinine production and release, and the concurrent decrease in mass seen with aging renders the serum creatinine (SCr) invalid as a measure of age-related renal decline. 2 However, the SCr may be used to calculate the creatinine clearance, and the following Crokcroft-Gault formula is most commonly used for estimating age-related declines l l : CCr (mL/min)
= (140 - age) x weight(kg) x 0.85 (females only) 72
x SCr
1. When considering drug therapy: • What is the therapeutic goal? What is the appropriate duration of therapy? • Is the problem being dismissed without treatment as a symptom solely of old age when drug therapy can contribute to improved quality of life? • Is drug treatment necessary or can alternatives to medications be used? • Is this medication the best choice for initial therapy for this patient based on efficacy, cost, ease of administration, patient risk, safety, potential adverse reactions, interactions, and the possibility of treating several medical conditions with one drug? • Is this medication being added to treat the side effect of a current medication? • Is the dose appropriate ("start low and go slow")? 2. When monitoring a patient: • Has the goal of drug therapy (cure vs. increased quality of life) been met (or is it being met), and is a particular medication still considered necessary? • What specific objective parameters should be monitored for this medication and how often should these be repeated? • Are there symptoms of adverse reactions or interactions? • Can the dose be decreased while still maintaining pharmacologic effect? • Is compliance a problem? • Is there redundant drug therapy?
Dosages of many medications that are renally cleared are based on CCr. When prescribed for the elderly, doses may have to be reduced or the dosing schedule modified to prevent toxicity. The use of multiple medications increases both the likelihood of pharmacokinetic drug interactions and the difficulty of predicting serum levels of medications.
3. When dispensing the medication:
Pharmacodynamic Problems
4. When counseling and providing patient education:
Alterations in end-organ responses to medications occur with aging when receptor sensitivity to the drug at a given plasma level either increases or decreases. Thus, lower levels of some drugs may produce marked clinical effects or higher dosages may be necessary for other medications to achieve the desired therapeutic effect. 9,12 These pharmacodynamic changes may be due to changes in receptor binding, decreases in receptor number, or altered translation of a receptor-initiated cellular response into a biochemical reaction. While the pharmacokinetic changes related to aging are well documented, the pharmacodynamic changes are known only for a few medications. Vol. NS36, No.7
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• Are there any potential physical problems with the use of this medication? (e.g., can the patient open safety containers, read the label, swallow solids, etc.)? • Is a dispensing device appropriate for this patient? If so, what type of device?
• Who should be educated-the patient, the caregiver, or both? (The pharmacist may have to assess the patient's memory and cognition.) • The patient or caregiver should understand and remember: • Which medications mayor may not be taken together • The timing of doses in relation to food intake • When to return for laboratory tests to monitor drug response or adverse reactions • Condition the medication is intended to treat • What to do when doses are missed • Potential adverse reactions and their signs and symptoms
journal of the American Pharmaceutical
Specific Diseases and Pharmacotherapy Problems While an understanding of the general problems that affect drug therapy in the elderly is essential for the provision of pharmaceutical care, the pharmacist must also consider the impact of aging on specific diseases and the implications of drug therapy. It is beyond the scope of this paper to present all of the specific diseases and pharmacotherapy problems that exist, so what follows is a discussion of some of the more common ones.
I
Cardiovascular Digoxin is renally eliminated and with its narrow therapeutic index has the potential for toxicity in elderly patients. The CCr should be calculated for all elderly patients and digoxin dosed accordingly. Also, since digoxin is a water-soluble medication, its Vd will be reduced. Therefore, loading doses should be reduced. 2 Patients should be monitored for signs of toxicity (arrhythmias, anorexia, nausea, and visual disturbances), and a digoxin serum level should be obtained once steady state is reached. This may take 10 days to 2 weeks because of the prolonged tw' Digoxin serum levels may be altered by many medications that may be either added or discontinued in the elderly, such as quinidine or verapamil, without thought to the interaction. Diuretics may produce several problems in the elderly. With the loss of renal function, the thiazide-type diuretics, with the exception of metolazone, lose their efficacy when the CCr drops below 20 mL/min.2 The loop diuretics and metolazone are considered effective to a CCr of 5 mL/min. Diuretics may cause dehydration and electrolyte disorders in the frail elderly, and this may pass the critical threshold of reserve for some patients. This potential volume depletion increases the risk of nonsteroidal anti-inflammatory drug (NSAID) and angiotensin-converting enzyme (ACE) inhibitor-induced renal toxicity. Finally, diuretics have great potential for drug interactions in the elderly. For example, diureticinduced potassium loss may increase the potential for digoxin toxicity, or diuretics may induce gout in a patient with hyperuricemia. Warfarin manifests a pharmacodynamic alteration in that the elderly may be more sensitive to its inhibition of the synthesis of vitamin K-dependent clotting factors and bleeding may be a problem. 13 The international normalization ratio (lNR) should be monitored closely in elderly patients on oral anticoagulants and maintained in the therapeutic range for the condition being treated. Many medications and foods rich in vitamin K may interact with warfarin, causing fluctuations in the INR. Journal of the American Pharmaceutical Association
Hypertension Beta-blocker and beta adrenergic stimulant response are diminished in the elderly due to altered pharmacodynami . The decrease in number of beta receptors and in their sensi. tivity with aging makes these medications less effective in the elderly. 14 Also, beta-blockers have the potential for antagoniz. ing compensatory mechanisms in elderly patients with cal} gestive heart failure. To compensate for the heart failure, the sympathetic nervous system is activated and its support of the failing myocardium is negated by beta-blockade. The use of beta-blockers may also be detrimental in patients with chron· ic obstructive pulmonary disease, diabetes, and peripheral claudication. Also, ocular beta-blockers may be sufficiently absorbed to cause systemic adverse reactions. The calcium channel blockers verapamil and diltiazem require increased serum concentrations to produce their pharmacologic effect of PR-interval prolongation on an elec· trocardiogram when compared with the concentrations need· ed to produce this effect in younger adults. This is considered an age-induced pharmacodynamic alteration and suggests a decreased sensitivity to the depressant effects of these medi· cations on cardiac conduction.
Psychologic disorders Antidepressant use in the elderly presents several prob· I lems. The older tricyclic antidepressants, such as amitriptyline I or imipramine, have high anticholinergic, cardiac, sedative, and orthostatic adverse reactions, all of which may be more I severe in the elderly because of lack of reserve and the poten· I tial for additive effects with other medications. Orthostatic I hypotension is a particular problem in that it may lead to falls in susceptible elderly patients, increasing the risk of fractures. Although incidence of depression does not differ between the elderly and the younger population, elderly patients may have more symptoms of depression. 15 Depression must also be considered as an underlying cause for dementia in the elderly. The potential for suicide may exist in the depressed elderly patient, and these medications have the potential for fatalities at relatively low toxic doses. For these reasons, the selective serotonin reuptake inhibitors (SSRIs) have been touted as the drug of choice for the treatment of depression in the elderly. However, these medications are generally more expensive, and they may also produce troublesome adverse reactions in elderly patients, such as anxiety, sexual dysfunction, weight loss, and gastrointestinal distress. Depression is a common adverse reaction for many medications. The drug list should be reviewed and any medications that cause depression discontinued before antidepressant treatment is started. Benzodiazepines pharmacodynamically produce an enhanced effect in the elderly. Also, many of the benzodi· azepines are metabolized by the oxidative cytochrome p-450 system and their metabolism may be slowed in elderly patients, leading to accumulation of the drug and its active July 1996
VoL NS36, No.
roetabolit and pr I n d a dati n.2 •6 Th exceptions ar I raz pam xaz pam and t maz pam hi h are metab liz d t ina ti mp un thr ugh njugati n. e eral tudi of ld rly pati n n b nz diaz pin h w that an incre in falls is iat d with only th b nzodiazepine who half-live ar prolong d with aging.16.1 veral medication , uch as cimetidine, may ven further compromise the cytochrome P-4 50 metaboli m of the benzodiazepine and prolong their half-li e . The potential for problems exists with the liberal use of elf-medication by the elderly and the availability of cimetidine over the counter. Finally, benzodiazepines are lipid-soluble and will accumulate in the increased adipose tissue seen in the elderly, further increasing these drugs' half-lives. Antipsychotic medications have been used to control agitation, aggression, hallucinations, and paranoia, primarily in residents of long-term care institutions. Pharmacodynamically, the elderly are very sensitive to the effects of the antipsychotic agents and particularly vulnerable to their adverse reactions. The low-potency, high-dose antipsychotics (chlorpromazine and thioridazine) are more sedating and cause more postural hypotension. The high-potency, low-dose antipsychotics (haloperidol and thiothixene) cause more extrapyramidal symptoms. Either type can cause tardive dyskinesia and arrhythmias. 2 ,3 These medications should be avoided in the elderly, but when used, initial daily doses should be very low (e.g., 0.5 mg haloperidol or equivalent) and given at bedtime (see "Managirig Dementia-Related Behavior in the Community."JAmPharmAssoc. April 1996;NS36:249-56).
Arth ritis and pain NSAIDs have the p harmacologic effect of blocking the production of prostaglandins through inhibition of cyclooxygenase. Unfortunately, a compensatory mechanism to maintain renal blood flow in some elderly patients is prostaglandin-mediated renal arterial dilation. This may be blocked by NSAIDs, precipitating congestive heart failure. 2 NSAIDs may also decrease the effect of many antihypertensive medications through this mechanism. NSAIDs with long halflives, such as piroxicam (Feldene-Pratt, t1l2 = 30 to 86 hours) are particularly problematic in that this effect on the kidneys may last a week or longer, causing some geriatricians to recommend against the routine use of these drugs in geriatric patients. Older patients should be educated about this effect and have their weight and blood pressure monitored for signs of its onset. Often, topical analgesics may be used effectively in the elderly, avoiding the potential for NSAID-induced adverse reactions. Acetaminophen may also be very effective if there is no history of hepatic dysfunction or ethanol abuse and is considered the drug of choice for osteoarthritis.18 If an NSAID is necessary, sulindac, which is inactivated by the kidney, and the non-acetylated salicylate do not affect renal blood flow and may be used as alternatives to the other Vol NS36, No.7
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AID in pati n h may be at risk. 19 ar tic pr duce a gr ater effect in the elderly through pharmacodynamic alterations, and this may lead to an incr in the dativ and respiratory depressant effects of th e medication .2 Generally, initial doses of narcotics hould be decreased in the geriatric patient and then titrated to maintain pain control.
Infectious disease and inappropriate antibiotic use Exce sive use of antibiotics may lead to the development of more resistant and virulent bacterial strains and to increased antibiotic-associated colitis. 2o Many antibiotics are renally cleared, and the normal decrease in renal function seen with aging is sufficient to lead to accumulation of these antibiotics and increase the potential for toxicity. Gentamicin is an antibiotic that has a narrow therapeutic range, and renal function must be considered when dosing in the elderly.
Peptic ulcer disease Histamine-2 receptor blockers are usually fairly safe for use in the elderly. The exception is cimetidine, a potent inhibitor of cytochrome P-450, which may block the Phase I metabolism of many medications, increasing the potential for toxicity. Cimetidine may also accumulate and cause delirium in those elderly patients who have renal dysfunction greater than that seen with aging. 2 With the availability of cimetidine over the counter, the pharmacist may see this problem more often. Antibiotic treatment may offer the elderly a cure for peptic ulcer disease. This treatment should be considered with recurrent ulcers, thereby avoiding the use of a chronic medication. Misoprostol is effective prophylaxis against peptic ulcers for the elderly patient taking an NSAID.21 The drug should not be used indiscriminately for all elderly patients taking NSAIDs, but its use should be considered in patients with a history of peptic ulcer disease or those who develop ulcers on NSAID therapy and for whom there is no alternative but to continue an NSAID.
Conclusion Helping the elderly avoid medication problems should be a primary component of pharmaceutical care . Table 2 lists questions that should be asked when developing a drug therapy plan for an elderly patient. Most important, elderly patients should be assessed to determine whether the goal of drug therapy is being met. Usually, the goal is not a cure, but an Elderly continued on p. 467 journal of the American phannaceutical Association