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DRUG PRESCRIBING FOR THE ELDERLY* PETER P. LAMY, Ph.D. Professor and Director, Institutional Pharmacy Programs Chairman, Department of Pharmacy Practice and Administrative Science University of Maryland School of Pharmacy Baltimore, Maryland

L ittle is known about drug effects in the elderly, except that all drugs can be hazardous to the elderly and that much uncertainty remains about the appropriate and safe use of drugs for older adults. The difficulty is to match the right drug to the right disease in the right patient. Yet, in the absence of explicit rules or appropriate tools, dealing successfully with that uncertainty remains one of the major tasks of clinicians caring for elderly patients. Even less is known about the effect of chronic drug use and its costeffectiveness, particularly in terms of such tertiary costs as loss of productivity, loss of quality of life, and additional nonhealth care costs such as long-term maintenance care and loss of productivity for family members who must provide care. Further, current patterns of care and treatment, as well as third-party reimbursement policies for institutionalization and technical procedures, focus primarily on acute care and cure. This philosophy of health care has literally been transposed to long-term care, and is a major barrier to quality care for older adults with chronic disorders and disabilities. Chronic diseases mandate disease management rather than cure. The major issue is the need to understand the appropriate balance between acute care (high technology, high cost, compulsive prescribing patterns) and long-term care. *Presented before the Section on Geriatric Medicine of the New York Academy of Medicine February 19, 1981. Address for reprint requests: University of Maryland School of Pharmacy, 636 West Lombard Street, Baltimore, Md. 21201.

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719 PRESCRIBING FOR THE ELDERLY ELDERLY719~~~~~~~~~~~~~~~~~ PRESCRIBING

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TABLE I. SOME KEY POINTS TO REMEMBER

1) All drug therapy can be hazardous to an elderly patient. 2) Drugs can reduce the quality of life. 3) The benefit/risk ratio of drug therapy changes with age, the benefit decreasing, risk increasing. 4) One of the major goals of therapy must be to reduce the risk. 5) Chronic care is constantly changing care. 6) Geriatric drug therapy must, therefore, become a precision practice, with exacting attention to detail, both by provider and patient. TABLE Ii. DIFFICULTIES IN GERIATRIC THERAPY

1) For most therapeutic agents there is no readily measured endpoint of drug effect. 2) There is wide variation between blood levels and therapeutic response following standard dosage. 3) The prediction of patient response to multiple drug therapy is difficult. 4) Disease state is likely to be relatively severe. 5) A drug may have a very narrow therapeutic index. 6) The elderly have a reduced capability to handle drugs.

As yet, geriatric drug therapy remains complicated, potentially dangerous, and inadequately understood' (Tables I and II). The "medicalization" of long-term care2 still motivates primary care providers to heal the sick, authoritatively dealing with elderly patients thought to need total assistance because they are supposed to be weak, bed-bound, and unable to meet the tasks of daily living.3 Consequently, care given to older patients is often deficient, superficial, and indifferent.4 There are indications that problems exist in prescribing drugs for older adults, particularly since many patients apparently receive drug treatment where there may be no true indication for its need.3 Need is, therefore, urgent to understand the basic biological and pharmacological interactions for more effective and less costly drug therapy for older adults. A much better understanding must also be gained of the pharmacologic and therapeutic goals of drug use for the elderly. A dearth of Vol. 57, No. 8, October 1981

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good scientific data on the action of drugs and the lack of guidelines for their appropriate use remains. As a result, there is now an overriding necessity to develop the scientific and clinical data base so necessary to insure better management of drug use for and by the elderly. Until such time as this is achieved, a better utilization of currently available information is necessary.

POPULATION DEMOGRAPHICS The baby boom is over and the United States is witnessing the rise of the elders. In 1970 one half of the population of the United States was 16 years old or younger. The median age in 1970 was below 28 years; it will pass 30 years in 1981, reach 35 years by the year 2000, and approach 40 years by the year 2030, only 50 years hence. It has also been reported that the 80-to-84 age group has grown by 19.2% and the 85-and-over group dramatically increased by 40% since 1970, compared to an overall population growth of 5.3%.5 The extreme aged. These population statistics still do not tell the entire story. A clearer picture is needed in view of the difficulties with drug therapy. During the three decades between the 1930s and 1960s, the mortality rate of the extreme aged, i.e., those 85 years of age and over, decreased by 10%. Incredibly, in the single following decade, that mortality rate decreased by another 26% . Between now and the year 2000 the 65-to-74 age group will increase less than 20% to 17.4 million, the 74-to-84 group will increase about 50% to 10.6 million, and the 85+ group will increase an unbelievable 80%, to 3.8 million.6.' Thus, proportionally more people will be in the most vulnerable part of the age spectrum, vulnerable to disease effects and, most important, to adverse drug effects. Yet we know little about this population. Next to nothing is known about their nutritional status, which can influence health and drug action, as The Health and Nutrition Examination Survey examined only persons who were not confined to institutions and between the ages of one and 74 years.89 Even the the recommended dietrary allowances speak only to the age group above 55 years, and no more.10 Though it has been predicted that chronic diseases will occupy a smaller proportion of the typical life-span,11 there is no question that many of the extreme aged have high systolic blood pressure and that there is still no agreement whether they should be treated or not."2 Similar sentiments could be presented for many other instances. Adding to these difficulties is the logical assumption that it is this Bull. N.Y. Acad. Med.

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TABLE III. HOARDING OF ILLNESS

1) The elderly accept physical limitations as a normal concommitant of aging. 2) The elderly are poor in self-referral. 3) The elderly may present only the chief complaint. 4) The elderly may be unable to give a detailed history.

age group that adds greatly to the difficulty in geriatric medicine by their socalled "hoarding of illness" (Table III). The female patient. In the United States the life span of women is now 81 years; for men it is 71.8 years. Yet, contrary to what has been believed, women have more significant risk factors associated with mortality than do men. Women are more likely to be physically inactive, over-or underweight, unmarried, socially isolated, and dissatisfied with life. Many surveys have shown that women receive more drugs than men. Yet, many drugs, such as penicillin and heparin among others, act differently in women,15 and even the normal adult dose is generally an overdose for a female patient. It is, therefore, not suprising to record that gender is a determinant of the frequency and characteristics of adverse drug reactions. Apparently, the frequency of adverse drug reactions in women is significantly higher than in men. Ninety-three percent of these adverse effects in women are dose-related.16 When one considers that among the extremely old, women outnumber men by a ratio of 2:1 and that 73% of nursing home residents are women, it is easy to see that this particular aged population is doubly jeopardized by drug therapy, a fact seldom recognized. To compound this difficulty, it should be noted that elderly women are far more likely than elderly men to live alone and those living alone are more likely to make medication errors than those living with others. 17'18 The income of the elderly. Statistics, particularly those on drug use, cite a high drug use among the elderly, including those living in the community. These statistics, sometimes citing as many as 17-18 prescriptions (both new and refill) a year for elderly patients, may well be deceiving. They speak to the number of drugs prescribed, not necessarily dispensed. There are still no good data on the number of prescriptions the elderly receive as compared to those they actually have filled in a pharmacy. Vol. 57, No. 8, October 1981

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Anecdotal evidence seems to indicate that only 60 to 80% of prescriptions are filled, so that clinicians really cannot follow their therapeutic regimens correctly. In 1976 the average income of older people living alone or with a nonrelative was about $4,000 compared to $7,000 for those less than 65 years of age living in similar circumstances. Elderly women, moreover, in general have less income than do elderly men.19 When one considers that 75% of prescription drug cost is out-of-pocket for the elderly living in the community or for their families, this clearly indicates how important it is for the prescriber to ascertain how much a new prescription may cost and whether the patient has the funds to obtain the prescribed drug. Drug-taking behavior. Even though an elderly patient may obtain the prescription drug, there is no guarantee that the drug will be taken correctly. Much has been written on misuse of drugs20 and as many as 60% of elderly patients may be committing an error in drug-taking.21'22 In addition, one should ascertain whether or not an elderly patient is also taking nonprescription drugs. While these have been found safe and effective individually, in a complex therapeutic regimen they can contribute to therapeutic error.23 DRUGS AND THE ELDERLY

Elderly patients have a reduced capability to handle drugs and often respond to drug therapy in an altered, unexpected, and even bizarre fashion, particularly when taking several drugs simultaneously. The effects of primary aging (physiologic aging), secondary aging (pathophysiologic changes), and sociogenic aging (loss of income, etc.) contribute to that reduced capability (see figure). Elderly patients do not respond to stress as well as do younger people and drugs, being foreign substances, impose stress. The degree of sophistication with which drugs should be prescribed for the elderly has been emphasized many times, most recently in connection with the antipsychotics. Drug therapy is made more difficult by the many factors which can affect drug action (Table IV). However, the oftenvoiced opinion that if one were merely to reduce the number of drugs administered to elderly patients, therapeutic problems would be largely alleviated is too simple. Management of multiple chronic diseases may well require several drugs, even as many as six or eight daily.20 Clearly, other steps are needed. Adverse drug reactions and side effects. The elderly are twice as likely to react adversely to medications and to experience side effects from a wider Bull. N.Y. Acad. Med.

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PRIMARY AGING

SECONDARY AGING

SOCIOGENIC AGING

Factors which combine to yield altered drug effects in the elderly patient.

variety of medications than do younger people.24 This problem can be approached in several ways. First, the provider can try to remember all the side effects of all drugs prescribed. This can include all drugs likely to cause depression in the elderly (Table V), those drugs that can cause confusion, or, for example, the cardiac effects of the antipsychotics (Table VI). This would obviously be a very taxing and overpowering problem. However, the prescriber could also try to group drugs according to their side effects. This would be particularly important with those drugs exhibiting an anticholinergic side effect. For example, if an elderly patient is treated with an antipsychotic agent, one would have to remember that this drug does, indeed, have an anticholinergic effect aside from the desired therapeutic effect. If that patient then presents with pseudoparkinsonism, another side effect of the antipsychotic drug, the patient is again likely to be treated with an anticholinergic antiparkinson drug. The patient may also receive a medication for a sleep disorder (possibly diphenhydramine) and a medication for a cold (possibly containing the alkaloids of belladonna for their drying effect). The cumulative effect of the anticholinergics may devastate an elderly patient. A more pervasive effect may also occur: the patient may exVol. 57, No. 8, October 1981

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TABLE IV. FACTORS WHICH CAN AFFECT DRUG ACTION Bedrest

Cardiovascular function Dehydration Diet Diseases Drugs Enzyme induction inhibition

Fever

Gastrointestinal function Hepatic blood flow Humidity Infection Malnutrition Stress Temperature

TABLE V. SOME DRUGS IMPLICATED IN THE DEVELOPMENT OF DEPRESSION

Barbiturates Benzodiazepines Beta-adrenergic blockers

Methyldopa Narcotic analgesics Phenothiazines Procainamide

Clonidine Propranolol

Digitalis Reserpine Guanethidine Indomethacin

TABLE VI. CARDIAC EFFECTS OF ANTIPSYCHOTICS

1) Cardiac conduction effect 2) Anticholinergic effect 3) Hypotensive effect 4) ? Arrhythmogenic effect ?


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TABLE VII. EVALUATE FREQUENTLY

Antianxiety agents Antiparkinson drugs (anticholinergic) Antipsychotics Aspirin Digoxin Diuretics Ferrous sulfate Hypoglycemic agents Sedatives/hypnotics Steroids

hibit signs and symptoms of an atropinelike psychosis, i.e., the central anticholinergic syndrome. Unless the cumulative anticholinergic side effect is recognized, it is likely that the psychotic symptoms will be ascribed to the primary disease. Thus, while the case calls for removal of all drugs, the dose of the original antipsychotic may well be increased in the belief that the dose had been insufficient. One could also pursue a more intensive knowledge of those drugs which pose the greatest risk to elderly patients. A recent study25 reported that the diuretics cause the largest number of side effects, but that the antihypertensives, the anticholinergic antiparkinson drugs, digoxin, and the antipsychotics pose the greatest risk to the elderly. Most achievable would be the realization and recognition that adverse drug effects and adverse drug reactions most often occur due to one of four factors: excessive dose, excessive duration, wrong drug, and wrong dosage form. It is generally accepted that most adverse reactions are not due to a wrong drug, even though aspirin is still sometimes used for gout. Little recognized is that the wrong dosage form (oral instead of parenteral) can often have the most serious consequences. Most often, though, an excessive dose or use of a drug for an excessive duration in responsible for adverse drug reactions. Therefore, a planned, periodic review of a patient's drug regimen is mandatory (Table VII). Drug interactions. A plethora of literature has developed on drug-drug interactions. It is now relatively easy to identify clinically important drugdrug interactions, yet it is still a field that does not yield the information Vol. 57, No. 8, October 1981

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TABLE VIII. SALICYLATE INFLUENCE ON SOME LABORATORY TEST VALUES

Laboratory

Results

URINE Diacetic acid Glucose

Phenylketone Proteins Uric acid

Elevated levels false-positive Possibly false-positive or falsenegative (with moderate to high doses Possible false-positive or falsenegative Elevated levels false-positive Elevated levels false-positive

TABLE IX. DRUGS WHICH MAY PRECIPITATE OR EXACERBATE CONGESTIVE HEART FAILURE Androgens, estrogens Corticosteroids Diazoxide Osmotic agents Phenylbutazone Propranolol Sodium-containing drugs

necessary to the practitioner. Information available most often addresses a possible interaction between two particular drugs, but, unfortunately, the elderly take many drugs, and it is most difficult to anticipate or to recognize a drug-drug interaction in a multiple drug regimen.26 It is conceivable that, in an effort to broaden the knowledge of drug-drug interactions and their possible clinical effects, other drug interactions have been forgotten. Among those are the interference of drugs with laboratory test values. Diagnosis is a most difficult undertaking in the elderly, and it is suggested that many drugs interfere with necessary laboratory tests (Table VIII). It is also quite likely that drug-disease interactions occur much more frequently than is recognized. Some are listed in Tables IX and X. The interference or alteration of drug action by some diseases has been observed in older adults,27 but documentation is still lacking for these types of interBull. N.Y. Acad. Med.

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TABLE X. DRUG-DISEASE INTERACTIONS

Timolol, given one or two drops daily for glaucoma, can destabilize stable elderly asthmatic, congestive cardiac failure and diabetic patients TABLE XI. FACTORS WHICH MAY AFFECT NUTRIENT INTAKE

1) Drugs that cause gastrointestinal distress 2) Drugs that cause "dry mouth" 3) Drugs that leave a metallic taste 4) Diseases (e.g., depression) that may cause reduction of salivary flow TABLE XII. SOME POSSIBLE DRUG-NUTRITION INTERACTIONS Drug

Phenytoin Phenobarbital Phenytoin Phenobarbital Colchicine

Can deplete

Causing

Vitamin D

Bone pain

Folic acid Vitamin Bs

Difficulty in walking Confusional states Mental changes

actions in patients with multiple diseases. Drugs used to treat one disease can and often do adversely affect another disease. For example, antidepressants, diuretics, sedatives, psychotropics, and vasodilators may induce syncope in elderly patients with cerebrovascular insufficiency. Thiazides can, in some patients, aggravate diabetic control. Barbiturates, amantadine, L-dopa, opiates, and many other drugs may cause mental confusion, nightmares, and hallucinations in patients with organic dementia. Digoxin may be responsible for confusional epidodes in patients with asymptomatic organic brain disease. Finally, more and more attention is being focused on possible drug-nutrition interactions. Drugs can and do interfere with nutrient intake (Table XI). What is often overlooked is that drugs, given chronically to patients suffering from subclinical malnutrition, may induce certain vitamin deficiencies (Table XII). It is important to note that these deficiencies often present as "problems of old age," i.e., difficulty in walking, confusion, Vol. 57, No. 8, October 1981

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TABLE XIII SOME KEY CONSIDERATIONS BEFORE PRESCRIBING FOR THE ELDERLY

1) Should this disease be treated? a. Should it be treated at this time? b. Are there more important diseases that should be treated first? 2) Should this patient be treated? 3) Should this particular drug be used? a. Is drug effective? In what percent of cases? b. Are side effects frequent? What are they? Will this particular patient be able to tolerate them? c. Is a simple dosage schedule possible? d. Is drug price reasonable?

lethargy, apathy, and others, which are then ascribed to the process of aging, rather than being treated.28'29 Pharmacokinetics. The modified drug response in the elderly is most often due to altered pharmacokinetics. These occur because of alterations in liberation of the drug from the dosage form, absorption, distribution, metabolism, and excretion of drugs. Underlying these alterations are physiologic and pathologic changes responsible for altered and diminished hepatic and renal function, alteration in body composition, alteration in blood flow, and a decrease and qualitative changes in protein binding of drugs.30'31 Thus, the application of pharmacokinetics has been strongly advocated for a more sophisticated drug use for the elderly. However, several questions need to be answered or underscored. Pharmacokinetics mainly determines a loading dose, often unnecessary in longterm care. However, it is logical to assume that pharmacokinetics would be helpful in changing a dose when the need for this has been established. Pharmokinetic sophistication is not a panacea. It is, rather, a tool that must be used in conjunction with clinically relevant information and good clinical judgement. If pharmacokinetics does not replace patient observation of a patient's response to a therapeutic regimen, it will permit the physician to individualize a patient's therapeutic regimen. It is necessary to add that reduced kidney function is probably the most important factor Bull. N.Y. Acad. Med.


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responsible for the high incidence of adverse drug reactions in the elderly, and that it is also the single most overlooked factor in the treatment of the elderly. A FINAL THOUGHT

Aging is a biologic process, over which man has virtually no influence and about which very little is known. In contrast, growing old is a social and possibly a medical process over which man has and should exercise a good deal of control.32 Until such time as more knowledge is gained that can be used to exercise greater and more positive control over drug therapy for the elderly, it would be prudent to follow the suggestions in Table XIII.

1.

2. 3. 4.

5. 6.

7. 8.

9.

REFERENCES Lamy, P.P.: Prescribing for the Elderand Clinical Findings. DHEW Publ. NO. (HRS) 75-1229. Hyattsville, ly. Littleton, PSG Pub., 1980. Eisdorfer, C.: Care of the aged: The Md., Nat. Center for Health Statisbarrier of tradition. Ann. Intern Med. tics, 1975. 95:256-60, 1981. 10. Recommended Dietary Allowances. Rabin, D.L.: Physician care in nursninth revised ed. Washington, D.C., ing homes. Ann. Intern Med. Nat. Acad. Sciences, 1980. 94:126-28, 1981. 11. Fries, J.F.: Aging, natural death, and Kane, R., Solomon, D., Beck, J., the compression of morbidity. N. Keeler, E., and Kane, R.: The future Engl. J. Med. 303:130-33, 1980. need for geriatric manpower in the 12. Fry, J.: Natural history of hypertenUnited States. N. Engl. J. Med. sion. A case for selective nontreat302:1327-32, 1980. ment. Lancet 2:431-33, 1974. Reidenberg, M.M.: Drugs in the 13. Jackson, G., Pierscianouski, T.A., elderly. Bull. N. Y. Acad. Med. Mahon, W., and Condon, J.: Inap56:703-14, 1980. propriate antihypertensive therapy in Brotman, H.B.: The aging society: A the elderly. Lancet 2:1317-18, 1976. demographic view. Aging 315-316: 14. Schwid, S.A. and Gifford, R.W.: The 2-5, 1981. use and abuse of antihypertensive Soldo, B.J.: America's elderly in the drugs in the aged. Geriatrics 1980's. Pop. Bull. 35: 3-47, 1980. 1:172-82, 1967. 15. Proksch, R.P. and Lamy, P.P.: Sex National Center for Health Statistics: variation and drug therapy. Drug InPreliminary Findings of the First tell. Clin. Pharm. 11:398-402, 1977. Health and Nutrition Examination 16. Domecq, C., Naranjo, C.A., Ruiz, I., Survey. U.S., 1971-1972. Dietary Itand Busto, U.: Sex-related variations take and Biochemical Findings. in the frequency and characteristics of DHEW Pub. No. (HRA) 74-1219-1. adverse drug reactions. ht. J. Cliil. Hyattsville, Md., Nat. Center for Pharmacol. Therapy Toxicol. Health Statistics, 1974. National Center for Health Statistics: 18:362-66, 1980. 17. Haynes, R.B., Sackett, D.L., and Prelimary Findings of the First Health and Nutrition Examination Survey, Taylor, D.W.: How to detect and U.S.. 1971-1972. Anthropometric manage low patient compliance in

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20.

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23. 24.

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chronic illness. Geriatrics 35:91-97, 1980. Blackwell, R.: Drug therapy: Patient compliance. N. Engl. J. Med. 289:249-52, 1972. U.S. Senate Special Committee on Aging: Developments in Aging. 1977 Report No. 95-771, Part I. Washington, D.C., Govt. Print. Off., 1978. Lamy, P.P.: Misuse and abuse of drugs by the elderly: Another view. Am. Pharmacy NS20:14-17, 1980. Chien, C., Townsend, E.J., and RossTownsend, A.: Substance use and abuse among the community elderly: The medical aspect. Addict. Dis. 3:357-72, 1978. Macdonald, E., Macdonald, J.B., and Phoenix, M.: Improving drug compliance after hospital discharge. Br. Med. J. 2:618-21, 1977. Lamy, P.P.: OTC drugs and the elderly. Current Prescr. 11:42-46, 1979. Schuckit, M.A.: Geriatric alcoholism and drug abuse. Gerontologist. 17:168-74, 1977. Williamson, J. and Chopin, J.M.: Ad-

26.

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verse reactions to prescribed drugs in the elderly: A multicentre investigation. Age Aging, 9:73-80, 1980. Lamy, P.P.: Drug interactions and the elderly-A new perspective. Drug Intell. Clin. Pharm. 14:513-16, 1980. Benet, L.Z.: The Effect of Disease States on Drug Pharmacokinetics. Washington, D.C., American Pharmaceutical Assoc., 1976. Lamy, P.P.: How your patient's diet can affect drug response. Drug Therapy 10:82-86, 1980. Roe, D.A.: Nutrition and chronic drug administration: Effects on the geriatric patient. Am. Pharm. NS20: 33-35, 1980. Ritschel, W.S.: Disposition of drugs in geriatric patients. Pharm. Int. 1:226-30, 1980. Vestal, R.E.: Drug use in the elderly: A review of problems and special considerations. Drugs 16:358-82, 1978. Gray, M. and Wilcock, G.: Our Elders. Oxford, Oxford Univ. Press, 1981, p. 5.
