Using medications appropriately in older adults

Using medications appropriately in older adults

Cynthia M. Williams

The U.S. population is aging. Patients 65 years and older represent approximately 13 percent of the population, but they consume about 30 percent of all prescription medications. (1) Older American consumers spend an average total of $3 billion annually on prescription medications. (2) Sixty-one percent of older people seeing a physician are taking at least one prescription medication, (3) and most older Americans take an average of three to five medications. (4,5) These data do not include the use of over-the-counter medications or herbal therapies. An estimated 40 percent of older Americans have used some form of dietary supplement within the past year (6) (Table 1). (7)

The physician who cares for aging patients with numerous chronic medical conditions must make daily decisions about appropriate drug therapy. More than 60 percent of all physician visits include a prescription for medication. (8) The multiple medications and complex drug schedules may be justified for older persons with complex medical problems. However, the use of too many medications can pose problems of serious adverse drug events and drug-drug interactions, and often can contribute to nonadherence (Table 2). (9)

Adherence and Adverse Drug Events

Many factors influence the efficacy, safety, and success of drug therapy with older patients. These factors include not only the effects of aging on the pharmacokinetics and pharmacodynamics of medications but also patient characteristics (Table 3) (10) and other issues, including atypical presentation of illness, the use of multiple health care professionals, and adherence to drug regimens (Table 4). (11,12)

Adherence or compliance with drug therapy is essential to successful medical management. Noncompliance or nonadherence with drug therapy in older patient populations ranges from 21 to 55 percent. (13,14) The reasons for nonadherence include more medication use (total number of pills taken per day), forgetting or confusion about dosage schedule, intentional nonadherence because of medication side effects, and increased sensitivity to drugs leading to toxicity and adverse events. (12) Older patients may intentionally take too much of a medication, thinking it will help speed their recovery, while others, who cannot afford the medications, may undermedicate or simply not take any of the medication. Simple interventions by the health care team, such as reinforcing the importance of taking the prescribed dose and encouraging use of pill calendar boxes, can improve adherence and overall compliance with drug therapy (Table 5). (11)

One study (15) revealed that adverse drug events in older patients led to hospitalizations in 25 percent of patients 80 years and older. Adverse drug reactions are a common cause of iatrogenic illness in this age group, with psychotropic and cardiovascular drugs accounting for many of these. (11) Many drugs can cause distressing and potentially disabling or life-threatening reactions (Table 6). (11) A basic understanding of how drugs affect the aging body is needed to appreciate the risk inherent in prescribing to older adults.

How Do Drugs Interact with the Aging Body?

Pharmacokinetics includes absorption, distribution, metabolism, and excretion. Of the four, absorption is least affected by aging. (16) In older persons, absorption is generally complete, just slower. In addition to age-related changes, common medical conditions such as heart failure may reduce the rate and extent of absorption. Distribution of most medications is related to body weight and composition changes that occur with aging (decreased lean muscle mass, increased fat mass, and decreased total body water). Drug dosage recommendations may have to be modified based on estimates of lean body mass. Loading doses of drugs may be lowered because of decreased total body water. Fat-soluble drugs may have to be administered in lower dosages because of the potential for accumulation in fatty tissues and a longer duration of action. (16)

How a drug is cleared, through hepatic metabolism or renal clearance, dramatically changes with aging. Hepatic metabolism is variable and depends on age, genotype, lifestyle, hepatic blood flow, hepatic diseases, and interactions with other medications. (16) Hepatic metabolism occurs through one of two biotransformation systems. Phase I reactions (oxidation, reduction, demethylation, or hydrolysis) via the cytochrome P450 system (CYP450) can produce biologically active metabolites. Phase I reactions tend to occur more slowly in older adults, which often leads to less than optimal drug metabolism. In contrast, phase II metabolism, including acetylation, sulfonation, conjugation, and glucuronidation, is little changed with aging (Table 7). (16) Cigarette smoking, alcohol use, and caffeine use may also affect hepatic metabolism of medications. (16)

Renal excretion of drugs is affected by aging, although there is great interindividual variation. Drug elimination is correlated with creatinine clearance, which declines by 50 percent between 25 and 85 years of age. (16) Because lean body mass decreases with aging, the serum creatinine level is a poor indicator of (and tends to overestimate) the creatinine clearance in older adults. The Cockroft-Gault formula17 should be used to estimate creatinine clearance in older adults:

Creatinine clearance = (140 – age) 3 weight (kg)/ 72 3 serum creatinine (3 0.85 for women)

For example, a 25-year-old man and an 85-year-old man, each weighing 72 kg (158.4 lb) and having a serum creatinine value of 1 mg per dL (76 [micro]mol per L), would have different estimated creatinine clearance even though their serum creatinine value is the same. The younger man would have an estimated creatinine clearance of 115 mL per minute (1.92 mL per second), while the older man’s would be 55 mL per minute (0.92 mL per second). This difference is especially important with drugs that have a low therapeutic index and appreciable renal excretion (aminoglycosides, lithium, digoxin, procainamide [Pronestyl], vancomycin [Vancocin]). (2)

Pharmacodynamics relates to how sensitive tissues are to drugs. Sensitivity to drugs may increase or decrease with aging, and these full effects are poorly understood as a component of the aging process. (16) Pharmacodynamic changes may be related to changes in receptor binding, decreased receptor number, or altered translation of a receptor-initiated cellular response. For older adults, complete elimination of a drug from body tissues, including the brain, can take weeks because of a combination of pharmacokinetic and pharmacodynamic effects.

How Many Drugs Are Too Many?

Polypharmacy is simply the use of many medications at the same time. Other definitions include prescribing more medication than is clinically indicated, a medical regimen that includes at least one unnecessary medication, or the empiric use of five or more medications. (18) Polypharmacy is particularly harmful when the patient receives too many medications for too long and in too high a dosage. The major concern about polypharmacy is the potential for adverse drug reactions and interactions. It has been estimated that for every dollar spent on pharmaceuticals in nursing homes, another dollar is spent treating the iatrogenic illnesses attributed to the medications. (19) Drug-induced adverse events can mimic other geriatric syndromes or precipitate confusion, falls, and incontinence (Table 6), (11) possibly causing the physician to prescribe yet another drug. This prescribing cascade (20,21) is a preventable problem that requires the physician to be certain that all medications being taken by the patient are appropriately indicated, safe, and effective.

To prevent an iatrogenic illness caused by overprescribing, it is important to consider any new signs and symptoms in an older patient to be a possible consequence of current drug therapy. (20) A 10-step approach to help reduce polypharmacy has been described (Table 8). (22) Another way to avoid adverse drug events is to use lower dosages for older patients. Many popular drugs do not have effective lower-dosage recommendations from the manufacturers. Physicians should remember to start low and go slow. Starting with one third to one half of the recommended dosage may help eliminate potential harmful effects. (22)

What Medications Could Potentially Cause Trouble?

Drug-related problems including therapeutic failure, adverse drug reactions, and adverse drug withdrawal events are common in older patients. (23) To address this problem, a list of drugs that may be inappropriate to prescribe to older persons, especially the frail elderly, was developed through a consensus of experts in geriatric medicine and pharmacology. (24,25) This list, known as the Beers criteria, was originally targeted at nursing homes but has been expanded for community-dwelling seniors. (26)

A recent review (27) of the Beers criteria applied to various health care settings, from community-dwelling seniors to frail nursing home patients, found that between one in four and one in seven older patients received at least one inappropriate medication. The problematic drugs most often prescribed were long-acting benzodiazepines, dipyridamole (Persantine), propoxyphene (Darvon), and amitriptyline (Elavil). (27) When applying these criteria to a patient, it is important to remember that if a drug has been used for a long time without a serious adverse effect, it may not need to be discontinued. The physician should continually monitor a patient’s drug list and carefully ascertain if any medication is causing harm. Physicians can address this issue by keeping a list of drugs that can cause serious adverse events when prescribed to older adults (Table 9). (24,25) [References 24 and 25, Evidence level C: expert opinion/consensus]

What Medications Can Benefit Older Patients?

To avoid adverse drug events and polypharmacy, drugs that are beneficial in the treatment or prevention of serious diseases may not be prescribed to older adults. (27,28) For example, clinical evidence is now available showing that older adults benefit from beta-blocker therapy after myocardial infarction, adequate control of hypertension, and adequate treatment of hyperlipidemia. Other medications that have shown benefit in older adults, but are sometimes not prescribed, include angiotensin-converting enzyme inhibitors for heart failure and anticoagulants for nonvalvular atrial fibrillation (Table 10). (29-39)

Prescribing medications for older adults requires maintaining a balance between using too few and too little, and too many and too much. (40) Frequent follow-up visits, especially if a new drug has been introduced, allow the physician to assess for adverse drug events and possible drug-disease and drug-drug interactions. One recommended strategy is to verify at each patient visit if there is an indication for each drug, if it is effective in this case, if there is any unnecessary duplication with other drugs, and if this is the least expensive drug available compared with others of equal benefit. Before deciding that a medication is a therapeutic failure, the physician should make sure that an adequate dosage has been administered for an appropriate length of time.41 The goals in using drug therapy are to treat disease, alleviate pain and suffering, and prevent the life-threatening complications of many chronic diseases. Being successful with these goals requires a balance between benefit and risk to optimize prescribing for the aging population.


Common Herbs Taken by Older Adults and Drug Interactions

Herb (uses) Drug Adverse events

Ginkgo biloba Aspirin Spontaneous hyphema

(Alzheimer’s and

vascular dementia; Warfarin (Coumadin) Intracerebral

peripheral vascular hemorrhage

disease, erectile

dysfunction, and Thiazide diuretic Hypertension


Acetaminophen and Subdural hematoma


St. John’s wort Protease inhibitors, Induction of CYP450

(mild depression) cyclosporine 3A4 system with

(Sandimmune), decreased levels of

theophylline, drugs available


Digoxin (Lanoxin) Decreased drug

absorption from the


Selective Lethargy/incoherence/

serotonin-reuptake mild serotonin

inhibitors syndrome

Saw palmetto (benign No specific drug Headaches, GI upset

prostatic interactions


Ginseng (cure-all Warfarin Decreased INR


Alcohol Increased alcohol


Phenelzine (Nardil); Headache, tremor,

MAOI) mania

Yohimbine (sexual Tricyclic Hypertension

dysfunction) antidepressants

Senna, cascara Possible interference Decreased drug

(laxative) with any intestinally availability

absorbed drug

CYP450 = cytochrome P-450; GI = gastrointestinal; INR = International

Normalized Ratio; MAOI = monoamine oxidase inhibitor.

Information from Fugh-Berman A. Herb-drug interactions.

Lancet 2000;355:134-8.


Factors Associated with Medication-Related Problems

Wrong or unnecessary drugs being prescribed

Unmet need for new or additional medications

Wrong medication (contraindications, inappropriate for condition

being treated)

Dosage too low or too high

Adverse drug reaction or event

Nonadherence or noncompliance (failure to take drugs properly,

cost, prescribing errors)

Information from Hepler CD, Strand LM. Opportunities and

responsibilities in pharmaceutical care. Am J Hosp

Pharm 1990;47:533-43.


Common Characteristics of Older Adults

with Medication-Related Problems

85 years and older

More than six active chronic medical diagnoses

Decreased kidney function (estimated creatinine

clearance < 50 mL per minute [0.83 mL per second])

Low body weight or body-mass index

Nine or more medications

More than 12 doses of medication per day

Previous adverse drug reaction

Information from Fouts M, Hanlon J, Pieper C, Perfetto E, Feinberg

J. Identification of elderly nursing facility residents at high risk

for drug-related problems. Consult Pharm 1997;12:1103-11.


Factors That Interfere with Safe

and Successful Drug Therapy

Impediments to the recognition of the need to obtain care (cultural,

economic, physical, psychologic)

Atypical presentation of illness

Multiple illnesses


Diminished vision or hearing

Impairments to adherence (cultural, economic, physical, psychologic)


Increased susceptibility to adverse drug events

Age-related changes in pharmacology (absorption,

distribution, metabolism, excretion)

Information from references 11 and 12.


Common Adverse Drug Events and Clinical Outcomes

Drug/drug class Common adverse reactions Common clinical


Anti-inflammatory Gastric irritation, Hemorrhage, anemia,

agents ulcers, chronic blood sodium retention, renal

loss, nephrotoxicity failure, may decrease

effectiveness of

antihypertensive drugs

Aminoglycosides Renal failure Increased serum

concentration of

medications; dialysis

Anticholinergics Dry mouth, decreased gut Constipation, urinary

motility, bladder retention, confusion,

hypotonia, decreased instability and falls

cognition, sedation,

orthostatic hypotension,

blurry vision

Anticoagulants Bleeding complications Hemorrhage

Antidepressants Anticholinergic effects, Falls, confusion,

(tricyclics) heart block urinary retention

Antipsychotics Sedation, tardive Falls, hip fractures,

dyskinesia, dystonia, confusion, social

anticholinergic effects, disability


Beta blockers Decreased myocardial Bradycardia, heart

contractility, decreased failure, possible

cardiac conduction, confusion, falls

mild sedation,

orthostatic hypotension

Digoxin Decreased cardiac Arrhythmias, nausea,

conduction, anorexia



Insulin, Hypoglycemia Falls, confusion, brain

sulfonylureas, injury

acarbose (Precose)

Narcotics Decreased gut motility, Confusion, constipation


Sedative hypnotics Excessive sedation, Falls and fractures,

cognitive impairment, confusion

gait disturbances,

impaired psychomotor


Information from Kane RL, Ouslander JG, Abrass IB. Essentials of

clinical geriatrics. 4th ed. New York: McGraw-Hill, 1999.


Drugs with Decreased Clearance in Older Adults

Route of clearance Representative drug

Renal All aminoglycosides, vancomycin (Vancocin),

ciprofloxacin (Cipro), levofloxacin

(Levaquin), ofloxacin (Floxin), sparfloxacin

(Zagam), imipenem (Primaxin), penicillins,

digoxin (Lanoxin), procainamide (Pronestyl),

lithium, enalapril (Vasotec), lisinopril

(Zestril), quinapril (Accupril), ramipril

(Altace), sotalol (Betapace), atenolol

(Tenormin), nadolol (Corgard), dofetilide

(Tikosyn), cimetidine (Tagamet), famotidine

(Pepcid), nizatidine (Axid), ranitidine

(Zantac), acetohexamide (Dymelor),

chlorpropamide (Diabinese), glyburide

(Micronase), tolazamide (Tolinase)

Phase I hepatic Alprazolam (Xanax), midazolam (Versed),

biotransformation via triazolam (Halcion), verapamil (Calan),

cytochrome P450 system diltiazem (Cardizem), dihydropyridine calcium

channel blockers, lidocaine (Xylocaine),

diazepam (Valium), phenytoin (Dilantin),

celecoxib (Celebrex), theophylline, imipramine

(Tofranil), desipramine (Norpramin), trazodone

(Desyrel), flurazepam (Dalmane)

Phase II hepatic Lorazepam (Ativan), oxazepam (Serax),

biotransformation isoniazid (INH), procainamide

Information from Luisi AF, Owens NJ, Hume AL. Drugs and the elderly.

In: Gallo JJ, Reichel W, eds. Reichel’s Care of the elderly:

clinical aspects of aging, 5th ed. Philadelphia: Williams & Wilkins,



10 Steps to Reducing Polypharmacy

1. Have patients “brown bag” all medications at each office visit,

and keep an accurate record of all medications, including

over-the-counter medications and herbs.

2. Get into the habit of identifying all drugs by generic name and

drug class.

3. Make certain the drug being prescribed has a clinical indication.

4. Know the side-effect profile of the drugs being prescribed.

5. Understand how pharmacokinetics and pharmacodynamics

of aging increase the risk of adverse drug events.

6. Stop any drug without known benefit.

7. Stop any drug without a clinical indication.

8. Attempt to substitute a less toxic drug.

9. Be aware of the prescribing cascade (treating an adverse drug

reaction as an illness with another drug).

10. As much as possible, use the motto, “one disease, one drug,


Information from Carlson JE. Perils of polypharmacy: 10 steps to

prudent prescribing. Geriatrics 1996;51;26-30,35.


Inappropriate Medication/Medication Classes for Use in Older Adults

Medication/medication class Problematic use

Antihistamines (chlorpheniramine Many of these are over-the-counter

[Extendryl], diphenhydramine drugs used to treat the common

[Benadryl], hydroxyzine [Atarax], cold with potent anticholinergic

cyproheptadine [Periactin], effects; many elderly persons use

dexchlorpheniramine [Polaramine], these drugs to induce sleep; if

promethazine [Phenergan], using to treat seasonal allergies,

tripelennamine [PBZ]) use lowest effective dose.

Blood products/modifiers/volume Platelet aggregation inhibitors

expanders (dipyridamole are used to prevent blood from

[Persantine], ticlopidine clotting in persons who have had

[Ticlid]) strokes or myocardial infarction;

ticlopidine has been shown to be

no better than aspirin, and it is

more toxic; dipyridamole is

beneficial in patients with

artifical valves.

Antihypertensives (methyldopa Methyldopa can slow heart rate and

[Aldomet], reserpine [Serpasil]) exacerbate depression; reserpine

causes depression, erectile

dysfunction, sedation, and


Peripheral vasodilators Used to treat dementia and

(cyclandelate [Cyclospasmol], migraines; not shown to be

ergot mesyloids [Hydergine]) effective for either in doses


Antiarrhythmics (disopyramide Potent negative inotrope, may

[Norpace]) induce heart failure; strongly


Narcotics (meperidine [Demerol], Meperidine is not an effective

pentazocine [Talwin], propoxyphene oral agent for pain and has many

[Darvon]) disadvantages over other

narcotics; pentazocine causes more

central nervous system effects,

including confusion and

hallucinations; propoxyphene

offers no advantages over

acetaminophen but has same side

effects as other narcotic drugs.

Barbiturates (except Highly addictive and cause more

phenobarbital) (butalbital side effects than other sedative

[Fiorinal], pentobarbital hypnotics; should not be started

[Nembutal], secobarbital as new therapy except to treat

[Seconal]) seizures

Benzodiazepines (chlordiazepoxide Long half-life benzodiazepines

[Librium],diazepam [Valium], produce prolonged sedation and

flurazepam [Dalmane], triazolam increase risk for falls and

[Halcion]) fractures; triazolam may cause

cognitive and behavioral


Meprobamate (Miltown, Equanil) Used to treat anxiety; highly

addictive and sedating

Antidepressants (amitriptyline Highly anticholinergic and

[Elavil], doxepin [Sinequan], sedating; amitriptyline is rarely

imipramine [Tofranil], combination the antidepressant of choice in

antidepressant/antipsychotics the elderly.

Methylphenidate (Ritalin) May cause agitation, stimulation

of the central nervous system, and


Antiemetic (trimethobenzamide Least effective, can cause

[Tigan]) extrapyramidal side effects

Gastrointestinal antispasmodics All are highly anticholinergic and

(Donnatal with belladonna, generally produce substantial

clidinium [Quarzan], dicyclomine toxic effects; best avoided in the

[Bentyl], hyoscyamine [Levsin], elderly; not for long-term use.

propantheline [Pro-Banthine])

Antidiarrheals (diphenoxylate Drowsiness, cognitive impairment,

[Lomotil]) and dependence; long-term use is

not recommended.

Genitourinary-antispasmodic Anticholinergic effects; use

(oxybutynin [Ditropan]) lowest effective dose.

Hypoglycemic agents Prolonged half-life with prolonged

(chlorpropamide [Diabinese]) and serious hypoglycemia; can

cause syndrome of inappropriate

antidiuretic hormone.

NSAIDs (indomethacin [Indocin], Indomethacin produces serious

phenylbutazone [Butazolidine], central nervous system effects;

ketorolac [Toradol], mefenamic phenylbutazone produces serious

acid [Ponstel], piroxicam hematologic effects (bone marrow

[Feldene]) suppression); ketorolac, mefenamic

acid, and piroxicam have greater

risk of upper gastrointestinal

bleeding than other NSAIDs.

Skeletal muscle relaxants (all) Effectiveness questionable;

anticholinergic effects, sedation,

and weakness

NSAIDs = nonsteroidal anti-inflammatory drugs.

Information from references 24 and 25.


Drugs with Proven Benefits in Older Adults

Clinical indication Drug Evidence

Status post MI, CAD, Aspirin, 75 mg per day Beneficial; most

transient ischemic benefit seen for

attacks, stable and high-risk patients

unstable angina, taking medium-dose

peripheral vascular aspirin for at least

disease, stroke three years; should

prevention, and probably be used for

embolic stroke life; no clear

prevention in those evidence of use in

unable to take low-risk

warfarin (Coumadin) patients. (29)

[Evidence level A,

systematic review of


Status post MI Beta blockers Beneficial; given

within hours of

infarction and

continued for at least

one year or until a


contraindicates use;

most benefit found

for those older than

65 years and those who

suffered large

infarcts. (30,31)

[Reference 30,

Evidence level B,

retrospective cohort

study; Reference 31,

Evidence level A,


Hypertension Any reduction in BP

appears to confer

Systolic Thiazide diuretic benefit; treatment of

hypertension BP reduces stroke,

CHD, cardiovascular

Status post MI/CAD Beta blocker disease, heart

failure, and

CHF/DM ACE inhibitor mortality; treatment

goal is BP < 140/90 mm

Hg; however, an

interim goal of

systolic BP below 160

mm Hg may be needed in

those with marked

systolic hypertension;

JNC VI recommends

starting BP treatment

with a low-dose

thiazide diuretic or

beta blockers in

combination with


diuretics. (32,33)

[References 32 and 33,

Evidence level A,


Heart failure ACE inhibitor (no Beneficial; reduction

significant in mortality,

difference between ACE admission to

inhibitors). (34) hospitals, and


events. (34,35)

[References 34 and 35,

Evidence level A,


Spironolactone Spironolactone

(Aldactone, 12.5 to additive effect in

25.0 mg per day) (36) reduction of morbidity

and death with severe

heart failure

(NYHA III-IV). (36)

[Evidence level A,


Hypercholesterolemia Statins Beneficial; consider

treatment for patients

Start with one half 50 to 80 years of age

lowest recommended without CAD who have

dose and titrate upward serum LDL levels > 130

to target mg per dL (3.35 mmol

LDL level per L) and serum HDL

levels < 50 mg per dL

Baseline liver function (1.30 mmol per L)

tests with repeat test because older patients

after six to 12 weeks are at increased risk

of therapy, then of CAD.

twice yearly

Treat all men and

women with CAD,

previous stroke, DM,

peripheral artery

disease, extracranial

carotid arterial

disease, and abdominal

aortic aneurysm to LDL

level < 100 mg per dL

(2.59 mmol per L).

Active liver disease

is a contraindication;

a history of liver

disease and alcohol

use requires cautious


Myopathy can be a

problem; have

patients report any

unusual muscle

tenderness. (37)

[Evidence level A,

systematic review of


Chronic nonvalvular Warfarin to maintain an Beneficial; as primary

atrial fibrillation INR between 2.0 and 3.0 prevention, about 25

strokes and about 12

disabling fatal

strokes would be

prevented yearly for

every 1,000 patients

given oral



Careful monitoring of

INR required to offset

potential hemorrhagic

risk. (38,39)

[References 38 and 39,

Evidence level A,


MI = myocardial infarction; CAD = coronary artery disease; RCT =

randomized controlled trial; CHF = congestive heart failure; DM =

diabetes mellitus; ACE = angiotensin-converting enzyme; BP = blood

pressure; CHD = coronary heart disease; JNC VI = sixth report of the

Joint National Committee; NYHA = New York Heart Association classes;

LDL = low-density lipoprotein; HDL = high-density lipoprotein; INR =

International Normalized Ratio.

Information from references 29 through 39.

The author indicates that she does not have any conflicts of interest. Sources of funding: none reported.

The opinions and assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the U.S. Navy Medical Department or the U.S. Navy Service at large.


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CYNTHIA M. WILLIAMS, CAPT, MC, USN, is an assistant professor of family medicine at Uniformed Services University of the Health Sciences, Bethesda, Md. She completed her family practice residency at Naval Hospital, Camp Pendleton, Calif., and a geriatric fellowship at East Carolina University School of Medicine, Greenville, N.C. Address correspondence to Cynthia M. Williams, CAPT, MC, USN, USUHS, 4103 Jones Bridge Rd., Bethesda, MD 20814 (e-mail: cwilliams@ Reprints are not available from the author.

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