Using medications appropriately in older adults -- american family physician
Using Medications Appropriately in Older Adults CYNTHIA M. WILLIAMS, CAPT, MC, USN, Uniformed Services University of the Health Sciences, Bethesda, Maryland Older Americans comprise 13 percent of the population, but they consume an average of 30 percent of all prescription drugs. Every day, physicians are faced with issues sur- rounding appropriate prescribing to older patients. Polypharmacy, use of supplements, adherence issues, and the potential for adverse drug events all pose challenges to effective prescribing. Knowledge of the interplay between aging physiology, chronic diseases, and drugs will help the physician avoid potential adverse drug events as well as drug-drug and drug-disease interactions. Evidence is now available showing that older patients may be underprescribed useful drugs, including aspirin for secondary prevention in high-risk patients, beta blockers following myocardial infarction, and warfarin for nonvalvular atrial fibrillation. There is also evidence that many older adults receive medications that could potentially cause more harm than good. Finding the right balance between too few and too many drugs will help ensure increased longevity, improved overall health, and enhanced functioning and quality of life for the aging population. (Am Fam Physician 2002;66:1917-24. Copyright 2002 American Academy of Family Physicians.)
ication.8 The multiple medications and com-
plex drug schedules may be justified for older
persons with complex medical problems.
Patients 65 years and older repre-sent approximately 13 percent ofthe population, but they consume
However, the use of too many medications can
pose problems of serious adverse drug events
tion medications.1 Older American consumers
and drug-drug interactions, and often can
spend an average total of $3 billion annually on
contribute to nonadherence (Table 2).9
prescription medications.2 Sixty-one percent of
Adherence and Adverse Drug Events
older people seeing a physician are taking atleast one prescription medication,3 and most
Many factors influence the efficacy, safety,
older Americans take an average of three to five
medications.4,5 These data do not include the
patients. These factors include not only the
use of over-the-counter medications or herbal
effects of aging on the pharmacokinetics and
therapies. An estimated 40 percent of older
patient characteristics (Table 3)10 and other
supplement within the past year6 (Table 1).7
issues, including atypical presentation of ill-
The physician who cares for aging patients
ness, the use of multiple health care profes-
must make daily decisions about appropriate
drug therapy. More than 60 percent of all
physician visits include a prescription for med-
apy is essential to successful medical manage-ment. Noncompliance or nonadherence withdrug therapy in older patient populationsranges from 21 to 55 percent.13,14 The reasons
Patients 65 years and older represent about 13 percent ofthe population, but consume about 30 percent of all
use (total number of pills taken per day), for-
getting or confusion about dosage schedule,intentional nonadherence because of medica-
TABLE 1 Common Herbs Taken by Older Adults and Drug Interactions
Ginkgo biloba (Alzheimer’s and vascular
Lethargy/incoherence/mild serotonin syndrome
Saw palmetto (benign prostatic hypertrophy)
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.
tion side effects, and increased sensitivity to drugs leadingto toxicity and adverse events.12 Older patients may inten-
tionally take too much of a medication, thinking it will
Factors Associated with Medication-Related Problems
help speed their recovery, while others, who cannot affordthe medications, may undermedicate or simply not take
Wrong or unnecessary drugs being prescribed
any of the medication. Simple interventions by the health
Unmet need for new or additional medications
care team, such as reinforcing the importance of taking the
Wrong medication (contraindications, inappropriate for condition
prescribed dose and encouraging use of pill calendar
boxes, can improve adherence and overall compliance with
Nonadherence or noncompliance (failure to take drugs properly,
One study15 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
Information from Hepler CD, Strand LM. Opportunities and responsi-
cause of iatrogenic illness in this age group, with psycho-
bilities in pharmaceutical care. Am J Hosp Pharm 1990;47:533-43.
tropic and cardiovascular drugs accounting for many ofthese.11 Many drugs can cause distressing and potentiallydisabling or life-threatening reactions (Table 6).11 A basicunderstanding of how drugs affect the aging body is needed
affected by aging.16 In older persons, absorption is gener-
to appreciate the risk inherent in prescribing to older adults.
ally complete, just slower. In addition to age-relatedchanges, common medical conditions such as heart failure
How Do Drugs Interact with the Aging Body?
may reduce the rate and extent of absorption. Distribution
Pharmacokinetics includes absorption, distribution,
of most medications is related to body weight and compo-
metabolism, and excretion. Of the four, absorption is least
sition changes that occur with aging (decreased lean mus-cle mass, increased fat mass, and decreased total bodywater). Drug dosage recommendations may have to bemodified based on estimates of lean body mass. Loading
Pharmacokinetics includes absorption, distribu-
doses of drugs may be lowered because of decreased total
tion, metabolism, and excretion. Of the four,
body water. Fat-soluble drugs may have to be administered
absorption is least affected by the aging process.
in lower dosages because of the potential for accumulationin fatty tissues and a longer duration of action.16
Common Characteristics of Older Adults Strategies to Enhance Adherence to Drug Therapy with Medication-Related Problems
More than six active chronic medical diagnoses
Decreased kidney function (estimated creatinine
clearance < 50 mL per minute [0.83 mL per second])
item, see the original print version of this publication.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.
How a drug is cleared, through hepatic metabolism or
renal clearance, dramatically changes with aging. Hepaticmetabolism is variable and depends on age, genotype,lifestyle, hepatic blood flow, hepatic diseases, and interac-tions with other medications.16 Hepatic metabolism occurs
correlated with creatinine clearance, which declines by 50
through one of two biotransformation systems. Phase I
percent between 25 and 85 years of age.16 Because lean
reactions (oxidation, reduction, demethylation, or hydroly-
body mass decreases with aging, the serum creatinine level
sis) via the cytochrome P450 system (CYP450) can produce
is a poor indicator of (and tends to overestimate) the crea-
biologically active metabolites. Phase I reactions tend to
tinine clearance in older adults. The Cockroft-Gault for-
occur more slowly in older adults, which often leads to less
mula17 should be used to estimate creatinine clearance in
than optimal drug metabolism. In contrast, phase II metab-
olism, including acetylation, sulfonation, conjugation, and
glucuronidation, is little changed with aging (Table 7).16
72 ϫ serum creatinine (ϫ 0.85 for women)
Cigarette smoking, alcohol use, and caffeine use may alsoaffect hepatic metabolism of medications.16
For example, a 25-year-old man and an 85-year-old
Renal excretion of drugs is affected by aging, although
man, each weighing 72 kg (158.4 lb) and having a serum
there is great interindividual variation. Drug elimination is
creatinine value of 1 mg per dL (76 µmol per L), wouldhave different estimated creatinine clearance even thoughtheir serum creatinine value is the same. The younger man
would have an estimated creatinine clearance of 115 mL
Factors That Interfere with Safe
per minute (1.92 mL per second), while the older man’s
and Successful Drug Therapy
would be 55 mL per minute (0.92 mL per second). Thisdifference is especially important with drugs that have a
Impediments to the recognition of the need to obtain care (cultural,
low therapeutic index and appreciable renal excretion
(aminoglycosides, lithium, digoxin, procainamide [Pron-
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
Impairments to adherence (cultural, economic, physical, psychologic)
Increased susceptibility to adverse drug events
Age-related changes in pharmacology (absorption, distribution,
Drug elimination correlates with creatinine clear-ance, which declines by 50 percent between Information from references 11 and 12.
TABLE 6 Common Adverse Drug Events and Clinical Outcomes
Gastric irritation, ulcers, chronic blood loss,
Hemorrhage, anemia, sodium retention, renal failure,
may decrease effectiveness of antihypertensive drugs
Increased serum concentration of medications; dialysis
Dry mouth, decreased gut motility, bladder
Constipation, urinary retention, confusion, instability
hypotonia, decreased cognition, sedation,
Falls, hip fractures, confusion, social disability
Decreased myocardial contractility, decreased cardiac
Bradycardia, heart failure, possible confusion, falls
conduction, mild sedation, orthostatic hypotension
Decreased cardiac conduction, gastrointestinal
Excessive sedation, cognitive impairment, gait
disturbances, impaired psychomotor performance
Information from Kane RL, Ouslander JG, Abrass IB. Essentials of clinical geriatrics. 4th ed. New York: McGraw-Hill, 1999.
component of the aging process.16 Pharmacodynamic
is particularly harmful when the patient receives too many
changes may be related to changes in receptor binding,
medications for too long and in too high a dosage. The
decreased receptor number, or altered translation of a
major concern about polypharmacy is the potential for
receptor-initiated cellular response. For older adults, com-
adverse drug reactions and interactions. It has been esti-
plete elimination of a drug from body tissues, including
mated that for every dollar spent on pharmaceuticals in
the brain, can take weeks because of a combination of
nursing homes, another dollar is spent treating the iatro-
pharmacokinetic and pharmacodynamic effects.
genic illnesses attributed to the medications.19 Drug-induced adverse events can mimic other geriatric syn-
How Many Drugs Are Too Many?
dromes or precipitate confusion, falls, and incontinence
Polypharmacy is simply the use of many medications at
(Table 6),11 possibly causing the physician to prescribe yet
the same time. Other definitions include prescribing more
another drug. This prescribing cascade20,21 is a preventable
medication than is clinically indicated, a medical regimen
problem that requires the physician to be certain that all
that includes at least one unnecessary medication, or the
medications being taken by the patient are appropriately
empiric use of five or more medications.18 Polypharmacy
To prevent an iatrogenic illness caused by overprescrib-
ing, it is important to consider any new signs and symp-toms in an older patient to be a possible consequence of
current drug therapy.20 A 10-step approach to help reducepolypharmacy has been described (Table 8).22 Another way
CYNTHIA M. WILLIAMS, CAPT, MC, USN, is an assistant professor offamily medicine at Uniformed Services University of the Health Sci-
to avoid adverse drug events is to use lower dosages for
ences, Bethesda, Md. She completed her family practice residency at
older patients. Many popular drugs do not have effective
Naval Hospital, Camp Pendleton, Calif., and a geriatric fellowship at
lower-dosage recommendations from the manufacturers.
East Carolina University School of Medicine, Greenville, N.C.
Physicians should remember to start low and go slow. Address correspondence to Cynthia M. Williams, CAPT, MC, USN,
Starting with one third to one half of the recommended
USUHS, 4103 Jones Bridge Rd., Bethesda, MD 20814 (e-mail: c[email protected]). Reprints are not available from the author.
dosage may help eliminate potential harmful effects.22
TABLE 7 Drugs with Decreased Clearance in Older Adults
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)
Alprazolam (Xanax), midazolam (Versed), triazolam (Halcion), verapamil (Calan), diltiazem (Cardizem),
dihydropyridine calcium channel blockers, lidocaine (Xylocaine), diazepam (Valium), phenytoin (Dilantin),
celecoxib (Celebrex), theophylline, imipramine (Tofranil), desipramine (Norpramin), trazodone (Desyrel), flurazepam (Dalmane)
Lorazepam (Ativan), oxazepam (Serax), 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 ofaging, 5th ed. Philadelphia: Williams & Wilkins, 1999:59-87.
example, clinical evidence is now available showing that
What Medications Could Potentially
older adults benefit from beta-blocker therapy after
myocardial infarction, adequate control of hypertension,
Drug-related problems including therapeutic failure,
and adequate treatment of hyperlipidemia. Other medica-
adverse drug reactions, and adverse drug withdrawal
tions that have shown benefit in older adults, but are
events are common in older patients.23 To address this
sometimes not prescribed, include angiotensin-convert-
problem, a list of drugs that may be inappropriate to pre-
ing enzyme inhibitors for heart failure and anticoagulants
scribe to older persons, especially the frail elderly, was
for nonvalvular atrial fibrillation (Table 10).29-39
developed through a consensus of experts in geriatric
Prescribing medications for older adults requires main-
medicine and pharmacology.24,25 This list, known as theBeers criteria, was originally targeted at nursing homes buthas been expanded for community-dwelling seniors.26
A recent review27 of the Beers criteria applied to various
10 Steps to Reducing Polypharmacy
health care settings, from community-dwelling seniors tofrail nursing home patients, found that between one in four
1. Have patients “brown bag” all medications at each office visit,
and one in seven older patients received at least one inap-
and keep an accurate record of all medications, including over-
propriate medication. The problematic drugs most often
prescribed were long-acting benzodiazepines, dipyridamole
2. Get into the habit of identifying all drugs by generic name and
(Persantine), propoxyphene (Darvon), and amitriptyline
3. Make certain the drug being prescribed has a clinical indication.
(Elavil).27 When applying these criteria to a patient, it is
4. Know the side-effect profile of the drugs being prescribed.
important to remember that if a drug has been used for a
5. Understand how pharmacokinetics and pharmacodynamics
long time without a serious adverse effect, it may not need
of aging increase the risk of adverse drug events.
to be discontinued. The physician should continually mon-
6. Stop any drug without known benefit.
itor a patient’s drug list and carefully ascertain if any med-
7. Stop any drug without a clinical indication.
ication is causing harm. Physicians can address this issue by
8. Attempt to substitute a less toxic drug.
keeping a list of drugs that can cause serious adverse events
9. Be aware of the prescribing cascade (treating an adverse drug
when prescribed to older adults (Table 9).24,25 [References
reaction as an illness with another drug).
24 and 25, Evidence level C: expert opinion/consensus]
10. As much as possible, use the motto, “one disease, one drug,
What Medications Can Benefit Older Patients?
To avoid adverse drug events and polypharmacy, drugs
Information from Carlson JE. Perils of polypharmacy: 10 steps to pru-
that are beneficial in the treatment or prevention of seri-
dent prescribing. Geriatrics 1996;51;26-30,35.
ous diseases may not be prescribed to older adults.27,28 For
TABLE 9 Inappropriate Medication/Medication Classes for Use in Older Adults
Antihistamines (chlorpheniramine [Extendryl],
Many of these are over-the-counter drugs used to treat the common cold
diphenhydramine [Benadryl], hydroxyzine [Atarax],
with potent anticholinergic effects; many elderly persons use these drugs
cyproheptadine [Periactin], dexchlorpheniramine
to induce sleep; if using to treat seasonal allergies, use lowest effective dose.
[Polaramine], promethazine [Phenergan], tripelennamine [PBZ])
Blood products/modifiers/volume expanders
Platelet aggregation inhibitors are used to prevent blood from clotting in persons who have
(dipyridamole [Persantine], ticlopidine [Ticlid])
had strokes or myocardial infarction; ticlopidine has been shown to be no better thanaspirin, and it is more toxic; dipyridamole is beneficial in patients with artifical valves.
Antihypertensives (methyldopa [Aldomet],
Methyldopa can slow heart rate and exacerbate depression; reserpine causes
depression, erectile dysfunction, sedation, and light-headedness.
Peripheral vasodilators (cyclandelate [Cyclospasmol],
Used to treat dementia and migraines; not shown to be effective for either
Potent negative inotrope, may induce heart failure; strongly anticholinergic
Narcotics (meperidine [Demerol], pentazocine
Meperidine is not an effective oral agent for pain and has many 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 phenobarbital) (butalbital [Fiorinal],
Highly addictive and cause more side effects than other sedative hypnotics;
pentobarbital [Nembutal], secobarbital [Seconal])
should not be started as new therapy except to treat seizures
Benzodiazepines (chlordiazepoxide [Librium],diazepam
Long half-life benzodiazepines produce prolonged sedation and increase risk for falls
[Valium], flurazepam [Dalmane], triazolam [Halcion])
and fractures; triazolam may cause cognitive and behavioral abnormalities.
Used to treat anxiety; highly addictive and sedating
Antidepressants (amitriptyline [Elavil], doxepin
Highly anticholinergic and sedating; amitriptyline is rarely the antidepressant
[Sinequan], imipramine [Tofranil], combination
May cause agitation, stimulation of the central nervous system, and seizures.
Least effective, can cause extrapyramidal side effects
Gastrointestinal antispasmodics (Donnatal with
All are highly anticholinergic and generally produce substantial toxic effects;
belladonna, clidinium [Quarzan], dicyclomine
best avoided in the elderly; not for long-term use.
[Bentyl], hyoscyamine [Levsin], propantheline [Pro-Banthine])
Drowsiness, cognitive impairment, and dependence; long-term use is not recommended.
Genitourinary-antispasmodic (oxybutynin [Ditropan])
Anticholinergic effects; use lowest effective dose.
Hypoglycemic agents (chlorpropamide [Diabinese])
Prolonged half-life with prolonged and serious hypoglycemia; can cause syndrome of
NSAIDs (indomethacin [Indocin], phenylbutazone
Indomethacin produces serious central nervous system effects; phenylbutazone produces
[Butazolidine], ketorolac [Toradol], mefenamic
serious hematologic effects (bone marrow suppression); ketorolac, mefenamic acid,
and piroxicam have greater risk of upper gastrointestinal bleeding than other NSAIDs.
Effectiveness questionable; anticholinergic effects, sedation, and weakness
NSAIDs = nonsteroidal anti-inflammatory drugs.Information from references 24 and 25.
taining a balance between using too few and too little, and
cation for each drug, if it is effective in this case, if there is
too many and too much.40 Frequent follow-up visits, espe-
any unnecessary duplication with other drugs, and if this is
cially if a new drug has been introduced, allow the physi-
the least expensive drug available compared with others of
cian to assess for adverse drug events and possible drug-
equal benefit. Before deciding that a medication is a thera-
disease and drug-drug interactions. One recommended
peutic failure, the physician should make sure that an ade-
strategy is to verify at each patient visit if there is an indi-
quate dosage has been administered for an appropriate
TABLE 10 Drugs with Proven Benefits in Older Adults
Beneficial; most benefit seen for high-risk patients taking
medium-dose aspirin for at least three years; should probably
be used for life; no clear evidence of use in low-risk
patients.29 [Evidence level A, systematic review of RCTs]
and embolic stroke prevention in those unable to take warfarin (Coumadin)
Beneficial; given within hours of infarction and continued for at least
one year or until a complication 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, meta-analysis]
Any reduction in BP appears to confer benefit; treatment of BP reduces
stroke, CHD, cardiovascular disease, heart failure, and 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 markedsystolic hypertension; JNC VI recommends starting BP treatment witha low-dose thiazide diuretic or beta blockers in combination with thiazide diuretics.32,33 [References 32 and 33, Evidence level A, meta-analyses]
Beneficial; reduction in mortality, admission to hospitals, and
ischemic events.34,35 [References 34 and 35, Evidence level A,
Spironolactone additive effect in reduction of morbidity and death
with severe heart failure (NYHA III-IV).36 [Evidence level A, RCT]
Beneficial; consider treatment for patients 50 to 80 years of age
without CAD who have serum LDL levels > 130 mg per dL
(3.35 mmol per L) and serum HDL levels < 50 mg per dL (1.30 mmol
per L) because older patients are at increased risk of CAD.
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).
six to 12 weeks of therapy, Active liver disease is a contraindication; a history of liver disease and then twice yearly
Myopathy can be a problem; have patients report any unusual muscle
tenderness.37 [Evidence level A, systematic review of RCTs]
Beneficial; as primary prevention, about 25 strokes and about
12 disabling fatal strokes would be prevented yearly for every 1,000 patients given oral anticoagulation therapy.
Careful monitoring of INR required to offset potential hemorrhagic
risk.38,39 [References 38 and 39, Evidence level A, meta-analyses]
MI = myocardial infarction; CAD = coronary artery disease; RCT = randomized controlled trial; CHF = congestive heart failure; DM = diabetes melli-tus; ACE = angiotensin-converting enzyme; BP = blood pressure; CHD = coronary heart disease; JNC VI = sixth report of the Joint National Commit-tee; NYHA = New York Heart Association classes; LDL = low-density lipoprotein; HDL = high-density lipoprotein; INR = International Normalized Ratio.Information from references 29 through 39.
length of time.41 The goals in using drug therapy are to
The author indicates that she does not have any conflicts of inter-
treat disease, alleviate pain and suffering, and prevent the
est. Sources of funding: none reported.
life-threatening complications of many chronic diseases. The opinions and assertions contained herein are the private views
Being successful with these goals requires a balance
of the author and are not to be construed as official or as reflect-
between benefit and risk to optimize prescribing for the
ing the views of the U.S. Navy Medical Department or the U.S. NavyDrugs in the Elderly
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Guidelines for the Management of Adverse Drug Effects of Antimycobacterial Agents Lawrence Flick Memorial Tuberculosis Clinic Philadelphia Tuberculosis Control Program November 1998 Table of Contents Drugs Used in the Treatment of Tuberculosis Section I: Most Common Adverse Drug Effects Listed by Adverse Effect Section II: Adverse Drug Effects and Drug Interactions Listed by D
1) El contrato de transporte se hace presente entre el pasajero y M.H. Bland & Co. Ltd. (“la Empresa”) y es inmediatamente aceptado por el cliente o su agente debidamente autorizado a través del ticket de pasajero. La Empresa se compromete a utilizar su mayor empeño en satisfacer al pasajero; y en particular en el caso de mal tiempo, o de fallo mecánico o eléctrico, la Empresa se re