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• Drug Therapy in the Elderly
4

Drug-related problems include

• Adverse effects
• Ineffectiveness

Adverse drug effects are effects that are unwanted, uncomfortable, or dangerous. Common examples are oversedation, confusion, hallucinations, falls, and bleeding. Among ambulatory people ≥ 65, adverse drug effects occur at a rate of about 50 events per 1000 person-years. Hospitalization rates due to adverse drug effects are 4 times higher in elderly patients (≈ 17%) than in younger patients (4%).

Reasons for Drug-Related Problems

Adverse drug effects can occur in any patient, but certain characteristics of the elderly make them more susceptible. For example, the elderly often take many drugs (polypharmacy) and have age-related changes in pharmacodynamics and pharmacokinetics; both increase the risk of adverse effects.

At any age, adverse drug effects may occur when drugs are prescribed and taken appropriately; eg, new-onset allergic reactions are not predictable or preventable. However, adverse effects are thought to be preventable in almost 90% of cases in the elderly (compared with only 24% in younger patients). Certain drug classes are commonly involved. In nursing home patients, preventable adverse drug effects commonly result from use of atypical antipsychotics, warfarinSome Trade Names
COUMADIN
Click for Drug Monograph
, antidepressants, and sedative-hypnotics. In community-dwelling elderly, the most common causes are hypoglycemic drugs, NSAIDs, and benzodiazepines.

In the elderly, a number of common reasons for adverse drug effects, ineffectiveness, or both are preventable (see Table 3: Drug Therapy in the Elderly: Preventable Causes of Drug-Related Problems). Several of these reasons involve inadequate communication with patients or among health care practitioners (particularly during health care transitions).

Table 3
Preventable Causes of Drug-Related Problems Category Definition Drug interactions Use of a drug results in a drug-drug, drug-food, drug-supplement, or drug-disease interaction, leading to adverse effects or decreased efficacy. Inadequate monitoring A medical problem is being treated with the correct drug, but the patient is not monitored for complications, efficacy, or both. Inappropriate drug selection A medical problem that requires drug therapy is being treated with a less-than-optimal drug. Inappropriate treatment A patient is taking a drug for no medically valid reason. Lack of patient adherence The correct drug for a medical problem is prescribed, but the patient is not taking it. Overdosage A medical problem is being treated with too much of the correct drug. Underprescribing A medical problem is being treated with too little of the correct drug. Untreated medical problem A medical problem requires drug therapy, but no drug is being used to treat that problem.

Inappropriate drugs: A drug is inappropriate if its potential for harm is greater than its potential for benefit. Inappropriate use of a drug may involve

• Choice of an unsuitable drug, dose, frequency of dosing, or duration of therapy
• Duplication of therapy
• Failure to consider drug interactions and correct indications for a drug
• Appropriate drugs that are mistakenly continued once an acute condition resolves (as may happen when patients move from one health care setting to another)

Adverse effects of inappropriate drugs account for about 3% of emergency department visits for patients ≥ 65; anticoagulants, antiplatelet drugs, drugs used to treat diabetes, and drugs with a narrow therapeutic index account for about half, and 3 drugs—warfarinSome Trade Names
COUMADIN
Click for Drug Monograph
, digoxinSome Trade Names
DIGITEK
LANOXIN
Click for Drug Monograph
, and insulinSome Trade Names
HUMULIN
NOVOLIN
Click for Drug Monograph
—account for about one third. Thus, some classes of drugs are of special concern in the elderly (see Drug Therapy in the Elderly: Drug Categories of Concern in the Elderly). Some are so problematic that they should be avoided in the elderly; others can be used with increased caution. The Beers Criteria (see Table 5: Drug Therapy in the Elderly: High-Risk Drugs in the Elderly (Based on the Beers Criteria)) lists inappropriate drugs for the elderly by drug class; other similar lists are available. However, there is no similar list of drugs that should be used in the elderly; clinicians must weigh benefits and risks of therapy in each patient.

Despite the Beers and other criteria, inappropriate drugs are still being prescribed for the elderly; typically, about 20% of community-dwelling elderly use at least one inappropriate drug. In such patients, risk of hospitalization is increased. In nursing home patients, inappropriate use increases risk of hospitalization and death. In one study of hospitalized patients, 27.5% were given an inappropriate drug.

Some inappropriate drugs are available OTC; thus, clinicians should specifically question patients about use of OTC drugs and tell patients about the potential problems such drugs can cause.

The elderly are often given drugs (typically, analgesics, H₂ blockers, hypnotics, or laxatives) for minor symptoms (including adverse effects of other drugs) that may be better treated nonpharmacologically. Using such drugs is often inappropriate; benefit is low, and use increases cost and may lead to toxicity.

Solving the problem of inappropriate use in the elderly requires more than avoiding a short list of drugs and noting drug categories of concern. A patient's entire drug regimen should also be assessed to determine its potential benefit vs harm.

Overdosage: An excessive dose of an appropriate drug may be prescribed for elderly patients if the prescriber does not consider age-related changes that affect pharmacokinetics (see Pharmacokinetics) and pharmacodynamics (see Pharmacodynamics). Doses of renally cleared drugs should be adjusted in patients with renal impairment, which is common among the elderly.

Generally, doses should be lower in the elderly, although dose requirements vary considerably from person to person. Typically, starting doses of about one third to one half the usual adult dose are indicated when a drug has a low therapeutic index or when another condition may be exacerbated by a drug. The dose is then titrated upward as tolerated to the desired effect. When the dose is increased, patients should be evaluated for adverse effects, and drug levels should be monitored when possible.

Overdosage can also occur when drug interactions (see see Drug Therapy in the Elderly: Drug-drug interactions) increase the amount of drug available or when different practitioners prescribe a drug and are unaware that another practitioner prescribed the same or a similar drug.

Underprescribing: Appropriate drugs may be underprescribed—not used for maximum effectiveness. Underprescribing may increase morbidity and mortality and reduce quality of life. Clinicians should use adequate drug doses and, when indicated, multidrug regimens.

Drugs that are often underprescribed in the elderly include those used to treat depression, Alzheimer's disease, pain (eg, opioids), heart failure, post-MI (β-blockers), atrial fibrillation (warfarinSome Trade Names
COUMADIN
Click for Drug Monograph
), hypertension, and incontinence and drugs to prevent glaucoma, influenza, and pneumococcal infection.

• Opioids: Clinicians are often reluctant to prescribe opioids for elderly patients with cancer or other types of chronic pain, typically because of concerns about adverse drug effects (eg, sedation, constipation, delirium) and development of dependence. When opioids are prescribed, the doses are often inadequate. Underprescribing opioids may mean that some elderly patients have needless pain and discomfort; elderly patients are more likely to report inadequate pain management than younger adults.
• β-Blockers: In patients with a history of MI, even in elderly patients at high risk of complications (eg, those with heart failure, pulmonary disorders, or diabetes mellitus), these drugs reduce mortality rates.
• Antihypertensives: Guidelines for treating hypertension (including isolated systolic hypertension) in the elderly are available, and treatment appears to be beneficial (reducing risk of stroke and major cardiovascular events). Nonetheless, studies indicate that hypertension is often not controlled in elderly patients.
• Drugs for Alzheimer's disease: Acetylcholinesterase inhibitors and NMDA (N-methyl-d-aspartate) antagonists have been shown to benefit patients with Alzheimer's disease. The amount of benefit is unclear, but patients and family members should be given the opportunity to make an informed decision about their use.

In elderly patients with a chronic disorder, acute or unrelated disorders may be undertreated (eg, hypercholesterolemia may be untreated in patients with emphysema). Clinicians may withhold these treatments because of concern about increasing the risk of adverse effects. Clinicians may think that treatment of the primary problem is all patients can or want to handle or that patients cannot afford the additional drugs.

Drug-disease interactions: A drug given to treat one disease can exacerbate another disease regardless of patient age, but such interactions are of special concern in the elderly, who are more likely to have multiple disorders. Distinguishing often subtle adverse drug effects from the effects of disease is difficult (see Table 4: Drug Therapy in the Elderly: Drug-Disease Interactions in the Elderly) and may lead to a prescribing cascade.

A prescribing cascade occurs when the adverse effect of a drug is misinterpreted as a symptom or sign of a new disorder and a new drug is prescribed to treat it. The new, unnecessary drug may cause additional adverse effects, which may then be misinterpreted as yet another disorder and treated unnecessarily, and so on.

Many drugs have adverse effects that resemble symptoms of disorders common among the elderly or changes due to aging. The following are examples:

• Antipsychotics may cause symptoms that resemble Parkinson's disease. In elderly patients, these symptoms may be diagnosed as Parkinson's disease and treated, possibly leading to adverse effects from the antiparkinson drugs (eg, orthostatic hypotension, delirium).
• Cholinesterase inhibitors (eg, donepezilSome Trade Names
  ARICEPT
  Click for Drug Monograph
  ) may be prescribed for patients with dementia. These drugs may cause diarrhea or urinary incontinence. Patients may then be prescribed an anticholinergic drug (eg, oxybutyninSome Trade Names
  DITROPAN
  Click for Drug Monograph
  ). Thus, an unnecessary drug is added, increasing the risk of adverse drug effects and drug-drug interactions. A better strategy is to reduce the dose of the cholinesterase inhibitor or consider a different treatment for dementia (eg, memantineSome Trade Names
  NAMENDA
  Click for Drug Monograph
  ) with a different mechanism of action.

In elderly patients, prescribers should always consider the possibility that a new symptom or sign is due to drug therapy.

Table 4
Drug-Disease Interactions in the Elderly Disease Drugs Possible Adverse Effects Arrhythmias Tricyclic antidepressants Heart block, proarrhythmic effect, QT-interval changes Bladder outflow obstruction Anticholinergic drugs Antihistamines Antidepressants Decongestants FlavoxateSome Trade Names URISPAS Click for Drug Monograph GI antispasmodics Muscle relaxants OxybutyninSome Trade Names DITROPAN Click for Drug Monograph TolterodineSome Trade Names DETROL Click for Drug Monograph Impaired outflow leading to urinary retention Bleeding disorders AspirinSome Trade Names BUFFERIN ECOTRIN GENACOTE Click for Drug Monograph ClopidogrelSome Trade Names PLAVIX Click for Drug Monograph DipyridamoleSome Trade Names PERSANTINE Click for Drug Monograph NSAIDs TiclopidineSome Trade Names TICLID Click for Drug Monograph Prolonged clotting time due to inhibition of platelet aggregation, resulting in increased risk of bleeding COPD Sedatives (eg, long-acting benzodiazepines) Respiratory depression Noncardioselective β-blockers (eg, propranololSome Trade Names INDERAL Click for Drug Monograph ) Bronchoconstriction Chronic renal impairment Aminoglycosides NSAIDs Radiopaque dyes Acute renal failure Constipation Anticholinergic drugs Ca and iron supplements Ca channel blockers Tricyclic antidepressants Exacerbation of constipation Dementia AmantadineSome Trade Names SYMMETREL Click for Drug Monograph Anticholinergic drugs Anticonvulsants Antispasmodics Levodopa Muscle relaxants Psychoactive drugs (eg, barbiturates, benzodiazepines) Increased confusion, delirium Depression Alcohol Antihypertensives (central-acting) Benzodiazepines (long-acting) β-Blockers Corticosteroids Precipitation or exacerbation of depression Diabetes Diuretics Hyperglycemia Falls Antihypertensives Antipsychotics Benzodiazepines Tricyclic antidepressants Increased risk of falls, risk of fractures (due to sedation or orthostasis) Glaucoma Anticholinergic drugs Exacerbation of glaucoma (closed-angle) Heart failure DiltiazemSome Trade Names CARDIZEM CARTIA DILACOR Click for Drug Monograph DisopyramideSome Trade Names NORPACE Click for Drug Monograph VerapamilSome Trade Names CALAN ISOPTIN Click for Drug Monograph Exacerbation of systolic heart failure Hypertension Amphetamines NSAIDs Phenylpropanolamine PseudoephedrineSome Trade Names AFRINOL SUDAFED Click for Drug Monograph Increased BP Hypokalemia DigoxinSome Trade Names DIGITEK LANOXIN Click for Drug Monograph Cardiac toxicity Incontinence α-Blockers Anticholinergics Benzodiazepines (long-acting) Diuretics Tricyclic antidepressants Polyuria; exacerbation of incontinence symptoms, possibly of multiple types (stress, overflow, or functional) Obesity OlanzapineSome Trade Names ZYPREXA Click for Drug Monograph Increased appetite, weight gain Orthostatic hypotension Antihypertensives Antipsychotics Diuretics Levodopa Tricyclic antidepressants Dizziness, falls, syncope Osteopenia Corticosteroids Fractures Parkinson's disease Antipsychotics (conventional) MetoclopramideSome Trade Names REGLAN Click for Drug Monograph Exacerbation of symptoms Peptic ulcer disease Anticoagulants NSAIDs Upper GI bleeding Prostate disease α-Agonists Anticholinergic drugs Urinary retention Seizure disorders BupropionSome Trade Names WELLBUTRIN ZYBAN Click for Drug Monograph ChlorpromazineSome Trade Names THORAZINE Click for Drug Monograph ClozapineSome Trade Names CLOZARIL Click for Drug Monograph MeperidineSome Trade Names DEMEROL Click for Drug Monograph ThioridazineSome Trade Names MELLARIL Click for Drug Monograph ThiothixeneSome Trade Names NAVANE Click for Drug Monograph Lowering of seizure threshold Undernutrition CNS stimulants (dextroamphetamineSome Trade Names DEXEDRINE DEXTROSTAT Click for Drug Monograph , fluoxetineSome Trade Names PROZAC SARAFEM Click for Drug Monograph , methylphenidateSome Trade Names CONCERTA RITALIN Click for Drug Monograph , methamphetamine, pemoline) Decreased appetite

Clinical Calculator

Drug-drug interactions: Because the elderly often take many drugs, they are particularly vulnerable to drug-drug interactions. The elderly also frequently use medicinal herbs and other dietary supplements (see Dietary Supplements) and may not tell their physician. Medicinal herbs can interact with prescribed drugs and lead to adverse effects. For example, ginkgo biloba extract taken with warfarinSome Trade Names
COUMADIN
Click for Drug Monograph
can increase risk of bleeding, and St. John's wort taken with an SSRI can increase risk of serotonin syndrome. Therefore, physicians should ask patients specifically about dietary supplements, including medicinal herbs and vitamin supplements.

Drug-drug interactions in the elderly differ little from those in the general population. However, induction of cytochrome P-450 drug metabolism by certain drugs (eg, dichloralphenazone, glutethimide, rifampinSome Trade Names
RIFADIN
RIMACTANE
Click for Drug Monograph
) may be decreased in the elderly; therefore, the change (increase) in drug metabolism may be less pronounced in the elderly. Concurrent use of ≥ 1 drug with similar toxicity can increase risk or severity of adverse effects.

Inadequate monitoring: Monitoring drug use involves

• Documenting the indication for a new drug
• Keeping a current list of drugs used by the patient in medical records
• Monitoring for achievement of therapeutic goals and other responses to new drugs
• Monitoring necessary laboratory tests for efficacy or adverse effects
• Periodically reviewing drugs for continued need

Such measures are especially important for elderly patients. Lack of close monitoring, especially after new drugs are prescribed, increases risk of adverse effects and ineffectiveness. Criteria to facilitate monitoring have been developed by the Health Care Financing Administration expert consensus panel as part of drug utilization review criteria. The criteria focus on inappropriate dosage or duration of therapy, duplication of therapy, and possible drug-drug interactions.

Poor communication: Poor communication of medical information at transition points (from one health care setting to another) causes up to 50% of all drug errors and up to 20% of adverse drug effects in the hospital. When patients are discharged from the hospital, drug regimens that were started and needed only in the hospital (eg, benzodiazepines, stool softeners, antacids) may be unnecessarily continued by another prescriber, who is reluctant to communicate with the previous prescriber. Conversely, at admission to a health care facility, lack of communication may result in unintentional omission of a necessary maintenance drug.

Lack of patient adherence: Drug effectiveness is often compromised by lack of patient adherence among the ambulatory elderly. Adherence is affected by many factors but not by age per se. Up to half of elderly patients do not take drugs as directed, usually taking less than prescribed (underadherence). Causes are similar to those for younger adults (see Concepts in Pharmacotherapy: Adherence to a Drug Regimen). In addition, the following contribute:

• Financial and physical constraints, which may make purchasing drugs difficult
• Dementia, which may make taking drugs as instructed difficult
• Use of multiple drugs
• Use of drugs that must be taken several times a day
• Lack of understanding about what a drug is intended to do

A regimen using too frequent dosing, multiple drugs, or both may be too complicated for patients to follow. Clinicians should assess patients' ability to adhere to a drug regimen (eg, dexterity, hand strength, cognition, vision) and try to accommodate their limitations—eg, by arranging for or recommending easy-access containers, drug labels and instructions in large type, containers equipped with reminder alarms, containers filled based on daily drug needs, or reminder telephone calls. Pharmacists and nurses may help by providing education and reviewing prescription instructions with elderly patients. Pharmacists may be able to identify a problem by noting whether patients obtain refills on schedule or whether a prescription seems illogical or incorrect.

Prevention

Before starting a new drug: To reduce the risk of adverse drug effects in the elderly, clinicians should do the following before starting a new drug:

• Consider nondrug treatment
• Document the indication for each new drug (to avoid using unnecessary drugs)
• Consider age-related changes in pharmacokinetics or pharmacodynamics and their effect on dosing requirements
• Choose the safest possible alternative (eg, for noninflammatory arthritis, acetaminophenSome Trade Names
  GENAPAP
  TYLENOL
  VALORIN
  Click for Drug Monograph
  instead of an NSAID)
• Check for potential drug-disease and drug-drug interactions
• Start with a low dose
• Use the fewest drugs necessary
• Note coexisting disorders and their likelihood of contributing to adverse drug effects
• Explain the uses and adverse effects of each drug
• Provide clear instructions to patients about how to take their drugs (including generic and brand names, spelling of each drug name, indication for each drug, and explanation of formulations that contain more than one drug)
• Anticipate confusion due to sound-alike drug names and pointing out any names that could be confused (eg, Glucophage and Glucovance)

After starting a drug: The following should be done after starting a drug:

• Assume a new symptom may be drug-related until proved otherwise (to prevent a prescribing cascade)
• Monitor patients for signs of adverse drug effects, including measuring drug levels and doing other laboratory tests as necessary
• Document the response to therapy and increase doses as necessary to achieve the desired effect

Ongoing: The following should be ongoing:

• Keep a current list of drugs (including OTC and dietary supplements) and periodically review it
• Evaluate the adverse effect profile for each drug
• Encourage patients to be responsible for and involved in adherence to their drug regimen
• At each move to another health care setting, review the drug list with the patient or a family member
• Use multidisciplinary interventions, including a pharmacist, as patients move from one health care setting to another
• Ensure clear, correct, and complete transfer of information when patients move from one health care setting to another

Medication reconciliation is a process that helps ensure transfer of information about drug regimens at any transition point in the health care system. The process includes identifying and listing all drugs patients are taking (name, dose, frequency, route) and comparing the resulting list with the physician's orders at a transition point. Medication reconciliation should occur at each move (admission, transfer, and discharge).

Computerized physician ordering programs can alert clinicians to potential problems (eg, allergy, need for reduced dosage in patients with impaired renal function, drug-drug interactions). These programs can also cue clinicians to monitor certain patients closely for adverse drug effects.

Last full review/revision September 2009 by J. Mark Ruscin, PharmD

Content last modified September 2009