Pharmacotherapy Considerations in Elderly Adults

• Dr. Safaa Hussein Ali• Lecturer of geriatric

medicine• Ain Shams university• Cairo – Egypt• Consultant of geriatric

medicine

Pharmacokinetics

• Pharmacokinetics describes how the body processes a specific drug after its administration.

• Drug researchers are hesitant to conduct large randomized controlled trials in elderly patients.

• the principles of pharmacokinetics (absorption, distribution, metabolism, and elimination) 

Absorption of Oral Medications

The aging process • reduce GI motility and GI blood flow. • Gastric acid secretion is reduced in older adults and this

can result in an elevation in gastric pH. • may cause reduced drug absorption, whereas reduced

GI motility may result in more of the drug(s) being absorbed.

• Concurrent use of antacids and overuse of proton pump inhibitors may contribute greatly to these changes. 

• Age-related absorptive changes can alter significantly a drug's absorption as well as its onset of action.

• The absorption of drugs that undergo first-pass metabolism also may be increased in older people. This action is seen with nitrates and the lipophilic [beta]-adrenergic blockers (e.g., propranolol).

• other problems that can affect absorption. include swallowing difficulties, poor nutrition, and dependence on feeding tubes.

Distribution

• Drug distribution refers to where the drug goes after it enters the bloodstream. For drugs that are administered orally, the distribution phase begins after absorption and first-pass metabolism. 

• Factors influence the volume of distribution of a drug, including protein binding (only unbound drug is distributed), pH, molecular size, and water or lipid solubility (lipid-soluble drugs, in general, have a greater volume of distribution).

• For instance, phenytoin is a highly protein (albumin)-bound anticonvulsant that may have a significant effect in elderly patients who have reduced albumin levels. This leaves more free phenytoin available to cause various adverse effects.

Distribution

• As the body ages, muscle mass declines and the proportion of body fat increases; therefore, drugs that are fat soluble will, in general, have a greater volume of distribution in an older person compared with a young person, but for drugs distributed in muscle tissue, the volume of distribution may be reduced. This effect is observed with diazepam, which is highly fat soluble, and this may necessitate dosing changes 

Metabolism

• The liver is the primary organ responsible for drug metabolism.

• Phase 1 reactions typically involve cytochrome P450 monooxygenase (CYP450) enzymes. There are various types of CYP450 enzymes and they can play a role in drug metabolism. The CYP450 system is also where many drug– drug interactions occur, because various drugs can act as inducers or inhibitors of other drugs undergoing metabolism. 

Metabolism

• Phase 2 reactions are conjugative. Products of conjugation reactions have increased molecular weight and are usually inactive, unlike phase 1 reactions, which often produce active metabolites. Some drugs undergo both phase 1 and 2 metabolism.

Metabolism

• The aging process also can affect drug metabolism. Several physiological changes can greatly influence metabolic capacity.

• In general, hepatic blood flow is reduced in elderly adults, which can significantly affect metabolism because the drug is introduced to the liver at a much lower rate. Liver mass and intrinsic metabolic activity (includes the CYP450 enzyme system) also is reduced during the aging process.

• Phase 1 reactions are affected much more than are phase 2 reactions. With a reduction of blood flow to the liver and a reduction in metabolic activity, the metabolic process is significantly reduced in older adults.

Metabolism

• Dosage adjustments are somewhat arbitrary, but in older adult patients, a general recommendation is to reduce the dosage for those drugs undergoing hepatic metabolism. The dose can then be titrated to efficacy or adverse effects.

Excretion

• Elimination of drugs from the body occurs primarily via renal excretion.

• As with metabolism, the half-life of drugs is increased as renal function is reduced. As the body ages, renal function declines, sometimes by a significant degree. This decline is the result of several physiological changes, which include a reduction in blood flow to the kidneys, a decrease in kidney mass, and a reduction in the size and number of functioning nephrons.

• Unlike hepatic effects, these changes are consistent from one patient to another.

• different from hepatic changes observed with aging, renal changes can be somewhat predictive, thus allowing drug dose adjustment based on renal function that is either measured or calculated.

• Calculations based on laboratory measurements (e.g., serum creatinine) or other data can be used to estimate a patient's renal function.

Excretion• There are several formulas that have been developed and

assessed for estimating a patient's renal function. Two such formulas are the Cockcroft-Gault formula and the modification of diet in renal disease (MDRD) formula. 

• The Cockcroft-Gault formula is the most commonly used calculation, although many practitioners prefer the MDRD formula, which may prove to be more accurate than other formulas even though it has not been used for as long as Cockroft-Gault.

• Another formula [Chronic Kidney Disease Epidemiology Collaboration equation] also has been suggested and it may offer advantages over the other formulas, although it is unclear which estimate would be best to use in elderly adults)

Excretion

• Pharmaceutical manufacturers have long used Cockroft-Gault when recommending dosage adjustments for renally excreted drugs.

• These recommendations appear on a drug's package insert, which is approved by the FDA. Drug manufacturers will not change their recommendations until required to do so by the FDA.

Summary of pharmacokinetic changes observed with aging 5,7,9,14,15,17,18

Pharmacokinetic parameter Altered physiology with aging Comments

Absorption↓Gastric secretion

↑Gastric pH↓GI motility

↓GI blood flow

Many drugs may diminish in their absorptive ability Time of

onset of action may be delayed

Absorption is the pharmacokinetic parameter

least affected by aging

Distribution↓Total body water↓Lean body weight

↓Albumin↑Body fat

Increased Vd of lipid-soluble drugs

Increased free fraction of drug

Metabolism

↓Enzyme induction↓Hepatic mass

↓Hepatic blood flow↓ Activity in mixed function

oxydase system

Reduced hepatic clearance of drugs

Increased potential for drug interactions

For elderly patients, dosage should be reduced for

hepatically cleared drugs

Elimination ↓ GFR↓ Renal blood flow

For elderly patients, drug accumulation will occur for

renally cleared drugs

GFR, glomerular filtration rate; GI, gastrointestinal; Vd, volume of distribution.

• In elderly adults, a low serum creatinine is not always indicative of normal renal function. Because older adults have lower muscle mass than younger people, low serum creatinine may not be indicative of normal renal function but rather indicative of a reduction in muscle mass. The same issue is noted in individuals with amputations, malnutrition, or muscle wasting. For patients in whom serum creatinine may not be an accurate indicator of renal function, an actual 24-hour creatinine collection may be necessary.

Pharmacodynamics

• Pharmacokinetics is essentially the science of how the body affects the drug and pharmacodynamics is the study of how a specific drug affects the body. 

• Because of the physiological aspects of aging, elderly adults also may be at high risk for certain drug adverse effects. For instance, anticholinergic/antihistamines frequently cause urinary retention. This may not be a problem for younger patients, but it may be a severe problem for older male patients with benign prostatic hypertrophy. Patients maintained on certain blood pressure medications for many years may experience sudden precipitous drops in blood pressure caused by age-induced orthostatic hypotension. 

• elderly patients, who can be extremely sensitive to any drug-induced action on the central nervous system including dizziness, sedation, seizures, and confusion. 

• care should be used whenever new medications are initiated in them. Starting with lower drug doses and titrating the dose as tolerated may help to prevent unwanted drug-related pharmacodynamic effects.

• The effectiveness of certain drugs that act on specific receptors may be diminished in elderly patients. [beta]-Adrenergic blockers are known to have a diminished effect in older people, probably because of a loss of sensitivity in the receptor. Proper titration of doses and patient monitoring will ensure that the correct therapy is prescribed.

• A common adverse effect of prazosin in many elderly patients is first-dose syncope. Because the aging process can affect the ability of the body to recover from orthostatic changes, [alpha]-blockers are commonly associated with orthostatic hypotension and patients must be instructed to anticipate this adverse effect until they become familiar with how the drug works in their body.

SPECIFIC ISSUES

1. ADRs/Drug Interactions

• ADRs are considered the sixth leading cause of death in the United States.

A number of factors in older individuals contribute to their increased risk for developing a drug-related problem. These include frailty, coexisting medical problems, memory issues, and use of multiple prescribed and non-prescribed medications 

Frailty is a common clinical syndrome in older adults that carries an increased risk for

poor health outcomes including falls, incident disability, hospitalization, and

mortality

Mood and behavior changesGI tract disturbances (constipation or diarrhea)

Table 4.  Drugs that commonly cause problems in elderly adultsDrug Adverse effectNonsteroidal anti-inflammatory drugs (eg, ibuprofen, naproxen)

Gastrointestinal bleeding, renal dysfunction

Diuretics (eg, hydrochlorothiazide, furosemide)

Hypotension, dehydration, electrolyte disturbance

Warfarin Bleeding, many drug interactions

Angiotensin-converting enzyme inhibitors (eg, lisinopril) Hypotension, renal dysfunction

Antidepressants (eg, amitriptyline)

Confusion, hypotension, constipation

Opiates (eg, morphine) Confusion, disorientation, constipation

Prednisone Osteoporosis, gastrointestinal problems, hyperglycemia

Benzodiazepines (eg, lorazepam) Drowsiness, confusion

 Common ADRs in elderly adults associated with various symptomatology and drug classes Adverse effect Manifestation of

effectPossible drugs or

drug classes involved Comments

Anticholinergic effects

Dry mouth, blurred near vision, hypotension, exacerbated narrow-angle glaucoma, excessive sedation, confusion or disorientation, constipation, dizziness, impaired gait and balance, impaired sweating, urinary hesitancy, urinary retention

First-generation antihistamines (diphenhydramine), antipsychotics, antidepressants, gastrointestinal tract motility agents, certain analgesics (tramadol), over-the-counter cough and cold preparations, etc

Common adverse effects from commonly used drugsAdverse effects are many times additive (eg, constipation from anticholinergics + narcotics)Central nervous system adverse effects can be insidious and develop over several years

Mental status changes

Confusion (acute or chronic), excessive sedation (drowsiness to soporific states), delirium, trouble concentrating, cognitive impairment, memory loss, dementia, impaired gait and balance, deficits in judgment or orientation to time, place, or person

All drug classes listed above plus muscle relaxants; drugs that may affect electrolytes (diuretics); central nervous system effects from other drug classes (eg, digoxin, amiodarone)

Adverse effects are additive and insidious, difficult to distinguish from metabolic problems, practitioner must take careful drug history to discern

Orthostatic hypotensionSudden drop in blood pressure, dizziness, falling down

All blood pressure medicines (eg, β-blockers, calcium channel blockers), narcotics, phenothiazines, antidepressants, others

Fall risk is a major problemIf this effect results in a fall causing broken hip or other bones, it can be devastating for patientMany effects are additive

Gastrointestinal tract disturbance; urinary incontinence

Constipation, diarrhea, nausea, vomiting, bladder problems

Diuretics, anticholinergics, antibiotics, almost all drugs can cause some form of GI problem

Results in less interaction for patientCan cause noncomplianceCan cause nutritional disturbancesCan contribute to bed sores, etc

Cardiac changesProlonged QTc leading to heart rhythm abnormality

Anticholinergics, antipsychotics, atypical antipsychotics, erythromycin

Effect can be fatalMay be more common in patients with electrolyte abnormalities or previous cardiac history

2. A common cause of adverse drug reactions in elderly patients is drug interactions.

•  As an example, the risk of bleeding with warfarin therapy is increased with coadministration of selective and non-selective NSAIDs, SSRIs, omeprazole, lipid-lowering agents, amiodarone, and fluorouracil .

•  case control study from Canada evaluated hospitalizations for drug-related toxicity in a population of older patients who had received one of three common drug therapies used in older adults: glyburide, digoxin, or ACE inhibitor . Hospitalization for hypoglycemia was six times more likely in patients who had received co-trimoxazole. Digoxin toxicity was 12 times more likely for patients who had been started on clarithromycin. Hyperkalemia was 20 times more likely for patients who were treated with a potassium sparing diuretic.

Table 6.  Selected disease states that may be aggravated by medications Disease state Aggravating drug Potential adverse

effect

Diabetes Corticosteroids (eg, prednisone)

Drug-induced hyperglycemia

Osteoporosis Corticosteroids (eg, prednisone)

Increased fracture risk

ConstipationAnticholinergics/antihistamines/narcotics

All slow gastrointestinal tract motility

Parkinson AntipsychoticsAggravate movement disorder

HypertensionNonsteroidal anti-inflammatory drugs

Fluid retention increases blood pressure

Benign prostatic hypertrophy

Anticholinergics/antihistamines Urinary problems

3. Polypharmacy

• Whatever the definition, polypharmacy is an important issue in elderly patients. Sometimes this issue cannot be helped, but many times polypharmacy occurs simply because healthcare providers fail to communicate proper patient recommendations to the patient's primary care provider. If each patient had a primary healthcare advocate who coordinated the patient's overall care, then the risk of polypharmacy could be reduced. 

4. Compliance

• Poor compliance in elderly adults also may be a product of health literacy. Studies have shown that as health literacy declines in older people, mortality increases. Several issues related to health literacy affect older adults, including poor education, language barriers, and mental health issues (eg, dementia, agitation), and all of them must be considered to improve compliance

Herbal and dietary supplements• three-quarters of respondents aged 18 years and older

reported that they did not inform their clinician that they were using unconventional medications .

•  Examples of herbal-drug therapy interactions include ginkgo biloba extract taken with warfarin, causing an increased risk of bleeding, and St. John's wort taken with serotonin-reuptake inhibitors, increasing the risk of serotonin syndrome in older adults.

Anticholinergic activity 

• Adverse effects associated with anticholinergic use in older adults include memory impairment, confusion, hallucinations, dry mouth, blurred vision, constipation, nausea, urinary retention, impaired sweating, and tachycardia.

Anticholinergic activity of medications

Class Drugs Relative anticholinergic potency

Antihistamines

H1 receptor antagonists (1st generation, eg, brompheniramine, chlorpheniramine, clemastine, cyproheptadine, dimenhydrinate, diphenhydramine, hydroxyzine, others)

High

H1 receptor antagonists (2nd generation, eg fexofenadine, cetirizine*, loratadine, desloratadine, levocetirizine, others)

Low

AntiparkinsonBenztropine, trihexyphenidyl High

Amantadine, bromocriptine, entacapone Low

AnalgesicOpioids (eg, codeine, hydrocodone, fentanyl, meperidine, methadone, morphine, oxycodone, tramadol, others)

Low

Antimuscarinic, overactive bladder Darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, trospium High

Antimuscarinic, spasmolyticDicyclomine, hyoscyamine, glycopyrrolate, methscopolamine, propantheline, scopolamine (hyoscine)

High

Antimuscarinic, inhaled bronchodilator Ipratropium, tiotropium High (local effect)Antimuscarinic, ophthalmic drops (mydriatic/cycloplegic)

Atropine, cyclopentolate, homatropine, scopolamine High (local effect)

Cardiovascular Disopyramide Low

Gastrointestinal

Antiemetics (eg, hydroxyzine, meclizine, promethazine, scopolamine); also refer to 1st generation antihistamines above

High

Domperidone, loperamide, prochlorperazine Low

H2 receptor antagonists (ranitidine, cimetidine, famotidine¶) Low

Muscle relaxantOrphenadrine, tizanidine HighCyclobenzaprine*, baclofen, methocarbamol Low

Psychotropic

Antipsychotics 1st generation: chlorpromazine, fluphenazine, methotrimeprazine (levomepromazine), thioridazine

High

Antipsychotics 1st generation: haloperidol, perphenazine*, others Low

Antipsychotics 2nd generation: (eg, olanzapine*, quetiapine, iloperidone, risperidone, others)

Low (exception clozapine-high)

Benzodiazepines: chlordiazepoxide, clonazepam, temazepam, triazolam Low

Selective serotonin reuptake inhibitors (SSRI) antidepressants: citalopram, fluoxetine, fluvoxamine, paroxetine*

Low

Tricyclic antidepressants (eg, amitriptyline, clomipramine, desipramine, doxepin, imipramine, nortriptyline, others)

HIGH

Other neurologic Carbamazepine, lithium, nefazodone, oxcarbazepine, phenelzine, trazodone Low

Affordability• A prescription may be written but not filled, or filled and

not taken regularly, due to financial considerations. This may be a particular problem in countries where there is no universal insurance coverage for drug therapy for older adults.

Prescribing cascades •  Prescribing cascades occur when a new drug is

prescribed to treat symptoms arising from an unrecognized adverse drug event related to an existing therapy .

• One of the best recognized examples of a prescribing cascade relates to the initiation of anti-Parkinson therapy for symptoms arising from use of drugs such as antipsychotics or metoclopramide . The anti-Parkinson drugs can then lead to new symptoms, including orthostatic hypotension and delirium.

Prescribing cascades• cholinesterase inhibitors (eg, donepezil, rivastigmine,

and galantamine) are commonly used for the management of dementia symptoms in older adults. The adverse events associated with these drugs can be viewed as the reverse of those that might be expected with anticholinergic therapies. Accordingly, while anticholinergic therapies may cause constipation and urinary retention, cholinesterase inhibitors may cause diarrhea and urinary incontinence. A prescribing cascade occurs when the prescription of a cholinesterase inhibitor is followed by a prescription for an anticholinergic therapy (eg, oxybutynin) to treat incontinence.

Adverse drug events in long-term care setting• Preventable adverse drug events were most frequently

associated with atypical antipsychotics and warfarin therapy

Atypical antipsychotics• Atypical antipsychotic medications, used for the

management of the behavioral and psychological symptoms of dementia, are among the drugs most frequently associated with adverse events in long-term care facilities . In particular, psychotropic medications are associated with an increased risk for falls. In one meta-analysis of patients age 60 or older, the odds ratio for any psychotropic use among patients who had one or more falls was 1.73

Atypical antipsychotics• Data from 17 trials of older adult patients with dementia

have shown that those treated with atypical antipsychotic therapy were 1.6 to 1.7 times more likely to die than those given placebo therapy. Similar concerns have been raised for haloperidol and other conventional antipsychotics.

• Mortality was further increased, again by a factor of 1.55, for patients receiving conventional antipsychotics compared to atypical antipsychotics. These data point to the need to rethink the role of these therapies in clinical practice.

Transitions in care settings• Transitions in care, between hospital and nursing home,

or institutional setting and home, are a common source of medication errors and confusions:

Tools for Appropriate Medication Decisions

• The Beers criteria is a list of medications that, based on the drugs' pharmacology (eg, mechanism of action, pharmacokinetics, adverse effect profile), may cause adverse effects in older people. 

• The list was initiated in 1991 and an update was completed by the American Geriatrics Society in 2012.

2012 American Geriatrics Society Beers Criteria for Potentially Inappropriate Medication Use in Older Adults

First-generation antihistamines (as single agent or as part of combination products)

Highly anticholinergic; clearance reduced with advanced age, and tolerance develops when used as hypnotic; greater risk of confusion, dry mouth, constipation, and other anticholinergic effects and toxicity.

Antispasmodics Highly anticholinergic, uncertain effectiveness

Avoid except in short-term palliative care to decrease oral secretions

Nitrofurantoin Potential for pulmonary toxicity; safer alternatives available; lack of efficacy in patients with CrCl < 60 ml/min due to inadequate drug concentration in the urine

Digoxin > 0.125 mg/d In heart failure, higher dosages associated with no additional benefit and may increase risk of toxicity; slow renal clearance may lead to risk of toxic effects

Nifedipine, immediate release* Potential for hypotension; risk of precipitating myocardial ischemia

Spironolactone > 25 mg/d In heart failure, the risk of hyperkalemia is higher in older adults especially if taking > 25 mg/d or taking concomitant NSAID, angiotensin converting-enzyme inhibitor, angiotensin receptor blocker, or potassium supplement

Tertiary TCAs, alone or in combination: Highly anticholinergic, sedating, and cause orthostatic hypotension; safety profile of low-dose doxepin (≥ 6 mg/d) is comparable with that of placebo

BenzodiazepinesShort and intermediate acting:

Older adults have increased sensitivity to benzodiazepines and slower metabolism of long-acting agents. In general, all benzodiazepines increase risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents in older adults. Avoid benzodiazepines (any type) for treatment of insomnia, agitation, or delirium

Long acting: May be appropriate for seizure disorders, rapid eye movement sleep disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, periprocedural anesthesia, end-of-life care

Insulin, sliding scale Higher risk of hypoglycemia without improvement in hyperglycemia management regardless of care setting

Sulfonylureas, long duration Chlorpropamide: prolonged half-life in older adults; can cause prolonged hypoglycemia; causes syndrome of inappropriate antidiuretic hormone secretion.

Metoclopramide Can cause extrapyramidal effects including tardive dyskinesia; risk may be even greater in frail older adult

Non–COX-selective NSAIDs, oral Increases risk of GI bleeding and peptic ulcer disease in high-risk groups, including those aged > 75 or taking oral or parenteral corticosteroids, anticoagulants, or antiplatelet agents. Use of proton pump inhibitor or misoprostol reduces but does not eliminate risk. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3–6 months and in approximately 2–4% of patients treated for 1 year. These trends continue with longer duration of use

Skeletal muscle relaxants Most muscle relaxants are poorly tolerated by older adults because of anticholinergic adverse effects, sedation, risk of fracture; effectiveness at dosages tolerated by older adults is questionable

Drug–Syndrome Interactions 

Heart failure NSAIDs and C0X-2 inhibitors

Chronic seizures or epilepsy Bupropion, TRAMADOL

Insomnia Oral decongestants

• The criteria are intended to provide physicians and healthcare providers who treat elderly patients with a comprehensive list of medications that may be harmful to older adult patients. The updated criteria are composed of three detailed lists. The first list is classified as drugs that have been demonstrated to be problematic in elderly adults. The second classification lists drugs that may be inappropriate for older people who have certain diseases or risk factors. The third classification lists drugs that should be used with caution in elderly patients. Most of the medications on the lists are well known, and medical evidence supports their potential to be harmful in this patient class. The Beers criteria do not ban the use of drugs on the list for all elderly patients; instead, they emphasize the drugs that may pose the most harm so that they are used judiciously and with caution

• Similar to but much more comprehensive than the Beers criteria is the Screening Tool of Older Persons' Prescriptions. Rather than a simple checklist of medications, it attempts to assess the use of a drug with a specific patient who has specific comorbidities.

• Whichever tool is used, the primary purpose is to prescribe medications to all elderly patients with care and consideration, which ensures that each older adult patient is provided with the best care possible. Achieving this goal will result in happy and healthy patients, less polypharmacy, fewer adverse drug effects, and lower healthcare costs.

Methods to improve drug-related problems in elderly adults 1–7Medication issues Comments

Improve compliance

Use as few drugs as possibleWritten instructionsCouncil patient and family/caregiverImprove communication skills (eg, language)Make medications affordableMemory techniques (eg, calendars)Recognize potential health literacy issues that may cause compliance issues (eg, language issues, dementia)

Reduce polypharmacy

Use only 1 primary care provider who communicates with specialistsUse only 1 pharmacyReduce the number of drugs necessary because of adverse effects of another agent (eg, laxatives for drugs that cause constipation)Review all medications on each visit to doctor (brown bag)Maximize doses when possible instead of adding a new drug

Always consider pharmacokinetics/pharmacodynamics

Assess patient's renal function using specific formula on each visit (or obtain measured creatinine clearance)Establish any new or previous hepatic problemsEnsure that patient can swallow and take oral medicationsCheck for any weight loss or nutritional issues that can affect pharmacokineticsAssess for drug-induced changes in renal or hepatic function on each visit

Interactions Assess for drugYdrug interactionsAssess for drugYdisease interactions

Monitoring

Implement monitoring plan for every drug the patient is receiving and put this plan in writingMonitoring plan must include ways to monitor for beneficial effect as well as adverse effectsAlways make patient and/or caregiver part of the monitoring processEnsure that this plan is shared with all of the patient's healthcare providers, including other physicians, nurses, pharmacists, nursing facility, hospiceAlways make sure patient and/or caregiver understands why medications are being used and instructions for use

Communication

Patients must be able to communicate with their healthcare providers easily and must be encouraged to do soHealthcare providers must work together and must be able to communicate with one another to ensure that the best possible care is provided to the patientPhysicians must be able to use the latest technology so that medical information is readily available for them to make proper pharmacotherapy plansRecognize potential health literacy issues that may cause communication problems

Practical recommendations to reduce medical errors in the community have been proposed

• Maintain an accurate list of all medications that a patient is currently using. This list should include the drug name (generic and brand), dosage, frequency, route, and indication.

• ●Advise periodic "brown bag check-ups." Instruct patients to bring all pill bottles to each medical visit; bottles should be checked against the medication list.

• ●Patients should be made aware of potential drug confusions: sound-alike names, look-alike pills, and combination medications.

• ●

Practical recommendations to reduce medical errors in the community have been proposed

• Patients should be informed of both generic and brand names, including spelling, as well as the reasons for taking their medications. This may prevent unnecessary confusion when drugs are inconsistently labeled. As an example, a patient may be unaware that digoxin (generic) and Lanoxin (brand) are the same therapy.

• ●Medication organizers that are filled by the patient, family member, or caregiver, can facilitate compliance with drug regimens. Blister packs for individual drugs, prepared by the pharmacist, can also be helpful in ensuring that patients take their medications correctly.

• ●Community pharmacists are an important resource and can play a key role in working with older adults to reduce medication errors.

A STEPWISE APPROACH TO PRESCRIBING• A concept of “time to benefit” (TTB) in relation to drug

prescribing for older patients with multiple morbidities can be applied to therapeutic decisions .

• TTB, defined as the time to significant benefit observed in trials of people treated with a drug compared to controls, can be estimated from data from randomized controlled trials. Such information, not currently available, may in the future help guide decision making for specific drug prescribing in individual patients.

Review current drug therapy• Periodic evaluation of a patient's drug regimen is an

essential component of medical care for an older person. • discontinuing a therapy prescribed for an indication that

no longer exists• substituting a therapy with a potentially safer agent,

changing drug dosage, or adding a new medication.• A medication review should consider whether a change in

patient status (eg renal or liver function) might necessitate dosing adjustment, the potential for drug-drug interaction, whether patient symptoms might reflect a drug side effect, or whether the regimen could be simplified

• Unintended medication discrepancies, particularly likely to occur at the time of hospital admissions, are a common source for medication errors. 

Discontinue unnecessary therapy• Clinicians are often reluctant to stop medications,

especially if they did not initiate the treatment and the patient seems to be tolerating the therapy. 

• A common example is the use of digoxin in older adults, often prescribed for indications that have not been well documented. Renal impairment or temporary dehydration may predispose older adults to digoxin toxicity . Although digoxin therapy can be safely discontinued in selected nursing home residents, it is important to recognize that discontinuation in patients with impaired systolic function can have a detrimental effect

Consider adverse drug events for any new symptom • Before adding a new therapy to the patient's drug

regimen

Consider nonpharmacologic approaches• The Trial of

Nonpharmacologic Interventions in the Elderly (TONE) demonstrated that weight loss and reduced sodium intake could allow discontinuation of antihypertensive medication in about 40 percent of the intervention group

Substitute with safer alternatives• As an example, in treatment of non-inflammatory

arthritis, acetaminophen may provide adequate pain relief and be a safer alternative to NSAIDs . (See "Initial pharmacologic therapy of osteoarthritis".) Numerous studies have documented adverse events associated with NSAID use in older persons, including gastrointestinal bleeds , renal impairment , and heart failure

Reduce the dose• As an example, one study evaluated the relationship

between prescribing of the newer atypical antipsychotic therapies (eg, olanzapine, risperidone, and quetiapine) and the development of parkinsonism in older adults . Relative to those dispensed a low-dose, those dispensed a high-dose were more than twice as likely to develop parkinsonism (HR 2.07, 95% CI 1.42-3.02). As another example, one case-control study in patients over age 70 who received thyroid supplementation identified a correlation between risk of fracture and dose of levothyroxine, indicating the importance of testing for thyroid levels in this population and adjusting the dose accordingly 

Simplify the dosing schedule• hen multiple medications are required, greater regimen

complexity will increase the likelihood of poor compliance or confusion with dosing. Older adults, and particularly those with low health literacy, are not able to efficiently consolidate prescription regimens to optimize a dosing schedule

Prescribe beneficial therapy • Avoiding medications with known benefits to minimize

the number of drugs prescribed is inappropriate. Patients must be informed about the reason to initiate a new medication, and what the expected benefits are.

INFORMATION FOR PATIENTS

References• Up-to-date 2015• Medscape