Some drug categories (eg, analgesics, anticoagulants, antihypertensives, antiparkinsonian drugs, diuretics, hypoglycemic drugs, psychoactive drugs) pose special risks for elderly patients. Some, although reasonable for use in younger adults, are so risky as to be considered inappropriate for the elderly. The Beers Criteria are most commonly used to identify such inappropriate drugs (see see High-Risk Drugs in the Elderly (Based on the Beers Criteria)). The Zhan expert panel further categorized some inappropriate drugs from the Beers Criteria into 3 groups:
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NSAIDs are used by > 30% of people aged 65 to 89, and half of all NSAID prescriptions are for people > 60. Several NSAIDs are available without prescription.
The elderly may be prone to adverse effects of these drugs, and adverse effects may be more severe because of the following:
Serious adverse effects include peptic ulceration and upper GI bleeding; risk is increased when an NSAID is begun and when dose is increased. Risk of upper GI bleeding increases when NSAIDs are given with warfarin, aspirin, or other antiplatelet drugs (eg, clopidogrel). NSAIDs may increase risk of cardiovascular events and can cause fluid retention and, rarely, nephropathy.
NSAIDs can also increase BP; this effect may be unrecognized and lead to intensification of antihypertensive treatment (a prescribing cascade). Thus, clinicians should keep this effect in mind when BP increases in elderly patients and ask them about their use of NSAIDs, particularly OTC NSAIDs.
Selective COX-2 (cyclooxygenase-2) inhibitors (coxibs) cause less GI irritation and platelet inhibition than other NSAIDs. Nonetheless, coxibs have a risk of GI bleeding, especially for patients taking warfarin or aspirin (even at a low dose) and for those who have had GI events. Coxibs, as a class, appear to increase risk of cardiovascular events, but risk may vary by drug; they should be used cautiously. Coxibs have renal effects comparable to those of other NSAIDs.
Lower-risk alternatives (eg, acetaminophen) should be used when possible. If NSAIDs are used in the elderly, the lowest effective dose should be used, and continued need should be reviewed frequently. If NSAIDs are used long-term, serum creatinine and BP should be monitored closely, especially in patients with other risk factors (eg, heart failure, renal impairment, cirrhosis with ascites, volume depletion, diuretic use).
Aging may increase sensitivity to the anticoagulant effect of warfarin. Careful dosing and scrupulous monitoring can largely overcome the increased risk of bleeding in elderly patients taking warfarin. Also, because drug interactions with warfarin are common, closer monitoring is necessary when new drugs are added or old ones are stopped; computer drug interaction programs should be consulted if patients take multiple drugs.
Tricyclic antidepressants are effective but should rarely be used in the elderly. SSRIs and mixed serotonin/dopamine reuptake inhibitors are as effective as tricyclic antidepressants and cause less toxicity; however, there are some concerns about some of these drugs:
Doses of these drugs should be reduced by up to 50%. Many SSRIs are available, but data on their use in the elderly are sparse.
Doses of antihyperglycemics should be titrated carefully in patients with diabetes mellitus. Risk of hypoglycemia due to sulfonylureas may increase with age. Chlorpropamide is not recommended because elderly patients are at increased risk of hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and because the drug's long duration of action is dangerous if adverse effects or hypoglycemia occurs. Risk of hypoglycemia is greater with glyburide than with other oral antihyperglycemics because like chlorpropamide, it is eliminated by the kidneys, and clearance can be reduced when renal function is impaired.
Metformin, a biguanide excreted by the kidneys, increases peripheral tissue sensitivity to insulin and can be effective given alone or with sulfonylureas. Risk of lactic acidosis, a rare but serious complication, increases with degree of renal impairment and with patient age. Heart failure is a contraindication.
In many elderly patients, lower starting doses of antihypertensives may be necessary to reduce risk of adverse effects; however, for most elderly patients with hypertension, achieving BP goals requires standard doses and multidrug therapy. Initially, a thiazide-type diuretic is usually given alone or with one of the other classes shown to be beneficial (ACE inhibitors, angiotensin II receptor blockers, β-blockers, Ca channel blockers). Short-acting dihydropyridines (eg, nifedipine) may increase mortality risk and should not be used. Sitting and standing BP can be monitored, particularly when multiple antihypertensives are used, to check for orthostatic hypotension, which may increase risk of falls and fractures.
Levodopa clearance is reduced in elderly patients, who are also more susceptible to the drug's adverse effects, particularly orthostatic hypotension and confusion. Therefore, elderly patients should be given a lower starting dose of levodopa and carefully monitored for adverse effects (see Levodopa). Patients who become confused while taking levodopa may also not tolerate newer dopamine agonists (eg, pramipexole, ropinirole). Because elderly patients with parkinsonism may be cognitively impaired, anticholinergic drugs should be avoided.
In nonpsychotic, agitated patients, antipsychotics control symptoms only marginally better than placebos and can have severe adverse effects. Antipsychotics should be reserved for psychosis.
When an antipsychotic is used, the starting dose should be about one quarter the usual starting adult dose and should be increased gradually. Clinical trial data relating to dosing, efficacy, and safety of these drugs in the elderly are limited.
Antipsychotics can reduce paranoia but may worsen confusion (see Conventional antipsychotics). Elderly patients, especially women, are at increased risk of tardive dyskinesia, which is often irreversible. Sedation, orthostatic hypotension, anticholinergic effects, and akathisia (subjective motor restlessness) can occur in up to 20% of elderly patients taking an antipsychotic, and drug-induced parkinsonism can persist for up to 6 to 9 mo after the drug is stopped.
The FDA has issued a warning regarding the use of 2nd-generation (atypical) antipsychotics, once thought to be safer, in the treatment of behavioral disorders in elderly patients with dementia; a review of placebo-controlled studies has shown a higher mortality rate associated with their use. Extrapyramidal dysfunction can develop when 2nd-generation antipsychotics (eg, olanzapine, quetiapine, risperidone) are used, especially at higher doses. Risks and benefits of using an antipsychotic should be discussed with the patient or the person responsible for the patient's care.
Anxiolytics and hypnotics:
Treatable causes of insomnia should be sought and managed before using hypnotics (see Hypnotics). Nonpharmacologic measures and sleep hygiene (eg, avoiding caffeinated beverages, limiting daytime napping, modifying bedtime) should be tried first. If they are ineffective, nonbenzodiazepine hypnotics (eg, the imidazopyridines, alpidem and zolpidem) are options. These drugs bind mainly to a benzodiazepine receptor subtype. Imidazopyridines disturb the sleep pattern less than benzodiazepines and have a more rapid onset, fewer rebound effects, fewer next-day effects, and less potential for dependence. Short- or intermediate-acting benzodiazepines with half-lives of < 24 h (eg, alprazolam, lorazepam, oxazepam, temazepam) are preferable to long-acting benzodiazepines but may have adverse effects, including those that lead to falls and fractures.
Longer-acting benzodiazepines (eg, clonazepam, diazepam, flurazepam) should be avoided because they have active metabolites, are likely to accumulate, and have adverse effects (eg, drowsiness, impaired memory, impaired balance leading to falls and fractures).
Duration of anxiolytic or hypnotic therapy should be limited if possible because tolerance and dependence may develop; withdrawal may lead to rebound anxiety or insomnia.
Antihistamines (eg, diphenhydramine, hydroxyzine) are not recommended as anxiolytics or hypnotics because they have anticholinergic effects.
Buspirone, a partial serotonin agonist, can be effective for general anxiety disorder; elderly patients tolerate doses up to 30 mg/day well. The slow onset of anxiolytic action (up to 2 to 3 wk) can be a disadvantage in urgent cases.
Digoxin, a cardiac glycoside, is used to increase the force of myocardial contractions and to treat supraventricular arrhythmias. However, it must be used with caution in patients with heart failure. In men with heart failure and a left ventricular ejection fraction of ≤ 45%, serum digoxin levels > 0.8 ng/mL are associated with increased mortality risk. Adverse effects are typically related to its narrow therapeutic index. One study found digoxin to be beneficial in women when serum levels were 0.5 to 0.9 ng/mL but possibly harmful when levels were ≥ 1.2 ng/mL. A number of factors increase the likelihood of digoxin toxicity in the elderly. Renal impairment, temporary dehydration, and NSAID use (all common among the elderly) can reduce renal clearance of digoxin. Furthermore, digoxin clearance decreases an average of 50% in elderly patients with normal serum creatinine levels. Also, if lean body mass is reduced, as may occur with aging, volume of distribution for digoxin is reduced. Therefore, starting doses should be low (0.125 mg/day) and adjusted according to response and serum digoxin levels (normal range 0.8 to 2.0 ng/mL). However, serum digoxin level does not always correlate with likelihood of toxicity.
Lower doses of thiazide diuretics (eg, hydrochlorothiazide or chlorthalidone 12.5 to 25 mg) can effectively control hypertension in many elderly patients and have less risk of hypokalemia and hyperglycemia than other diuretics (see Diuretics). Thus, K supplements may be required less often.
K-sparing diuretics should be used with caution in the elderly; the K level must be carefully monitored, particularly when these diuretics are given with ACE inhibitors.
Last full review/revision September 2009 by J. Mark Ruscin, PharmD
Content last modified August 2013