Author Topic: Drug Categories of Concern in the Elderly  (Read 9069 times)

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Drug Categories of Concern in the Elderly
« on: November 25, 2007, 06:35:03 PM »

Drug Categories of Concern in the Elderly
 
 
 
 
Some drug categories (eg, analgesics, anticoagulants, antihypertensives, antiparkinsonian drugs, diuretics, hypoglycemic drugs, psychoactive drugs) pose special risks for elderly patients.

Analgesics

NSAIDs are widely used; several are available without prescription. 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 or aspirin. NSAIDs may increase risk of cardiovascular events and can cause fluid retention. Selective COX-2 inhibitors (coxibs) cause less GI irritation and platelet inhibition than other NSAIDs. Nonetheless, coxibs have a risk of GI bleeding, especially in patients taking warfarin or aspirin (even at low dose) and in those who have had GI events. Coxibs, as a class, appear to increase risk of cardiovascular events, but that risk may vary by drug; their use should be approached cautiously. Coxibs have renal effects comparable to those of other NSAIDs. Monitoring serum creatinine is necessary, especially in patients with other risk factors (eg, heart failure, renal impairment, cirrhosis with ascites, volume depletion, diuretic use).

Anticoagulants

Aging does not alter the pharmacokinetics of warfarin but may increase sensitivity to its anticoagulant effect. Careful dosing and scrupulous monitoring can largely overcome the increased risk of bleeding in elderly patients taking warfarin.

Antihypertensives

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 (ACE inhibitors, angiotensin II receptor blockers, β-blockers, Ca channel blockers) shown to be beneficial. Short-acting dihydropyridines (eg, nifedipine) may increase mortality risk and should not be used.

Antiparkinsonian drugs

Levodopa clearance is reduced in elderly patients, who are also more susceptible to orthostatic hypotension and confusion. Therefore, elderly patients should be given a lower starting dose of levodopa and carefully monitored for adverse effects (see Movement and Cerebellar Disorders: Treatment). Patients who become confused while taking levodopa may also not tolerate newer dopamine agonists (eg, bromocriptine, pergolide, pramipexole, ropinirole). Because elderly patients with parkinsonism may be cognitively impaired, anticholinergic drugs should be avoided.

Digoxin

Digoxin clearance decreases an average of 50% in elderly patients with normal serum creatinine levels. Therefore, maintenance doses should be started low (0.125 mg/day) and adjusted according to response and serum digoxin levels. Digoxin 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. Among women with heart failure and depressed left ventricular function, digoxin, regardless of serum level, is associated with increased mortality risk.

Diuretics

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 (see also Arterial Hypertension: 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.

Antihyperglycemics

Doses of antihyperglycemics should be titrated carefully in patients with diabetes mellitus. Risk of hypoglycemia due to sulfonylureas may increase with aging. Chlorpropamide is not recommended because elderly patients are at increased risk of hyponatremia due to 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.

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.

Psychoactive drugs


In nonpsychotic, agitated patients, antipsychotics control symptoms only marginally better than do placebos. Antipsychotics can reduce paranoia but may worsen confusion (see also Schizophrenia and Related Disorders: Conventional antipsychotics). Elderly patients, especially women, are at increased risk of tardive dyskinesia, which is often irreversible. The FDA has issued a warning regarding the use of atypical antipsychotics in the treatment of behavioral disorders in elderly patients with dementia. A review of placebo-controlled studies has shown a higher death rate associated with their use. 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 stopping the drug. Antipsychotic drugs should be reserved for psychosis. When an antipsychotic is used, the starting dose should be about 1⁄4 the usual starting adult dose and should be increased gradually. Extrapyramidal dysfunction can develop when atypical antipsychotics (eg, olanzapine, quetiapine, risperidone) are used, especially at higher doses. Clinical trial data relating to dosing, efficacy, and safety of these drugs in the elderly are limited; thus, dose reduction is prudent.

Use of anxiolytics and hypnotics can be problematic. Treatable causes of insomnia should be sought and managed before using hypnotics (see also Sleep and Wakefulness Disorders: Hypnotics). Nonbenzodiazepine hypnotics (eg, the imidazopyridines, alpidem and zolpidem) are options for treating insomnia in the elderly if nonpharmacologic measures (eg, avoiding caffeinated beverages, limiting daytime napping, modifying bedtime) are ineffective. 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, and less potential for dependence. Longer-acting benzodiazepines (eg, clonazepam, diazepam, flurazepam) should be avoided because they 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 and insomnia. Short- or intermediate-acting benzodiazepines with half-lives < 24 h (eg, alprazolam, lorazepam, oxazepam, temazepam) may be preferable to long-acting benzodiazepines, but these drugs may also have adverse effects, including those that lead to falls and fractures. 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.

Of antidepressants, SSRIs and mixed serotonin/dopamine reuptake inhibitors are generally preferred. These drugs appear to be as effective as tricyclic antidepressants and cause less toxicity. A possible disadvantage of fluoxetine is the long elimination half-life, especially of its active metabolite. Paroxetine is more sedating than other SSRIs, has anticholinergic effects, and, like some other SSRIs, can inhibit hepatic cytochrome P-450 2D6 enzyme activity, possibly impairing the metabolism of several drugs, including some antipsychotics, antiarrhythmics, and tricyclic antidepressants. Sertraline is more activating; diarrhea is a common adverse effect. 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. Tricyclic antidepressants are effective but should rarely be used in the elderly because safer alternatives exist.
 


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