Pedigo NW., Jr. in these patients render them more susceptible to developing cognitive toxicity. Most of the frequently implicated medications carry documentation of their ability to cause cognitive disturbances in their package labeling, suggesting that the level of vigilance for adverse effects during the course of their use should always be high. Such caution can be used to guide appropriate drug treatment of the CEP-32496 aged so that clinicians do not need to opt for undertreatment to avoid toxicity. As age increases, renal blood flow and glomerular filtration rate decrease, and drugs eliminated by the kidneys generally exhibit, reduced clearance. Similary, a number of drugs cleared in the liver by oxidative metabolism also show reduced clearance because of reductions in enzymatic activity The most frequent problems include delirium, hallucinations, agitation, and overall sedation.71 Used as a sole agent or in combination with carbidopa, a variety of cognitive problems have been reported to be associated with its use.72,73 Used as an antiviral as well as in Parkinson’s disease, therapy has been linked to suicide attempts in patients with and without, previous psychiatric problems. These patients exhibit, a variety of abnormal mental states, including confusion, depression, paranoia, personality changes, and aggressive behavior.74,75 In aging populations, where its use would most likely occur, clearance is reduced and plasma levels are higher at standard doses. The CNS is the most common site of toxicity, which appears to be dose-related, but can occur CEP-32496 even within the usual effective serum concentration range of 40 to 79 mol/L. Confusion CEP-32496 as well as speech and coordination difficulties are common.76 Some data indicate that this drug ranks first, in the number of prescriptions made out. to the elderly in the US.77 A spectrum of CNS-related effects can occur, including depression and anxiety as well as confusion and delirium with hallucinations. Such symptoms may appear in the absence of cardiac toxicity and at therapeutic plasma levels (0.6-2.6 nmol/L).78 Clearance of digoxin correlates with renal function as determined by creatinine clearance, which generally declines with age. Symptoms ranging CEP-32496 from depression to memory disturbances and pseudodementia have been attributed to individual drugs, including propranolol and local use of timolol in glaucoma.79,80 Symptoms ranging from confusion to delirium are common manifestations of toxicity.81 Penicillins, cephalosporins, quinoloncs, and imipenem/cilastatin have all been shown to cause cognitive disturbances, particularly at high doses in renal insufficiency, severely ill patients, and/or patients with increased blood-brain barrier permeability. Quinoloncs such as ciprofloxacin can cause events such as anxiety and agitation, while imipenem can precipitate confusion (as well as convulsions).82-89 Particularly at higher doses, drugs such as prednisone can precipitate psychosis. Memory and attention deficits have also occurred during chronic therapy.87,88 Both interferon-alpha and interleukin-2 have been linked with serious depression.89,90 Symptoms CEP-32496 ranging Cd163 from overt sedation to depression and delirium have occurred with many of the narcotics and vary with the clinical setting (postoperative vs chronic pain management). Some investigators feel that meperidine may be more likely to cause symptoms because of the anticholinergic nature of its metabolite, normeperidine.91,92 However, all opiate agonists have anticholinergic effects, which in turn may precipitate delirium. Long-term codeine use has been associated with depressive symptoms.93 Comment As clinicians in adult medicine settings worldwide see an increasingly aging patient population, it will be necessary to remain abreast of which medications or health aids, both prescription and nonprescription, can cause disorders of cognition, as well as to recognize the variety of presentations. It should not be necessary to undertrcat the elderly and deprive them of the benefits of pharmacotherapy in order to avoid toxicity.94 A high level of care and vigilance should keep the therapy that is intended to extend life and enhance its quality from diminishing vital cognitive capacity. Notes Supported by Grants.