Withdrawal has been accompanied by delirium. In settings of single-dose administration, such as for insomnia or discrete anxiety episodes, appropriate drug choice and dosing can virtually ensure that drug effect, and its associated impairment will terminate at a reasonably predictable time. Simply substituting

highly anticholinergic drugs or older, less studied medications such as meprobamate68,70 in place of benzodiazepines will not in itself reduce the risk of cognitive toxicity. Other medications The following drugs or drug classes have been implicated in the concurrence of cognitive toxicity. Selegiline. Inhibitors,research,lifescience,medical The most frequent problems include delirium, hallucinations, agitation, and overall sedation.71 L-dopa. 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 Amantadine. Used as an antiviral as well as in Parkinson’s disease, therapy has Inhibitors,research,lifescience,medical 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 Inhibitors,research,lifescience,medical use would most likely occur, clearance is reduced and plasma levels are higher at standard doses. Phenytoin. The CNS is the most common site of toxicity, which appears to be dose-related, Inhibitors,research,lifescience,medical but can occur even within the usual

effective serum concentration range of 40 to 79 µmol/L. Confusion as well as speech and coordination difficulties are common.76 Digoxin. 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 Inhibitors,research,lifescience,medical correlates with renal function as determined by creatinine clearance, which generally declines with age. β-Blockers. Symptoms ranging from depression to memory disturbances and pseudodementia tuclazepam have been attributed to individual drugs, including propranolol and local use of timolol in glaucoma.79,80 Lidocaine. Symptoms ranging from confusion to delirium are common manifestations of toxicity.81 Antibiotics. 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. Dabrafenib mouse quinoloncs such as ciprofloxacin can cause events such as anxiety and agitation, while imipenem can precipitate confusion (as well as convulsions).82-89 Corticosteroids. Particularly at higher doses, drugs such as prednisone can precipitate psychosis.