Donepezil: an anticholinesterase inhibitor for Alzheimer's disease.

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of donepezil are reviewed. Donepezil is a synthetic noncovalent reversible inhibitor of acetylcholinesterase (AChE) for the treatment of mild to moderate dementia associated with Alzheimer's disease. In contrast to tacrine hydrochloride, the only comparable agent currently approved by FDA, donepezil exhibits a relatively high degree of selectivity for neuronal AChE as opposed to butyrylcholinesterase. It has a half-life of 60 hours in young adults and 104 hours in elderly patients. In clinical trials, donepezil has been associated with significant improvements in Alzheimer's Disease Assessment Scale-cognitive subscale and Clinical Interview-Based Impression of Change scores. The most common adverse effects associated with donepezil are nausea, diarrhea, anorexia, and vomiting, which are most likely to occur during dose initiation or adjustment. Hepatotoxicity, a dose-limiting adverse effect that sometimes requires discontinuation of tacrine, has not been reported with donepezil. Donepezil does not appear to interact with theophylline, cimetidine, warfarin, or digoxin. Ketoconazole and quinidine inhibit the metabolism of donepezil in vitro, but there is a lack of clinical data showing that these drugs decrease the clearance of donepezil. The initial recommended dosage is 5 mg daily before bedtime, with a dosage increase to 10 mg after four to six weeks according to the patient's response and tolerance. Donepezil appears to be preferable to tacrine as the initial agent for patients with mild to moderate dementia associated with Alzheimer's disease.

Identifying costs of intravenous solution wastage.

A monitoring programme to systematically evaluate and decrease wastage of intravenous (i.v.) solutions was developed. Documentation of type and quantity of wasted solutions can help identify potential causes of waste. Subsequent systems changes intended to decrease waste can then be evaluated. Pharmacy technicians daily recorded the number, identity and locations of discarded i.v. solutions. A computer spreadsheet application was developed and used to produce a monthly summary identifying the number, drug cost and solutions wasted by hospital unit, thus establishing specific areas to target for i.v. wastage control. Investigators conducted a 12-month retrospective evaluation of i.v. wastage, revealing that over 14,000 i.v. preparations were destroyed at an estimated $US90,000 in drug costs. This equates to 2.5% of total drug costs wasted in small volume parenterals. Target programmes were implemented for drugs that were frequently wasted and systems changes implemented that decreased overall wastage of i.v. solutions.

Isolation and characterization of Escherichia coli birA intragenic suppressors.

The biotin (bio) operon in Escherichia coli is negatively regulated by BirA, a bifunctional protein with both repressor and biotin-activating functions. Twenty-five heat-resistant revertants of three temperature-sensitive birA alleles (birA85, birA104 and birA879) were isolated and categorized into five growth and six repression classes. The revertants appear to increase biotin activation by raising the specific activity of BirA and/or increasing the number of enzyme molecules. The 19 birA85 revertants displayed a broad range of activity for both enzyme and repressor functions, and may represent intragenic second-site suppressor mutations. The birA85 revertants included a novel class of bio superrepressor mutations. Repressor titration experiments suggested that many of the birA85 revertants increase BirA concentrations above wild-type levels because the repressors were not competed from the chromosomal bio operator by multicopy bio operator plasmids. The majority of the birA104 revertants resulted in both wild-type repressor and enzyme activity; they are possibly true revertants in which the amino acid residue altered by the birA104 mutation has been substituted by the wild-type or a chemically similar amino acid.