Adverse drug events in high risk older outpatients.

OBJECTIVE: To describe the prevalence, types, and consequences of adverse drug events (ADEs) in older outpatients with polypharmacy. DESIGN: A cohort study. SETTING: General Medicine Clinic at the Durham Veterans Affairs Medical Center. PATIENTS: A total of 167 high risk (taking > or = 5 scheduled medications) ambulatory older veterans who participated in a year long health service intervention trial. MEASUREMENTS: Potential ADEs were identified by asking patients during closeout interviews whether, in the past year, they had experienced any side effects, unwanted reactions, or other problems from any medication. All reported medications and corresponding adverse experiences were assessed for plausibility by a research clinical pharmacist using two standard pharmacological textbooks and categorized by predictability, therapeutic class, and organ system. RESULTS: Eighty self-reported ADEs involving 72 medications taken by 58 (35%) of 167 patients were textbook confirmed. Seventy-six of 80 (95%) ADEs were classified as Type A (predictable) reactions. Cardiovascular (33.3%) and central nervous system (27.8%) medication classes were most commonly implicated. Gastrointestinal (30%) and central nervous system (28.8%) ADE symptoms were common. Sixty-three percent of patients with ADEs required physician contacts, 10% emergency room visits, and 11% hospitalization. Twenty percent of medications implicated with ADEs required dosage adjustments, and 48% of ADE-related medications were discontinued. No significant differences (P > .05) were observed when ADE reporters (n = 58) and nonreporters (n = 109) were compared. CONCLUSION: Predictable ADEs are common in high risk older outpatients, resulting in considerable medication modification and substantial healthcare utilization.

Relation of prescription nonsteroidal antiinflammatory drug use to cognitive function among community-dwelling elderly.

PURPOSE: To evaluate the relationship of nonsteroidal antiinflammatory drug (NSAID) use to level of cognitive function in community-dwelling elderly persons. METHODS: The prospective cohort study included 2765 nonproxy subjects from the Duke University Established Populations for Epidemiologic Studies of the Elderly who were cognitively intact at baseline (1986-1987) and alive at follow-up three year later. Cognitive function was assessed by the Short Portable Mental Status Questionnaire (i.e., intact vs. impaired and change in score) and by the individual domains of the Orientation-Memory-Concentration Test (i.e., number of errors). NSAID use, determined from in-home interviews, was coded for chronicity, dose, frequency of use, and prescription status. RESULTS: After controlling for demographic factors as well as health status and behavior, continuous, regularly-scheduled, prescription use of NSAID was associated with preservation of one aspect of cognitive functioning: concentration (beta coefficient, 0.29; 95% confidence interval [CI] -0.54 to -0.04, indicating fewer errors). However, no consistent dose-response relationship was found. Current and prior NSAID use was unrelated to level of cognitive functioning across all five measures; among current users, those taking moderate or high doses (beta coefficient, 0.41; 95% CI, 0.08 to 0.74) made more errors on the memory test compared with those taking low doses (beta coefficient 0.03; 95% CI, -.85 to 0.91). CONCLUSIONS: These results suggest no substantial or consistent protective effect of prescription NSAID use on cognitive function in community-dwelling elderly. However, recent use at higher doses may be associated with memory deterioration in this population.

Finasteride: the first 5 alpha-reductase inhibitor.

Finasteride is a synthetic 4-azasteroid that is a specific competitive inhibitor of 5 alpha-reductase, an intracellular enzyme that converts testosterone to dihydrotestosterone (DHT). It has no binding affinity for androgen receptor sites and itself possesses no androgenic, antiandrogenic, or other steroid hormone-related properties. It is well absorbed after oral administration, with absolute bioavailability in humans of 63% (range 34-108%). The mean time to maximum concentration is 1-2 hours, and it is approximately 90% plasma protein bound. The elimination half-life averages 6-8 hours. The agent is metabolized to a series of five metabolites, of which two are active and possess less than 20% of the 5 alpha-reductase activity of finasteride. Little is known about potential drug interactions, although they appear to be minimal and not clinically relevant. The drug is indicated for the treatment of symptomatic benign prostatic hyperplasia. Its efficacy in regression of prostate gland enlargement is rapid and predictable, although correlation with subsequent improvement in urinary flow and symptoms is highly variable. Dosages of 0.5-100 mg/day regress prostate enlargement; the recommended dosage is 5 mg once/day. Finasteride may hold promise for other DHT-mediated disorders such as acne, facial hirsutism, frontal lobe alopecia, and prostate cancer, but its use in these conditions remains investigational. The frequency of adverse drug events is low, with the most common side effects being impotence, decreased libido, and decreased volume of ejaculate. No reports of intentional overdose have been reported, and dosages of up to 80 mg/day for 3 months have been taken without adverse effect.