Intervention assessment in an Indian health service pharmacy.

OBJECTIVE: To document and evaluate pharmacists' interventions in a setting that has complete and immediate access to patient information. DESIGN: Descriptive report evaluating self-reported interventions made by pharmacists during the conduct of routine dispensing activities. The data collection period was from February 15 to April 1, 1994. SETTING: Ambulatory care facility offering medical and dental care to high school residents, Native Americans, and Alaska Natives in Northwestern Oregon. MAIN OUTCOME MEASURES: Intervention rate per 100 new prescriptions dispensed. Each intervention was evaluated with regard to the information used to initiate it, when during the dispensing process it was initiated, and the intervention type. Outside evaluators determined the clinical significance of the interventions, including potential adverse health consequences, the likelihood of their occurrence, and the level of medical care that would have been required to treat the problem. RESULTS: Of 2,535 orders screened, 104 interventions (4.1%) were collected; 71% of these occurred during chart screening. Pharmacists most often used the medication order itself (60.6%) to detect prescribing problems, followed by other records in the patient's chart (29.8%). Outside evaluators identified 47.1% of the 104 interventions as clinically significant. The most common adverse health consequence prevented was inadequate control of the patient's condition. Outside evaluators also found that the most common level of corrective care that would have been needed if the intervention had not occurred, was a scheduled physician office visit (59.2%). CONCLUSION: This information suggests that pharmacists who have access to patient information may intervene at higher rates and that more of their interventions may be deemed clinically significant. However, larger, double-blinded, case-controlled studies are needed to definitively draw these conclusions.

Interaction between cyclosporine and grapefruit juice requires long-term ingestion in stable renal transplant recipients.

STUDY OBJECTIVE: To examine the effect of the concurrent administration of increasing amounts of grapefruit juice, an inhibitor of drug metabolism, on the steady-state pharmacokinetics of cyclosporine. DESIGN: Open-label, three-period crossover, food-drug interaction study in stable renal transplant patients. SETTING: A university-affiliated clinical research center. PATIENTS: Sixteen stable renal transplant recipients. INTERVENTION: Cyclosporine was administered with 240 ml of water, 240 ml of grapefruit juice, or several 240-ml glasses of grapefruit juice, and serial blood samples were taken to estimate the effect of grapefruit juice on cyclosporine pharmacokinetics. MEASUREMENTS AND MAIN RESULTS: Grapefruit juice caused a significant increase in cyclosporine area under the curve, however, no significant effect was seen in other pharmacokinetic parameters. Grapefruit juice caused an increase in the 24-hour trough cyclosporine concentration, which may be of clinical significance if long-term ingestion of grapefruit juice is recommended. CONCLUSION: A drug interaction exists between cyclosporine and grapefruit juice, and it is likely at the level of intestinal drug absorption.

Molecular basis of Alzheimer's disease.

Information on the molecular biology of Alzheimer's disease (AD) pointing to new methods of diagnosis and drug therapies is explored. AD is the most common cause of dementia in the elderly and is characterized by senile plaques and neurofibrillary tangles in the brain and loss of cholinergic neurons in the basal forebrain. The disease has a strong genetic component. A definitive diagnosis can be made only by neuropathologic examination at autopsy or biopsy; however, the accuracy of diagnosis based on standard neuropsychological testing and inclusion criteria has improved considerably. Senile plaques consist of a central core of amyloid fibrils surrounded by dystrophic axons. The main component of senile plaque amyloid is a 39-to 42-amino-acid segment referred to as beta-amyloid, which is derived from amyloid precursor protein (APP). APP exists as multiple isoforms encoded by a single gene on chromosome 21. Factors that may influence APP metabolism include activation of phospholipase C, phosphorylation, and the cholinergic system. The microtubule-associated protein tau may contribute to the neurofibrillary tangles of AD. In AD all six adult isoforms of tau can become maximally phosphorylated and can, rather than binding to microtubules, bind to each other, destabilizing the neuronal cytoskeleton. One of the most important discoveries in AD research was the linking of apolipoprotein E phenotype to familial late-onset AD. Acetylcholinesterase inhibitors appear to improve cognitive function but may be limited in utility by adverse effects. Nicotinic agonists are also being investigated as symptomatic therapies. Other possible strategies include nerve growth factor, agents that potentiate the action of endogenous glutamate, antioxidants, nonsteroidal anti-inflammatory drugs, and estrogens. Research into the molecular biology of Alzheimer's disease has begun to point to possible causes of and treatments for this condition.

Extraction of diethylhexylphthalate from total nutrient solution-containing polyvinyl chloride bags.

Total nutrient solution (TNS) is a new method for delivering total parenteral nutrition (TPN) by admixing dextrose, amino acids, and lipids in a single container. Recommendations are to use nonpolyvinyl chloride (PVC) containers for admixture of these solutions. PVC is a hard, brittle, and inflexible substance, and plasticizers, predominantly diethylhexylphthalate (DEHP), are added to impart flexibility. DEHP is a lipid soluble suspected carcinogen, hepatotoxin, and teratogen which has been shown to leach from PVC products containing lipophilic admixtures. The purpose of this study was to quantitate the amount of DEHP which leaches from PVC bags containing TNS. Six study groups, which contained three formulas stored at 25 degrees C +/- 2 degrees C and 4 degrees C +/- 1 degree C, were assayed for DEHP at time 0, 12, 24, 48 and 72 hr, 1 wk, and 3 wk using high-performance liquid chromatography. The control group contained an amino acid source, a carbohydrate source, and standard electrolytes, and the other groups contained a 10% lipid source or a 20% lipid source in addition to the constituents of the control group. Lipid-containing groups demonstrated detectable levels of DEHP at 48 hr, and DEHP content increased in these groups throughout the 21-day study. DEHP concentrations were lower in lipid-containing groups stored at 4 degrees C than comparable groups stored at 25 degrees C.

Sterility testing of home and inpatient parenteral nutrition solutions.

The microbial contamination rate was compared for parenteral nutrition solutions prepared by patients for home use and by pharmacy personnel for inpatient use. Phase I validated the Ivex 0.22-micron inline filter as a tool for microbiological testing by inoculating small numbers of organisms in 5% dextrose injection and testing for recovery. Phase II validated the same method for determining microbial contamination of total parenteral nutrition (TPN) solutions. Phase III compared inpatient and home TPN microbial contamination rates using the methodology validated in phase II. Test organism inocula used in phase I and II were Candida albicans, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes. All contaminated solutions in phase I showed visual turbidity within 48 hr, and all test organisms were recovered and identified. All phase II-contaminated TPN solutions showed visual turbidity after 96 hr, and all test organisms were recovered and identified. One hundred postinfusion TPN samples were collected randomly during phase III from inpatient parenteral nutrition patients. Six patients and two hospitals participated in the study. None of the 44 home parenteral nutrition samples and none of the 56 inpatient TPN samples developed visible turbidity. Subcultures of each sample on blood agar were negative for microbial growth. This described methodology offers an effective means to establish contamination rates of parenteral nutrition solutions after administration.

Precipitate analysis from an indwelling total parenteral nutrition catheter.

The composition of a precipitate obtained from a silastic right atrial catheter was determined. The precipitate was collected and washed with deionized water thoroughly before subjecting portions of it to organic and inorganic analysis. Inorganic analysis was conducted using scanning electron microscopy and x-ray spectroscopy for sodium, aluminum, silicone, sulfur, chlorine, and calcium. Phosphorus analysis was conducted by a commercial laboratory. Organic analysis was conducted by thin layer chromatography with cholesterol, phosphatidyl serine, phosphatidyl choline, phosphatidyl ethanolamine, and sphingomyelin as standards. Silicone, calcium, and phosphorus and three organic compounds, which could not be conclusively identified, were found. The precipitate was most likely calcium phosphate intermixed with silicone oil lubricant and residual total parenteral nutrition (TPN) solution. This formed in the catheter at body temperature probably due to incomplete catheter flushing.

Stability of levodopa in 5% dextrose injection at pH 5 or 6.

The stability of solutions of levodopa 1 mg/mL in 5% dextrose injection adjusted to pH 5 or 6 and stored at one of three temperatures was determined. Solutions were adjusted to pH 5 or 6 with sodium acetate injection or sodium phosphate injection, respectively. Three samples of solution adjusted to pH 5 were stored at each of three temperatures (4, 25, and 45 degrees C), and three samples of solution adjusted to pH 6 were stored at 25 degrees C. Samples were assayed for levodopa concentration by high-performance liquid chromatography at various times during the 21-day study period. All solutions maintained at least 90% of the initial concentration of levodopa for seven days. Discoloration of all solutions except those stored at 4 degrees C was noted at some point during the study period; solutions stored at 45 degrees C began to darken within 12 hours. The pH values of the solutions did not change during the study period. Under the conditions studied, solutions of levodopa 1 mg/mL in 5% dextrose injection adjusted to pH 5 or 6 are stable for seven days. Slight degradation of levodopa may cause a brownish-black discoloration of the admixtures.

Effects of pH, temperature, concentration, and time on particle counts in lipid-containing total parenteral nutrition admixtures.

It has been standard practice in the United States to separate lipid emulsion from the other components of total parenteral nutrition (TPN) due to the reported instability of admixed intravenous lipid emulsions. Some clinicians, however, have combined all TPN components into one container and administered these admixtures to patients without apparent difficulties. Infusion of all nutrients from one container has many advantages. In this study standard and concentrated admixtures were aseptically prepared using generally accepted guidelines of the nutritional requirements for a 70-kg patient. Treatments of standard and concentrated admixtures consisted of: storing at 4 degrees C without adjusting the pH; increasing the pH to 6.6 and storing at 4 degrees C; increasing the pH to 6.6 and storing at room temperature. Samples were monitored for 3 weeks by means of Coulter Counter analysis, pH determinations, and visual observations. The pH of the admixtures did not change over 3 weeks. Mean counts of particles with sizes between 1.6 and 25.4 mu increased over time for each treatment group. Within treatments, concentrated admixtures had significantly greater particle counts than the corresponding standard admixtures. Within the standard and within the concentrated admixtures, the particle counts were significantly greater for group one than for group three. Particle counts in group two tended to lie between the values of group one and three. Visual signs of emulsion deterioration were greatest in those admixtures in which the pH was not adjusted and occurred earlier in concentrated admixtures.

Stability of dopamine hydrochloride exposed to blue-light phototherapy.

The stability of dopamine hydrochloride in 5% dextrose injection when exposed to blue-light phototherapy was assessed. Solutions of dopamine hydrochloride (1000 micrograms/mL) were prepared, and samples were subjected to one of three light sources (fluorescent, dark, phototherapy) and two flow rates (2 mL/hr and no flow) at ambient room temperature. Irradiation levels were maintained between 5.1 and 6.6 microwatts/sq cm throughout the experiment. Samples obtained at 0 to 36 hours were assayed using high-performance liquid chromatography. There were no significant differences in dopamine stability among the sample groups exposed to the various light and flow conditions over the 36-hour study period. Dopamine hydrochloride in 5% dextrose injection exposed to phototherapy is stable for 36 hours at 1000 micrograms/mL. It is not necessary to protect dopamine solutions from blue-light irradiance to ensure clinically acceptable stability.

Stability of folic acid in 25% dextrose, 3.5% amino acids, and multivitamin solution.

The chemical stability of folic acid in 25% dextrose, 3.5% amino acids, and multivitamin solution was investigated. Solutions of 0.25, 0.5, 0.75, and 1.0 mg/liter of folic acid admixed in the study solution were prepared. Solutions were stored in light-room temperature, light-refrigeration, dark-room temperature, or dark-refrigeration. Samples were drawn to determine folic acid concentration and again at 4, 8, 12, 18, 24, 36, and 48 hr after admixture. Folic acid concentration was determined by competitive binding radioassay, and results are expressed as percent of initial folic acid concentration. Folic acid was stable for 48 hr with each tested concentration and stability was found to be independent of temperature or light storage effects. Folic acid admixed in the study solution is chemically stable for up to 48 hr after initial admixture under normal total parenteral nutrition storage conditions.

Description of an undergraduate sterile products clerkship.

A description of a ten week, full-time, elective sterile products clerkship designed for fifth year pharmacy students is presented. The course refines the student's written and oral communication skills and meets the NCCLVP standard for education of IV therapy personnel.

Eleven years of experience with capitation reimbursement for pharmacy services.

Pharmacy services encompass more than dispensing medications. However, traditional pharmacy reimbursement methods are based heavily on the dispensing of medications--i.e., on selling a commodity rather than providing a service. The capitation reimbursement method described provides the pharmacist with a means of reimbursement for professional services independent of the number of medications consumed by the patient. The pharmacist is thus free to encourage reductions in the consumption of medications without incurring an economic penalty. Such reductions are not only of potential benefit to the patient but can also reduce the workload of the nursing home staff. The feasibility of this capitation system is demonstrated by the successful pharmacy practice described.

Estimation of serum digoxin levels in geriatric patients.

The correlation in geriatric patients between estimated serum digoxin levels based on pharmacokinetic calculations and serum digoxin levels measured by radioimmunoassay was studied. Serum digoxin levels were estimated for 17 geriatric patients recieving digoxin using the "total body stores" concept. A statistically significant correlation between calculated and measured digoxin levels was shown (p less than 0.05, r = 0.51); however, 95% confidence limits were so large (+/- 1.75 ng/ml) that the results were clinically unacceptable. Until data describing specific causes of variance are available and calculations modified to account for specific variations, pharmacokinetic models should not be relied upon for accurate estimates of digoxin levels in geriatric patients.

Payment for nondistributive hospital pharmacy services--a regional survey.

Questionnaires were mailed to all (464) nongovernment, not-for-profit and investor owned for-profit hospital pharmacies in Washingon, Oregon and California. Responses were received from 350 institutions, a return rate of 75.4 percent. Pharmacists were asked to report data relating to the incidence of, the range of fees charged, and the extent of reimbursement received from third party carriers for the provision of nondistributive pharmacy services. The data received indicate that pharmacy consultation to physicians was provided by 77.9 percent of the respondents, drug therapy monitoring by 48.1 percent, generalized patient discharge consultation by 40.8 percent, CPR team participation by 27.2 percent, indepth patient discharge consultation by 17.5 percent and admitting medication history by 8.8 percent. Additionally, 12 institutions charged for providing 16 nondistributive pharmacy services. Directors of pharmacy from six hospitals indicated that they billed third party carriers for nondistributive pharmacy services as part of their total pharmacy charge via their usual billing procedure. All third party carriers billed in this manner paid for the nondistributive pharmacy service.

Pharmaceutical services in nongovernmental hospitals on the West Coast.

A survey of nongovernment, nonprofit and for-profit hospitals in Washington, Oregon and California was conducted to determine the incidence of selected hospital pharmacy services (1) directly related to drug distribution and (2) not directly related to drug distribution. Questionnaires were mailed to all qualifying hospitals in the three states; the return rate was 75.4%. Unit dose drug distribution was used in combination with other delivery systems by 58.3% of the respondents; 26.5% used unit dose exclusively. Over half of the respondents provided i.v. admixture programs, outpatient and inpatient discharge prescriptions, and inpatient medication profiles. Additionally, 77.9% provided pharmacy consultation to physicians. Nonprofit hospitals had significantly higher pharmacy staffing levels (both pharmacists and supportive personnel) than for-profit hospitals in the categories, "open seven days per week," "open nine to 16 hours per day," "open 17 to 24 hours per day, "101 to 200 beds" and "201 or more beds." Hospitals that provided the following services had significantly higher pharmacy staffing levels than those that did not provide the serices: unit dose drug distribution, i.v. admixture services, inpatient discharge prescriptions, inpatient medication profiles, drug therapy monitoring, and cardiopulmonary resuscitation team participation (difference of supportive staff only).