Pharmacist's management of drug-related problems: a tool for teaching and providing pharmaceutical care.

During the development of education and practice models based on the philosophy of pharmaceutical care (PC), six pharmacists worked with the University of Toronto Faculty of Pharmacy to implement the PC model in their practice sites. These pharmacists found it necessary to modify existing tools to create one that explicitly guided them through the PC process, including the phase of monitoring patients for desired outcomes. This resulted in the development of the Pharmacist's Management of Drug Related Problems. This tool requires pharmacists to collect patient drug and medical data and write responses to specific questions about the data to interpret their significance. As proficiency in providing PC is attained, the questions and space for written responses can be eliminated, leaving a comprehensive documentation system of patient outcomes and the data collected, recommendations made, and monitoring completed by the pharmacist. This tool has been adopted by the University of Toronto Faculty of Pharmacy and is being used in various continuing education programs and by practicing pharmacists across Canada.

Practice functions necessary for the delivery of pharmaceutical care.

Pharmaceutical care is a concept outlining the responsibilities of individual pharmacists to individual patients. Although widely accepted on a philosophical basis, there is a lack of comprehensive information about the functions and responsibilities pharmacists undertake when providing pharmaceutical care. Pharmacy educators and practitioners at the faculty of pharmacy, University of Toronto, developed and informally tested a process that details the practice functions required of pharmacists when providing pharmaceutical care as originally defined.

Single-dose accumulation pharmacokinetics of tobramycin and netilmicin in normal volunteers.

The two-compartment tissue accumulation pharmacokinetics of tobramycin and netilmicin were compared in 11 normal volunteers by using a crossover design. After each 1.0-mg/kg (body weight) dose, serum was collected for 96 h, and complete 24-h urine collections were obtained for a total of 30 days. Two months of washout were required before crossover. Concentrations in serum and urine were measured by radioimmunoassay, and concentrations in serum and urinary excretion rates were simultaneously fitted to a two-compartment pharmacokinetic model. Netilmicin exhibited significantly lower total body clearance (48 versus 90 ml/min) and longer terminal elimination half-life (161 versus 96 h) than tobramycin. As a result of these pharmacokinetic differences, the predicted tissue accumulation of netilmicin at steady state was significantly higher than that of tobramycin (P less than 0.05). Relative rates of aminoglycoside nephrotoxicity probably depend on both the differential tissue uptake (accumulation) and the concentration of the aminoglycoside which produces intracellular toxicity. Because the steady-state tissue accumulation of netilmicin is nearly 2.5 times greater than that of tobramycin, its potency in the production of intracellular toxicity needs to be that much less for the two agents to produce the same incidence of clinical nephrotoxicity.

Pharmacokinetics and extravascular penetration of aztreonam in patients with abdominal sepsis.

Patients with abdominal sepsis were enrolled in a clinical trial of aztreonam vs. tobramycin. All were given clindamycin concomitantly. The pharmacokinetics of aztreonam in 21 patients randomly assigned to receive treatment with aztreonam are reported. The mean age of these patients was 68 years; most had underlying disorders such as malnutrition and cardiac or pulmonary disease. Creatinine clearance (Clcr) ranged from 11.2 to 133.1 ml/min. The usual dose of aztreonam was 2.0 g every 8-12 hr. A single pharmacokinetic study was performed over one dosing interval after steady-state conditions were achieved. In approximately one-half of the patients, peritoneal fluid was collected during the interval between doses. Penetration of aztreonam, as expressed as the ratio of concentration in the peritoneal fluid to that in serum, was higher for aztreonam (0.95:1) than for tobramycin (0.46:1). The ratio of the concentration in peritoneal fluid to the minimum inhibitory concentration (MIC) of the infecting bacteria was also higher for aztreonam. Serum pharmacokinetic data were analyzed by both two-compartment and moment analysis. For both the steady-state volume of distribution (Vdss) and total body clearance (TBC), the values determined by both methods were highly correlated (r = .96, .99, respectively). Average values for Vdss and TBC were 0.28 liters/kg and 80 ml/min. TBC for aztreonam correlated strongly with CLcr and was described by the regression equation TBC = 1.1 (Clcr) + 1.6, r = .87, P less than .01.

Treatment with aztreonam or tobramycin in critical care patients with nosocomial gram-negative pneumonia.

During the course of one year, 47 critical care patients with gram-negative bacillary pneumonia at Millard Fillmore Hospital were randomly assigned to aztreonam or tobramycin therapy (two to one). Of these, 40 were fully evaluable for microbiologic and clinical response. All evaluable patients had gram-negative organisms in tracheal aspirate culture specimens and confirmed susceptibility of the organism to both study drugs. There was no difference between the two groups with respect to the percentage of patients who received concurrent antibiotics for gram-positive organisms. More than 60 percent of the patients received mechanical ventilation. Essentially, all had new lung infiltrates as shown by chest radiography, leukocytosis, recent onset of fever, and increased volume of purulent secretions. Half had multilobar pulmonary infiltrates. Their mean age was 73 years, with none under age 50. Most had chronic obstructive pulmonary disease, congestive heart failure, or both. By the prognostic nutritional index criteria, over 70 percent were nutritionally deficient at entry. The majority of infections were caused by Pseudomonas, Enterobacter, Klebsiella, and Escherichia coli. Aztreonam eradicated 92 percent of the causative gram-negative organisms, compared with 57 percent for tobramycin (p less than 0.05). Aztreonam produced a favorable clinical response (cure or improvement) in 93 percent of patients, compared with 50 percent for tobramycin (p less than 0.05). There were no differences in the minor adverse effects observed in the two treatment groups. Overall, aztreonam was superior to tobramycin for treatment of pneumonia due to susceptible gram-negative bacteria in these critical care patients.