Robert J. Cipolle

Drug-related problems : their structure and function

In order to better focus the role of the pharmacist on patient need and patient outcome, a means of categorizing drug-related problems (DRPs) is presented. A DRP exists when a patient experiences or is likely to experience either a disease or symptom having an actual or suspected relationship with drug therapy. Eight different categories of DRPs are described and examples of each category are offered. This categorization serves a number of functions, such as: (1) to illustrate how adverse drug reactions form but one category of extant DRPs, (2) to make tangible the pharmacists role for the future, (3) to serve as a focus for developing a systematic process whereby the pharmacist contributes significantly to the overall positive outcome of patients, (4) to bring to pharmacy practice a vocabulary consistent with that of other healthcare professionals, and (5) to aid in the development of standards of practice for pharmacists.

Clinical efficacy of antimicrobial drugs for acute otitis media: Metaanalysis of 5400 children from thirty-three randomized trials

OBJECTIVE To reconcile conflicting published reports concerning the absolute and comparative clinical efficacy of antimicrobial drugs for acute otitis media in children. STUDY SELECTION Articles were identified by MEDLINE search, Current Contents, and references from review articles, textbook chapters, and retrieved reports. Randomized, controlled trials of therapeutic antimicrobial drugs used in the initial empiric therapy for simple acute otitis media were selected by independent, blinded observers, and scored on 11 measures of study validity. Thirty English and three foreign-language articles met all inclusion criteria. DATA EXTRACTION Data were abstracted for an end point of complete clinical resolution (primary control), exclusive of middle ear effusion, within 7 to 14 days after therapy started. DATA SYNTHESIS The spontaneous rate of primary control--without antibiotics or tympanocentesis--was 81% (95% confidence interval, 69% to 94%). Compared with placebo or no drug, antimicrobial therapy increased primary control by 13.7% (95% confidence interval, 8.2% to 19.2%). No significant differences were found in the comparative efficacy of various antimicrobial agents. Extending antimicrobial coverage to include beta-lactamase-producing organisms did not significantly increase the rates of primary control or resolution of middle ear effusion. Pretreatment tympanocentesis was positively associated with individual group primary control rates, negatively associated with the ability to detect differences in clinical efficacy and unassociated with resolution of MEE. CONCLUSIONS Antimicrobial drugs have a modest but significant impact on the primary control of acute otitis media. Treatment with beta-lactamase-stable agents does not increase resolution of acute symptoms or middle ear effusion; initial therapy should be guided by considerations of safety, tolerability, and affordability, and not by the theoretical advantage of an extended antibacterial spectrum.

Kinetic model for gentamicin dosing with the use of individual patient parameters

Multiple‐infusion dosing regimens for gentamicin were established for 84 patients with the use of individually calculated values of elimination kinetic parameters. Serum level‐time data obtained after a single infusion were used to determine the patients gentamicin half‐life (t½) and distribution volume. Patients with serum creatinine (Cr) <1.2 mg per 100 ml had t½s (mean, 2.25 hr) and total body clearances (mean, 0.082 L/hr/kg) significantly different from those with Cr ≥1.2 mg/100 ml (means, 5.3 and 0.039, respectively). Distribution volumes were not significantly different (means, 0.22 and 0.21 L/kg, respectively). Calculations of dosing intervals and infusion rates, based on each patients kinetic parameters and desired steady‐state peaks and nadirs, assumed a one‐compartment model with first‐order elimination and 1‐hr constant‐rate input at fixed intervals. Follow‐up steady‐state peak and nadir levels were measured in 63 of the regimens. Differences between predicted and measured peak levels averaged ‐0.05 µg/ml with 60% of the measured values falling within 1 µg/ml of that predicted. Predicted‐measured nadir differences averaged −0.62 µg/ml (significantly different from zero) indicating slight bias in the model. Fifty‐six percent of these nadirs were within 1 µg/ml of that predicted.

Gentamicin pharmacokinetics in 1,640 patients: method for control of serum concentrations.

The pharmacokinetics and dosage requirements of gentamicin were studied in 1,640 patients receiving treatment for gram-negative infections. A wide interpatient variation in the kinetic parameters of the drug occurred in all patients and in patients who had normal serum creatinine or normal creatinine clearance. The half-life ranged from 0.4 to 32.7 h in 331 patients who had normal creatinine clearance. The factors related to the elimination rate constant were creatinine clearance, age, distribution volume, weight, gender, and hematocrit. The daily dose necessary to obtain therapeutic serum concentrations ranged from 0.5 to 25.8 mg/kg in patients with normal serum creatinine and from 0.7 to 25.8 mg/kg in patients with normal creatinine clearance. In 13 patients (0.9%), a significant change in base-line serum creatinine (greater than or equal to 0.5 mg/dl) occurred during or after treatment, which may have been gentamicin-associated toxicity. Overt cochlear or vestibular toxicity did not occur in these patients. The method of individualizing dosage regimens provided a clinically useful means of rapidly attaining therapeutic peak and trough serum concentrations.

Heparin kinetics: Variables related to disposition and dosage

A method to determine heparin kinetics and dosage requirements was examined in 20 patients with active thromboembolic disease. Pretreatment heparin sensitivities were determined to establish the relationship between heparin concentration and activated partial thromboplastin times (APTTs). After an initial bolus dose, serial APTTs were measured, heparin concentrations were estimated, and kinetic determinations followed. Heparin elimination rate, distribution volume, and clearance were used to calculate dosage requirements. There was a 500% range in pretreatment heparin sensitivities. Smokers had more rapid heparin elimination rates and t½s than nonsmokers did. Men had more rapid drug clearances than women did. Body weight was related to heparin dosage requirements. Patients treated early after onset of symptoms required higher doses than patients in whom treatment was delayed. A multiple regression model was developed for heparin dosage requirements from body weight, sex, delay between onset of symptoms and treatment, and smoking. This statistical model explained 78% of the variance in heparin requirements.

The Impact of Pharmaceutical Care Practice on the Practitioner and the Patient in the Ambulatory Practice Setting: Twenty-five Years of Experience

This manuscript reviews 25 years of experience that include developing the practice of pharmaceutical care and initiating new practices. The impact this practice has on practitioners in the ambulatory setting is described as well as data that reflect its clinical and economic impact. There is a great need to prepare new practitioners to provide pharmaceutical care. A focused training program was developed and delivered to over 300 practitioners. The practitioners were prepared by providing direct patient care. They learned the philosophy of pharmaceutical care practice, to identify, resolve and prevent drug therapy problems, to document care using a specially designed software program called the Assurance Pharmaceutical Care program. The practitioners who participated in the training program reported that the average amount of time spent with patients increased three-fold, they now see four times more patients than prior to training, and the number of new patients referred by physicians increased nine-fold as a result of the program. These practitioners have now provided care to more than 25,000 patients in their practices. These data have now been consolidated and analyzed, and a portion of these results is reported here. The clinical and economic outcomes from 2,985 adult patients, who received pharmaceutical care between January, 2000 and December, 2003, are presented. At the first assessment by the pharmaceutical care practitioner, 61% of the patients had one or more drug therapy problems identified and resolved. This resulted in an improvement in the clinical status or maintaining a stable status in 83% of the patients. The health care savings realized from pharmaceutical care were

Heparin-associated thrombocytopenia: A prospective evaluation of 211 patients

1,134,162. This represented a benefit to cost ratio of 2:1. Physicians who collaborate with pharmaceutical care practitioners have validated the work of the practitioners, and patients are recognizing the benefits of pharmaceutical care.

Heparin‐induced thrombocytopenia in patients with cerebrovascular ischemic disease

Two hundred eleven consecutive patients treated for acute thromboembolic disease were evaluated prospectively for the incidence of thrombocytopenia while receiving heparin treatment. One hundred patients received beef lung heparin and 111 patients received porcine intestinal mucosal heparin. All patients received a minimum of 4 consecutive days of continuous intravenous heparin, and platelet counts were determined prior to, at least twice weekly, and at the cessation of heparin therapy. Heparin-associated thrombocytopenia was defined as a decline from a normal platelet count (100,000-400,000/mm3) to less than 100,000/mm3 with a return to above 100,000/mm3 after the discontinuation of heparin. Heparin-associated thrombocytopenia developed in 11 patients (5.2% incidence). Ten of the thrombocytopenic patients had received beef lung heparin and one received porcine mucosal heparin. Chi-square analysis of these data was significant (p = 0.007). Plasma from seven of nine thrombocytopenic patients demonstrated a plasma factor compatible with a heparin-sensitive antiplatelet antibody. Heparin-associated thrombocytopenia appeared on days 2 to 10 of therapy. Cessation of heparin resulted in remission of thrombocytopenia within 4 days in all patients. Serial quantitative platelet count determinations are indicated in all patients receiving therapeutic heparinization for the early recognition and resolution of heparin-associated thrombocytopenia.

Effect of Obesity on Gentamicin Pharmacokinetics

We studied 137 patients who were treated with heparin for cerebral infarction (73), partially reversible ischemic neurologic deficit (22), or transient ischemic attack (42). Platelet counts were performed before therapy, twice weekly, and at cessation of therapy. Platelets decreased in 118 patients (86%). In 21 (15.3%), platelets dropped ≥40%; 9 of 14 new ischemic events and three of six deaths occurred in this group of patients. Because there was a significant association between poor outcome and platelet drop ≥40% (p < 0.001), we believe that platelets should be monitored frequently when patients are treated with heparin for ischemic cerebrovascular disease.

Increased gentamicin dosage requirements: Rapid elimination in 249 gynecology patients

Abstract: The effect of obesity on gentamicin disposition was studied in 60 obstetric and gynecologic patients receiving treatment for Gram‐negative infections. Thirty patients whose body weights were within 20 per cent of their ideal body weight were the control group. Thirty additional patients had body weights at least 30 per cent greater than ideal body weight and were the obese group. The two groups had similar ages, heights, ideal body weights (IBW), lean body weights (LBW), and elimination rates of gentamicin. The distribution volumes, expressed as liters or standardized to ideal body weight, lean body weight, or total body weight, were significantly different in the controls from those in obese patients. The distribution volume averaged (± S.D.) 0.19 ± 0.06 l./kg in controls. The contribution of excess weight to additional drug volume averaged (± S.D.) 0.05 ± 0.16 l./kg. Excess weight thus contributes less volume per kilogram than ideal body weight or lean body weight. A substantial interpatient variability existed in the measured distribution volume for all groups. Measuring serum concentrations and adjusting a patients dosage regimen are imperative to ensure therapeutic serum concentrations.