Hypertension is common in hospitalized patients and there are many causes. Some patients have no prior history of hypertension, few symptoms, and no apparent morbidity related to acute rises in blood pressure. Though there is no established guideline for therapy in these cases, patients often receive therapy directed at the abnormal vital sign. It is hypothesized that this practice is common and the associated costs are significant. Using the inpatient pharmacy database at the University of Kentucky Chandler Medical Center, a verified Level I trauma center and quaternary referral center, patients on the emergency general surgery or orthopedic surgery services receiving intravenous hydralazine, metoprolol, or labetalol were identified. Subjects were analyzed for indications, parameters, associated history of hypertension, and direct costs. Over the 4-month study period, 114 subjects received 522 drug doses. More than half (55%) of subjects had a prior history of hypertension but only 75 per cent were started on their home medication. Of those without hypertension before admission, 18 per cent required therapy at discharge. Labetalol was the most frequently used agent and total pharmacy costs for this cohort of patients was over $1200. Pro re nata (PRN), short-acting antihypertensive therapy has little evidence base in asymptomatic patients, but its prevalence is high on surgical services. The cost is significant, especially when extrapolated to the larger hospital population at this single institution. Further research is warranted to determine the prevalence of this practice in other centers or national regions, as well as its cost and benefit.
Deferiprone is a bidentate oral iron chelator used for the treatment of transfusional iron overload in people. The purpose of this study was to determine the pharmacokinetic disposition of deferiprone in the white leghorn chicken as a potential model upon which to base therapeutic regimens for the treatment of iron storage disease (hemochromatosis) in affected avian species. A suspension of deferiprone (DFP) was administered orally at a single dose of 50 mg/kg to 10 birds that were iron-loaded (IL-DFP) and 10 non--iron-loaded control birds (NIL-DFP). After a 30-day washout period, 5 birds from the NIL-DFP group were used for a bioavailability study of deferiprone administered intravenously at the same dose. Blood samples were collected at varying intervals over a 24-hour period and were analyzed for deferiprone by high-performance liquid chromatography, then plasma concentration versus time curves were developed. Deferiprone was rapidly absorbed from the gastrointestinal tract of the chicken, with plasma concentrations effective for iron chelation in humans (>20 micromol/L) maintained for at least 8 hours after oral dosing. The half-life (mean +/- SD) of the orally administered deferiprone in the IL-DFP and NIL-DFP groups was 2.91 +/- 0.78 hours and 3.61 +/- 0.90 hours, respectively, and was 2.42 +/- 0.24 hours for deferiprone administered intravenously. The mean oral bioavailability was 93%. Deferiprone is well absorbed and widely distributed in the chicken, with a longer half-life than reported in mammals.
The pharmacologic effect of a highly protein-bound drug is a function of the free serum concentration. In vitro studies have demonstrated that phenytoin is displaced from its protein-binding sites by acetylsalicylic acid. This resulted in increased concentrations of free serum phenytoin and raised the possibility of clinical toxicity. We have studied the effects of salicylates on six patients receiving long-term phenytoin therapy. This reduced the total serum phenytoin concentration but did not alter the free serum concentration. There was no loss of seizure control or toxicity. Total phenytoin concentrations in such patients may not accurately reflect pharmacologic activity and may be misleading.
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