Pharmacotherapy
-
To evaluate the safety and cost-effectiveness of a clinical protocol adopted in June 2006 that included a comprehensive, objective assessment of snake bite envenomations and standardized the use of Crotalidae polyvalent immune Fab antivenom (FabAV). ⋯ Use of a clinical protocol related to snake envenomations resulted in approximately two fewer vials of FabAV required for each patient. In addition, the treatment group experienced a shorter hospital length of stay without a corresponding increase in adverse events or envenomation progression. Data show that use of the protocol was cost-effective. The development of institution-specific multidisciplinary protocols regarding snake bite envenomations is recommended. Clinical pharmacists can play a vital role in the protocol development to ensure that optimal care is provided for this distinct patient population.
-
Etomidate is a potent imidazole hypnotic used widely in single doses in the rapid sequence intubation of critically ill patients with sepsis due to its presumed hemodynamic safety, fast onset, and short duration of action. However, the literature is conflicting regarding the hemodynamic advantages of etomidate over other induction agents, and its safety in this population is a matter of strong debate in the critical care community as the drug is associated with suppression of adrenal steroidogenesis, which can last up to 72 hours after a single dose, primarily through potent inhibition of the 11β-hydroxylase enzyme. However, the clinical impact of this adrenal suppressive effect is not certain. ⋯ Nevertheless, mortality data of single-dose etomidate are still controversial, with no strong evidence of benefit over other agents and a tendency toward harm (keeping in mind the limitations of the available literature). Proponents of single-dose etomidate use in patients with sepsis suggest that the increased mortality associated with etomidate is merely a reflection of the patients' severity of illness and not related to the drug itself, whereas others believe that the drug causes true harm and increases mortality in this population. In view of the lack of a clear clinical advantage of etomidate over other agents used in rapid sequence intubation, it would be prudent to favor other agents until further conclusive evidence of etomidate safety is available in critically ill patients with sepsis.
-
Evaluation of vancomycin dosing regimens in preterm and term neonates using Monte Carlo simulations.
To compare four common dosing regimens for vancomycin in preterm and term neonates by assessing the probability that each regimen would achieve the widely used therapeutic target serum trough concentrations of 5-15 mg/L and the newly suggested target of 15-20 mg/L. ⋯ Monte Carlo simulations based on our population pharmacokinetic model suggest that vancomycin dosing guidelines based on serum creatinine concentration have a greater likelihood of achieving trough concentrations in the 5-15-mg/L range compared with other evaluated dosing regimens. None of the four dosing regimens is suitable to produce target trough concentration of 15-20 mg/L in an acceptable number of patients.
-
Dabigatran etexilate is a new oral anticoagulant used for the prevention of systemic thromboembolism in patients with atrial fibrillation. Acute bleeding episodes are known to occur with dabigatran etexilate therapy; however, only a few case reports in the literature describe such events. We describe a 70-year-old man treated with dabigatran etexilate for newly diagnosed, nonvalvular atrial fibrillation who developed a large hemopericardium that appeared to be temporally related to dabigatran etexilate administration. ⋯ To our knowledge, this report is the first to describe a case of potentially life-threatening pericardial bleeding that was temporally related to starting dabigatran etexilate therapy. Although we found that the DTT was a viable method of monitoring coagulation status in a patient receiving dabigatran etexilate therapy, the assay lacks approval by the United States Food and Drug Administration, which limits its clinical utility and widespread use at this time. Clinicians should be aware of the potential for life-threatening bleeding with use of this agent and the difficulty associated with monitoring and reversing this therapy in the setting of acute bleeding.
-
The mammalian target of rapamycin (mTOR) is a signaling kinase of the phosphatidylinositol 3-kinase/protein kinase B (also known as Akt) signaling pathway that mediates cell growth and metabolism. Dysregulation of the mTOR pathway creates a favorable environment for the development and progression of many cancers, including breast cancer, and is associated with the development of resistance to endocrine therapy and to the anti-human epidermal growth factor receptor-2 (HER2) monoclonal antibody trastuzumab. Therefore, the addition of mTOR inhibitors to conventional breast cancer therapy has the potential to enhance therapeutic efficacy and/or overcome innate or acquired resistance. ⋯ Everolimus is generally well tolerated; hematologic abnormalities and stomatitis are most common adverse events when this drug is combined with cytotoxic chemotherapy. Based on these promising results, everolimus is currently under evaluation in a series of phase III Breast Cancer Trials of Oral Everolimus (BOLERO) trials of women with HER2-positive and estrogen receptor-positive breast cancer. Results of these trials will help to establish the role of everolimus in the treatment of clinically important breast cancer subtypes.