Pharmacokinetics of prolonged-release tacrolimus and implications for use in solid organ transplant recipients.

Prolonged-release tacrolimus was developed as a once-daily formulation with ethylcellulose as the excipient, resulting in slower release and reduction in peak concentration (Cmax ) for a given dose compared with immediate-release tacrolimus, which is administered twice daily. This manuscript reviews pharmacokinetic information on prolonged-release tacrolimus in healthy subjects, in transplant recipients converted from immediate-release tacrolimus, and in de novo kidney and liver transplant recipients. As with the immediate-release formulation, prolonged-release tacrolimus shows a strong correlation between trough concentration (Cmin ) and area under the 24-hour time-concentration curve (AUC24 ), indicating that trough whole blood concentrations provide an accurate measure of drug exposure. We present the pharmacokinetic similarities and differences between the two formulations, so that prescribing physicians will have a better understanding of therapeutic drug monitoring in patients receiving prolonged-release tacrolimus.

Use of topical tranexamic acid or aminocaproic acid to prevent bleeding after major surgical procedures.

OBJECTIVE: To evaluate the literature describing topical use of tranexamic acid or aminocaproic acid for prevention of postoperative bleeding after major surgical procedures. DATA SOURCES: Literature was retrieved through MEDLINE (1946-September 2011) and International Pharmaceutical Abstracts (1970-September 2011) using the terms tranexamic acid, aminocaproic acid, antifibrinolytic, topical, and surgical. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All identified articles in English were evaluated. Clinical trials, case reports, and meta-analyses describing topical use of tranexamic acid or aminocaproic acid to prevent postoperative bleeding were included. DATA SYNTHESIS: A total of 16 publications in the setting of major surgical procedures were included; the majority of data were for tranexamic acid. For cardiac surgery, 4 trials used solutions containing tranexamic acid (1-2.5 g in 100-250 mL of 0.9% NaCl), and 1 trial assessed a solution containing aminocaproic acid (24 g in 250 mL of 0.9% NaCl). These solutions were poured into the chest cavity before sternotomy closure. For orthopedic procedures, all of the data were for topical irrigation solutions containing tranexamic acid (500 mg-3 g in 50-100 mL of 0.9% NaCl) or for intraarticular injections of tranexamic acid (250 mg to 2 g in 20-50 mL of 0.9% sodium chloride, with or without carbazochrome sodium sulfate). Overall, use of topical tranexamic acid or aminocaproic acid reduced postoperative blood loss; however, few studies reported a significant reduction in the number of packed red blood cell transfusions or units given, intensive care unit stay, or length of hospitalization. CONCLUSIONS: Topical application of tranexamic acid and aminocaproic acid to decrease postsurgical bleeding after major surgical procedures is a promising strategy. Further data are needed regarding the safety of this hemostatic approach.

Diabetes care: model for the future of primary care.

OBJECTIVE: To review relevant trends threatening primary care and the evidence supporting use of nonphysicians in primary and chronic care of patients with diabetes. DATA SOURCES: Current medical and pharmacy literature as selected by authors. SUMMARY: The care needed by patients with diabetes does not fit well into our current medical model for primary care, and an adequate supply of physicians is not likely to be available for primary care roles in coming years. Patients with diabetes who are placed on evidence-based regimens, are educated about their disease, are coached in ways that motivate them to lose weight and adopt other therapeutic lifestyle changes, and are adhering to and persisting with therapy will soon have improved clinical parameters. These quickly translate into fewer hospitalizations and emergency department visits. A growing body of literature supports the use of pharmacists and other nonphysicians in meeting the needs of patients with diabetes. Pharmacists should join nurse practitioners, specially trained nurses, and physician assistants as integral members of the health care team in providing care to patients with diabetes and, by logical extension, other chronic conditions. CONCLUSION: Demand for primary care is likely to outstrip the available supply of generalist physicians in the coming years. In addition to nurse practitioners and physician assistants, pharmacists should be considered for key roles in future interdisciplinary teams that triage and provide direct care to patients, including those with diabetes and other chronic conditions.

Paradoxical reactions to benzodiazepines: literature review and treatment options.

Benzodiazepines frequently are administered to patients to induce sedation. Paradoxical reactions to benzodiazepines, characterized by increased talkativeness, emotional release, excitement, and excessive movement, are relatively uncommon and occur in less than 1% of patients. The exact mechanism of paradoxical reactions remains unclear. Most cases are idiosyncratic; however, some evidence suggests that these reactions may occur secondary to a genetic link, history of alcohol abuse, or psychological disturbances. This review evaluates the numerous cases of paradoxical reactions to benzodiazepines in adult and pediatric patients that have been reported in the biomedical literature. It also explores the advantages and disadvantages of the various available treatment options.

Association between honey consumption and infant botulism.

Infant botulism, a disease that results in a blockade of voluntary motor and autonomic functions, was first recognized in the United States in the late 1970s. Since then, more than 1000 cases in this country have been reported to the Centers for Disease Control and Prevention (CDC). Numerous studies have shown that the ingestion of honey is linked with infant botulism. In addition, honey samples across the United States have tested positive for Clostridium botulinum spores and toxins. Such substantial evidence led the CDC to recommend that honey not be given to infants younger than 12 months old. It is important that clinicians be familiar with this risk and should not recommend honey-containing products or supplements or the use of honey as a flavoring agent for infants in this age group.