Parent and Metabolite Opioid Drug Concentrations in Unintentional Deaths Involving Opioid and Benzodiazepine Combinations.

Effects of benzodiazepines on postmortem opioid parent and parent/metabolite blood concentration ratios were determined for fentanyl-, hydrocodone-, methadone-, or oxycodone-related accidental deaths. These opioids are partially metabolized by the CYP3A4 enzyme system, which is also affected by diazepam and alprazolam. Opioid/metabolite combinations examined were as follows: fentanyl/norfentanyl, hydrocodone/dihydrocodeine, methadone/EDDP, and oxycodone/oxymorphone. Parent opioid concentrations were analyzed for 877 deaths. Parent/metabolite concentration ratios were analyzed for 349 deaths, excluding cases with co-intoxicants present known to interfere with opioid elimination. Alprazolam in combination with diazepam significantly decreased median hydrocodone concentrations by 48% (p = 0.01) compared to hydrocodone alone. The methadone parent/metabolite concentration ratio was reduced by 35% in the presence of diazepam compared to methadone alone (p = 0.03). Benzodiazepines did not statistically significantly affect fentanyl or oxycodone concentrations. Possible factors affecting opioid concentrations and possible toxicity development, including any differential effects on specific opioids, should continue to be explored.

Dabigatran etexilate: A novel oral direct thrombin inhibitor.

PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, tolerability, dosage and administration, and place in therapy of dabigatran etexilate are reviewed. SUMMARY: Dabigatran is a reversible direct thrombin inhibitor (DTI) that has rapid and predictable anticoagulant effects and does not require the anticoagulation monitoring seen with oral vitamin K antagonists. Dabigatran etexilate has demonstrated efficacy in several clinical studies in preventing venous thromboembolism (VTE) for patients undergoing total hip or knee replacement, in preventing strokes in patients with nonvalvular atrial fibrillation, and in treating acute VTE. Dabigatran etexilate is a prodrug that is orally absorbed and completely converted to the active form dabigatran by carboxylesterases. Neither the conversion of dabigatran etexilate nor the metabolism of active dabigatran involves the cytochrome P-450 isoenzyme system. Other than hemorrhage, dabigatran is generally well tolerated, with gastrointestinal effects being the most commonly reported adverse events. All dosages should be adjusted in patients with reduced renal function. Dabigatran is currently being investigated for several thromboembolic disorders. It was approved by the Food and Drug Administration in October 2010 for stroke and VTE prevention in adult patients with nonvalvular atrial fibrillation, and it was approved by the European Medicines Agency in March 2009 for the prevention of VTE in adult patients undergoing elective total hip or knee replacement. CONCLUSION: Dabigatran etexilate, the first oral DTI marketed in the United States, is indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Dabigatran may be a viable option for anticoagulation in some patients due to its oral administration, rapid onset of action, and predictable anticoagulant effects.

A rubric to assess critical literature evaluation skills.

OBJECTIVE: To develop and describe the use of a rubric for reinforcing critical literature evaluation skills and assessing journal article critiques presented by pharmacy students during journal club exercises. DESIGN: A rubric was developed, tested, and revised as needed to guide students in presenting a published study critique during the second through fourth years of a first-professional doctor of pharmacy degree curriculum and to help faculty members assess student performance and provide formative feedback. Through each rubric iteration, the ease of use and clarity for both evaluators and students were determined with modifications made as indicated. Student feedback was obtained after using the rubric for journal article exercises, and interrater reliability of the rubric was determined. ASSESSMENT: Student feedback regarding rubric use for preparing a clinical study critique was positive across years. Intraclass correlation coefficients were high for each rubric section. The rubric was modified a total of 5 times based upon student feedback and faculty discussions. CONCLUSION: A properly designed and tested rubric can be a useful tool for evaluating student performance during a journal article presentation; however, a rubric can take considerable time to develop. A rubric can also be a valuable student learning aid for applying literature evaluation concepts to the critique of a published study.

Pregabalin: an antiepileptic agent useful for neuropathic pain.

PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of pregabalin are reviewed. SUMMARY: Pregabalin is the first drug to receive approved labeling from the Food and Drug Administration (FDA) for the treatment of painful diabetic neuropathy and postherpetic neuralgia and is the first antiepileptic agent to receive FDA-approved labeling since 1999. Pregabalin is the pharmacologically active S-enantiomer of racemic 3-isobutyl gamma-aminobutyric acid. Pregabalin has demonstrated efficacy in the management of neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and as adjunctive therapy for adult patients with partial onset seizures. Its exact mechanism of action is unknown. Pregabalin is rapidly absorbed and exhibits linear pharmacokinetics after oral administration. The lack of hepatic metabolism and lack of interaction with cytochrome P-450 isoenzymes explain the absence of drug interactions with pregabalin. Several clinical studies have demonstrated pregabalin's efficacy for each of the FDA-approved indications, with dizziness and somnolence reported as the most common adverse events. Pregabalin has been designated as a Schedule V controlled substance because of its potential for abuse and dependence. The starting dosage for patients with neuropathic pain associated with diabetic peripheral neuropathy is 50 mg three times daily and may be increased to 300 mg daily within one week based on efficacy and tolerability. The starting dosage for patients with partial-onset seizures is 75 mg twice daily or 50 mg three times daily and may be increased to 600 mg daily based on individual response and tolerability. CONCLUSION: Pregabalin may be beneficial for the treatment of neuropathic pain or partial-onset seizures in patients who do not respond to conventional treatments or cannot tolerate their adverse effects.

Self-assessment tool for drug information advanced pharmacy practice experience.

OBJECTIVE: To describe the use of student self-assessments as a measure of the effectiveness of a drug information advanced pharmacy practice experience (APPE) and to determine whether other APPEs reinforced information-related skills. DESIGN: Students taking a drug information APPE completed a self-assessment survey instrument focusing on key information-related skills on the first day and again on the last day of that APPE. Findings were used to determine the effect of this and other APPEs on perceived information skills. Student ratings were compared with faculty ratings for items with similar wording. ASSESSMENT: Student self-ratings improved after completing the drug information APPE. Other APPEs, gender, and course grade did not significantly impact student perceptions of their information-related knowledge and skills. Student and faculty ratings were similar, although individual variability occurred. CONCLUSION: Student self-assessments, along with other direct and indirect data, can provide useful information needed to assess and change aspects of the experiential program and curriculum.