Possible Drug-Associated Sialolithiasis From the Bicarbonate Anhydrase Inhibitor Topiramate: A Case Report and Literature Review.

Topiramate is an antiepileptic drug indicated for the treatment of seizure disorders, migraine prophylaxis, and, more recently, weight loss. This new indication will likely increase the use of this agent significantly. As a carbonic anhydrase inhibitor, topiramate can affect the pH of bodily fluids and is known to increase the risk of nephrolithiasis. However, as discussed in the present report, these properties also result in an as yet unaddressed risk of the development of sialoliths, calcified stones formed in the salivary duct or glands. The physiologic mechanisms for stone development in the salivary gland are reviewed and the pharmacologic effects of topiramate on sialolith formation discussed. The present report describes a female patient treated with topiramate for migraine prophylaxis who subsequently presented with a sialolith in the left submandibular duct.

Tolerance, physical dependence, and addiction: Knowledge gaps and misconceptions of first-year pharmacy students.

INTRODUCTION: Misconceptions related to terminology used in the diagnosis and treatment of substance use disorders are common among healthcare providers and may contribute to inappropriate management and education of patients. The objective of this study was to evaluate baseline knowledge of addiction, tolerance, and physical dependence in first-year pharmacy students completing a unit on the neurobiological basis of addiction. METHODS: Students were asked to define the terms addiction, tolerance, and dependence at the beginning of a didactic unit on nervous system pathophysiology and pharmacology. Handwritten responses were transcribed to a spreadsheet and deidentified by sequential assignment to a single numeric identifier. Data were analyzed by three reviewers through open coding and thematic analysis. Descriptive statistics were used to describe the results. RESULTS: One hundred eighty-seven individual student submitted responses were included in the analysis. Many students were unable to provide a substantive definition for the terms physical dependence (32%) and addiction (27%). The definition of tolerance was partially correct in >80% of student responses, though no students provided a complete description. Approximately 5% of students defined physical dependence as addiction, and > 18% incorrectly attributed withdrawal symptoms to addiction. CONCLUSIONS: Significant knowledge gaps or misconceptions regarding terminology related to substance use disorder exists among first-year pharmacy students despite continuing efforts within professional organizations to develop consensus definitions. Developing effective teaching methods to identify and correct misinformation and preconceptions related to care for patients with substance use disorders should continue to be a priority for pharmacy educators.

nNOS immunoreactivity co-localizes with GABAergic and cholinergic neurons, and associates with ß-endorphinergic and met-enkephalinergic opioidergic fibers in rostral ventromedial medulla and A5 of the mouse.

The present study examined the co-expression of neuronal nitric oxide synthase (nNOS) in the rostral ventromedial medulla (RVM) and A5 regions of the mouse brainstem within several neurochemical populations involved in nociceptive modulation. Double immunohistochemical methods showed that nNOS+ neurons do not co-localize with serotonergic neurons within any of these regions. Within the RVM, the nuclei raphe magnus and gigantocellularis contain a population of nNOS+/GAD67+ neurons, and within the paragigantocellularis lateralis, there is a smaller population of nNOS+/CHAT+ neurons. Further, nNOS+ neurons overlap the region of expression of ß-endorphinergic and met-enkephalinergic fibers within the RVM. No co-labeling was found within the A5 for any of these populations. These findings suggest that pain-modulatory serotonergic neurons within the brainstem do not directly produce nitric oxide (NO). Rather, NO-producing neurons within the RVM belong to GABAergic and cholinergic cell populations, and are in a position to modulate or be modulated by local opioidergic neurons.

Role of spinal GABA receptors in the acute antinociceptive response of mice to hyperbaric oxygen.

New pain treatments are in demand due to the pervasive nature of pain conditions. Hyperbaric oxygen (HBO2) has shown potential in treating pain in both clinical and preclinical settings, although the mechanism of this effect is still unknown. The aim of this study was to investigate whether the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) is involved in HBO2-induced antinociception in the central nervous system (CNS). To accomplish this goal, pharmacological interactions between GABA drugs and HBO2 were investigated using the behavioral acetic acid abdominal constriction test. Western blotting was used to quantify protein changes that might occur as a result of the interactions. GABAA but not GABAB receptor antagonists dose-dependently reduced HBO2 antinociception, while antagonism of the GABA reuptake transporter enhanced this effect. Western blot results showed an interaction between the pain stimulus and HBO2 on expression of the phosphorylated ß3 subunit of the GABAA receptor at S408/409 in homogenates of the lumbar but not thoracic spinal cord. A significant interaction was also found in neuronal nitric oxide synthase (nNOS) expression in the lumbar but not thoracic spinal cord. These findings support the notion that GABA may be involved in HBO2-induced antinociception at the GABAA receptor but indicate that more study will be needed to understand the intricacies of this interaction.

Forecasting academic success through implementation of an online prerequisite review tutorials program for first year pharmacy students.

OBJECTIVE: Online prerequisite review (OPR) tutorials were designed and implemented to reinforce foundational scientific material in order to protect in-class time, foster self-directed learning, and ensure all students have similar baseline knowledge. METHODS: Twenty-one tutorials covering undergraduate prerequisite material were developed by faculty and organized into six core modules, comprising basic biology, chemistry, and physiology topics. A quiz on this material was given on the first day of each course. This score was correlated with the final exam score at course completion. Additional student and faculty feedback was collected through surveys. RESULTS: 2372 quiz-exam pairings were collected over three consecutive fall semesters. A one point increase in the quiz score was associated with a 3.6 point (95% confidence interval 3.1-4.0) higher exam score, as well as a greater probability of passing the exam (P<0.0001). Furthermore, simple linear regression revealed a positive correlation between quiz and exam scores (P<0.0001). Three full years of student survey data revealed an overwhelmingly positive perception of the OPR tutorials, and surveyed faculty reported better use of class time and improved student competency and participation. CONCLUSIONS: Implementation of OPR tutorials may give faculty more efficient use of class time, and their associated quizzes serve as an early indicator for students at-risk of not passing who are candidates for early interventions. Furthermore, the OPR tutorial design gives it great transferability to biomedical post-graduate programs.

Learning bridge: curricular integration of didactic and experiential education.

OBJECTIVES: To assess the impact of a program to integrate introductory pharmacy practice experiences with pharmaceutical science topics by promoting active learning, self-directed learning skills, and critical-thinking skills. DESIGN: The Learning Bridge, a curriculum program, was created to better integrate the material first-year (P1) students learned in pharmaceutical science courses into their introductory pharmacy practice experiences. Four Learning Bridge assignments required students to interact with their preceptors and answer questions relating to the pharmaceutical science material concurrently covered in their didactic courses. ASSESSMENT: Surveys of students and preceptors were conducted to measure the effectiveness of the Learning Bridge process. Feedback indicated the Learning Bridge promoted students' interaction with their preceptors as well as development of active learning, self-directed learning, and critical-thinking skills. Students also indicated that the Learning Bridge assignments increased their learning, knowledge of drug information, and comprehension of relevant data in package inserts. CONCLUSION: The Learning Bridge process integrated the didactic and experiential components of the curriculum, enhancing student learning in both areas, and offered students educational opportunities to interact more with their preceptors.

Peer-level patient presenters decrease pharmacy students' social distance from patients with schizophrenia and clinical depression.

OBJECTIVES: To create a doctor of pharmacy curricular experience that will decrease students' social barriers to interaction with and treatment of mentally-ill patients. DESIGN: We created a survey instrument to measure 4 aspects of students' conceptions of schizophrenia and clinical depression: (1) understanding of the medical nature of each disease, (2) understanding of patient behavior, (3) belief in the efficacy of treatment, and (4) social distance. We delivered this instrument before and after a neuropsychiatry curriculum including "peer-level patient presenters" in addition to the traditional first-year pharmacy curriculum. ASSESSMENT: Social-distance scores significantly decreased in first-year pharmacy students who attended peer-level patient presentations, indicating increased willingness to interact with persons with schizophrenia and clinical depression. In addition, students' understanding of the causes of illness, behavior of patients, and most importantly, efficacy of drug counseling for these diseases increased. CONCLUSIONS: Changes to the curriculum including the addition of peer-level patient presentations can quantitatively decrease pharmacy students' social barriers to the treatment of mentally-ill patients.

Electrophysiological heterogeneity of spinally projecting serotonergic and nonserotonergic neurons in the rostral ventromedial medulla.

This study examined the passive membrane and action potential properties of serotonergic and nonserotonergic neurons in the rostral ventromedial medulla (RVM) of the rat using whole cell patch-clamp recording techniques in the slice. Serotonergic neurons were identified by immunoreactivity for tryptophan hydroxylase (TrpH). Spinally projecting neurons were retrogradely labeled with 1'-dioactadecyl-3,3,3',3'-tetramethylindocarbodyanine perchlorate (DiI). Three types of neurons were identified within both spinally projecting serotonergic and nonserotonergic populations. Type 1 neurons exhibited irregular or sporadic spontaneous activity interspersed with periods of quiescence. Type 2 neurons were not spontaneously active and were additionally discriminated by a more negative resting membrane potential and a larger-amplitude action potential. Type 3 neurons fired repetitively without pause. Serotonergic neurons had a higher membrane resistance and greater action potential half-width than their nonserotonergic counterparts and rarely exhibited a fast afterhyperpolarization. Serotonergic type 3 neurons also fired more slowly and regularly than nonserotonergic type 3 neurons. Comparison of electrophysiological and immunohistochemical characteristics suggested that the smallest type 3 serotonergic neurons had an increased risk of immunohistochemical "misclassification" due to failure to detect TrpH, possibly due to more complete dialysis of intracellular contents during lengthy recordings. This risk was minimal for type 1 or 2 serotonergic neurons. The three different types of spinally projecting serotonergic neurons also differed markedly in their responsiveness to the mu opioid receptor agonist D-Ala2, NMePhe4, Gly5-ol]enkephalin. These results provide important new electrophysiological and pharmacological evidence for a significant heterogeneity among spinally projecting serotonergic RVM neurons. They may also provide a basis for resolving the controversy concerning the role of serotonergic RVM neurons in opioid analgesia.