Regulating gabapentin as a drug of abuse: A survey study of Kentucky community pharmacists.

OBJECTIVES: As the number of gabapentin prescriptions has increased, so have reports of its misuse and diversion. This trend has led some states to closer monitoring of gabapentin dispensing through prescription drug monitoring programs (PDMPs). The objective of this study was to collect and analyze Kentucky community pharmacists' perceptions of gabapentin misuse and diversion, and their support or opposition to regulatory efforts to reclassify the drug as a controlled substance (CS). METHODS: Responses were collected using an online survey sent by e-mail to all pharmacists practicing in Kentucky in August 2016. The survey collected basic demographic characteristics and pharmacists' experience with gabapentin dispensing. Descriptive statistics were calculated using question response frequencies. Pearson's chi-squared statistics were calculated to examine the distribution of support for gabapentin as a CS in Kentucky across each of the categories of the individual variables. Logistic regression was used to estimate the effects of pharmacist demographic characteristics and experiences with gabapentin on their support of gabapentin reclassification as a CS. RESULTS: One thousand seven hundred sixty-nine surveys were collected (response rate = 34.2%). Responding community pharmacists (n = 1084) believe that the abuse and diversion of gabapentin are a problem in their communities, with 9 in 10 (89.6%) indicating that they agree or strongly agree. More than three-fourths (87.5%) indicated support for reclassifying gabapentin as a CS. Common reasons for opposition to gabapentin regulatory changes were that they would not reduce or eliminate abuse (45.8%) and that they would be an inconvenience to patients (17.0%). Pharmacists practicing in independent pharmacies and pharmacists in practice greater than 20 years were less likely to indicate support for gabapentin reclassification. CONCLUSION: Kentucky community pharmacists express considerable concern over the possible misuse and diversion of gabapentin and widely support regulatory changes reclassifying gabapentin as a CS.

Pharmacists' role in opioid overdose: Kentucky pharmacists' willingness to participate in naloxone dispensing.

OBJECTIVES: To assess pharmacists' willingness to initiate the dispensing of naloxone. As of 2015, Kentucky law permits certified pharmacists to dispense naloxone under a physician-approved protocol. DESIGN: Electronic survey (e-mail) gauging perception of pharmacists' role in opioid overdose and attitudes toward, and barriers to, naloxone dispensing. SETTING AND PARTICIPANTS: All Kentucky pharmacists with active licenses in 2015. MAIN OUTCOME MEASURES: Ordinal logistic regression was used to estimate the impact of pharmacist characteristics and attitudes on willingness to initiate naloxone dispensing, where the dependent variable was operationalized as a Likert-type question on a scale of 1 (not at all willing) to 6 (very willing). RESULTS: Of 4699 practicing Kentucky pharmacists, 1282 responded, of which 834 were community practitioners (response rate 27.3%). Pharmacists reported varying willingness to initiate naloxone dispensing, with 37.3% very willing (score 5 or 6) and 27.9% not willing (score 1 or 2). However, a majority of pharmacists reported willingness to dispense naloxone with a valid prescription (54.0%, score 5 or 6). Women pharmacists were 1.3 times more likely than men to be willing to initiate naloxone dispensing (95% confidence interval [CI] 1.0-1.6). Those who reported confidence in identifying individuals at risk for overdose were 1.2 times more likely to initiate dispensing, and those who reported confidence in ability to educate patients about overdose were 1.6 times more likely to express willingness to initiate naloxone dispensing (95% CIs, respectively, 1.0-1.3 and 1.4-1.8). Community pharmacists reported barriers to naloxone access at higher rates than pharmacists from other practice settings. CONCLUSION: Kentucky pharmacists are divided in their willingness to initiate naloxone dispensing; however, those who are confident in their ability to identify overdose risks are more willing. Increasing pharmacist confidence through appropriately designed education programs could facilitate pharmacist participation in naloxone dispensing.

Temperature-sensitive mutant in the vaccinia virus E6 protein produce virions that are transcriptionally inactive.

The vaccinia virus E6R gene encodes a late protein that is packaged into virion cores. A temperature-sensitive mutant was used to study the role of this protein in viral replicative cycle. Cts52 has a P226L missense mutation in the E6R gene, shows a two-log reduction in plaque formation, but displays normal patterns of gene expression, late protein processing and DNA replication during infection. Mutant virions produced at 40 degrees C were similar in their morphology to wt virions grown at 40 degrees C. The particle to infectivity ratio was 50 times higher in purified Cts52 grown at 40 degrees C when compared to the mutant grown at permissive temperature. In vitro characterization of Cts-52 particles grown at 40 degrees C revealed no differences in protein composition or in DNA content and the mutant virions could bind and enter cells. However, core particles prepared from Cts52 grown at 40 degrees C failed to transcribe in vitro. Our results show that E6 in the virion has either a direct or an indirect role in viral transcription.

Marker rescue mapping of the combined Condit/Dales collection of temperature-sensitive vaccinia virus mutants.

Complementation analysis of the combined Condit/Dales collection of vaccinia virus temperature-sensitive mutants has been reported (Lackner, C.A., D'Costa, S.M., Buck, C., Condit, R.C., 2003. Complementation analysis of the Dales collection of vaccinia virus temperature-sensitive mutants. Virology 305, 240-259), however not all complementation groups have previously been assigned to single genes on the viral genome. We have used marker rescue to map at least one representative of each complementation group to a unique viral gene. The final combined collection contains 124 temperature-sensitive mutants affecting 38 viral genes, plus five double mutants.

Temperature-sensitive mutants in the vaccinia virus 4b virion structural protein assemble malformed, transcriptionally inactive intracellular mature virions.

Two noncomplementing vaccinia virus temperature-sensitive mutants, Cts8 and Cts26, were mapped to the A3L gene, which encodes the major virion structural protein, 4b. The two ts mutants display normal patterns of gene expression, DNA replication, telomere resolution, and protein processing during infection. Morphogenesis during mutant infections is normal through formation of immature virions with nucleoids (IVN) but appears to be defective in the transition from IVN to intracellular mature virus (IMV). In mutant infections, aberrant particles that have the appearance of malformed IMV accumulate. The mutant particles are wrapped in Golgi-derived membranes and exported from cells. Purified mutant particles are indistinguishable from wt particles in protein and DNA composition; however, they are defective in a permeabilized-virion-directed transcription reaction despite containing significant (Cts8) or even normal (Cts26) levels of specific transcription enzymes. These results indicate that the 4b protein is required for proper metamorphosis of IMV from IVN and that proper organization of the IMV structure is required to produce a transcriptionally active virion particle.