Automated Dispensing Cabinet Overrides-An Evaluation of Necessity in a Pediatric Emergency Department.

OBJECTIVE: Automated dispensing cabinets, or ADCs, are often used at health care facilities to aid in the medication-use process. Although ADCs minimize certain medication errors, they introduce a new type of error involving overrides. Although helpful when used appropriately in emergencies, overrides bypass pharmacist verification and increase potential for patient harm through drug-drug interactions, medication allergies, inappropriate dosing, and more. The purpose of this study was to evaluate automated dispensing cabinets override pulls in a pediatric hospital's emergency department. The authors sought to discover whether overridden medications were being administered before verification (indicating it was needed emergently, thus justifying override) or after verification (indicating the override did not result in quicker administration and/or the medication was not emergent). METHODS: This was a retrospective, observational study. Data were collected from electronic health record reports from a 343-bed pediatric hospital's emergency department from October 13, 2019, to December 22, 2019. RESULTS: A total of 445 override pulls were identified during this time, and after data analysis, 99 override pulls remained in the data set. Overall, time from input of prescription into the electronic medical record to medication override was approximately 4 minutes. Pharmacist verification also took a median of four minutes after prescription input. However, administration took twice as long, at 8 minutes. On average, pharmacist verification occurred 4 minutes before medication administration. CONCLUSION: This research from a pediatric emergency department suggests that most situations did not require an immediate administration, and perhaps an override was unnecessary and could have been avoided.

Arginyl aminopeptidase-like 1 (RNPEPL1) is an alternatively processed aminopeptidase with specificity for methionine, glutamine, and citrulline residues.

A previously uncharacterized member of the M1 family of zinc metallopeptidases, arginyl aminopeptidase-like 1 (RNPEPL1; EC 3.4.11.1), was cloned and expressed, and the recombinant enzyme characterized. RNPEPL1 was a broad specificity aminopeptidase with preference for a P1 methionine, glutamine, or citrulline residue, and exhibited a broad pH preference, with maximal activity observed between pH 6.6 and 8.0. The enzyme was inhibited by calcium ions but unaffected by chloride ions, and was insensitive to specific inhibitors of the closely-related arginyl aminopeptidase, indicating similarity to leukotriene A(4) hydrolase. RT-PCR analysis of RNPEPL1 expression revealed a ubiquitous tissue distribution, consistent with a general housekeeping function, but also revealed alternative splicing of the mRNA in all tissues examined. The inclusion of intron 5 was predicted to result in a truncated protein product, while an alternative 3' splice site of exon 9 of the reference sequence was predicted to result in the omission of a conserved eleven amino acid stretch from the C-terminal domain.

Gedunin, a novel hsp90 inhibitor: semisynthesis of derivatives and preliminary structure-activity relationships.

Gedunin (1), a tetranortriterpenoid isolated from the Indian neem tree ( Azadirachta indica), was recently shown to manifest anticancer activity via inhibition of the 90 kDa heat shock protein (Hsp90) folding machinery and to induce the degradation of Hsp90-dependent client proteins similar to other Hsp90 inhibitors. The mechanism of action by which gedunin induces client protein degradation remains undetermined, however, prior studies have demonstrated that it does not bind competitively versus ATP. In an effort to further probe the mechanism of action, 19 semisynthetic derivatives of gedunin were prepared and their antiproliferative activity against MCF-7 and SkBr3 breast cancer cells determined. Although no compound was found to exhibit antiproliferative activity more effective than the natural product, functionalities critical for antiproliferative activity have been identified.

Pharmacokinetics of the plant-derived kappa-opioid hallucinogen salvinorin A in nonhuman primates.

Salvinorin A, a potent hallucinogen isolated from the leaves of Salvia divinorum, has gained popularity among adolescents in the USA. No detailed study of the pharmacokinetics has been conducted in vivo. The present study investigates the in vivo pharmacokinetics of salvinorin A (0.032 mg/kg, i.v. bolus) in rhesus monkeys (n=4, 2 male, 2 female). The elimination t(1/2) was rapid (56.6+/-24.8 min) for all subjects. Pharmacokinetic differences (distribution t(1/2), elimination t(1/2), and AUC) were observed between males and females, suggesting potential sex differences in its pharmacologic effects. Salvinorin B, the presumed major metabolite, is observed to accumulate ex vivo; however, in this study it never reached the limit of detection.