Chemical Actions and Uses Commons^™

Chemical Restraints In The Emergency Department, Nicholas Noffsinger

Rowan-Virtua Research Day

Chemical restraint is a critical intervention used in emergency departments to manage acutely agitated or violent patients. It involves the administration of medication to induce sedation and control behavior, with the goal of ensuring patient and staff safety while allowing necessary medical interventions to be performed. However, the use of chemical restraints necessitates close observation of vital signs and any potential side effects, as well as careful consideration of patient-specific considerations.

Uplc-Ms/Ms Analysis Of The Michaelis-Menten Kinetics Of Cyp3a-Mediated Midazolam 1′- And 4-Hydroxylation In Rat Brain Microsomes, Devaraj Venkatapura Chandrashekar, Barent Dubois, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ) is a short-acting benzodiazepine with rapid onset of action, which is metabolized by CYP3A isoenzymes to two hydroxylated metabolites, 1′-hydroxymidazolam and 4-hydroxymidazolam. The drug is also commonly used as a marker of CYP3A activity in the liver microsomes. However, the kinetics of CYP3A-mediated hydroxylation of MDZ in the brain, which contains much lower CYP content than the liver, have not been reported. In this study, UPLC-MS/MS and metabolic incubation methods were developed and validated for simultaneous measurement of low concentrations of both hydroxylated metabolites of MDZ in brain microsomes. Different concentrations of MDZ (1–500 µM) were incubated with …

Measuring The Effects Of Lobinaline-N-Bioxide (419) On Alcohol Consumption, Nicotine Locomotor Sensitization, And Conditioned Place Preference In Mice And Rats, Cocanut M. Suhail

Theses and Dissertations--Medical Sciences

Objective: Novel drug 419 was examined to see the effect it has in vivo mice and rats on alcohol consumption, nicotine locomotor sensitization, and conditioned place preference (CPP) models regarding behavioral tests on dopamine transporter activity.

Methods: Mice and rats were used to see how they react to the drug 419 and control vehicle, in each of the models. The animals were assessed to pre- and post- drug administration of novel drug 419. We examined each model to see the association between how drug 419 will help with treating drug abuse.

Results: We found that in alcohol consumption model the …

Chlorhexidine Gluconate Vs Povidone-Iodine In The Prevention Of Clean-Contaminated Surgical Site Infections, Erin Layne, Abigail Stone

Physician Assistant Capstones, 2016 to 2019

Abstract

Background:

A patient’s skin is the major source of pathogens that can cause post-operative complications such as surgical site infections (SSIs). Optimization of pre-operative skin antisepsis is obtained with chlorhexidine gluconate (CG) and povidone-iodine (PI). These two solutions are the most widely used antiseptics for pre-operative purposes.

Objective:

Among surgical patients greater than 18 years of age undergoing clean-contaminated surgery, which antiseptic, iodophors or chlorhexidine gluconate, is more effective at reducing postoperative surgical site infections?

Methods:

A search was done in PubMed utilizing the terms chlorhexidine, infection control, iodophors, and surgical site infection. The limits applied included randomized …

A V-To-F Substitution In Sk2 Channels Causes Ca2+ Hypersensitivity And Improves Locomotion In A C. Elegans Als Model, Young-Woo Nam, Sabia N. Baskoylu, Dimitris Gazgalis, Razan Orfali, Meng Cui, Anne C. Hart, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca2+-activated K+ (SK) channels mediate medium afterhyperpolarization in the neurons and play a key role in the regulation of neuronal excitability. SK channels are potential drug targets for ataxia and Amyotrophic Lateral Sclerosis (ALS). SK channels are activated exclusively by the Ca2+-bound calmodulin. Previously, we identified an intrinsically disordered fragment that is essential for the mechanical coupling between Ca2+/calmodulin binding and channel opening. Here, we report that substitution of a valine to phenylalanine (V407F) in the intrinsically disordered fragment caused a ~6 fold increase in the Ca2+ sensitivity of SK2-a channels. This substitution resulted in a novel interaction between …

Tumor-Targeted Delivery Of Sirna Using Fatty Acyl-Cgkrk Peptide Conjugates, Meenakshi Sharma, Naglaa Salem El-Sayed, Hung Do, Keykavous Parang, Rakesh Tiwari, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Tumor-targeted carriers provide efficient delivery of chemotherapeutic agents to tumor tissue. CGKRK is one of the well-known tumor targeting peptides with significant specificity for angiogenic blood vessels and tumor cells. Here, we designed fatty acyl conjugated CGKRK peptides, based on the hypothesis that hydrophobically-modified CGKRK peptide could enhance cellular permeation and delivery of siRNA targeted to tumor cells for effective silencing of selected proteins. We synthesized six fatty acyl-peptide conjugates, using a diverse chain of saturated and unsaturated fatty acids to study the efficiency of this approach. At peptide:siRNA weight/weight ratio of 10:1 (N/P ≈ 13.6), almost all the peptides …

Antimicrobial Hydroxyapatite-Gelatin-Silica Composite Pastes With Tunable Setting Properties, Vuk Uskoković, Shreya Ghosh, Victoria M. Wu

Pharmacy Faculty Articles and Research

Bone grafting is one of the commonest surgical procedures, yet all bone substitutes developed so far suffer from specific weaknesses and the search for a bone graft material with ideal physical and biological properties is still ongoing. Calcium phosphate pastes are the most frequently used synthetic bone grafts, yet they (a) often take an impractically long time to set, (b) release the drug content too fast, and (c) do not form pores large enough to accommodate host cells and foster osseointegration. To make up for these deficiencies, we introduced gelatin and silica to pastes composed of 5–15 nm sized hydroxyapatite …

Synthesis And Evaluation Of Antimicrobial Activity Of [R4w4k]-Levofloxacin And [R4w4k]-Levofloxacin-Q Conjugates, Neda Riahifard, Kathy Tavakoli, Jason Yamaki, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

The development of a new class of antibiotics to fight bacterial resistance is a time-consuming effort associated with high-cost and commercial risks. Thus, modification, conjugation or combination of existing antibiotics to enhance their efficacy is a suitable strategy. We have previously reported that the amphiphilic cyclic peptide [R4W4] had antibacterial activity with a minimum inhibitory concentration (MIC) of 2.97 g/mL against Methicillin-resistant Staphylococcus aureus (MRSA). Herein, we hypothesized that conjugation or combination of the amphiphilic cyclic peptide [R4W4] with levofloxacin or levofloxacin-Q could improve the antibacterial activity of levofloxacin and levofloxacin-Q. Fmoc/tBu solid-phase chemistry was employed to synthesize conjugates of …

Structure Activity Relationship Studies Of Novel Diarylpentanoid Analogs Targeting The Androgen Receptor In Prostate Cancer Cells, Haili Coffin, Marco Bisoffi

Student Scholar Symposium Abstracts and Posters

The development of prostate cancer (PCa) relies strongly on the activation of the androgen receptor (AR) signaling pathway by its natural ligand dihydrotestosterone. Furthermore, PCa progression to metastatic disease represents oncogene addiction to AR activity. Androgen ablation therapy is thus a mainstay therapy against this disease, but the development of ligand-independent AR activation and persisting AR expression eventually leads to castration resistant PCa (CRPC). Therefore, down-regulation of AR expression in PCa cells may be an effective therapeutic modality. The diarylpentanoid ca27 has previously been shown to down-regulate AR expression by an unknown mechanism of action. The present work represents a …

Countercurrent Chromatography Fractions Of Plant Extracts With Anti-Tuberculosis Activity, Douglas Armstrong, Nathan C. Krause, Drew Frey, J. Brent Friesen, Baojie Wan, Jordan Gunn, Scott Franzblau

Faculty Scholarship – Chemistry

Samples of numerous plant species were received from the southwestern part of the USA, from Richard Spjut, and plant samples were collected here in Illinois. All were extracted with typical solvents, giving crude residues, some of which were subjected to chromatographic methods. Some of the crude residues and some of the fractions were tested for anti-tuberculosis activity and/or antibacterial activity.

In a general way, bioactive natural products are dealt with very well by Liang & Fang. More specifically, the southwestern part of the United States has a large variety of indigenous plants many of which have not been investigated for …

Inhibition Of Human Α7 Nicotinic Acetylcholine Receptors By Cyclic Monoterpene Carveol, Yusra Lozon, Ahmed Sultan, Stuart J. Lansdell, Tatiana Prytkova, Bassem Sadek, Keun-Hang Susan Yang, Frank Christopher Howarth, Neil S. Millar, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Cyclic monoterpenes are a group of phytochemicals with antinociceptive, local anesthetic, and anti-inflammatory actions. Effects of cyclic monoterpenes including vanilin, pulegone, eugenole, carvone, carvacrol, carveol, thymol, thymoquinone, menthone, and limonene were investigated on the functional properties of the cloned α₇ subunit of the human nicotinic acetylcholine receptor expressed in Xenopus oocytes. Monoterpenes inhibited the α₇ nicotinic acetylcholine receptor in the order carveol>thymoquinone>carvacrol>menthone>thymol>limonene>eugenole>pulegone≥carvone≥vanilin. Among the monoterpenes, carveol showed the highest potency on acetylcholine-induced responses, with IC₅₀ of 8.3 µM. Carveol-induced inhibition was independent of the membrane potential and could not be …

Development Of A Chemical Genetic Screen To Determine Synergistic Compounds With Laromustine In Treating Glioblastoma Multiforme Cultured Cells, Ryan Weeks

Honors Theses

Laromustine is a chemotherapeutic sulfonylhydrazine prodrug used in clinical trials to treat acute myeloid leukemia (AML) and glioblastoma multiforme (GBM). While treatment of AML with laromustine has more demonstrative clinical success, there are enough promising data against GBM to pursue additional pre-clinical and clinical experiments. To determine the synergistic effects caused by treating cultured GBM cells with laromustine and a library of FDA-approved compounds, a chemical genetic screen was developed. To optimize the screen, optimal cultured GBM cell seed density, growth period and maximum well capacity were determined. The treatment period for a lethal dose of laromustine in cultured GBM …

Dynamic Modeling Of Nonmedical Opioid Initiation: Epidemic And Access, Alexandra Nielsen, Teresa D. Schmidt, Dennis Mccarty, Wayne W. Wakeland

Systems Science Faculty Publications and Presentations

We report development of a systems level dynamic model of initiation and nonmedical use of pharmaceutical opioids in the US. The model calibrated to 1995-2005 National Survey of Drug Use and Health (NSDUH) data, predicts 2006-2011 data well. Preliminary findings indicate that interventions which reduce the perceived attractiveness of opioids for recreational use may be able to reduce initiation and nonmedical use most significantly, while supply restriction effected through drug take back days and prescribing changes may have more modest effects. We argue that system dynamics is an effective approach for evaluating potential interventions to this complex system where the …

Data On The Diversion, Nonmedical Use And Adverse Outcomes Associated With Pharmaceutical Opioids, Amanuel Zimam, Teresa D. Schmidt, Alexandra Nielsen, Wayne W. Wakeland

Systems Science Faculty Publications and Presentations

Background: Recent increases in the nonmedical use of pharmaceutical opioids and the adverse outcomes associated with them have stimulated a large amount of research and data collection on this public health problem. Systematic organization of the available data sources is needed to facilitate ongoing research, analysis, and evaluation.

Method: A list of keywords associated with diversion, nonmedical use, and adverse outcomes of pharmaceutical opioid use generated 94 peer-reviewed academic articles and a number of governmental and nongovernmental sources. All sources were in English, contained quantitative data, and were published between January 1995 and April 2012. A list of 20 topics …

System Dynamics Modeling Of Medical Use, Nonmedical Use And Diversion Of Prescription Opioid Analgesics, Wayne W. Wakeland, Teresa D. Schmidt, J. David Haddox

Wayne W. Wakeland

A dramatic rise in the nonmedical of pharmaceutical opioids has presented the United States with a substantial public health problem. Nonmedical use of prescription pain relievers has become increasingly prevalent in the US over the last two decades, and diversion of medicines obtained by prescription is assumed to be a major source of supply for nonmedical opioid use. Policymakers striving to protect population health by ameliorating the adverse outcomes of nonmedical use of opioid analgesics could benefit from a systems-level model which reflects the complexity of the system and incorporates the full range of available data. To address this need, …

System Dynamics Modeling Of Medical Use, Nonmedical Use And Diversion Of Prescription Opioid Analgesics, Wayne Wakeland, Alexandra Nielsen, Teresa D. Schmidt

Systems Science Faculty Publications and Presentations

The objective of the study was to develop a system dynamics model of the medical use of pharmaceutical opioids to treat pain, and the associated diversion and nonmedical use of these drugs. The model was used to test the impact of simulated interventions in this complex system. The study relied on secondary data obtained from the literature and from other public sources for the period 1995 to 2008. In addition, an expert panel provided recommendations regarding model parameters and model structure. The behavior of the resulting systems level model compared favorably with reference behavior data (R2=.95). After the base model …

Key Data Gaps For Understanding Trends In Prescription Opioid Analgesic Abuse And Diversion Among Chronic Pain Patients And Nonmedical Users, Wayne W. Wakeland, John Fitzgerald, Aaron Gilson, J. David Haddox, Jack Homer, Lewis Lee, Louis Macovsky, Dennis Mccarty, Teresa D. Schmidt, Lynn Webster

Systems Science Faculty Publications and Presentations

Population dynamics of medical and nonmedical prescription opioid usage and adverse outcomes were modeled. Critical parameter values were determined by their amount of influence on model behavior. Results suggest that closing these data gaps would help researchers to better identify ways to reduce the risk of adverse outcomes.