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Full-Text Articles in Medicine and Health Sciences
Studies Toward The Development Of An Improved Countermeasure For Synthetic Opioid Overdose, Sidnee L. Hedrick
Studies Toward The Development Of An Improved Countermeasure For Synthetic Opioid Overdose, Sidnee L. Hedrick
Theses and Dissertations--Pharmacy
One of the most prominent opioid analgesics in the United States is the high potency agonist fentanyl. It is used in the treatment of acute and chronic pain and as an anesthetic adjuvant. When used inappropriately, however, ingestion of just a few milligrams of fentanyl or other synthetic opioid can cause opioid-induced respiratory depression (OIRD), often leading to death. Currently, the treatment of choice for OIRD is the opioid receptor antagonist naloxone. Recent reports, however, suggest that higher doses or repeated dosing of naloxone (due to recurrence of respiratory depression) may be required to fully reverse fentanyl-induced respiratory depression, rendering …
Serotonin Syndrome And/Or Opioid Withdrawal After The First Dose Of Naltrexone Hcl/Bupropion Hcl: An Observational Study, Stefanie J. Logothetis
Serotonin Syndrome And/Or Opioid Withdrawal After The First Dose Of Naltrexone Hcl/Bupropion Hcl: An Observational Study, Stefanie J. Logothetis
Pharmaceutical Sciences ETDs
In 2014, the Food and Drug Administration approved naltrexone HCl/bupropion HCl, a combination of an antidepressant and an opioid antagonist for chronic weight management therapy. Concurrent use of antidepressants and opioids has the potential to cause drug interactions involving serotonin syndrome. Our primary objective is to identify cases of serotonin syndrome and/or opioid withdrawal after initiation of naltrexone HCl/bupropion HCl. Our secondary objective is to assess which specific opioids are more likely to cause a drug interaction with naltrexone HCl/bupropion HCl. We performed an observational study by reviewing cases in the RADARS® database from January 2014 through December 2018. …
Design, Synthesis And Pharmacological Characterization Of Potential Mu Opioid Receptor Selective Ligands, Abhishek S. Kulkarni
Design, Synthesis And Pharmacological Characterization Of Potential Mu Opioid Receptor Selective Ligands, Abhishek S. Kulkarni
Theses and Dissertations
Selective Mu Opioid Receptor (MOR) antagonists possess immense potential in the treatment of opioid abuse/addiction. Utilizing the “message-address” concept, our laboratory reported a novel, reversible, non-peptide MOR selective antagonist 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4՛-pyridyl)carboxamido]morphinan (NAP). Molecular modeling studies revealed that the selectivity of NAP for the MOR is because of a π-π stacking interaction of its pyridine ring with the Trp318residue in theMOR. Pharmacological characterization showed that NAP is a P-glycoprotein substrate, thereby limiting its use in the treatment of opioid abuse/addiction. Thus, to modify NAP, we replaced the pyridine ring with its isosteric counterpart thiophene. Isosteric replacement …
Design, Synthesis, And Biological Screening Of Selective Mu Opioid Receptor Ligands As Potential Treatments For Opioid Addiction, Samuel Obeng
Theses and Dissertations
Today, more Americans die each year because of drug overdoses than are killed in motor vehicle accidents. In fact, in 2015, more than 33,000 individuals died due to an overdose of heroin or prescription opioids. Sadly, 40-60 % of patients on current opioid addiction treatment medications relapse. Studies have shown that the addiction/abuse liability of opioids are abolished in mu opioid receptor (MOR) knock-out mice; this indicates that the addiction and abuse liability of opioids are mainly mediated through MOR. Utilizing the “message-address concept”, the our laboratory reported a novel non-peptide, reversible MOR selective ligand 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α (isoquinoline-3-carboxamido)morphinan (NAQ). Molecular modeling …
Formulation Optimization For Pore Lifetime Enhancement And Sustained Drug Delivery Across Microneedle Treated Skin, Priyanka Ghosh
Formulation Optimization For Pore Lifetime Enhancement And Sustained Drug Delivery Across Microneedle Treated Skin, Priyanka Ghosh
Theses and Dissertations--Pharmacy
Microneedle (MN) enhanced drug delivery is a safe, effective and efficient enhancement method for delivery of drug molecules across the skin. The “poke (press) and patch” approach employs solid stainless steel MN to permeablize the skin prior to application of a regular drug patch over the treated area. It has been previously shown that MN can be used to deliver naltrexone (NTX) at a rate that provides plasma concentrations in the lower end of the therapeutic range in humans. The drug delivery potential of this technique is, however, limited by the re-sealing of the micropores in a 48-72h timeframe. The …
Clinical Evaluation Of Novel Methods For Extending Microneedle Pore Lifetime, Nicole K. Brogden
Clinical Evaluation Of Novel Methods For Extending Microneedle Pore Lifetime, Nicole K. Brogden
Theses and Dissertations--Pharmacy
Microneedles are a minimally invasive method for delivering drugs through the impermeable skin layers, and have been used to deliver a variety of compounds including macromolecules, vaccines, and naltrexone. Microneedles can be applied to the skin once, creating micropores that allow for drug delivery into the underlying circulation from a drug formulation. The utility of this technique, however, is blunted by rapid micropore closure. This research project sought to: 1) characterize micropore lifetime and re-sealing kinetics, and 2) prolong micropore lifetime via inhibition of the skin’s barrier restoration processes. Impedance spectroscopy was used as a surrogate technique in animals and …
Microneedle-Assisted Transdermal Delivery Of Naltrexone Species: In Vitro Permeation And In Vivo Pharmacokinetic Studies, Mikolaj Milewski
Microneedle-Assisted Transdermal Delivery Of Naltrexone Species: In Vitro Permeation And In Vivo Pharmacokinetic Studies, Mikolaj Milewski
University of Kentucky Doctoral Dissertations
Naltrexone (NTX) is a drug used primarily in the management of alcohol dependence and opioid dependence. Based on several drawbacks associated with the oral and injectable intramuscular dosage forms of naltrexone currently available on the market, there is substantial interest in delivering naltrexone transdermally. Although naltrexone does not permeate skin at the rate sufficient to reach therapeutic plasma concentrations in humans, novel flux enhancement methods such as microneedles help address this challenge. Earlier work in humans has demonstrated that the use of microneedles achieves plasma concentrations in the lower end of expected therapeutic values. Further flux enhancement is desired to …