Browsing by Author "Kaye, Alan D."

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    Intravenous Lidocaine Infusion for the Management of Early Postoperative Pain: A Comprehensive Review of Controlled Trials
    (MedWorks Media, 2020-10-15) Chu, Robert; Umukoro, Nelly; Greer, Tiashi; Roberts, Jacob; Adekoya, Peju; Odonkor, Charles A.; Hagedorn, Jonathan M.; Olatoye, Dare; Urits, Ivan; Orhurhu, Mariam Salisu; Umukoro, Peter; Viswanath, Omar; Hasoon, Jamal; Kaye, Alan D.; Orhurhu, Vwaire; Medicine, School of Medicine
    Previously used as anti-arrhythmic, intravenous lidocaine infusion is becoming popular for use in management of acute pain. There is still much to be understood about its pharmacokinetics and pharmacodynamics, especially with regard to optimal dosing to avoid side effects. In this article, we selected and reviewed randomized controlled trials to summarize the pharmacokinetics, antinociceptive effects, anti-hyperalgesic effects, anti-inflammatory effects, side effects, and role of intravenous lidocaine in the management of early postoperative pain. The mechanisms of action of lidocaine are still unclear but there are many theories postulated. Optimal dosing of lidocaine is not known but general consensus indicates that a loading dose of 1-2 mg/kg, followed by 1-2 mg/kg/hr continuous infusion during early postoperative pain control while recovering from anesthesia to achieve therapeutic levels of 0.5-5 mcg/kg clearly improves analgesia in the immediate postoperative period. Although lidocaine was initially studied and proven to have clear analgesic effects following laparoscopic and open abdominal surgeries, it has now been shown to be applicable in different clinical settings perioperatively including following spinal, breast, ENT and other surgeries. It is generally safe, with hypotension, headache and vomiting being the more common side effects. Serious adverse effects include cardiovascular block and arrhythmias, neuro-excitability and hypersensitivity, although the frequency of these are not known.
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    Tacrolimus- and Mycophenolate-Mediated Toxicity: Clinical Considerations and Options in Management of Post-Transplant Patients
    (MDPI, 2024-12-24) Kaye, Alan D.; Shah, Shivam S.; Johnson, Coplen D.; De Witt, Adalyn S.; Thomassen, Austin S.; Daniel, Charles P.; Ahmadzadeh, Shahab; Tirumala, Sridhar; Bembenick, Kristin Nicole; Kaye, Adam M.; Shekoohi, Sahar; Medicine, School of Medicine
    Tacrolimus and mycophenolate are important immunosuppressive agents used to prevent organ rejection in post-transplant patients. While highly effective, their use is associated with significant toxicity, requiring careful management. Tacrolimus, a calcineurin inhibitor, is linked to nephrotoxicity, neurotoxicity, metabolic disturbances such as diabetes mellitus and dyslipidemia, and cardiovascular complications such as hypertension and arrhythmias. Mycophenolate, a reversible inhibitor of inosine monophosphate dehydrogenase, frequently causes gastrointestinal disturbances, including diarrhea and colitis, as well as hematologic side effects like anemia and leukopenia, which increase infection risk. Therapeutic drug monitoring (TDM) and pharmacogenomics have emerged as essential strategies for mitigating these toxicities. TDM ensures tacrolimus trough levels are maintained within a therapeutic range, minimizing the risks of nephrotoxicity and rejection. Pharmacogenomic insights, such as CYP3A5 polymorphisms, allow for personalized tacrolimus dosing based on individual metabolic profiles. For mycophenolate, monitoring inosine monophosphate dehydrogenase activity provides a pharmacodynamic approach to dose optimization, reducing gastrointestinal and hematologic toxicities. Emerging tools, including dried blood spot sampling and pharmacokinetic modeling, offer innovative methods to simplify monitoring and enhance precision in outpatient settings. Despite their utility, the toxicity profiles of these drugs, including those of early immunosuppressants such as cyclosporine and azathioprine, necessitate further consideration of alternative immunosuppressants like sirolimus, everolimus, and belatacept. Although promising, these newer agents require careful patient selection and further research. Future directions in immunosuppressive therapy include integrating individual pharmacogenetic data to refine dosing, minimize side effects, and improve long-term graft outcomes. This narrative review underscores the importance of personalized medicine and advanced monitoring in optimizing post-transplant care.
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    Xylazine: A Drug Adulterant of Clinical Concern
    (Springer, 2024) Edinoff, Amber N.; Sall, Saveen; Upshaw, William C.; Spillers, Noah J.; Vincik, LeighAnn Y.; De Witt, Adalyn S.; Murnane, Kevin S.; Kaye, Adam M.; Kaye, Alan D.; Medicine, School of Medicine
    Purpose of review: The opioid epidemic has been responsible for significant morbidity and mortality in the USA and worldwide. As a result, it is essential to recognize the threat these potent drugs can cause when illicitly used. Specifically, introducing fentanyl as a drug adulterant has been shown to impact overdose rates drastically. In this regard, the Drug Enforcement Agency recently released a public safety alert announcing the new threat of a new adulterant called xylazine. Xylazine is a powerful animal sedative with a different mechanism of action when compared to illicit opioids such as heroin and fentanyl. Xylazine is typically injected intravenously via a syringe, often in combination with multiple other drugs. One of the most common drugs, xylazine, is taken in combination with fentanyl, with users of this drug combination describing xylazine as prolonging the euphoric sensation produced by fentanyl. Recent findings: Xylazine may cause adverse effects such as bradycardia, brief hypertension followed by hypotension, premature ventricular contractions, ataxia, slurred speech, sedation, and respiratory depression. Much of the recent literature on xylazine use in humans comes from case reports and review articles. Related to widespread use in veterinary medicine and increasing circulation in illicit drug markets, there is a critical need for public awareness and additional clinical-based studies to further increase understanding of mediated or modulated pharmacological effects of xylazine in humans. Further research is urgently needed to more clearly understand the implications of unregulated xylazine in the illicit drug market, to formulate public health interventions, and to implement harm reduction strategies.