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Perfusion Mar 2023Procainamide is a useful agent for management of ventricular arrhythmia, however its disposition and appropriate dosing during extracorporeal membrane oxygenation (ECMO)...
Procainamide is a useful agent for management of ventricular arrhythmia, however its disposition and appropriate dosing during extracorporeal membrane oxygenation (ECMO) is unknown. We report experience with continuous procainamide infusion in a critically ill adult requiring venoarterial ECMO for incessant ventricular tachycardia. Pharmacokinetic analysis of procainamide and its metabolite, N-acetylprocainamide (NAPA), was performed using serum and urine specimens. Kidney function was preserved, and sequencing of the N-acetyltransferase 2 gene revealed the patient was a phenotypic slow acetylator. Procainamide volume of distribution and half-life were calculated and found to be similar to healthy individuals. However, despite elevated serum procainamide concentrations, NAPA concentrations remained far lower in the serum and urine. The magnitude of procainamide and NAPA discordance suggested alternative contributors to the deranged pharmacokinetic profile, and we hypothesized NAPA sequestration by the ECMO circuit. Ultimately, the patient received orthotopic cardiac transplantation and was discharged home in stable condition. Procainamide should be used cautiously during ECMO, with close therapeutic drug monitoring of serum procainamide and NAPA concentrations. The achievement of therapeutic NAPA concentrations while maintaining safe serum procainamide concentrations during ECMO support may be challenging.
Topics: Adult; Humans; Procainamide; Extracorporeal Membrane Oxygenation; Acecainide; Arrhythmias, Cardiac; Tachycardia, Ventricular
PubMed: 34617854
DOI: 10.1177/02676591211050606 -
American Journal of Translational... 2021Intersubject variability in drug response, whether related to efficacy or toxicity, is well recognized clinically. Over the years, drug selection from our pharmacologic... (Review)
Review
Intersubject variability in drug response, whether related to efficacy or toxicity, is well recognized clinically. Over the years, drug selection from our pharmacologic armamentarium has moved from providers' preferred choices to more personalized treatments as clinicians' decisions are guided by data from clinical trials. Since the advent of more accessible and affordable pharmacogenomic (PGx) testing, the promise of precise pharmacotherapy has been made. Results have accumulated in the literature with numerous examples demonstrating the value of PGx to improve drug response or prevent drug toxicity. Unfortunately, limited availability of reimbursement policies has dampened the enthusiasm of providers and organizations. The clinical application of PGx knowledge remains difficult for most clinicians under real-world conditions in patients with numerous chronic conditions and polypharmacy. This may be due to phenoconversion, a condition where there is a discrepancy between the genotype-predicted phenotype and the observed phenotype. This condition complicates the interpretation of PGx results and may lead to inappropriate recommendations and clinical decision making. For this reason, regulatory agencies have limited the transfer of information from PGx laboratories directly to consumers, especially recommendations about the use of certain drugs. This mini-review presents cases (mexiletine, propafenone, clopidogrel, warfarin, codeine, procainamide) from historical observations where drug response was modified by phenoconversion. The cases illustrate, from decades ago, that we are still in great need of advanced clinical decision systems that cope with conditions associated with phenoconversion, especially in patients with polypharmacy.
PubMed: 35035679
DOI: No ID Found -
Methods in Molecular Biology (Clifton,... 2022Glycan profiling is a common strategy that is used to determine the distribution of N-linked glycans, O-linked glycans and glycolipid associated complex carbohydrate...
Glycan profiling is a common strategy that is used to determine the distribution of N-linked glycans, O-linked glycans and glycolipid associated complex carbohydrate structures that are part of various cell and tissue sources. Such data are central to our understanding of functional glycomics, and this knowledge can also be used for pathway construction and other applications in the field of Systems Glycobiology. Glycans released from cell/tissue samples are often studied in their free-form. They can also be functionalized with aglycones like 2-aminobenzamide (2AB) and procainamide to enhance separation and improve ionization during liquid chromatography/mass spectrometry. Additionally, these released glycans may be permethylated in order to improve glycan quantitation. In such work, besides studying the glycans in a single sample, there is also interest in comparing multiple samples in order to determine underlying similarities and differences, for example in terms of specific epitopes that are changed when cells of the same origin differentiate along different pathways. The current chapter describes the development and usage of cGlyco ("comparative Glycomics"), an open-source program that can be used to compare data from multiple mass spectrometry runs. As an example, we apply cGlyco to compare the glycan profile of multiple MALDI-TOF glycomics profiling data collected by core-C of the Consortium for Functional Glycomics (CFG).
Topics: Chromatography, Liquid; Glycomics; Glycoproteins; Polysaccharides; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 34611866
DOI: 10.1007/978-1-0716-1685-7_5 -
Annals of Pediatric Cardiology 2021Junctional ectopic tachycardia (JET) is more common in its postoperative form. A thorough understanding of its etiology, pathophysiology, and management strategies is... (Review)
Review
Junctional ectopic tachycardia (JET) is more common in its postoperative form. A thorough understanding of its etiology, pathophysiology, and management strategies is essential. Classically, postoperative JET is considered to arise from surgical trauma. Genetic susceptibility and an intrinsic morphologic/functional defect in the conduction system inherent in congenital heart diseases likely play a significant role. The devastating effects on postoperative hemodynamics warrant prompt attention. A multipronged management approach with general measures, pharmacotherapy, and pacing has decreased morbidity and mortality. Amiodarone and procainamide remain the preferred drugs, while ivabradine appears promising. Carefully planned randomized trials can go a long way in developing a systematic management protocol for postoperative JET.
PubMed: 34667411
DOI: 10.4103/apc.apc_35_21 -
Analytical Biochemistry Jun 2022Sialylated and core-fucosylated N-glycans in human transferrin (HTF) are used as glycan biomarkers due to their increased or decreased characteristics in certain...
Sialylated and core-fucosylated N-glycans in human transferrin (HTF) are used as glycan biomarkers due to their increased or decreased characteristics in certain diseases. However, their absolute quantities remain unclear. In this study, N-glycans of HTF were identified by UPLC and LC-MS/MS using fluorescence tags [2-aminobenzamide (AB) and procainamide (ProA)] and columns [HILIC and anion exchange chromatography-HILIC (AXH)]. The structures of 14 (including five core-fucosylated) N-glycans in total comprising two non-, six mono-, four di-, and two tri-sialylated N-glycans were identified. The quantities (%) of each N-glycan relative to the total N-glycans (100%) were obtained. HILIC and AXH were better for peak identification and separability except for desialylation, respectively. Specifically, sialylated (in ProA-HILIC and ProA-AXH by UPLC or LC-MS/MS) and core-fucosylated (in AB-HILIC and ProA-AXH by UPLC) N-glycans were efficiently identified. Seven neuraminidase-treated (including three core-fucosylated) N-glycans were efficiently identified in ProA-AXH, even their poor separation. Additionally, ProA-AXH was more efficient for the estimation of the absolute quantities of N-glycans from the results of fluorescence intensity (by UPLC) and relative quantity (by LC-MS/MS). These results first demonstrate that ProA is useful for identifying and quantifying sialylated, core-fucosylated, and neuraminidase-treated desialylated N-glycans in HTF using AXH by UPLC and LC/MS.
Topics: Chromatography, Liquid; Humans; Neuraminidase; Polysaccharides; Tandem Mass Spectrometry; Transferrin
PubMed: 35331694
DOI: 10.1016/j.ab.2022.114650