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Journal of Chromatography. B,... Jun 2024Antiarrhythmic and antihypertensive drugs are frequently encountered in post mortem analysis, and the question may arise as to whether they were administered in...
Antiarrhythmic and antihypertensive drugs are frequently encountered in post mortem analysis, and the question may arise as to whether they were administered in therapeutic doses, and if they were taken in accidental, intentional, or suicidal overdose scenarios. Therefore, a novel analytical method was developed and validated for the quantification of 35 drugs with toxicological relevance, including antihypertensive and antiarrhythmic drugs (ajmaline, amlodipine, amiodarone, atenolol, bisoprolol, carvedilol, clonidine, desethylamiodarone, diltiazem, donepezil, doxazosin, dronedarone, esmolol, flecainide, lercanidipine, lidocaine, metoprolol, nebivolol, nimodipine, pindolol, prajmaline, propafenone, propranolol, sotalol, urapidil, and verapamil), as well as other medications commonly found in combination (sildenafil, tadalafil, atorvastatin, clopidogrel, dapoxetine, memantine, pentoxifylline, rivastigmine, and ivabradine). The method enables simultaneous identification and quantification in blood samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Validation exhibited excellent linearity across the concentration range for all analytes. Precision and accuracy were within acceptable limits, with bias and relative standard deviation (RSD) values consistently below 9 % and 10 %, respectively. Selectivity and specificity assessments confirmed the absence of any interference from contaminants or co-extracted drugs. The method demonstrated very high sensitivity, with limits of detection (LOD) as low as 0.01 ng/ml and limits of quantification (LOQ) as low as 0.04 ng/ml. Extraction recovery exceeded 57.5 % for all analytes except atenolol, and matrix effects were <17 % for all analytes except pindolol. Processed sample stability evaluations revealed consistent results with acceptable deviations for all analytes. In addition, the method was specifically tested for the use in post mortem analysis. The applicability of our method was demonstrated by the analysis of two authentic human autopsy blood samples.
PubMed: 38878710
DOI: 10.1016/j.jchromb.2024.124196 -
Heliyon May 2024- Cocaine use disorder (CUD) is a complex disease. Several studies have shown the efficacy of multitarget drugs used to treat CUD. Here we compare the efficacy of...
PURPOSE
- Cocaine use disorder (CUD) is a complex disease. Several studies have shown the efficacy of multitarget drugs used to treat CUD. Here we compare the efficacy of mirtazapine (MIR), pindolol (PIN), fluoxetine (FLX), risperidone (RIS), trazodone (TRZ), ziprasidone (ZPR), ondansetron (OND), yohimbine (YOH), or prazosin (PRZ), to reduce long-term cocaine-induced locomotor activity and the expression of cocaine-induced locomotor sensitization in rats.
METHODS
- The study consists of four experiments, which were divided into four experimental phases. Induction (10 days), cocaine withdrawal (30 days), expression (10 days), and post-expression phase (10 days). Male Wistar rats were daily dosed with cocaine (10 mg/kg; i.p.) during the induction and post-expression phases. During drug withdrawal, the MIR, PIN, FLX, RIS, TRZ, ZPR, OND, YOH, or PRZ were administered 30 min before saline. In the expression, the multitarget drugs were administered 30 min before cocaine. After each administration, locomotor activity for each animal was recorded for 30 min.During the agonism phase, in experiment four, 8-OH-DPAT, DOI, CP-809-101, SR-57227A, or clonidine (CLO) was administered 30 min before MIR and 60 min before cocaine. After each administration, locomotor activity for each animal was recorded for 30 min.
RESULTS
-MIR, FLX, RIS, ZPR, OND, or PRZ attenuated the cocaine-induced locomotor activity and cocaine locomotor sensitization. PIN, TRZ, and YOH failed to decrease cocaine locomotor sensitization. At the optimal doses used, PIN, FLX, RIS, TRZ, ZPR, OND, YOH, or PRZ failed to attenuate long-term cocaine locomotor activation. MIR generated a decrease in cocaine-induced locomotor activity of greater magnitude and duration than the other multitarget drugs evaluated.
CONCLUSION
- At the optimal doses of multitarget drugs evaluated, MIR was the multitarget drug that showed the greatest long-term cocaine-induced behavior effects compared to other multitarget drugs.
PubMed: 38726128
DOI: 10.1016/j.heliyon.2024.e29979 -
Neurobiology of Disease May 2024Whether there is hypothalamic degeneration in Parkinson's disease (PD) and its association with clinical symptoms and pathophysiological changes remains controversial.
BACKGROUND
Whether there is hypothalamic degeneration in Parkinson's disease (PD) and its association with clinical symptoms and pathophysiological changes remains controversial.
OBJECTIVES
We aimed to quantify microstructural changes in hypothalamus using a novel deep learning-based tool in patients with PD and those with probable rapid-eye-movement sleep behavior disorder (pRBD). We further assessed whether these microstructural changes associated with clinical symptoms and free thyroxine (FT4) levels.
METHODS
This study included 186 PD, 67 pRBD, and 179 healthy controls. Multi-shell diffusion MRI were scanned and mean kurtosis (MK) in hypothalamic subunits were calculated. Participants were assessed using Unified Parkinson's Disease Rating Scale (UPDRS), RBD Questionnaire-Hong Kong (RBDQ-HK), Hamilton Depression Rating Scale (HAMD), and Activity of Daily Living (ADL) Scale. Additionally, a subgroup of PD (n = 31) underwent assessment of FT4.
RESULTS
PD showed significant decreases of MK in anterior-superior (a-sHyp), anterior-inferior (a-iHyp), superior tubular (supTub), and inferior tubular hypothalamus when compared with healthy controls. Similarly, pRBD exhibited decreases of MK in a-iHyp and supTub. In PD group, MK in above four subunits were significantly correlated with UPDRS-I, HAMD, and ADL. Moreover, MK in a-iHyp and a-sHyp were significantly correlated with FT4 level. In pRBD group, correlations were observed between MK in a-iHyp and UPDRS-I.
CONCLUSIONS
Our study reveals that microstructural changes in the hypothalamus are already significant at the early neurodegenerative stage. These changes are associated with emotional alterations, daily activity levels, and thyroid hormone levels.
Topics: Humans; Parkinson Disease; REM Sleep Behavior Disorder; Surveys and Questionnaires; Pindolol
PubMed: 38479482
DOI: 10.1016/j.nbd.2024.106472 -
BMC Cardiovascular Disorders Sep 2023Older adults with heart failure often experience adverse drug events with high doses of heart failure medications. Recognizing whether a patient is on a high or low dose... (Review)
Review
BACKGROUND
Older adults with heart failure often experience adverse drug events with high doses of heart failure medications. Recognizing whether a patient is on a high or low dose intensity heart failure medication can be helpful for daily practice, since it could potentially guide the physician on which symptoms to look for, whether from overdosing or underdosing. However, the current guideline does not provide sufficient information about the dose intensity below the target dose. Furthermore, the definition of high or low-intensity heart failure medication is unclear, and there is no consensus.
METHODS
To close the knowledge gap, we conducted a scoping review of the current literature to identify the most frequently used definition of high versus low doses of heart failure medications. We searched Pubmed, Embase, CINAHL, and Cochrane Library using comprehensive search terms that can capture the intensity of heart failure medications.
RESULTS
We reviewed 464 articles, including 144 articles that had information about beta-blockers (BB), 179 articles about angiotensin-converting enzyme inhibitors (ACEi), 75 articles about angiotensin receptor blockers (ARB), 80 articles about diuretics, 37 articles about mineralocorticoid receptor antagonists (MRA), and 33 articles about angiotensin receptor-neprilysin inhibitor (ARNI). For hydralazine with isosorbide dinitrate or ivabradine, we could not identify any eligible articles. We identified 40 medications with most frequently used definitions of dose intensity. Four medications (nadolol, pindolol, cilazapril, and torsemide) did not reach consensus in definitions. Most of the BBs, ACEis, or ARBs used the definition of low being < 50% of the target dose and high being ≥ 50% of the target dose from the guideline. However, for lisinopril and losartan, the most commonly used definitions of high or low were from pivotal clinical trials with a pre-defined definition of high or low.
CONCLUSION
Our comprehensive scoping review studies identified the most frequently used definition of dose intensity for 40 medications but could not identify the definitions for 4 medications. The results of the current scoping review will be helpful for clinicians to have awareness whether the currently prescribed dose is considered high - requiring close monitoring of side effects, or low - requiring more aggressive up-titration.
Topics: Humans; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Isosorbide Dinitrate; Adrenergic beta-Antagonists; Stroke Volume
PubMed: 37759279
DOI: 10.1186/s12872-023-03514-2