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Dextromethorphan

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https://www.readbyqxmd.com/read/28562262/safety-profile-of-cough-and-cold-medication-use-in-pediatrics
#1
Jody L Green, George Sam Wang, Kate M Reynolds, William Banner, G Randall Bond, Ralph E Kauffman, Robert B Palmer, Ian M Paul, Richard C Dart
BACKGROUND AND OBJECTIVES: The safety of cough and cold medication (CCM) use in children has been questioned. We describe the safety profile of CCMs in children <12 years of age from a multisystem surveillance program. METHODS: Cases with adverse events (AEs) after ingestion of at least 1 index CCM ingredient (brompheniramine, chlorpheniramine, dextromethorphan, diphenhydramine, doxylamine, guaifenesin, phenylephrine, and pseudoephedrine) in children <12 years of age were collected from 5 data sources...
May 4, 2017: Pediatrics
https://www.readbyqxmd.com/read/28553835/pharmacological-manipulation-of-cortical-inhibition-in-the-dorsolateral-prefrontal-cortex
#2
Bahar Salavati, Tarek K Rajji, Reza Zomorrodi, Daniel M Blumberger, Robert Chen, Bruce G Pollock, Zafiris J Daskalakis
Cortical inhibition (CI) occurs largely through GABA receptor mediated inhibitory neurotransmission, which can be modulated by cholinergic, dopaminergic, and glutamatergic inputs. Transcranial magnetic stimulation (TMS) can be used to index CI through a paradigm known as long interval cortical inhibition (LICI). When TMS is combined with electroencephalography (EEG), LICI can index GABA receptor mediated inhibitory neurotransmission in the dorsolateral prefrontal cortex (DLPFC). We conducted a hypothesis-driven pharmacological study to assess the role of cholinergic, dopaminergic, GABAergic, and glutamatergic neurotransmission on LICI from the DLPFC using TMS-EEG...
May 29, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28515935/methotrexate-encephalopathy-two-cases-in-adult-cancer-patients-who-recovered-with-pathophysiologically-based-therapy
#3
Shodeinde A Coker, David A Pastel, Melissa C Davis, Elizabeth M Bengtson, Camilo E Fadul, Lionel D Lewis
BACKGROUND/OBJECTIVES: Neurotoxicity is a serious and sometimes fatal adverse effect that can occur following methotrexate treatment. We describe two adult patients with hematological malignancies with methotrexate encephalopathy who recovered with dextromethorphan therapy. RESULTS: Case 1: A 24-year-old male with acute lymphoblastic leukemia developed the acute onset of bilateral facial weakness and slurred speech after his first treatment with high-dose intravenous methotrexate...
2017: SAGE open medical case reports
https://www.readbyqxmd.com/read/28512430/cyp2d6-phenotyping-using-urine-plasma-and-saliva-metabolic-ratios-to-assess-the-impact-of-cyp2d6-%C3%A2-10-on-interindividual-variation-in-a-chinese-population
#4
Rui Chen, Xin Zheng, Pei Hu
Purpose: Asian populations have around 40-60% frequency of reduced function allele CYP2D6(∗)10 compared to 1-2% in Caucasian populations. The wide range of CYP2D6 enzyme activities in subjects with the CYP2D6(∗)10 variant is a big concern for clinical practice. The quantitative analysis measuring the impact of CYP2D6 enzyme activity as a result of one CYP2D6(∗)10 allele or two CYP2D6(∗)10 alleles has not been reported in large Asian populations. Methods: A total of 421 healthy Chinese subjects were genotyped for CYP2D6 by polymerase chain reaction and direct DNA sequencing...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28512368/-analysis-of-the-phenomenon-of-over-the-counter-drug-abuse-and-not-controlled-herbs-trade-by-polish-adolescents-part-i
#5
REVIEW
Daria Suchecka, Jolanta Kucharska-Mazur, Katarzyna Groszewska, Monika Mak, Jerzy Samochowiec, Agnieszka Samochowiec
The phenomenon of stupefying by the use of available over-the-counter drugs (OTC) among adolescents is an essential problem in both Poland and throughout the world. Popular analgesics, cold medicine and antihistamines contain psychedelic substances, such as dextromethorphan (DXM), pseudoephedrine/ephedrine, codeine (methylmorphine), dimenhydrinate, paracetamol (acetaminophren) and others. Cases of fatal addiction to dextromethorphan, one of the active substances contained in medicines, e.g., the common cold, have been reported...
May 16, 2017: Medycyna Pracy
https://www.readbyqxmd.com/read/28506817/in-vitro-cyp-mediated-drug-metabolism-in-the-zebrafish-embryo-using-human-reference-compounds
#6
Moayad Saad, An Matheeussen, Sebastiaan Bijttebier, Evy Verbueken, Casper Pype, Christophe Casteleyn, Chris Van Ginneken, Sandra Apers, Louis Maes, Paul Cos, Steven Van Cruchten
The increasing use of zebrafish embryos as an alternative model for toxicological and pharmacological studies necessitates a better understanding of xenobiotic biotransformation in this species. As cytochrome P450 enzymes (CYPs) play an essential role in this process, in vitro drug metabolism of four human CYP-specific substrates, i.e. dextromethorphan (DXM), diclofenac (DIC), testosterone (TST) and midazolam (MDZ) was investigated in adult male and female zebrafish, and in zebrafish embryos and larvae up to 120hours post-fertilization...
May 12, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28477358/are-exposure-predictions-used-for-the-prioritization-of-pharmaceuticals-in-the-environment-fit-for-purpose
#7
Emily E Burns, Jane Thomas-Oates, Dana W Kolpin, Edward T Furlong, Alistair B A Boxall
Prioritization methodologies are often used for identifying those pharmaceuticals that pose the greatest risk to the natural environment and to focus laboratory testing or environmental monitoring toward pharmaceuticals of greatest concern. Risk-based prioritization approaches, employing models to derive exposure concentrations, are commonly used, but the reliability of these models is unclear. The present study evaluated the accuracy of exposure models commonly used for pharmaceutical prioritization. Targeted monitoring was conducted for 95 pharmaceuticals in the Rivers Foss and Ouse in the City of York (UK)...
May 6, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28449367/metoprolol-pridopidine-drug-drug-interaction-and-food-effect-assessments-of-pridopidine-a-new-drug-for-treatment-of-huntington-disease
#8
Laura Rabinovich-Guilatt, Lilach Steiner, Hussein Hallak, Gina Pastino, Pierandrea Muglia, Ofer Spiegelstein
AIM: Pridopidine is an oral drug in clinical development for treatment of patients with Huntington disease. This study examined the interactions of pridopidine with in vitro cytochrome P450 activity and characterized the effects of pridopidine on CYP2D6 activity in healthy volunteers using metoprolol as a probe substrate. The effect of food on pridopidine exposure was assessed. METHODS: The ability of pridopidine to inhibit and/or induce in vitro activity of drug metabolising enzymes was examined in human liver microsomes and fresh hepatocytes...
April 27, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28448746/pharmaceutical-chemicals-steroids-and-xenoestrogens-in-water-sediments-and-fish-from-the-tidal-freshwater-potomac-river-virginia-usa
#9
Golala Arya, Sara Tadayon, James Sadighian, Jennifer Jones, Kim de Mutsert, Thomas B Huff, Gregory D Foster
Selected pharmaceutical chemicals, steroids and xenoestrogens (PCSXs) consisting of 29 endocrine modulators, therapeutic drugs, pesticides, detergents, plastics, and active ingredients in household products were measured in water, riverbed sediments and fish collected in a tributary embayment of the Potomac River (Hunting Creek, Alexandria, VA, USA) in the vicinity of wastewater discharge. A total of 17 PCSXs were found in the Hunting Creek samples, with steroid hormones (e.g., progesterone and 17α-ethinylestradiol), triclosan, dextromethorphan and bisphenol A being the most prominent micropollutants detected...
April 27, 2017: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
https://www.readbyqxmd.com/read/28413907/interaction-of-dextromethorphan-hydrobromide-with-dna-multispectral-voltammetric-and-molecular-docking-technology
#10
Shuyun Bi, Huifeng Zhou, Jun Wu, Yu Wang
No abstract text is available yet for this article.
April 16, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28396528/human-enterocytes-as-an-in-vitro-model-for-the-evaluation-of-intestinal-drug-metabolism-characterization-of-drug-metabolizing-enzyme-activities-of-cryopreserved-human-enterocytes-from-twenty-four-donors
#11
Ming-Chih David Ho, Nick Ring, Kirsten Amaral, Utkarsh Doshi, Albert Li
We report here successful isolation and cryopreservation of enterocytes from human small intestine. The enterocytes were isolated by enzyme digestion of the intestinal lumen followed by partial purification via differential centrifugation. The enterocytes were cryopreserved directly after isolation without culturing to maximize retention of in vivo drug metabolizing enzyme activities. Post-thaw viability of the cryopreserved enterocytes was consistently over 80% based on trypan blue exclusion. Cryopreserved enterocytes pooled from 8 donors (4 male and 4 female) were evaluated for their metabolism of 14 pathway-selective substrates: CYP1A2 (phenacetin hydroxylation), CYP2A6 (coumarin 7-hydroxylation), CYP2B6 (bupropion hydroxylation), CYP2C8 (paclitaxel 6α-hydroxylation), CYP2C9 (diclofenac 4-hydroxylation), CYP2C19 (s-mephenytoin 4-hydroxylation), CYP2D6 (dextromethorphan hydroxylation), CYP2E1 (chlorzoxazone 6-hydroxylation), CYP3A4 (midazolam 1'-hydroxylation and testosterone 6β-hydroxylation), CYP2J2 (astemizole O-demethylation), UDP-glucuronosyltransferase (UGT; 7-hydroxycoumarin glucuronidation), sulfotransferase (SULT; 7-hydroxycoumarin sulfation), and carboxylesterase 2 (CES2; irinotecan hydrolysis) activities...
April 10, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28377827/anti-yo-mediated-paraneoplastic-cerebellar-degeneration-associated-with-pseudobulbar-affect-in-a-patient-with-breast-cancer
#12
Allison N Martin, Patrick M Dillon, David E Jones, David R Brenin, David A Lapides
Paraneoplastic cerebellar degeneration (PCD) is a rare anti-Yo mediated paraneoplastic syndromes rarely that is infrequently associated with breast cancer. We present a case of a 52-year-old female presenting with diplopia, gait instability, dysarthria, dysphagia, nystagmus, and, most notably, new onset paroxysmal episodes of uncontrollable crying concerning for pseudobulbar affect (PBA). Serologic testing showed anti-Yo antibodies. The patient was found to have stage IIIA breast cancer as the inciting cause of the paraneoplastic syndrome...
2017: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/28376072/dextromethorphan-and-methylxanthines-might-be-useful-in-the-treatment-of-methotrexate-induced-neurotoxicity
#13
Francisco José Fernández-Fernández, Eugenia Ameneiros-Lago, Cristina Lijó-Carballeda, Pascual Sesma
No abstract text is available yet for this article.
May 2017: Pediatric Emergency Care
https://www.readbyqxmd.com/read/28370447/trial-of-dextromethorphan-quinidine-to-treat-levodopa-induced-dyskinesia-in-parkinson-s-disease
#14
Susan H Fox, Leonard Verhagen Metman, John G Nutt, Matthew Brodsky, Stewart A Factor, Anthony E Lang, Laura E Pope, Nadine Knowles, João Siffert
BACKGROUND: Nondopaminergic pathways represent potential targets to treat levodopa-induced dyskinesia in Parkinson's disease (PD). This pilot-study (NCT01767129) examined the safety/efficacy of the sigma-1 receptor-agonist and glutamatergic/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa-induced dyskinesia. METHODS: PD patients were randomized to dextromethorphan/quinidine (45 mg/10 mg twice daily)/placebo in two 2-week double-blind, crossover treatment periods, with intervening 2-week washout...
March 30, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28302194/-clinical-and-molecular-genetic-study-of-nonketotic-hyperglycinemia-in-a-chinese-family
#15
Zhi-Jie Gao, Qian Jiang, Qian Chen, Ke-Ming Xu
Nonketotic hyperglycinemia (NKH) is a rare, inborn error of metabolism. In this case report, a Chinese male infant was diagnosed with NKH caused by GLDC gene mutation. The clinical characteristics and genetic diagnosis were reported. The infant presented with an onset of early metabolic encephalopathy and Ohtahara syndrome. Both blood and urinary levels of metabolites were in the normal range. Brain MRI images indicated a poor development of corpus callosum, and a burst suppression pattern was found in the EEG...
March 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28300462/an-update-on-the-advancements-in-the-treatment-of-agitation-in-alzheimer-s-disease
#16
REVIEW
Anton P Porsteinsson, Inga M Antonsdottir
Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are associated with significant negative outcomes for patients and their caregivers. Agitation, one of the most distressing NPS, lacks safe and effective long term interventions. Nonpharmacological interventions are suggested as first-line treatment, but aren't effective for every patient, resulting in pharmacological interventions for some patients, consisting of off-label use of antipsychotics, sedative/hypnotics, anxiolytics, acetylcholinesterase inhibitors, memantine, and antidepressants; where efficacy doesn't necessarily outweigh associated risks...
April 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28290770/in-vivo-characterization-of-cyp2d6-12-29-and-84-using-dextromethorphan-as-a-probe-drug-a-case-report
#17
Andrea Gaedigk, Greyson P Twist, Emily G Farrow, Jennifer A Lowry, Sarah E Soden, Neil A Miller
CYP2D6*84 was first described in a Black South African subject, however, its function remains unknown. Astrolabe, a probabilistic scoring tool developed in our laboratory to call genotypes from whole genome sequence, identified CYP2D6*84 in a trio. The father presented with intermediate metabolism when challenged with the CYP2D6 probe drug dextromethorphan (DM/dextrorphan [DX] = 0.0839). Since his second allele, CYP2D6*12, is nonfunctional, the observed activity is derived by CYP2D6*84. This finding suggests that the allele's hallmark P267H causes decreased activity toward DM and that this allele should receive a value of 0...
March 14, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28288109/in-silico-design-of-novel-probes-for-the-atypical-opioid-receptor-mrgprx2
#18
Katherine Lansu, Joel Karpiak, Jing Liu, Xi-Ping Huang, John D McCorvy, Wesley K Kroeze, Tao Che, Hiroshi Nagase, Frank I Carroll, Jian Jin, Brian K Shoichet, Bryan L Roth
The primate-exclusive MRGPRX2 G protein-coupled receptor (GPCR) has been suggested to modulate pain and itch. Despite putative peptide and small-molecule MRGPRX2 agonists, selective nanomolar-potency probes have not yet been reported. To identify a MRGPRX2 probe, we first screened 5,695 small molecules and found that many opioid compounds activated MRGPRX2, including (-)- and (+)-morphine, hydrocodone, sinomenine, dextromethorphan, and the prodynorphin-derived peptides dynorphin A, dynorphin B, and α- and β-neoendorphin...
May 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28271978/lessons-from-cuba-for-global-precision-medicine-cyp2d6-genotype-is-not-a-robust-predictor-of-cyp2d6-ultrarapid-metabolism
#19
Pedro Dorado, Idilio González, María Eugenia G Naranjo, Fernando de Andrés, Eva María Peñas-Lledó, Luis Ramón Calzadilla, Adrián LLerena
A long-standing question and dilemma in precision medicine is whether and to what extent genotyping or phenotyping drug metabolizing enzymes such as CYP2D6 can be used in real-life global clinical and societal settings. Although in an ideal world using both genotype and phenotype biomarkers are desirable, this is not always feasible for economic and practical reasons. Moreover, an additional barrier for clinical implementation of precision medicine is the lack of correlation between genotype and phenotype, considering that most of the current methods include only genotyping...
January 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28254952/effects-of-microrna-34a-on-the-pharmacokinetics-of-cytochrome-p450-probe-drugs-in-mice
#20
Joseph L Jilek, Ye Tian, Ai-Ming Yu
MicroRNAs (miRNAs or miRs), including miR-34a, have been shown to regulate nuclear receptor, drug-metabolizing enzyme, and transporter gene expression in various cell model systems. However, to what degree miRNAs affect pharmacokinetics (PK) at the systemic level remains unknown. In addition, miR-34a replacement therapy represents a new cancer treatment strategy, although it is unknown whether miR-34a therapeutic agents could elicit any drug-drug interactions. To address this question, we refined a practical single-mouse PK approach and investigated the effects of a bioengineered miR-34a agent on the PK of several cytochrome P450 probe drugs (midazolam, dextromethorphan, phenacetin, diclofenac, and chlorzoxazone) administered as a cocktail...
May 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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