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https://www.readbyqxmd.com/read/28108820/prevention-of-chemotherapy-induced-nausea-the-role-of-neurokinin-1-nk1-receptor-antagonists
#1
Snežana M Bošnjak, Richard J Gralla, Lee Schwartzberg
Chemotherapy-induced nausea (CIN) has a significant negative impact on the quality of life of cancer patients. The use of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists (RAs) has reduced the risk of vomiting, but (except for palonosetron) their effect on nausea, especially delayed nausea, is limited. This article reviews the role of NK1RAs when combined with 5-HT3RA-dexamethasone in CIN prophylaxis. Aprepitant has not shown consistent superiority over a two-drug (ondansetron-dexamethasone) combination in nausea control after cisplatin- or anthracycline-cyclophosphamide (AC)-based highly emetogenic chemotherapy (HEC)...
January 20, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28047407/su-f-t-110-lkb-modeling-of-acute-hematologic-toxicity-in-rectal-cancer
#2
H Deng, K Cheng, X Wan
PURPOSE: To investigate dosimetric parameters correlated with acute hematologic toxicity (HT) in patients with rectal cancer treated with IMRT and concurrent chemotherapy. METHODS: We analyzed 127 rectal cancer patients receiving IMRT and concurrent chemotherapy. Whole pelvic bone marrow (PBM) was contoured for each patient including lumbosacral spine (LSSP), ilium and lower pelvic (LP). The equivalent uniform dose (EUD) of each region and the PBM were calculated...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28034961/role-of-prefrontal-serotonergic-and-dopaminergic-systems-in-encounter-induced-hyperactivity-in-methamphetamine-sensitized-mice
#3
Tatsunori Tanaka, Yukio Ago, Chiaki Umehara, Emina Imoto, Shigeru Hasebe, Hitoshi Hashimoto, Kazuhiro Takuma, Toshio Matsuda
BACKGROUND: Isolation-reared mice show social encounter-induced hyperactivity with activation of prefrontal serotonergic and dopaminergic systems, but it is not known whether this stress response is observed in other pathological conditions. Here we examined whether the social encounter stimulation induces abnormal behavior during withdrawal in chronic methamphetamine (METH)-treated mice. METHODS: To induce METH-induced behavioral sensitization, male mice were injected with METH (1 mg/kg) once daily for 7 days...
December 29, 2016: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28032216/effectiveness-of-aprepitant-in-addition-to-ondansetron-in-the-prevention-of-nausea-and-vomiting-caused-by-fractionated-radiotherapy-to-the-upper-abdomen-avert
#4
Steven Ades, M Halyard, K Wilson, T Ashikaga, R Heimann, S Kumar, W Blackstock
PURPOSE: Despite a lower risk of nausea and vomiting in patients receiving radiotherapy to the upper abdomen (UA-RINV) with prophylactic 5-HT3 antagonist therapy, patients can still experience UA-RINV. The aim of this multicenter phase II study was to assess effectiveness, safety, and tolerability of protracted dual NK1-receptor and 5-HT3 antagonist prophylaxis against UA-RINV. METHODS: Patients receiving fractionated radiotherapy with radiosensitizing chemotherapy received oral ondansetron 8 mg po q12 h and aprepitant 125/80/80 mg on a Monday, Wednesday, Friday schedules throughout radiotherapy...
December 28, 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28025094/serotonergic-mechanisms-of-trigeminal-meningeal-nociception-implications-for-migraine-pain
#5
Erkan Kilinc, Cindy Guerrero-Toro, Andrey Zakharov, Carmela Vitale, Max Gubert-Olive, Ksenia Koroleva, Arina Timonina, Liliana L Luz, Irina Shelukhina, Raisa Giniatullina, Fatma Tore, Boris V Safronov, Rashid Giniatullin
Serotonergic mechanisms play a central role in migraine pathology. However, the region-specific effects of serotonin (5-HT) mediated via multiple types of receptors in the nociceptive system are poorly understood. Using extracellular and patch-clamp recordings, we studied the action of 5-HT on the excitability of peripheral and central terminals of trigeminal afferents. 5-HT evoked long-lasting TTX-sensitive firing in the peripheral terminals of meningeal afferents, the origin site of migraine pain. Cluster analysis revealed that in majority of nociceptive fibers 5-HT induced either transient or persistent spiking activity with prevailing delta and theta rhythms...
December 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28017279/cardiovascular-remodeling-and-the-peripheral-serotonergic-system
#6
REVIEW
Estelle Ayme-Dietrich, Gaëlle Aubertin-Kirch, Luc Maroteaux, Laurent Monassier
Plasma 5-hydroxytryptamine (5-HT; serotonin), released from blood platelets, plays a major role in the human cardiovascular system. Besides the effect of endogenous serotonin, many drugs targeting serotonergic receptors are widely used in the general population (antiobesity agents, antidepressants, antipsychotics, antimigraine agents), and may enhance the cardiovascular risk. Depending on the type of serotonin receptor activated and its location, the use of these compounds triggers acute and chronic effects...
December 21, 2016: Archives of Cardiovascular Diseases
https://www.readbyqxmd.com/read/28007031/comparative-safety-and-effectiveness-of-serotonin-receptor-antagonists-in-patients-undergoing-chemotherapy-a-systematic-review-and-network-meta-analysis
#7
Andrea C Tricco, Erik Blondal, Areti Angeliki Veroniki, Charlene Soobiah, Afshin Vafaei, John Ivory, Lisa Strifler, Roberta Cardoso, Emily Reynen, Vera Nincic, Huda Ashoor, Joanne Ho, Carmen Ng, Christy Johnson, Erin Lillie, Jesmin Antony, Derek J Roberts, Brenda R Hemmelgarn, Sharon E Straus
BACKGROUND: Although serotonin (5-HT3) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy. METHODS: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT3 receptor antagonists with each other or placebo in chemotherapy patients...
December 23, 2016: BMC Medicine
https://www.readbyqxmd.com/read/28002639/clinical-pharmacogenetics-implementation-consortium-cpic-guideline-for-cyp2d6-genotype-and-use-of-ondansetron-and-tropisetron
#8
Gillian C Bell, Kelly E Caudle, Michelle Whirl-Carrillo, Ronald J Gordon, Keiko Hikino, Cynthia A Prows, Andrea Gaedigk, Jose A G Agundez, Senthilkumar Sadhasivam, Teri E Klein, Matthias Schwab
5-hydroxytryptamine type 3 (5-HT3 ) receptor antagonists are used in the prevention of chemotherapy- induced, radiation-induced and postoperative nausea and vomiting. CYP2D6 polymorphisms can influence the metabolism of some of these drugs (i.e. ondansetron and tropisetron) thereby affecting drug efficacy. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for ondansetron and tropisetron based on CYP2D6 genotype (updates at www.pharmgkb...
December 21, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28002447/influence-of-polymorphisms-in-the-htr3a-and-htr3b-genes-on-experimental-pain-and-the-effect-of-the-5-ht3-antagonist-granisetron
#9
Sofia Louca Jounger, Nikolaos Christidis, Britt Hedenberg-Magnusson, Thomas List, Peter Svensson, Martin Schalling, Malin Ernberg
The aim of this study was to investigate experimentally if 5-HT3 single nucleotide polymorphisms (SNP) contribute to pain perception and efficacy of the 5-HT3-antagonist granisetron and sex differences. Sixty healthy participants were genotyped regarding HTR3A (rs1062613) and HTR3B (rs1176744). First, pain was induced by bilateral hypertonic saline injections (HS, 5.5%, 0.2 mL) into the masseter muscles. Thirty min later the masseter muscle on one side was pretreated with 0.5 mL granisetron (1 mg/mL) and on the other side with 0...
2016: PloS One
https://www.readbyqxmd.com/read/27996982/-vortioxetine-in-the-treatment-of-major-depression
#10
Andrea de Bartolomeis, Andrea Fagiolini, Giuseppe Maina
Notwithstanding the high prevalence, functional burden, negative consequences and risk of chronicity of major depressive disorder, few innovative medications have been developed in recent years for the treatment of this heterogeneous disease. Vortioxetine is a multi-modal antidepressant that functions both as serotonin transporter (SERT) inhibitor and as 5-HT3, 5-HT7 and 5-HT1D receptors antagonist, 5-HT1A receptor agonist and 5-HT1B receptor partial agonist. A recent meta-analysis of 11 randomized, double-blind, placebo controlled, acute (6-8 weeks) treatment studies has demonstrated the efficacy of vortioxetine 5-20 mg/day in the treatment of depression, with an increasing effect associated with increasing dose...
November 2016: Rivista di Psichiatria
https://www.readbyqxmd.com/read/27992509/palonosetron-and-ramosetron-compared-for-effectiveness-in-preventing-postoperative-nausea-and-vomiting-a-systematic-review-and-meta-analysis
#11
EunJin Ahn, GeunJoo Choi, Hyun Kang, ChongWha Baek, YongHun Jung, YoungCheol Woo, SangSeok Lee, YeoGoo Chang
Previous randomized controlled trials have reported conflicting findings on the superiority of palonosetron over ramosetron for preventing postoperative nausea and vomiting (PONV). Therefore, the present systematic review was registered in PROSPERO (CRD42016038120) and performed to compare the efficacy of perioperative administration of palonosetron to that of ramosetron for preventing PONV. We searched MEDLINE, EMBASE, and CENTRAL to identify all randomized controlled trials that compared the effectiveness of perioperative administration of palonosetron to that of ramosetron...
2016: PloS One
https://www.readbyqxmd.com/read/27988869/comparative-pharmacology-and-guide-to-the-use-of-the-serotonin-5-ht3-receptor-antagonists-for-postoperative-nausea-and-vomiting
#12
Anthony L Kovac
Since the introduction of the serotonin 5-hydroxy tryptamine 3 (5-HT3) receptor antagonists in the early 1990s, the incidence of postoperative nausea and vomiting (PONV) and post-discharge nausea and vomiting (PDNV) has decreased, yet continues to be a problem for the surgical patient. The clinical application of the 5-HT3 receptor antagonists has helped define the approach and role of these antiemetics in the prevention and treatment of PONV and PDNV. Pharmacological and clinical differences exist among these medications resulting in corresponding differences in effectiveness, safety, optimal dosage, time of administration, and use as combination and rescue antiemetic therapy...
December 2016: Drugs
https://www.readbyqxmd.com/read/27927740/chronic-vortioxetine-treatment-reduces-exaggerated-expression-of-conditioned-fear-memory-and-restores-active-coping-behavior-in-chronically-stressed-rats
#13
Lauren Hatherall, Connie Sánchez, David A Morilak
BACKGROUND: Stress is a risk factor for depression and anxiety disorders, disrupting neuronal processes leading to exaggerated fear and compromised coping behaviors. Current antidepressants are only partially effective. Vortioxetine, a novel multimodal antidepressant, is a serotonin transporter inhibitor; 5-HT3, 5-HT7, and 5-HT1D receptor antagonist; 5-HT1B partial agonist; and 5-HT1A agonist. We have shown that chronic dietary vortioxetine administration reversed stress-induced deficits in cognitive flexibility...
December 29, 2016: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27915445/granisetron-extended-release-injection-a-review-in-chemotherapy-induced-nausea-and-vomiting
#14
Emma D Deeks
An extended-release (ER) subcutaneously injectable formulation of the first-generation 5-HT3 receptor antagonist granisetron is now available in the USA (Sustol(®)), where it is indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) following moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide combination chemotherapy regimens in adults. Granisetron ER is administered as a single subcutaneous injection and uses an erosion-controlled drug-delivery system to allow prolonged granisetron release...
December 2016: Drugs
https://www.readbyqxmd.com/read/27909835/breakthrough-chemotherapy-induced-nausea-and-vomiting-report-of-a-nationwide-survey-by-the-cinv-study-group-of-japan
#15
Kazuo Tamura, Keisuke Aiba, Toshiaki Saeki, Yoichi Nakanishi, Toshiharu Kamura, Hideo Baba, Kazuhiro Yoshida, Nobuyuki Yamamoto, Yuko Kitagawa, Yoshihiko Maehara, Mototsugu Shimokawa, Koichi Hirata, Masaki Kitajima
BACKGROUND: We conducted a nationwide survey on chemotherapy-induced nausea and vomiting (CINV) in Japan and demonstrated good compliance with Japanese CINV guidelines, resulting in good control of vomiting. However, almost half the patients experienced breakthrough CINV. We analyzed the survey results in relationship to the management of patients with breakthrough CINV. METHODS: This multicenter, prospective, observational study analyzed data for 1910 patients in Japan scheduled for moderately or highly emetogenic chemotherapy (MEC and HEC, respectively)...
December 1, 2016: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27905561/anti-hu-antibodies-activate-enteric-and-sensory-neurons
#16
Qin Li, Klaus Michel, Anita Annahazi, Ihsan E Demir, Güralp O Ceyhan, Florian Zeller, Lars Komorowski, Winfried Stöcker, Michael J Beyak, David Grundy, Gianrico Farrugia, Roberto De Giorgio, Michael Schemann
IgG of type 1 anti-neuronal nuclear antibody (ANNA-1, anti-Hu) specificity is a serological marker of paraneoplastic neurological autoimmunity (including enteric/autonomic) usually related to small-cell lung carcinoma. We show here that IgG isolated from such sera and also affinity-purified anti-HuD label enteric neurons and cause an immediate spike discharge in enteric and visceral sensory neurons. Both labelling and activation of enteric neurons was prevented by preincubation with the HuD antigen. Activation of enteric neurons was inhibited by the nicotinic receptor antagonists hexamethonium and dihydro-β-erythroidine and reduced by the P2X antagonist pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid (PPADS) but not by the 5-HT3 antagonist tropisetron or the N-type Ca-channel blocker ω-Conotoxin GVIA...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27894202/rolapitant-for-the-prevention-of-delayed-nausea-and-vomiting-over-initial-and-repeat-courses-of-emetogenic-chemotherapy
#17
Bernardo Rapoport, Ronwyn van Eeden, Teresa Smit
Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect of many cytotoxic chemotherapy regimens. Although sustained antiemetic control across repeated chemotherapy cycles is important for cancer treatment continuation, few studies have investigated the efficacy of antiemetic prophylaxis over multiple chemotherapy cycles. Areas covered: Here we discuss the use of antiemetic hydroxytryptamine type 3 (5-HT3) receptor and neurokinin (NK)-1 receptor antagonists for prevention of CINV, limiting our review to clinical trials in the context of multiple-cycle chemotherapy, with a focus on the NK-1 receptor antagonist rolapitant...
January 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/27889278/safety-and-efficacy-of-nepa-an-oral-fixed-combination-of-netupitant-and-palonosetron-in-older-patients
#18
Matti Aapro, Karin Jordan, Richard J Gralla, Giada Rizzi, Giorgia Rossi, Marco Palmas, Anna V Alyasova, Alla S Lisyanskaya, Snežana M Bošnjak, Paul J Hesketh
OBJECTIVES: Prevention of chemotherapy-induced nausea and vomiting is critical in older cancer patients. NEPA is an oral fixed combination of netupitant 300mg, a new NK1 receptor antagonist (RA), and palonosetron 0.5mg, a pharmacologically distinct 5-HT3 RA. This retrospective analysis evaluated the efficacy and safety of NEPA in older patients. METHODS: Patients aged ≥65 and ≥70years from one phase II and two phase III trials were considered. Chemotherapy-naive patients with malignant tumors were treated with anthracycline-cyclophosphamide (AC), non-AC-based moderately emetogenic chemotherapy (non-AC MEC), or highly emetogenic chemotherapy (HEC)...
November 23, 2016: Journal of Geriatric Oncology
https://www.readbyqxmd.com/read/27885469/nepa-a-fixed-oral-combination-of-netupitant-and-palonosetron-improves-control-of-chemotherapy-induced-nausea-and-vomiting-cinv-over-multiple-cycles-of-chemotherapy-results-of-a-randomized-double-blind-phase-3-trial-versus-oral-palonosetron
#19
Matti Aapro, Meinolf Karthaus, Lee Schwartzberg, Igor Bondarenko, Tomasz Sarosiek, Cristina Oprean, Servando Cardona-Huerta, Vincent Hansen, Giorgia Rossi, Giada Rizzi, Maria Elisa Borroni, Hope Rugo
PURPOSE: Antiemetic guidelines recommend co-administration of targeted prophylactic medications inhibiting molecular pathways involved in emesis. NEPA is a fixed oral combination of a new NK1 receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3 RA. NEPA showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with oral PALO in a single chemotherapy cycle; maintenance of efficacy/safety over continuing cycles is the objective of this study...
November 24, 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/27870735/combination-of-5-ht3-antagonist-and-dexamethasone-is-superior-to-5-ht3-antagonist-alone-for-ponv-prophylaxis-after-laparoscopic-surgeries-a-meta-analysis
#20
Anirban Som, Sulagna Bhattacharjee, Souvik Maitra, Mahesh K Arora, Dalim Kumar Baidya
INTRODUCTION: 5-Hydroxytryptamine type 3 (5-HT3) receptor antagonists are the most commonly used drugs for postoperative nausea vomiting (PONV) prophylaxis. Dexamethasone is another antiemetic with proven efficacy in reducing PONV. The aim of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the combination of dexamethasone and 5-HT3 antagonist versus a 5-HT3 antagonist alone as prophylaxis of PONV in laparoscopic surgical patients...
December 2016: Anesthesia and Analgesia
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