China
Africa
Explore chapters and articles related to this topic
Neuropharmacology Of Respiration
Published in Alan D. Miller, Armand L. Bianchi, Beverly P. Bishop, Neural Control of the Respiratory Muscles, 2019
Monique Denavit-Saubié, Arthur S. Foutz
Most 5-HT cell clusters are located in the raphe nuclei in the medial part of the brainstem. There are several subtypes of 5-HT receptors; 5-HT1, 5-HT2, and 5-HT3 receptors were identified in the nucleus tractus solitarius (NTS), in vagal afferent terminals, and in the area postrema. 5-HT afferents alone or associated with other neurotransmitters project to brainstem respiratory areas. Of particular interest is the localization of 5-HT boutons on presumed respiratory neurons of the DRG. Sometimes, varicosities of functionally unidentified neurons from the NTS contain both 5-HT and substance R The colocalization of 5-HT and substance P is important since functional interactions have been demonstrated in the NTS.41
Clinical Pharmacogenomics Of Human Cyp2d6
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
Ondansetron, a potent and selective 5-HT3 receptor antagonist used mainly as an antiemetic to treat and prevent nausea and vomiting induced by chemotherapy and radiotherapy and postoperative nausea, is a substrate of CYP2D6, 3A4, and 1A2 (Fischer et al. 1994; Sanwald et al. 1996). In healthy volunteers, there is no difference in the AUC, Cmax, and t1/2β of ondansetron between EMs (n = 6) and PMs (n = 6) receiving a single dose (8 mg intravenously) (Ashforth et al. 1994).
Classifications
Published in Fazal-I-Akbar Danish, Ahmed Ehsan Rabbani, Pharmacology in 7 Days for Medical Students, 2018
Fazal-I-Akbar Danish, Ahmed Ehsan Rabbani
Selective 5-HT3 receptor antagonistsDolasetronGranisetronOndansetronPalonosetron
A pharmacological overview of aprepitant for the prevention of postoperative nausea and vomiting
Published in Expert Review of Clinical Pharmacology, 2023
Andrew Padilla, Ashraf S Habib
The pathogenesis of PONV is complex, involving both central and peripheral pathways. The central pathway involves the area postrema in the fourth ventricle that is sensitive to neurotransmitters, toxins, and drugs in the blood and cerebrospinal fluid due to the lack of a blood-brain-barrier [9]. Stimulation of the chemoreceptor trigger zone (CTZ) in the area postrema projects to the nucleus tractus solitarius (NTS), an important coordinator of the vomiting response. Peripherally, enterochromaffin cells in the stomach and intestine release serotonin which then binds to 5-HT3 receptors in the gastrointestinal tract and sends afferent impulses that converge at the area postrema. Additionally, inputs from enterochromaffin cells, the vagal nerve via the pharynx, as well as from the vestibular and limbic system stimulate the NTS. The neurons that mediate these signals frequently include serotonin, dopamine, NK-1, histamine H1 and cholinergic receptors. Stimulation of the NTS via the area postrema and peripheral afferent signals then projects to a central pattern generator (CPG) which coordinates efferent pathways to abdominal muscles, salivatory center and cranial nerves, causing vomiting [10,11].
Gastroparesis syndromes: emerging drug targets and potential therapeutic opportunities
Published in Expert Opinion on Investigational Drugs, 2023
Le Yu Naing, Matthew Heckroth, Prateek Mathur, Thomas L Abell
5-HT3 receptors differ from all other 5-HT receptors in that they are ligand-gated ion channels, whereas the others are G-protein linked receptors. Activation of 5-HT3 receptors inhibits gastric secretions, stimulates migrating motor complexes, and increases intestinal secretions, accelerating small bowel transit. They also stimulate gastric antral contractions and vagal afferent nerves initiating the vomiting reflex[31]. 5-HT3 receptor antagonists are potent antiemetics often used to treat the symptoms of Gp. They block serotonin both peripherally on vagal nerve terminals in the GI tract, as well as centrally in the area postrema and nucleus tractus solitarius. Available 5-HT3 receptor antagonists include ondansetron (Zofran), granisetron (Kytril), tropisetron (Navoban), dolasetron (Anzamet), ramosetron (Nasea), and palonosetron (Aloxi). Some of them have been associated with QT prolongation on EKG, and it is recommended that patients with congenital long QT syndrome need to be cautious with their use. For patients with significant electrolyte abnormalities, congestive heart failure, or those taking other medications that prolong the QT interval, monitoring with serial EKGs is recommended.
Trastuzumab deruxtecan and other HER2-targeting agents for the treatment of HER2-positive gastric cancer
Published in Expert Review of Anticancer Therapy, 2021
In the DESTINY-Gastric01 trial, neutropenia (51% in T-DXd vs. 24% in the physician’s choice of CTx), anemia (38% vs. 23%), leukopenia (21% vs. 11%), and decreased appetite (17% vs. 13%) were the most common grade 3 or worse adverse events. Of these adverse events, the low-grade rate was 2% vs. 11% in neutropenia, 20% vs. 8% in anemia, 17% vs. 24% in leukopenia, 43% vs. 32% in decreased appetite, respectively. Of note, T-DXd-induced interstitial lung disease was observed in 10% of the patients treated with T-DXd. Hematological adverse events can be managed by dose modification [17], granulocyte colony-stimulating factor [40,41], antibiotics, or blood transfusion. Nausea and vomiting would be managed by a combination of antiemetics such as dexamethasone, serotonin (5HT3) receptor antagonists, and/or neurokinin 1 (NK1) antagonists or olanzapine [42]. Before interstitial lung disease occurs, treating physicians should be vigilant of this adverse event. If interstitial lung disease occurs in patients treated with T-DXd, laboratory tests, CT scans, and pulmonary consultations are necessary for early diagnosis, and corticosteroids are used. Based on the results, T-DXd was approved as a treatment for HER2-positive GC after trastuzumab-containing CTx in Japan [43]. Table 3 shows the overall safety of T-DXd treatment.