5-hydroxytryptamine type receptor antagonists 5-HT3




The 5-HT3 antagonists, (5-hyroxytryptamine 3) act as receptor antagonists at the 5-HT3 receptor, a subtype of serotonin receptor found in terminals of the vagus nerve and in certain areas of the brain. 



5-HT3 antagonists are antiemetics, and are used in the prevention and treatment of nausea and vomiting. 



They are particularly effective in controlling the nausea and vomiting produced by cancer chemotherapy.



((Ondansetron)), is the prototypical 5-HT3 antagonist.



The 5-HT3 antagonists are identified by the suffix -setron



5-HT3 antagonists are most effective in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV).



They are especially effective in highly emetogenic drugs.



They are usually given intravenously, shortly before administration of the chemotherapeutic agent.



The concomitant administration of a NK1 receptor antagonist, such as aprepitant, significantly increases the efficacy of 5-HT3 antagonists in preventing both acute and delayed CINV.



5-HT3 antagonists are also indicated in the prevention and treatment of radiation-induced nausea and vomiting,  and postoperative nausea and vomiting (PONV). 



5-HT3 antagonists are more effective at controlling CINV, stopping  symptoms altogether in up to 70% of people, and reducing  them in the remaining 30%.



5-HT3 antagonists are just as effective as other agents for postoperative nausea and vomiting.



5-HT3 antagonists are ineffective in controlling motion sickness.



Agents include: Ondansetron, granisetron, Dolasetron, Palonosetron 



Side  effects related to the use of 5-HT3 antagonists; the most common are constipation or diarrhea, headache, and dizziness.



5-HT3 antagonists do not produce sedation, nor do they cause extrapyramidal effects, as phenothiazines.



All 5-HT3 antagonists areassociated with asymptomatic electrocardiogram changes: prolongation of the PT and QTc intervals and certain arrhythmias.



The 5-HT3 receptors are present in several sites involved in emesis,: including vagal afferents, the solitary tract nucleus (STN), and the area postrema itself. 



Serotonin is released by the enterochromaffin cells of the small intestine in response to chemotherapy drugs and may stimulate vagal afferents working through 5-HT3 receptors to initiate the vomiting reflex. 



The 5-HT3 receptor antagonists suppress vomiting and nausea by inhibiting serotonin binding to the 5-HT3 receptors. 



The highest concentration of 5-HT3 receptors in the central nervous system (CNS) are found in the solitary tract nucleus and chemoreceptor trigger zone (CTZ).



5-HT3 antagonists may also suppress vomiting and nausea by acting at these sites.



5-HT3 antagonists are well-absorbed and effective after oral administration.



5-HT3 receptor antagonists are metabolized in the liver by various isoenzymes of the cytochrome P450 system. 



Patients who are resistant to one antagonist might benefit from a different 5-HT3 receptor antagonist.



Patients with multiple alleles of active  CYP 2DD6 tend to be unresponsive to the antiemetic drug and vice versa.



They are safe and effective for treatment of postoperative nausea and vomiting.



Serotonin (5-HT) is found widely distributed throughout the gut and the central nervous system. 



In the gut, 5-HT is found mostly in mucosal enterochromaffin cells. 



The enterochromaffin cells are sensory transducers that release 5-HT to activate intrinsic and extrinsic primary afferent nerves.



Chemotherapy drugs that cause vomiting have been found to cause release of large amounts of serotonin from enterochromaffin cells in the gut: serotonin then acts on 5-HT3 receptors in the gut and brain stem.



The first-generation 5-HT3 receptor antagonists: ondansetron, dolasetron, granisetron, and tropisetron are especially effective in treating acute emesis, occurring in the first 24 hours following chemotherapy.



Palonosetron is a second generation 5-HT3 receptor antagonist has a longer half-life (40h) and greater receptor binding affinity when compared to first generation antagonists.











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