Antiemetics, Serotonin 5-HT3-Receptor Antagonists

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Give eg's of & indications for serotonin 5-HT3-receptor antagonists. eg's: ondansetron, granistron Indications: • Prophylaxis & Rx of N & V - especially in context of GA & chemotherapy
MOA of serotonin 5-HT3-receptor antagonists. N & V are triggered by a variety of factors, including gut irritation, drugs, motion & vestibular disorders, & higher stimuli (sights, smells, emotions). The various pathways converge on a ‘vomiting centre’ in the medulla, which receives inputs from the CTZ, the solitary tract nucleus (which is innervated by the vagus nerve), the vestibular system & higher neurological centres. Serotonin (5-HT) plays an important role in two of these pathways. First, there is a high density of 5-HT3 receptors in the CTZ, which are responsible for sensing emetogenic substances in the blood (e.g. drugs). Second, serotonin is the key neurotransmitter released by the gut in response to emetogenic stimuli. Acting on 5-HT3 receptors, it stimulates the vagus nerve, which activates the vomiting centre via the solitary tract nucleus. Serotonin is not involved in communication between the vestibular system & the vomiting centre. Thus 5-HT3 antagonists are effective against N & V due to CTZ stimulation (eg drugs) & visceral stimuli (GI infxn, radiotherapy), but not in motion sickness.
SE's of serotonin 5-HT3-receptor antagonists. • Constipation • Diarrhoea • Headache
CI's, cautions, & important interactions of serotonin 5-HT3-receptor antagonists. CI's: • Avoid in pt's who are taking drugs that prolong the QT interval - eg antipsychotics, quinine, SSRI's Cautions: • See above Important interactions: Avoid 5-HT3 antagonists when pt's are taking drugs that prolong the QT interval, such as antipsychotics, quinine & selective serotonin reuptake inhibitors. If in doubt, check the BNF.

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