Serotonin Antagonists - 5HT-3 Antagonists Flashcards
What is the main site of 5HT-3 receptors?
The terminals of vagal and enteric afferents in the mucosa of the gastrointestinal tract
What causes the release of mucosal serotonin?
Irritation of the G.I. mucosa by chemotherapy, radiation therapy, distention, or acute infectious gastroenteritis
Binding of serotonin to the 5HT-3 receptors on the afferent terminals of the G.I. tract stimulates transmission of the afferents which terminate where?
The chemo receptor trigger zone and vomiting center in the CNS.
What does increased afferent input into the CTZ NVC lead to?
Release of serotonin and other emetogenic substances in these two areas
What receptors are present in the vomiting center?
H1 and 5HT-3
Why is the CTZ accessible to a emetogenic stimuli in the bloodstream?
The blood vessels are fenestrated instead of being part of the blood brain barrier
What receptors are present in the CTZ?
5HT-3, D2, mu-opioid
What happens upon activation of the 5HT-3 receptors in the CNS or G.I. tract?
It will induce emesis. Blockade of these receptors will yield an anti-emetic effect
What is the prototype 5HT-3 receptor antagonist?
Ondasetron (Zofran).
What is Ondasetron (Zofran) used for?
It is more effective than metoclopramide against nausea induced by high-dose cisplatin (an anticancer agent associated with a particularly high incidence of emesis)
What is unique about Ondasetron vs D2 receptor antagonists?
It does not produce extrapyramidal effects
What are the most frequent side effects of Ondasetron?
Headache and (surprisingly) diarrhea.
What are the common side effects of 5HT-3 antagonists?
They all cause headache, constipation or diarrhea.
Which are the 5HT-3 antagonists?
The SETRONS
- Ondasetron (Zofran)
- Granisetron (Kytril)
- Dolasetron (Anzemet)
- Palonsetron (Aloxi)
- Alosetron (Lotronex)
Which 5HT-3 antagonist controls diarrhea instead of causing it?
Alosetron (Lotronex)
