Two generations of 5HT3 receptor antagonists

Q; 44 years old male is admitted to ICU with severe hypovolemia due to chemotherapy-induced vomiting. Which of the following is the second-generation 5-HT3 receptor antagonist? (select one)

A) dolasetron

B) ondansetron

C) ramosetron

D) tropisetron

E) palonosetron

Answer: E

This question aims to introduce two generations of 5-HT3 receptor antagonists, which are used in severe nausea and vomiting, particularly in oncology patients. 5HT3 receptor antagonists are 5hydroxytryptamine receptor antagonists, also known as serotonin blockers or receptor antagonists.

The most common 5HT3 receptor antagonists are first-generation, such as azasetron, dolasetron, granisetron, ondansetron, ramosetron, and tropisetron. They particularly have an effect on QTc and may induce arrhythmia.

Palonosetron is the only second-generation agent available in the USA. It has 30- to 100-fold higher affinity for 5-HT3 receptor with a marked longer half-life of up to 40 hours. Moreover, QTc prolongation is very unlikely. Also, when combined with glucocorticoids, it effectively on delays emesis.

Updated antiemetic guidelines from the National Comprehensive Cancer Network (NCCN) recommend palonosetron as the preferred 5-HT3 antagonist for patients who receive moderately emetogenic chemotherapy.

Oral and intravenous (IV) forms have similar efficacy. The dose is 0.5 mg. 

#pharmacology

#oncology

References:

1. Likun Z, Xiang J, Yi B, et al. A systematic review and meta-analysis of intravenous palonosetron in the prevention of chemotherapy-induced nausea and vomiting in adults. Oncologist 2011; 16:207.

2. Saito M, Aogi K, Sekine I, et al. Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial. Lancet Oncol 2009; 10:115.

3. Gonullu G, Demircan S, Demirag MK, et al. Electrocardiographic findings of palonosetron in cancer patients. Support Care Cancer 2012; 20:1435.

4. Gralla R, Lichinitser M, Van Der Vegt S, et al. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol 2003; 14:1570.