Prevention of Nausea and Vomiting after Surgery with Granisetron and Dolasetron

An article published in the Journal of Anaesthesia and Analgesia studied the effectiveness of granisetron and dolasetron in preventing nausea and vomiting after surgery. It also reviewed the effect of certain ‘metabolising systems’ responsible for clearing such drugs from the body, known as CYP liver enzymes. These enzymes control the breakdown of certain medications; however, they may perform this to a greater or lesser extent depending on certain characteristics of the patient involved. This study employed ‘double blind’ researching techniques on 150 adult patients, where neither the patients nor the doctors were aware of which drug was being given to any of the patients. In this way, the study found that there were differences in the effectiveness of both drugs, and these could be linked to the individual patient differences in the CYP 2D6 system expression.

‘Serotonin antagonists’ such as granisetron and dolasetron are commonly used to prevent and treat nausea and vomiting in patients following surgical procedures. These two medications share the same drug class; however, they both have their distinct pathways of clearance from the body. Granisetron is usually broken down by the CYP 3A4 enzymes, while dolasetron uses the CYP 2D6 enzymes. Studies have found that the 3A4 form is more predictable than the 2D6 forms, which often vary in their level of expression.This study performed a direct comparison of the effectiveness of granisetron and dolasetron in preventing nausea and vomiting related to surgery. Furthermore, it also examined the effect of the CYP 2D6 enzymes on the effectiveness of the two drugs. One hundred and fifty adult patients were randomly grouped into two sets, and each set of patients were given either granisetron 1 mg or dolasetron 12.5 mg during the surgical procedure. All patients were then observed for 24 hours after the surgery for episodes of vomiting, retching, or dry heaving. Observers also recorded if any of the patients requested or required further medication for their bouts of nausea and vomiting. Specialised genetic techniques were employed to determine the CYP 2D6 expression in patients, and 4 different levels of expression were found. These ranged from ‘slow metabolisers’ to ‘ultra metabolisers’ of the drugs, and displayed the relative ‘speed’ with which patients could clear the drugs from their bodies. Patient examination revealed that a greater number of patients required further medications for their symptoms of nausea and vomiting in the dolasetron set compared to the granisetron set. Also, patients in the dolasetron group revealed to be ‘ultra metabolisers’ of the drug appeared to suffer more vomiting episodes than the granisetron group. This lead to the conclusion that CYP 2D6 variability may indeed be related to the effectiveness of such medications; and the finding of greater effect with granisetron rather than dolasetron supported the theory of a difference. This theory will only be fully understood through performing further studies on the topic with larger and more varied patient groups. Reference:Janicki PK, Schuler HG, Jarzembowski TM, et al. Prevention of post operative nausea and vomiting with granisetron and dolasetron. Anaesth Analg 2006; 102(4); 1127-33.