Description

Ondansetron is a synthetic antiemetic drug that belongs to the class of medications known as serotonin 5-HT3​ receptor antagonists. The “HCL” in its name refers to the hydrochloride salt form, which is the most common formulation for oral, intravenous, and suppository preparations. Ondansetron is one of the most widely used and effective drugs for controlling nausea and vomiting.

Indications

Ondansetron is primarily used for the prevention and treatment of nausea and vomiting caused by certain medical procedures and treatments. Its key indications include:

• Chemotherapy-Induced Nausea and Vomiting (CINV): It is a cornerstone of antiemetic therapy for patients receiving cancer chemotherapy, particularly for highly emetogenic regimens. It is effective in preventing both acute (within 24 hours) and delayed (1-5 days after) CINV.
• Radiotherapy-Induced Nausea and Vomiting (RINV): It is used to prevent nausea and vomiting in patients undergoing radiotherapy, especially when the radiation targets the abdomen.

• Postoperative Nausea and Vomiting (PONV): It is widely used to prevent and treat nausea and vomiting following surgical procedures.

Mechanism of Action

Ondansetron’s mechanism of action is based on its ability to block serotonin receptors, thereby interrupting a key signaling pathway that triggers nausea and vomiting.

1. Targeting the 5-HT3​ Receptor: Ondansetron is a selective and competitive antagonist of the serotonin 5-HT3​ receptors. These receptors are found in two critical locations involved in the emetic reflex:
   • In the Periphery: They are located on the vagal nerve terminals in the gastrointestinal (GI) tract. When chemotherapeutic agents, radiation, or other emetogenic stimuli are introduced, they can cause the release of serotonin from enterochromaffin cells in the gut. This serotonin then activates the 5-HT3​ receptors on the vagal nerve, sending a nausea signal to the brain.

• • In the Central Nervous System: The receptors are also present in the chemoreceptor trigger zone (CTZ) of the brain. The CTZ can independently trigger the vomiting reflex in response to various stimuli in the blood and cerebrospinal fluid.

2. Blocking the Emetic Reflex: By binding to and blocking the 5-HT3​ receptors, ondansetron prevents serotonin from activating them. This action effectively stops the nausea and vomiting signals from being transmitted from the gut to the brain. It also directly inhibits the vomiting center by blocking the receptors in the CTZ. This dual action in both the periphery and the brain makes ondansetron a very effective antiemetic.

In summary, ondansetron works by interrupting the signaling pathway of serotonin, a key mediator of the emetic reflex, thereby preventing nausea and vomiting from both peripheral (gut) and central (brain) triggers.