Ondansetron / Zofran

Ondansetron is the go-to antiemetic for chemotherapy and post-op nausea, yet one overlooked cardiac side effect can turn a routine order into a code. Know the mechanism and the risk.

Ondansetron is a selective serotonin 5-HT3 receptor antagonist. It works in two places: it blocks 5-HT3 receptors on vagal afferents in the GI tract and in the chemoreceptor trigger zone (CTZ) of the medulla. When chemotherapy, radiation, or anesthesia triggers massive serotonin release from enterochromaffin cells in the gut, ondansetron intercepts that signal before it reaches the vomiting center. This makes it first-line for chemotherapy-induced nausea and vomiting (CINV), radiation-induced nausea, and postoperative nausea and vomiting (PONV). It can be given PO, IV, or ODT (orally disintegrating tablet — useful when the patient is already vomiting). The critical safety concern is QT prolongation, which can lead to torsades de pointes; ondansetron is contraindicated in congenital long QT syndrome. A baseline ECG should be reviewed in patients with electrolyte imbalances (hypokalemia, hypomagnesemia) or heart failure, and electrolyte imbalances should be corrected before administration. The maximum single IV dose is 16 mg. Common side effects are headache, constipation, and dizziness — far milder than the sedation and extrapyramidal symptoms seen with older antiemetics like promethazine or metoclopramide.

Key Distinctions

Don't confuse ondansetron's 5-HT3 blockade with the dopamine blockade of metoclopramide or promethazine — ondansetron does NOT cause extrapyramidal symptoms or significant sedation. Students often think all antiemetics are interchangeable; ondansetron lacks the anticholinergic and antidopaminergic burdens that make older agents riskier in elderly patients. While QT prolongation is a key concern with ondansetron, other antiemetics (e.g., droperidol, metoclopramide) can also prolong QT — always check the specific drug profile.

Clinical Pearl

Think "Zofran blocks the Serotonin Storm" — 5-HT3 block at the gut and the brain, no sedation, but watch the QT.