Indications
Granisetron is approved for the prevention of nausea and vomiting associated with both initial and subsequent courses of emetogenic cancer therapies, which includes treatments with high-dose cisplatin. Additionally, it is indicated for managing post-operative nausea and vomiting, as well as nausea and vomiting induced by radiation, including total body irradiation and daily fractionated abdominal radiation.
Pharmacodynamics
Granisetron functions as a selective inhibitor of type 3 serotonergic (5-HT3) receptors, exhibiting minimal to no affinity for other serotonin receptor types, such as 5-HT1, 5-HT1A, 5-HT1B/C, or 5-HT2. It also does not affect alpha 1, alpha 2, or beta-adrenoreceptors, dopamine D2 receptors, histamine H1 receptors, benzodiazepine receptors, picrotoxin receptors, or opioid receptors. Clinical studies indicate that granisetron typically has negligible impact on blood pressure, heart rate, or electrocardiogram results. Structurally and pharmacologically akin to ondansetron, another 5-HT3 receptor inhibitor, granisetron blocks receptors situated on vagal nerve terminals and in the chemoreceptor trigger zone of the area postrema. The release of serotonin from enterochromaffin cells in the small intestine, triggered by chemotherapeutic agents, activates the vomiting reflex through stimulation of vagal and splanchnic nerve receptors projecting to the medullary vomiting center and the 5-HT3 receptors in the area postrema.
Absorption
Granisetron is rapidly and completely absorbed following administration; however, its oral bioavailability is approximately 60%, a reduction attributed to the first-pass metabolism effect.
Metabolism
Granisetron undergoes primary metabolism in the liver, where it experiences N-demethylation and aromatic ring oxidation, followed by conjugation. Animal studies suggest that some metabolites of granisetron may retain activity as 5-HT3 receptor antagonists.
Mechanism of Action
Granisetron functions as a highly effective and selective antagonist of 5-HT3 receptors, exhibiting its antiemetic properties by targeting these receptors both centrally in the medullary chemoreceptor zone and peripherally in the gastrointestinal tract. By blocking 5-HT3 receptor activity, Granisetron effectively reduces visceral afferent stimulation of the vomiting center, indirectly influencing the area postrema. Furthermore, it directly inhibits serotonin activity within the area postrema and the chemoreceptor trigger zone, thereby mitigating the emetic response.
