Definition
ChEBI: A monocarboxylic acid amide resulting from the formal condensation of the carboxy group of 1-methyl-1H-indazole-3-carboxylic acid with the primary amino group of (3-endo)-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine. A sele
tive 5-HT3 receptor antagonist, it is used (generally as the monohydrochloride salt) to manage nausea and vomiting caused by cancer chemotherapy and radiotherapy, and to prevent and treat postoperative nausea and vomiting.
Indications
granisetron (Kytril) is potent
antagonists of 5-HT3 receptors,which is found peripherally
on vagal nerve terminals and centrally in the
CTZ. During chemotherapy that induces vomiting, mucosal
enterochromaffin cells in the GI tract release serotonin,
which stimulates 5-HT3 receptors.
Clinical Use
Prevention or treatment of nausea and vomiting induced
by cytotoxic chemotherapy, radiotherapy, or postoperative
nausea and vomiting (PONV)
Side effects
This causes vagal
afferent discharge, inducing vomiting. In binding to
5-HT3 receptors, granisetron blocks
serotonin stimulation, hence vomiting, after emetogenic
stimuli such as cisplatin. Headache is the most frequently
reported adverse effect of these medications.
Drug interactions
Potentially hazardous interactions with other drugs
Cytotoxics: possible increased risk of ventricular
arrhythmias with panobinostat.
Metabolism
Granisetron is metabolised primarily in the liver by
oxidation followed by conjugation. The major compounds
are 7-OH-granisetron and its sulphate and glycuronide
conjugates. Although antiemetic properties have
been observed for 7-OH-granisetron and indazoline
N-desmethyl granisetron, it is unlikely that these
contribute significantly to the pharmacological activity
of granisetron in man. Clearance is predominantly by
hepatic metabolism. Urinary excretion of unchanged
granisetron averages 12% of dose whilst that of
metabolites amounts to about 47% of dose. The
remainder is excreted in faeces as metabolites.
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