Ondansetron and Rare Neurologic Side Effects

Indication/Dosing:
PONV PPx and Treatment 4mg IV q4-8hr. Up to 32mg IV for highly emetogenic
chemo. MC Neuro side effect is Headache.
MOA:
Antagonize 5-HT3 receptors (Serotonin subtype receptor which mediates
vomiting) present peripherally in enterochromaffin cells in GI mucosa blocking
abdominal vagal afferents and centrally in the CRT zone of the area postrema and
the nucleus tractus solitarius.
Ondansetron is not known to affect dopamine, histamine, adrenergic, or
cholinergic receptor activity, thus its thought to be free of any adverse neuro
effects.
Ondansetron and Extrapyramidal Side Effects:
Initial clinical trial data failed to detect any EPS.
However, several case reports point to an association of EPS with ondansetron
administration.
Ondansetron may play a role in DA transmission although the MOA is unknown:
Animal studies have shown ondansetron inhibiting DA activity in mesolimbic
area and clinically ondansetron has been observed to prevent levodopa induced
psychosis in pts with Parkinsons disease.
Most case reports describing EPS are associated with Chemo related emesis
treatment, however few case reports exist relating EPS with periop ondansetron
use.
EPS secondary to ondansetron use may be dose dependent and is described as a
stimulus sensitive generalized clonus. Pts with a prior h/o drug induced EPS
side effects may be susceptible.
Ondansetron and Seizures:
Several case reports point to an association of generalized tonic-clonic seizures
and ondansetron use, although EEG was WNL in all cases. Seizures may have
actually been aforementioned EPS Sxs.
Studies have shown that ondansetron can competitively suppress Cl ion current
activated by GABA and Glycine, thereby possibly lowering the seizure threshold.
References:
1. Sprung J, Choudhry FM, Hall BA. Extrapyramidal Reactions to Ondansetron:
Cross-Reactivity between Ondansetron and Prochlorperazine. Anesth Analg
2003;96:1374-1376
2. Singh NN, Rai A, Selhorst JB, Acharya JN. Ondansetron and Seizures. Epilepsia
2009;50(12): 2663-66

3. Perioperative extrapyramidal reactions associated with ondansetron.

Anesthesiology 1999; 90:340-341.