Ondansetron antiemetic action

Ondansetron is not a dopamine-receptor antagonist. Becanse serotonin receptors of the 5-HT3 type are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone, it is not certain if ondansetron s antiemetic action is mediated centrally, peripherally, or in both sites (see Fignre 73). 

Ondansetron, granisetron, and dolasetron are selective 5-HTj receptor blockers and have a central antiemetic action in the area postrema of the medulla and also on peripheral sensory and enteric nerves. 

The 5-HT3 receptor is the only monoamine neurotransmitter receptor that functions as a lig-and-gated ion channel, controlling the flux of Na-i- and K+ ions. 5-HT3 receptors are located on parasympathetic nerve terminals in the gastrointestinal tract, and high densities are found in areas of the brain associated with the emetic response, such as the area postrema. The antiemetic effects of 5-HT3 antagonists, such as ondansetron, result from actions at these sites. 5-HT3 receptors in the dorsal horn of the spinal cord have been implicated in nociception and development of new 5-HT3 receptor-related compounds may have potential as non-opioid, non-addictive analgesics. 

Antiemetics that act on the vomiting centre have antimuscarinic (their principal mode) and anti-histaminic action (hyoscine, promethazine) they alleviate vomiting from any cause. In contrast, drugs that act on the CTZ (haloperidol, ondansetron) are effective only for vomiting mediated by stimulation of the chemoreceptors (by morphine, digoxin, cytotoxics, uraemia). The most efficacious drugs act at more than one site (Table 31.1). 

Phenothiazines such as prochlorperazine, thiethylperazine, and chlorpromazine see Chapter 18) are among the most commonly used antinauseants and antiemetics. Their principal mechanism of action is dopamine receptor antagonism at the CTZ. Compared to metoclopramide or ondansetron see above), these drugs do not appear to be as uniformly effective in cancer chemotherapy-induced emesis. On the other hand, they also possess antihistaminic and anticholinergic activities, which are of value in other forms of nausea, such as motion sickness. 

Note that prochlorperazine should not be given if apomorphine is used for Parkinson s disease, as its dopamine antagonist actions can worsen the disease (see also Levodopa + Antiemetics , p.682). Because apomorphine is highly emetogenic at the doses required for the treatment of Parkinson s disease (1 to 4 mg/hour by subcutaneous infusion), patients with Parkinson s disease requiring apomorphine should be pretreated with domperidone 20 mg three times daily for at least 2 days. Rare reports of extrapyramidal adverse effects have been reported with ondansetron, which may be of relevance in patients with Parkinson s Disease. 

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