24.4: Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists

Dopamine receptor antagonists, also known as antipsychotic agents, are critical in managing chemotherapy-induced vomiting. These antiemetic agents block dopamine receptors in the chemoreceptor trigger zone (CTZ), inhibiting signal transmission to the vomiting center. Antipsychotic agents encompass phenothiazines (PTZ), butyrophenones, benzamides, and thienobenzodiazepines (Zyprexa), which are utilized for their antiemetic and sedative properties.

Phenothiazines, such as prochlorperazine (Compazine), are effective against low or moderately emetogenic chemotherapy regimens. Metoclopramide, a substituted benzamide, demonstrates antiemetic activity and enhances gastric motility. This dual functionality makes metoclopramide a versatile therapeutic option. Trimethobenzamide, another substituted benzamide, exhibits antiemetic action via dopamine-receptor blockade and has weak antihistaminic activity, further expanding the spectrum of antiemetic options. Butyrophenones, represented by droperidol and haloperidol, function similarly by blocking dopamine receptors, proving to be moderately effective antiemetics. Specifically, olanzapine, a thienobenzodiazepine, inhibits dopamine D2 and serotonin receptors, making it an effective preventive measure against delayed nausea or vomiting associated with chemotherapy.

Despite their effectiveness, central dopamine antagonists can cause significant adverse effects, primarily extrapyramidal symptoms such as restlessness, dystonias, and Parkinsonian symptoms. Their use must be balanced with the potential for significant adverse effects.

Vomiting is a distressing symptom often triggered by cancer chemotherapy.

Dopamine receptor antagonists are key antiemetics. They bind to dopamine receptors in the chemoreceptor trigger zone and prevent receptor-dopamine interaction. This inactivates the receptor and reduces signal transmission to the vomiting center.

Common dopamine receptor antagonists belong to phenothiazines, butyrophenones, thienobenzodiazepines, and benzamides.

Phenothiazines, like prochlorperazine and promethazine, are available as tablets, injectables, or suppositories. As they also block histamine and muscarinic receptors, they are effective for motion sickness and GI disorder-related emesis.

Butyrophenones, such as droperidol, are given intramuscularly or intravenously to control acute chemotherapy-induced emesis.

Thienobenzodiazepines, like olanzapine, inactivate both dopamine and 5HT₂ receptors, preventing delayed vomiting post-chemotherapy.

Benzamides comprise metoclopramide, which inhibits vomiting and treats gastroparesis by increasing GI tract motility.

Adverse effects of these drugs include sedation, hypotension, dystonia, and cardiac arrhythmias.